for thePublic Health Strategic Health Care Gr

Veterans Health Administra

U.S. Department of Veterans A

APRIL 2

Primary Care of

Veterans with HIV

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IB 10-227

P96188 www.h
The editors of this manual are committed to providing accurate 

information on HIV-related care. However, please be aware 

that therapy options and protocols continue to change. Readers are 

invited to check for updates to drug information at Drugs@FDA 

(http://www.accessdata.fda.gov/scripts/cder/drugsatfda/) 

and to treatment guidelines at AIDS Info (http://aidsinfo.nih.gov/). 

We hope that you will send feedback and suggestions for future 

editions to: publichealth@va.gov.

IMPORTANT NOTICE

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PRIMARY CARE OF VETERANS WITH HIV 

Table of Contents

Contributors....................................................................................................................... v

Introduction .......................................................................................................................ix

Abbreviations ...................................................................................................................x

Behavior and Prevention

Alcohol Misuse ......................................................................................................................3

Cancer Screening ................................................................................................................17

Immunizations ......................................................................................................................37

Prevention for Positives .....................................................................................................39

Smoking Cessation..............................................................................................................53

Substance Use ......................................................................................................................69

Organ Systems and Metabolic

Anal Dysplasia ......................................................................................................................83

Androgen Defi ciency ..........................................................................................................89

Asthma ..................................................................................................................................97

Chronic Obstructive Pulmonary Disease (COPD) .................................................. 107

Dermatologic Conditions .............................................................................................. 115

Diabetes ............................................................................................................................. 127

Dyslipidemia ...................................................................................................................... 143

Gastroesophageal Refl ux Disease (GERD) ................................................................ 155

Hypertension .................................................................................................................... 17

Liver Disease and Cirrhosis ........................................................................................... 185

Osteoarthritis ................................................................................................................... 203

Renal Disease .................................................................................................................... 21

Urology............................................................................................................................... 227

Women’s Health

Women’s Health ............................................................................................................... 249

Neurology, Psychiatry, and Pain 

Depression ........................................................................................................................ 27

Low Back Pain ................................................................................................................... 285

Peripheral Neuropathy ................................................................................................... 295

Drug Tables 

Common Medications: ARV Interactions ................................................................... 307

Food and Supplements: ARV Interactions .................................................................. 313

Lipid-Lowering Medications: ARV Interactions ......................................................... 315 

Pain Medications: Dosage and Indications ................................................................. 32

Psychoactive Medications: ARV Interactions ............................................................. 327

Index .................................................................................................................................. 33

PRIMARY CARE OF VETERANS WITH HIV

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PRIMARY CARE OF VETERANS WITH HIV 

EDITOR-IN-CHIEF

David Ross, MD, PhD

Director, Clinical Public 

Health Programs

Public Health Strategic 

Health Care Group, VHA

Washington, DC

AUTHORS

Oliver Bacon, MD

Assistant Clinical Professor

University of California 

San Francisco

Rena Fox, MD

Associate Professor of 

Clinical Medicine

University of California 

San Francisco

Sophy Shiahua Wong, MD

Assistant Clinical Professor

University of California 

San Francisco

EDITOR AND AUTHOR

Susa Coffey, MD

Assistant Clinical Professor

University of California 

San Francisco

EDITORIAL STAFF

Patricia Long, MS

Project Manager

Carrie Clark Walsh, ELS

Editorial Manager

David Alexander, MA

Sr. Copy Editor

Contributors

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VI PRIMARY CARE OF VETERANS WITH HIV

REVIEWERS

Lisa Backus, MD, PhD

Palo Alto VA Medical Center

Palo Alto, CA 

Pamela S. Belperio, 

PharmD, BCPS

Center for Quality Management in 

Public Health, VHA 

Palo Alto, CA 

Sonya Borrero, MD, MS

VA Pittsburgh Healthcare System

Pittsburgh, PA 

Monique V. Chireau, MD, MPH

Durham VA Medical Center 

Durham, NC 

George F. Cohen, MD

Washington, DC VA Medical Center

Washington, DC 

Michael Craine, PhD

Denver VA Medical Center

Denver, CO 

Kristina Crothers, MD

VA Connecticut Healthcare System

West Haven, CT 

Rajvir Dahiya, PhD

San Francisco VA Medical Center

San Francisco, CA 

Vicky Davey, RN, MPH

Offi ce of Public Health and

Environmental Hazards, VHA

Washington, DC

John Davison, MBA, PhD

Public Health Strategic 

Health Care Group, VHA

Washington, DC

Lawrence Deyton, MD, MSPH 

Offi ce of Public Health and 

Environmental Hazards, VHA

Washington, DC

Patricia Dumas, RN, MPH 

Primary Care-Mental 

Health Integration, VHA

Washington, DC 

Steven J. Farber, PA-C, 

JD, AAHIVS

West Haven VA Medical Center

West Haven, CT 

David Fiellin, MD

Yale University School of Medicine

West Haven, CT 

Guadalupe Garcia-Tsao, MD

VA Connecticut Healthcare System

West Haven, CT 

Janet Gearin, BSN, MS 

Tulsa Behavioral Medicine Clinic

Tulsa, OK 

Cynthia Livingstone Gibert, 

MD, MSc

Washington, DC VA Medical Center

Washington, DC 

Matthew B. Goetz, MD 

VA Greater Los Angeles 

Healthcare System

Los Angeles, CA 

Carl Grunfeld, MD, PhD

San Francisco VA Medical Center

San Francisco, CA

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PRIMARY CARE OF VETERANS WITH HIV V

David M. Guidot, MD

Atlanta VA Medical Center

Decatur, GA 

Kim Hamlett-Berry, PhD

Public Health Strategic 

Health Care Group, VHA

Washington, DC 

Patricia Hayes, PhD

Women Veterans Health 

Strategic Health Care Group

Washington, DC 

Mark Holodniy, MD

Palo Alto VA Medical Center

Palo Alto, CA

Sheryl Horwitz, RN, MS, 

WHCNP

Westover Heights Clinic

Portland, OR

Amy C. Justice, MD, PhD

VA Connecticut Healthcare System

West Haven, CT 

Christopher J. Kane MD, FACS

San Diego VA Medical Center

San Diego, CA

Lois Anne Katz, MD

VA New York Harbor 

Healthcare System

New York, NY 

Dan Kivlahan, PhD

VA Puget Sound Health Care System

Seattle, WA

David A. Leaf, MD, MPH

VA Greater Los Angeles 

Healthcare System

Los Angeles, CA 

Michael R. Littner, MD

VA Greater Los Angeles 

Healthcare System

Sepulveda, CA

Edward Lott, PA-MPAS

VA Greater Los Angeles 

Healthcare System

Los Angeles, CA 

Gayle Lyke, BS, MT (ASCP)

Public Health Strategic 

Health Care Group, VHA

Washington, DC

Alexander Monto, MD

San Francisco VA Medical Center

San Francisco, CA

Mark S. Nanes, MD, PhD

Atlanta VA Medical Center

Atlanta, GA 

Eric Nylen, MD

Washington, DC VA Medical Center

Washington, DC 

David Rimland, MD

Atlanta VA Medical Center

Atlanta, GA

Gordon Schectman, MD

Milwaukee VA Medical Center

Milwaukee, WI

Ronald O. Valdiserri, MD, MPH

Public Health Strategic 

Health Care Group, VHA

Washington, DC

Kevin L. Wright, LCSW

VA New York Harbor 

Healthcare System

Brooklyn, NY 

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PRIMARY CARE OF VETERANS WITH HIV I

Introduction

In many ways, veterans with HIV infection represent the future wave of the HIV 

epidemic. Compared with the overall HIV-infected population in the United States, 

veterans with HIV are older, more likely to be members of minority groups, and 

more likely to have a history of substance use.1 Thus, it is not surprising that 

they are experiencing an increasing burden of medical and psychiatric comorbid 

disease.2 Indeed, some data suggest that residual racial disparities in survival 

of individuals living with HIV may be explained in part by a greater burden of 

comorbid illness.3

Depending upon the study cited, approximately 60% of the deaths occurring 

among individuals with HIV infection are now attributed to “non-AIDS” causes.4-

That does not mean those conditions are unassociated with HIV disease or 

its treatment. Many of the most common and serious comorbid conditions, 

including liver fi brosis/cirrhosis, anemia, renal insuffi ciency or failure, selected 

cancers, thrombosis, intracranial hemorrhage, and obstructive lung disease, are 

more likely to occur among HIV-infected individuals than among uninfected, 

demographically similar controls.7-10 Among persons with HIV infection, these 

conditions are more likely to be found in those with advanced disease. Further, 

the liver, renal, and bone marrow toxicities associated with antiretroviral 

treatment are well known and more likely to occur among persons with 

preexisting organ injury.11 It must be recognized that HIV infection has become 

a complex, chronic disease, one for which there are likely multiple etiologies of 

any problem. Although this disease is substantially improved by antiretroviral 

treatment, some individuals experience substantial toxicities from treatment.11,12

As individuals age with HIV infection, organ injury associated with HIV infection, 

aging-related comorbid illnesses, and substance use and abuse likely will lead to 

even more “non-AIDS” mortality.

We must learn to prioritize and coordinate screening and treatment for importan

comorbid conditions while maintaining excellence in the care of HIV infection. 

Although most VA HIV providers consider themselves primary care providers for 

their patients with HIV infection, their degree of comfort with many of the staple

of primary care screening and treatment is not as high as it is among general 

health care providers.13 This manual offers a practical approach to addressing 

many of these issues. Further, it attempts to appropriately tailor recommendation

to the special issues facing patients who are receiving treatment for HIV infection

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X PRIMARY CARE OF VETERANS WITH HIV

Combination antiretroviral therapy has revolutionized the care of HIV infection. 

Randomized trial data now support continuous antiretroviral management 

of HIV infection, even among patients with comorbid disease.12 Earlier data 

have demonstrated that many “non-AIDS” conditions improve with effective 

antiretroviral therapy.14,15 Clearly, it remains paramount to get patients started on 

an effective regimen and ensure that they are acceptably adherent. Yet, there are 

patients who will require careful attention to alcohol and drug use and depressive 

symptoms before they can achieve acceptable adherence.

Once adherent to an effective regimen, patients may have substantial 

comorbidities that require targeted screening and treatment. The approach to 

these conditions must be guided by the costs and benefi ts in our population of 

patients. Screening and treatment that require a life expectancy beyond 10 years, 

such as colon cancer screening, should be undertaken only for patients who are 

deemed likely to live that long. Otherwise, we will be exposing our patients 

to immediate potential harms (eg, risk of perforation from colonoscopy 

and the pain and discomfort of the preparation and the procedure) without 

the likelihood of future benefi t.16 We also will need to think carefully about 

conditions for which our patients are at particularly high risk, including 

hepatitis C infection and alcohol and tobacco use, and target these accordingly. 

Finally, as more data become available, we need to consider how mechanisms of 

common comorbid diseases may differ among persons with HIV infection and 

determine the implications for management.

Thus, it is with great pleasure that I have written the introduction to what I 

hope will be the fi rst of many editions of this manual, which is the brainchild of 

Dr. David Ross, the HIV Technical Advisory Group, and the Public Health Strategic 

Health Care Group. The manual, and this introduction, are dedicated to the hard 

work, commitment, and good will of the excellent providers who are taking care 

of our veterans with HIV infection.

Amy C. Justice, MD, PhD

Principal Investigator, Veterans Aging Cohort Study

Section Chief, General Internal Medicine, VA Connecticut

Associate Professor of Medicine and Public Health, Yale University 

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PRIMARY CARE OF VETERANS WITH HIV X

REFERENCES

1. Justice AC, Dombrowski E, Conigliaro J, et al. Veterans Aging Cohort Study (VACS): Overview and 

description. Med Care. 2006 Aug;44(8 Suppl 2):S13-24.

2. Justice AC. Prioritizing primary care in HIV: comorbidity, toxicity, and demography. Top HIV Med. 

2006 Dec-2007 Jan;14(5):159-63.

3. McGinnis KA, Fine MJ, Sharma RK, et al. Understanding racial disparities in HIV using data from 

the veterans aging cohort 3-site study and VA administrative data. Am J Public Health. 2003 

Oct;93(10):1728-33.

4. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in 

Denmark, 1995-2005. Ann Intern Med. 2007 Jan 16;146(2):87-95.

5. Kohli R, Lo Y, Howard AA, et al. Mortality in an urban cohort of HIV-infected and at-risk drug users 

in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005 Sep 15;41(6):864-72.

6. Palella FJ Jr, Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: 

changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defi c Syndr. 

2006 Sep;43(1):27-34.

7. Justice AC, Lasky E, McGinnis KA, et al. Medical disease and alcohol use among veterans with huma

immunodefi ciency infection: A comparison of disease measurement strategies. Med Care. 2006 

Aug;44(8 Suppl 2):S52-60.

8. McGinnis KA, Fultz SL, Skanderson M, et al. Hepatocellular carcinoma and non-Hodgkin’s lymphoma

the roles of HIV, hepatitis C infection, and alcohol abuse. J Clin Oncol. 2006 Nov 1;24(31):5005-9.

9. Fultz SL, McGinnis KA, Skanderson M, et al. Association of venous thromboembolism with human 

immunodefi ciency virus and mortality in veterans. Am J Med. 2004 Mar 15;116(6):420-3.

10. Crothers K, Butt AA, Gibert CL, et al. Increased COPD among HIV-positive compared to HIVnegative veterans. Chest. 2006 Nov;130(5):1326-33.

11. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 

antiretroviral agents in HIV-1-infected adults and adolescents. Washington: Department of Health 

and Human Services; January 28, 2008.

12. El-Sadr WM, Lundgren JD, Neaton JD, et al; Strategies for Management of Antiretroviral Therapy 

(SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 

2006 Nov 30;355(22):2283-96. 

13. Fultz SL, Goulet JL, Weissman S, et al. Differences between infectious diseases-certifi ed physicians 

and general medicine-certifi ed physicians in the level of comfort with providing primary care to 

patients. Clin Infect Dis. 2005 Sep 1;41(5):738-43. 

14. Moore RD, Forney D. Anemia in HIV-infected patients receiving highly active antiretroviral therapy. 

J Acquir Immune Defi c Syndr. 2002 Jan 1;29(1):54-7.

15. Sulkowski MS, Thomas DL, Chaisson RE, et al. Hepatotoxicity associated with antiretroviral therapy 

in adults infected with human immunodefi ciency virus and the role of hepatitis C or B virus infection

JAMA. 2000 Jan 5;283(1):74-80.

16. Braithwaite RS, Concato J, Chang CC, et al. A framework for tailoring clinical guidelines to 

comorbidity at the point of care. Arch Intern Med. 2007 Nov 26;167(21):2361-5.

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XII PRIMARY CARE OF VETERANS WITH HIV

DOSING TERMINOLOGY

BID = twice daily

IM = intramuscular 

IV = intravenous 

PO = orally

PRN = as needed 

Q2H, Q4H, etc = every 2 hours, 

 every 4 hours, etc

QAM = every morning

QD = once daily

QH = every hour

QHS = every night at bedtime

QID = 4 times per day

QOD = every other day

TID = 3 times per day

TIW = 3 times per week 

ANTIRETROVIRAL TERMINOLOGY

ART = antiretroviral therapy

ARV = antiretroviral

FI = fusion inhibitor

NNRTI = nonnucleoside 

 reverse transcriptase inhibitor

NRTI = nucleoside (or nucleotide)

 reverse transcriptase inhibitor

PI = protease inhibitor

ANTIRETROVIRAL DRUGS

3TC = lamivudine

ABC = abacavir

APV = amprenavir

ATV = atazanavir

d4T = stavudine

ddC = zalcitabine

ddI = didanosine

DLV = delavirdine

DRV = darunavir

EFV = efavirenz

ENF = enfuvirtide

ETR = etravirine

FPV = fosamprenavir

FTC = emtricitabine

IDV = indinavir

LPV/r = lopinavir/ritonavir

MVC = maraviroc

NFV = nelfi navir

NVP = nevirapine

RAL = raltegravir

RTV = ritonavir

/r = ritonavir, low dose

SQV = saquinavir

TDF = tenofovir

TPV = tipranavir

ZDV = zidovudine

Abbreviations for 

Antiretroviral Drugs and Dosing Instructions 

Commonly Used in This Manual

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PRIMARY CARE OF VETERANS WITH HIV 

Alcohol Misuse

KEY POINTS

■ Alcohol misuse is common among HIV-infected patients.

■ It is the third leading preventable cause of death in the United 

States.

■ Screening, followed by brief counseling interventions or treatment, 

can decrease drinking and improve health outcomes. 

■ At the initial visit and at least annually thereafter, all patients should 

be screened for alcohol misuse with the AUDIT-C questionnaire.

■ Evaluate and treat at-risk and disordered alcohol drinkers with the 

4 A’s: Ask, Assess, Advise, and Assist. 

■ Consider referrals to Alcoholics Anonymous, cognitive-behavioral 

therapy, addiction specialists, and detoxifi cation programs.

■ Consider giving the pharmacologic abstinence adjunct naltrexone 

at 100 mg QD for 3-4 months to assist with continued abstinence. 

Monitor LFTs closely.

■ Evaluate and treat comorbid psychiatric and substance use 

disorders.

BACKGROUND

Defi nitions 

Alcohol misuse refers to the spectrum from risky drinking to alcohol 

dependence. 

Risky drinking refers to drinking beyond 

recommended drinking limits (see 

below).

Alcohol abuse and alcohol dependence (also called “alcohol use disorders”) refer to diagnoses based on problems patients experience as a result of 

drinking, and are defi ned by the DSM-IV-TR. Both abuse and dependence are 

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Veterans with HIV*

Alcohol use disorder: 33%

*Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition 

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ALCOHOL MISUSE

4 PRIMARY CARE OF VETERANS WITH HIV

or distress. 

Alcohol abuse is a maladaptive pattern of use associated with 1 or more of the 

following: 

• Failure to fulfi ll work, school, or social obligations

• Recurrent alcohol use in physically hazardous situations

• Recurrent legal problems related to alcohol use

• Continued alcohol use despite alcohol-related social or interpersonal 

problems

Alcohol dependence is defi ned as a maladaptive pattern of use associated 

with 3 or more of the following:

• Tolerance

• Withdrawal

• Alcohol taken in larger quantity than intended

• Persistent desire to cut down or control use

• Time is spent obtaining, using, or recovering from alcohol

• Social, occupational, or recreational tasks are sacrifi ced

• Alcohol use continues despite physical and psychological problems

Recommended drinking limits:

Based on the accumulated epidemiological evidence, individuals who drink 

beyond the following levels are at increased risk of adverse consequences of 

drinking (National Institute for Alcohol Abuse and Alcoholism [NIAAA]):

■ An average of 2 drinks daily (14 drinks per week) for younger men; an 

average of 1 drink daily (7 drinks per week) for women or older adults 

(≥65 years)

■ A maximum of 4 drinks on any occasion for men; a maximum of 3 drinks on 

any occasion for women or older adults

Defi nition of a standard drink: 

12 g of alcohol

Roughly equivalent to:

• 12 oz beer

• 5 oz wine 

• 1.5 oz distilled spirits (80 proof)

Note that safe drinking limits may be substantially lower for some patients, 

depending on factors such as comorbidities (eg, liver disease), pregnancy, and 

interacting medications.

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PRIMARY CARE OF VETERANS WITH HIV 

meet criteria for alcohol dependence. These nondependent drinkers account for 

the majority of alcohol-related morbidity and mortality in the general population

All patients who misuse alcohol should receive focused medical attention and 

intervention.

Epidemiology

■ 35-40% of HIV-infected patients in primary care settings have documented 

diagnoses of alcohol use disorder; many more probably drink above recommended levels in ways that pose health risks. 

■ Alcohol misuse causes substantial morbidity and mortality. Medical conditions associated with alcohol misuse include alcohol withdrawal syndrome, 

hepatitis, cirrhosis, pancreatitis, thiamine defi ciency, neuropathy, cardiomyopathy, hypertension, depression, and cancers of the oropharynx, larynx, and 

esophagus.

■ Excessive alcohol consumption is the third leading preventable cause of death 

in the United States.

■ Alcohol use is associated with:

• 40% of all traffi c fatalities (2000)

• 20-37% of emergency department trauma cases (1990)

• 66% of all drownings

• 50% of all deaths from cirrhosis

■ Alcohol use compounds the liver damage associated with hepatitis C and 

hepatitis B, and accelerates progression to cirrhosis. 

■ Concomitant use of alcohol and hepatotoxic drugs (including some ARVs) 

may increase the risk of early and severe liver damage.

■ The risk of pancreatitis caused by ddI is higher among patients who use alcohol chronically. 

EVALUATION

Alcohol Misuse Screening

At the initial visit and at least annually thereafter: Screen all patients for 

alcohol misuse. Ask drinkers the AUDIT-C questions. 

The VHA recommends universal screening to identify patients who misuse alcohol. Screening followed by brief counseling interventions or treatment has been 

shown to decrease drinking and improve health outcomes. 

SCREENING

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ALCOHOL MISUSE

6 PRIMARY CARE OF VETERANS WITH HIV

use, and about family history of alcohol-related problems. 

■ For drinkers, use the AUDIT-C screening questionnaire (see below) to assess 

for risky drinking (see above for recommended drinking limits).

■ For drinkers, ask more specifi c questions to determine whether they fulfi ll 

criteria for alcohol abuse or dependence (see DSM-IV-TR criteria, above) and 

whether they have signs or symptoms of liver disease, psychiatric comorbidities, behavioral complications such as violent episodes, or other substance 

abuse.

■ Goals for evaluation:

• Determine whether the patient is drinking above safe levels.

• Determine whether the patient has loss of control over the use of 

alcohol.

• Determine whether tolerance, dependence, or abuse is present.

• Determine whether adverse consequences of excessive drinking have 

occurred.

The AUDIT-C: Alcohol Use Disorder Identifi cation Test – Consumption 

Questions

The AUDIT-C is a validated 3-question screening tool for alcohol misuse and 

alcohol use disorders (including alcohol abuse or dependence). It is the required 

screening tool for alcohol misuse in the VHA.

It can identify patients with alcohol misuse who would benefi t from counseling 

to decrease their drinking and those who use alcohol and need referral to treatment services.

1. How often have you had a drink containing alcohol in the last 

year? Consider a “drink” to be a 12 oz can or bottle of beer, a 

glass of wine, a wine cooler, or 1 cocktail or shot of hard liquor 

(such as scotch, gin, or vodka).

Never (0 points); monthly or less (1); 2-4 times/month (2); 2-3 times/week 

(3); ≥4 times/week (4)

2. How many drinks containing alcohol did you have on a typical 

day when you were drinking in the last year?

I do not drink (0 points); 1-2 drinks (0); 3-4 drinks (1); 5-6 drinks (2); 7-9 

drinks (3); ≥10 drinks (4)

3. How often in the last year have you had 6 or more drinks on 

one occasion?

Never (0 points); less than once a month (1); monthly (2); weekly (3); 

daily or almost daily (4)

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PRIMARY CARE OF VETERANS WITH HIV 

indicate higher likelihood that the patient’s health and safety are at risk. AUDIT-C 

scores of ≥4 for men and ≥3 for women suggest alcohol misuse, whereas scores 

of ≥5 require brief follow-up alcohol counseling. An AUDIT-C score of ≥8 indicates a high probability of current dependence; a score of ≥5 for a patient with a 

history of alcohol treatment indicates high risk of current dependence.

 MANAGEMENT

Brief counseling with specialty referral as indicated can be effective in reducing 

hazardous drinking. Patients with alcohol use disorders may require comprehensive treatment programs that include the services of medical providers, psychiatrists to assist with comorbid psychiatric conditions, social workers, housing 

counselors, case managers, and substance abuse counselors.

■ Short-term goals: treating alcohol withdrawal as needed; encouraging 

abstinence and attendance at Alcoholics Anonymous or other counseling pro

grams for the fi rst 3 months; engaging family and community support; ensuring adequate resources for housing, food, and income

■ Long-term goals: sustained abstinence from alcohol use; recovery of selfesteem, health, and social functioning 

Simple, offi ce-based interventions can be made using the 4-A approach: Ask, 

Assess, Advise, and Assist.

■ Ask about alcohol use, using AUDIT-C (see above)

■ Assess for alcohol use disorders (see below)

■ Advise all patients, even those with no reported heavy drinking, to stay 

within healthy drinking limits, keeping comorbidities in mind. Particularly for 

those with liver disease, there is no known “safe” level of alcohol consumption, and alcohol may be particularly dangerous for patients with HIV/HCV 

coinfection.

■ Assist patients with brief interventions, pharmacotherapy, and referral for 

treatment services

• Brief (<5 min) alcohol intervention (BAI) can be extremely effective for 

alcohol misuse. Useful information on BAI can be found at http://www.

hepatitis.va.gov/vahep?page=prtop03-wp-01-res. Key components:

Aim to reach agreement on a drinking goal. _

Let the patient lead the discussion; for example, ask patients (rather _

than tell them) how they think alcohol use affects their health.

Aim for a nonjudgmental atmosphere, using open-end questions and _

eye contact.

Give choices in the discussion rather than force topics on the patient

_

For example, ask about stressors and how alcohol use fi ts in with 

these.

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ALCOHOL MISUSE

8 PRIMARY CARE OF VETERANS WITH HIV

Patients need to understand the importance of change, to have _

a sense of confi dence about their ability to change, and to have a 

support system.

Avoid lecturing or cheerleading; if it happens, take a step back and ask _

an open-end question such as “What do you think of this?”

• Referral to Alcoholics Anonymous is helpful to many patients; AA meetings are held worldwide, and information is available at http://www.aa.org.

• Patients at risk of withdrawal should be referred to detoxifi cation 

programs; those in withdrawal should be referred to an emergency 

department.

■ Reinforce and reevaluate intervention messages at each visit.

The following is an algorithmic representation of screening and intervention 

using this approach from the NIAAA.

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PRIMARY CARE OF VETERANS WITH HIV 

National Institute on Alcohol Abuse and Alcoholism. A Pocket Guide for Alcohol 

Screening and Brief Intervention. Rockville, MD: NIAAA; 2005

X

• 

• 

• 

• 

• 

• 

HOW TO SCREEN FOR HEAVY DRINKING

STEP 1 Ask About Alcohol Use

Screening complete.

Is the answer I or more times? 

NO YES 

Ask: Do you sometimes drink beer, wine,

or other alcoholic beverages? 

On average, how

many days a week

do you have an

alcoholic drink? 

On a typical 

drinking day, how

many drinks do

you have? 

Weekly average 

Record heavy drinking days 

in past year and weekly

average in chart. 

Advise staying within these

limits: 

Maximum Drinking Limits 

For healthy men up to age 65— 

no more than 4 drinks

in a day AND 

no more than14 drinks

in a week

For healthy women (and 

healthy men over age 65)— 

no more than 3 drinks

in a day AND 

no more than 7 drinks 

in a week 

Rescreen annually GO TO 

STEP 2 

NO YES 

How many times in the past year

have you had . . . 

5 or more

drinks in a day?

(for men)

4 or more

drinks in a day?

(for women) 

Ask the screening question about

heavy drinking days: 

One standard drink is equivalent to

12 ounces of beer, 5 ounces of wine,

or 1.5 ounces of 80-proof spirits. 

Recommend lower limits or 

abstinence as indicated: for 

example, for patients who take 

medications that interact 

with alcohol, have a healthy

condition exacerbated by

alcohol, or are pregnant 

(advise abstinence) 

Your patient is an at-risk

drinker. For a more complete

picture of the drinking

pattern, determine the

weekly average: 

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ALCOHOL MISUSE

10 PRIMARY CARE OF VETERANS WITH HIV

National Institute on Alcohol Abuse and Alcoholism. A Pocket Guide for Alcohol 

Screening and Brief Intervention. Rockville, MD: NIAAA; 2005

HOW TO ASSESS FOR ALCOHOL USE DISORDERS

STEP 2 Assess For Alcohol Use Disorders 

Does patient meet criteria for abuse or dependence? 

NO YES 

Next, determine if there is a maladaptive pattern of alcohol 

use, causing clinically significant impairment or distress. 

Determine whether, in the past 12 months, your patient’s 

drinking has repeatedly caused or contributed to 

risk of bodily harm (drinking and driving, operating 

machinery, swimming)

relationship trouble (family or friends) 

role failure (interference with home, work, or school 

obligations) 

run-ins with the law (arrests or other legal problems) 

If yes to one or more your patient has alcohol abuse.

In either case, proceed to assess for dependence symptoms.

Determine whether, in the past 12 months, your patient has

GO TO

STEPS 3 & 4

for

AT-RISK

DRINKING

GO TO

STEPS 3 & 4

for 

ALCOHOL USE

DISORDERS

not been able to cut down or stop (repeated failed

attempts)

not been able to stick to drinking limits (repeatedly

gone over them)

shown tolerance (needed to drink a lot more to get

the same effect)

shown signs of withdrawal (tremors, sweating, nausea,

or insomnia when trying to quit or cut down) 

kept drinking despite problems (recurrent physical

or psychological problems) 

spent a lot of time drinking (or anticipating or 

recovering from drinking)

spent less time on other matters (activities that had

been important or pleasurable) 

If yes to three or more your patient has alcohol 

dependence. 

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PRIMARY CARE OF VETERANS WITH HIV 1

National Institute on Alcohol Abuse and Alcoholism. A Pocket Guide for Alcohol 

Screening and Brief Intervention. Rockville, MD: NIAAA; 2005

STEP 3 Advise and Assist 

STEP 4 At Followup: Continue Support 

FOR AT-RISK DRINKING (no abuse or dependence) 

Is patient ready to commit to change? 

Was patient able to meet and sustain drinking goal?

NO YES 

NO YES 

Gauge readiness to change drinking habits. 

State your conclusion and recommendation clearly and 

relate them to medical concerns or findings. 

Restate your concern. 

Encourage reflection. 

Address barriers to change. 

Reaffirm your willingness

to help. 

Help set a goal. 

Agree on a plan. 

Provide educational 

materials. (See

http://www.niaaa.nih.gov/guide.) 

REMINDER: Document alcohol use and review goals at each visit. 

Acknowledge that 

change is difficult.

Support positive change 

and address barriers.

Renegotiate goal and 

plan; consider a trial of 

abstinence.

Consider engaging 

significant others. 

Reassess diagnosis if

patient is unable to either 

cut down or abstain. 

Reinforce and support 

continued adherence 

to recommendations.

Renegotiate drinking 

goals as indicated (e.g., 

if the medical condition 

changes or if an abstaining patient wishes to

resume drinking).

Encourage to return

if unable to maintain

adherence.

Rescreen at least annually. 

HOW TO CONDUCT A BRIEF INTERVENTION

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ALCOHOL MISUSE

12 PRIMARY CARE OF VETERANS WITH HIV

National Institute on Alcohol Abuse and Alcoholism. A Pocket Guide for Alcohol 

Screening and Brief Intervention. Rockville, MD: NIAAA; 2005

STEP 3 Advise and Assist 

STEP 4 At Followup: Continue Support 

FOR ALCOHOL USE DISORDERS (abuse or dependence) 

Was patient able to meet and sustain drinking goal?

NO YES 

Acknowledge that change

is difficult.

Support efforts to cut down

or abstain. 

Relate drinking to ongoing 

problems as appropriate. 

Consider (if not yet done): 

• consulting with an

 addiction specialist. 

• recommending a mutual 

 help group. 

• engaging significant 

 others. 

• prescribing a medication

 for alcohol-dependent 

 patients who endorse 

 abstinence as a goal. 

Address coexisting

disorders—medical and 

psychiatric—as needed. 

Reinforce and support 

continued adherence.

Coordinate care with

specialists as appropriate.

Maintain medications

for alcohol dependence 

for at least 3 months 

and as clinically indicated 

thereafter.

Treat coexisting nicotine 

dependence.

Address coexisting 

disorders—medical and 

psychiatric—as needed. 

REMINDER: Document alcohol use and review goals at each visit. 

State your conclusion and recommendation clearly and

relate them to medical concerns or findings. 

Negotiate a drinking goal.

Consider evaluation by an addiction specialist.

Consider recommending a mutual help group.

For patients who have dependence, consider

• the need for medically managed withdrawal (detoxification)

 and treat accordingly.

• prescribing a medication for alcohol dependence for patients 

 who endorse abstinence as a goal.

Arrange followup appointments, including medication 

management support if needed. 

HOW TO CONDUCT A BRIEF INTERVENTION

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PRIMARY CARE OF VETERANS WITH HIV 1

Pharmacotherapy for Relapse Prevention

Although pharmacotherapy may help to prevent relapse, multimodal treatment 

that includes medical therapy with or without behavioral therapy may be more 

effective.

Note: Caution should be used, as no trials have demonstrated the safety of 

these medications in HIV-infected patients who are receiving ARVs. Although it 

is expected that the effi cacy of these medications will be similar in patients with 

and without HIV infection, increased monitoring for adverse effects should be 

exercised until more data are available.

A randomized controlled trial involving HIV-uninfected patients compared various combinations of medical management, medication, and behavioral therapy 

for treatment of alcohol dependence in recently abstinent patients. The study 

showed that:

■ All treatment groups had substantial increases in the percentage of days absti

nent from alcohol.

• The highest percentage of days abstinent (77-80%) was seen in 3 treatment groups: patients who received naltrexone (100 mg QD) + medical 

management (9 sessions with a health care professional), naltrexone + 

medical management + a combined behavioral intervention (CBI) (20 

sessions), or medical management + CBI + placebo pills. 

• Patients who received CBI alone (no medical management or pills 

[whether placebo or naltrexone]) had the lowest abstinence rates.

• Acamprosate was no more effective than placebo.

• Treatment effects largely dissipated after 1 year; thus ongoing monitoring 

is important, and treatment of relapse may be necessary.

Most patients with moderate or severe alcohol misuse should be referred 

to specialized alcohol or substance use disorder treatment services. Patients 

with comorbid conditions that are adversely affected by alcohol, such as 

HCV infection or depression, may need treatment even if they do not meet 

typical criteria for alcohol use disorders.

Patients in withdrawal (tremors, sweats, anxiety, disorientation, or visual, 

auditory, or tactile hallucinations) should be referred to an emergency 

department for immediate evaluation and treatment, and should be referred 

to a detoxifi cation program if available.

WHEN TO REFER

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ALCOHOL MISUSE

14 PRIMARY CARE OF VETERANS WITH HIV

g

Naltrexone 

(oral)

50-100 mg QD for ≥3 

months

• Start upon cessation of 

alcohol use

• Optimal duration of 

therapy not known; most 

study subjects treated for 

3-4 months; treatment 

effects tend to wane after 

therapy is stopped

• Pure opioid receptor antagonist

• Avoid in patients who use opioids (precipitates withdrawal 

symptoms) 

• Avoid in patients with liver 

failure

• Possible adverse effects: nausea, 

vomiting, headache, insomnia, 

hepatotoxicity

• Check LFTs before and after 

treatment

Naltrexone (IM) 190 mg IM monthly for 

≥3 months

• Start upon or just after 

cessation of alcohol use; 

greater benefi t may be 

seen in patients who 

achieve some duration 

of alcohol abstinence (eg, 

2-4 days) before the initial 

injection of naltrexone

• Useful for patients with 

adherence issues

• See PBM Criteria for Use 

at http://www.pbm.va.gov/

CriteriaForUse.aspx

• Pure opioid receptor 

antagonist 

• Possible adverse effects: nausea, 

vomiting, headache, hepatotoxicity, injection site reactions

• Avoid in patients who use opioids (precipitates withdrawal 

symptoms)

• Avoid in patients with liver 

failure

• 380 mg dose has been standard 

but does not confer more 

abstinence advantage and 

causes more side effects

Disulfi ram 

(Antabuse)

250 mg QD as adjunct 

during outpatient treatment period

• Start ≥12 hours after last 

alcohol consumption

• Disulfi ram acts as an acetaldehyde dehydrogenase 

inhibitor

• Concurrent alcohol consumption increases plasma acetaldehyde concentrations 5-10 

times, causing fl ushing, tachycardia, hypotension, nausea, 

vomiting, vertigo, and anxiety 

within 15 minutes

• Other possible adverse effects 

include delirium, hepatotoxicity 

(monitor LFTs before treatment and every 3 months during treatment), neuropathy

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PRIMARY CARE OF VETERANS WITH HIV 1

p

who take ARV syrups or other 

medications that contain alcohol or propylene glycol (eg, 

RTV, LPV/r, and FPV liquid formulations) 

• Patients must avoid OTC medications containing alcohol (eg, 

cough syrup), as well as sauces, 

vinegars, and foods containing 

alcohol 

• Multiple other drug interactions, including with phenytoin, 

rifampin, isoniazid, and warfarin

Acamprosate 666 mg TID for 3 

months

• See PBM Criteria for Use 

at http://www.pbm.va.gov/

criteria/Acamprosate

Criteria.pdf

• Should only be used in 

patients with at least 4 

days of abstinence and 

only mild withdrawal 

symptoms who are in a 

comprehensive management program including 

appropriate behavioral 

interventions

• Start as soon as possible after abstinence is 

established and continue 

through relapses

• Adjust dosage for renal 

failure:

CrCl 30-50: 333 mg TID

CrCl <30: contraindicated

• GABA analogue; decreases 

excitatory glutamergic neurotransmission during withdrawal

• Patients should be closely 

monitored for depression or 

suicidal thinking 

• Other possible adverse effects: 

diarrhea, somnolence

• COMBINE study did not show 

that acamprosate was more 

effective than placebo

REFERENCES

AIDS Education and Training Centers National Resource Center. Recreational Drugs and 

Antiretroviral Therapy. In: Clinical Manual for Management of the HIV-Infected Adult; July 

2006. Available at http://www.aids-etc.org/aidsetc?page=cm-314_rec_drugs. Accessed 

December 10, 2008.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 

Text Revision, 4th Edition. Washington, D.C.: American Psychiatric Publishing; 2000.

UCS-PCM-08-0701-Alcohol Misuse.indd 15 CS-PCM-08-0701-Alcohol Misuse.indd 15 3/20/09 /20/09 
ALCOHOL MISUSE

16 PRIMARY CARE OF VETERANS WITH HIV

National Institute for Alcohol Abuse and Alcoholism. Helping Patients Who Drink Too 

Much: A Clinician’s Guide. 2005. Available at http://www.niaaa.nih.gov/Publications/EducationTrainingMaterials/guide.htm. Accessed December 10, 2008.

VA/DoD Evidence-Based Clinical Practice Guideline Working Group. Management of 

Substance Use Disorder in the Primary Care Setting. Washington, D.C.: Department of 

Veterans Affairs, Offi ce of Quality and Performance; September 2001. Available at http://

vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. Accessed December 18, 2008.

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PRIMARY CARE OF VETERANS WITH HIV 1

Cancer Screening

KEY POINTS

■ General recommendations from the United States Preventive 

Services Task Force (USPSTF) regarding cancer screening include 

the following:

• Men and women at average risk should be screened for colorectal 

carcinoma (CRC) starting at age 50, using fecal occult blood 

testing (FOBT), fl exible sigmoidoscopy with or without FOBT, 

colonoscopy, or double-contrast barium enema. Offi ce-based digital 

rectal examination (DRE) plus FOBT should not be used. 

• Women aged 40 and older at average risk should be screened every 

1-2 years for breast cancer using mammography.

• Sexually active women should be screened every 3 years for 

cervical cancer using the Papanicolaou (“Pap”) smear.

• There is not adequate evidence to recommend for or against 

screening men for prostate cancer.

■ These recommendations may be applied to HIV-infected patients 

with CD4 counts of >350 cells/μL or completely suppressed HIV 

RNA. For patients with lower CD4 counts, screening should be 

discussed in the context of the patient’s prognosis, preferences, and 

health goals.

BACKGROUND

■ HIV-infected persons are at higher risk than HIV-uninfected persons of developing the following cancers:

Anal squamous cell carcinoma Non-small-cell lung carcinoma

Cervical carcinoma Melanoma

Colorectal carcinoma Non-Hodgkin lymphoma

Hepatocellular carcinoma Oropharyngeal cancer

Hodgkin lymphoma Vaginal cancer

Kaposi sarcoma

In addition, HIV-infected patients with chronic HBV or HCV infection may be 

at much higher risk of developing hepatocellular carcinoma (see Liver Disease, 

p. 185).

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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CANCER SCREENING

18 PRIMARY CARE OF VETERANS WITH HIV

regarding cervical and colorectal cancers, which are presented in this chapter. 

In addition, this chapter includes USPSTF recommendations on screening for 

breast cancer and prostate cancer. Additional screening recommendations can 

be found in other chapters (see Anal Dysplasia, p. 83; Liver Disease, p. 185; 

GERD, p. 155, and Women’s Health, p. 249).

■ Because most cancer screening requires a 5- to 10-year life expectancy to 

show a favorable cost/benefi t ratio, it is reasonable to screen HIV-infected 

persons for cancer if they have a CD4 count of >350 cells/μL or a suppressed 

HIV viral load. Screening patients with more advanced HIV disease is unlikely 

on average to extend life expectancy or be cost-effective, and should be discussed with patients in the context of their prognosis, preferences, and health 

goals. However, screening for cervical carcinoma is recommended for all HIVinfected women, regardless of CD4 count.

■ For cancers in which there is a hereditary component of risk, the following 

defi nitions of degree of relatedness are used: 

• 1st degree relative: a parent, sibling, or child

• 2nd degree relative: a grandparent, uncle, or aunt

• 3rd degree relative: a great-grandparent or cousin

Colorectal Cancer

Summary

Most CRC arises from adenomatous polyps, which grow relatively slowly; polyps 

and colorectal tumors can be detected with varying degrees of sensitivity by any 

one of several screening techniques, including FOBT, endoscopic visualization 

and biopsy (fl exible sigmoidoscopy and colonoscopy), and barium enema. The 

incidence of CRC increases with age. The USPSTF and the VA/DoD recommend that persons at average risk be screened for CRC starting at 

age 50. In persons at above-average risk, screening should start at an earlier age. 

The choice of screening procedure (see Table 1) depends on patient preferences and availability of procedures at particular facilities.

HIV-infected persons are at increased risk of CRC compared with HIVuninfected persons. A low nadir CD4 count is associated with an increased 

risk, whereas ART is associated with a decreased risk.

Epidemiology/Pathogenesis

■ Most colon cancers develop from adenomatous polyps; polyps >1 cm in size 

carry a higher risk than smaller polyps of development of CRC.

■ Prevalence of adenomatous polyps increases with age.

■ Average lifetime risk of developing colon cancer in the United States is 6%.

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PRIMARY CARE OF VETERANS WITH HIV 1

• History of CRC in a 1st degree relative

• Family history of large polyps before age 60

• Ulcerative colitis or Crohn disease

• Polyps >1 cm in size

■ Patients with specifi c genetic predisposition to CRC such as familial adenomatous polyposis (FAP) or hereditary nonpolyposis colon cancer (HNCC) are 

at extremely high risk of developing CRC.

Screening Methods

■ FOBT: Detection of blood in a stool specimen, usually done by smearing 

a stool specimen onto absorbent paper impregnated with guaiac, followed 

by application of hydrogen peroxide; any blood present in the specimen will 

catalyze the oxidation of guaiac by peroxide, producing a rapid color reaction

Samples blood loss from any point in the GI tract. Specimens can be prepared 

at home using commercial test cards.

■ Flexible sigmoidoscopy: Examination of the colon from the rectum to the 

splenic fl exure, a region in which the majority of malignant lesions arise, with 

a 60 cm fl exible fi beroptic endoscope with biopsy capability. 

■ Colonoscopy: Examination of the entire colon with a 100-160 cm fl exible 

fi beroptic endoscope with biopsy capability.

■ Effi cacy of screening methods is shown in Table 1.

Recommendations for CRC Screening

■ 80% of CRCs occur in people at average risk. 

■ Multiple recommended screening methods for average-risk patients (see 

Table 1).

■ Screening recommendations for higher-risk patients are shown in Table 2.

■ Screening recommendations for persons at very high risk (individuals with, 

or relatives of persons with, familial colon cancer syndromes such as FAP or 

HNCC) are beyond the scope of this chapter; consultation with GI or Oncol

ogy is recommended.

■ FOBT on specimens obtained by DRE is not recommended.

• DRE is not sensitive and ↓ FOBT specifi city

• If performed, a positive result should be followed up with colonoscopy

■ Fecal immunochemical test (FIT) and stool DNA test (sDNA) have not been 

recommended by the VHA.

■ Virtual colonoscopy is under investigation but is not yet recommended.

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CANCER SCREENING

20 PRIMARY CARE OF VETERANS WITH HIV

Risk of Developing CRC

Screening Method 

Recommended by 

USPSTF

Accuracy and 

Effectiveness

Comments/

Limitations/Risks

Home FOBT every year • mortality 15-33%, ↓

depending on frequency 

of screening

• Positive predictive value 

(percentage of patients 

with positive test result 

who have cancer or 

large polyp): 

• Rehydrated specimens: 6-8%

• Unrehydrated specimens: 20-40%

• Rehydration before adding developer:

• sensitivity from ↑

40% to >50%

• specifi city from ↓

98% to 90%

• Leads to more 

colonoscopies

• Annual screening found 

49% of cancers; 38% of 

patients tested required 

colonoscopy

• Screening every 2 years 

found 39% of cancers; 

28% of patients tested 

required colonoscopy

• Patient submits three 

2-window cards, 1 card 

each from 3 consecutive stools collected at 

home.

• Do not use DRE to collect specimens.

• The American Gastrointestinal Association 

(AGA) recommends 

against rehydrating 

specimens.

• If result is positive 

in any card window, 

obtain colonoscopy.

• FOBT itself is extremely 

low risk, but leads to 

many colonoscopies 

being performed, with 

associated risks of 

bleeding and perforation.

Flexible sigmoidoscopy 

every 5 years

• mortality 59% for ↓

cancers within reach of 

sigmoidoscope

• Sensitivity: 70-80%

• Specifi city diffi cult to 

defi ne 

• Complete or partial 

bowel prep required.

• Misses lesions proximal 

to the splenic fl exure.

• Proximal lesions more 

common in women than 

men.

• Estimated to fi nd 80% of 

patients with abnormal 

fi ndings, as distal abnormalities will prompt 

examination of entire 

colon with colonoscopy.

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PRIMARY CARE OF VETERANS WITH HIV 2

yg

copy alone would have 

missed 65% of women 

with advanced lesions 

detected by colonoscopy.

• In another study, 52% of 

patients with advanced 

proximal lesions (by 

colonoscopy) had no 

distal lesions.

• Presence of an 

adenoma generally necessitates full 

colonoscopy. Controversy exists regarding 

presence of small tubular adenomas, though 

many providers would 

perform colonoscopy.

• Complication rate:

• Perforation: <0.01%

• Bleeding: 2.5-5.5%

FOBT + fl exible sigmoidoscopy every 5 years• In one study, rigid sigmoidoscopy + 3-card 

FOBT (hydrated) 

detected 76% of 

advanced lesions vs 70% 

for sigmoidoscopy alone; 

24% of advanced lesions 

were missed; incidence 

of death from cancer 

decreased by approximately 50% in sigmoidoscopy + FOBT group 

vs sigmoidoscopy alone

• Studies of adding fl exible 

sigmoidoscopy to FOBT 

show doubling of diagnostic yield

• Positive FOBT 

result necessitates 

full colonoscopy, so 

perform FOBT before 

sigmoidoscopy.

• Complete or partial 

bowel prep required 

before fl exible sigmoidoscopy.

Colonoscopy every 

10 years

• mortality >50% ↓

• Sensitivity: 

• 90% for polyps 

>1 cm

• 75% for polyps 

<1 cm

• Complete bowel prep 

required.

• Colonoscopy can visualize entire colon. Suspicious lesions can be 

removed for biopsy and 

as treatment.

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CANCER SCREENING

22 PRIMARY CARE OF VETERANS WITH HIV

py 

the reference standard 

against which FOBT 

and sigmoidoscopy have 

been studied

y

colonoscopy (most 

sensitive test for polyps) 

must be weighed against 

risks of perforation, 

bleeding, and conscious 

sedation, as well as 

inconvenience of full 

colonic preparation and 

conscious sedation.

• Risk of screening 

colonoscopy 

• Any major complication: 0.3%

• Perforation: 0.05%

• Bleeding: 0.15-

0.18%

• Risk of colonoscopy as 

therapeutic procedure 

is higher

• Perforation: 0.07-

0.72%

• Bleeding: 0.2-2.7%

• Risks of procedure are 

greater in persons >70 

years of age, but so are 

benefi ts, as proximal 

lesions are more common in this population. 

Double-contrast barium 

enema

• Has low sensitivity compared with colonoscopy:

• 32% for polyps 

<0.5 cm

• 53% for polyps 

0.6-1 cm

• 48% for polyps 

>1 cm

• Complete bowel prep 

required.

• Option for patients who 

refuse colonoscopy.

Table 2. Screening Recommendations for Persons at Increased 

Risk of CRC*

Risk Factor Increase in Risk Screening Recommendations

1st degree relative with 

CRC or AP diagnosed 

≥60 years of age

OR

1st degree relative: ↑

2- to 3-fold

Screen as for person at average 

risk (see Table 1), but start at 

age 40.

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PRIMARY CARE OF VETERANS WITH HIV 2

g

tives with CRC or AP 

at any age

g

tive: ↑ 1.5-fold (2- to 

3-fold if >1 relative)

1st degree relative with 

CRC or AP diagnosed 

<60 years of age 

OR

Two 1st degree relatives with CRC or AP 

diagnosed at any age

1st degree relative aged 

≤60: ↑ 3- to 4-fold

1st degree relative: ↑

2- to 3-fold

Screening colonoscopy every 5 

years, starting at age 40, or 10 

years before age at which relative 

was diagnosed, whichever comes 

fi rst.

2nd or 3rd degree 

relative(s) with CRC

↑ 1.5- to 3-fold Screen as for person at average 

risk (see Table 1).

Infl ammatory bowel 

disease (UC or CD)

↑ 2.4-fold in UC (if 

disease widespread)

↑ up to 5.6-fold in CD, 

depending on location

Colonoscopy every 1-2 years 

with biopsies for dysplasia.

Younger age at diagnosis of CD 

seems to increase risk, as does 

distal (colon) vs proximal (ileum) 

disease. 

Personal history of 

CRC

Patients with CRC should 

undergo high-quality perioperative 

colonoscopy to detect synchronous lesions. Colonoscopy should 

be performed 1 year after the 

resection (or 1 year following 

the colonoscopy that confi rmed 

absence of synchronous disease). 

If the examination performed at 

1 year is normal, then the next 

examination should be performed 

in 3 years. If that colonoscopy is 

normal, then the interval to the 

subsequent examination should be 

5 years. Following the examination 

at 1 year, the intervals between 

subsequent examinations may be 

shortened if there is evidence of 

HNCC or if adenoma fi ndings 

warrant earlier colonoscopy.

If an obstructing tumor prevents 

high-quality colonoscopy at 

the time of resection, examination for synchronous tumors 

can be performed by doublecontrast barium enema or CT 

colonography.

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CANCER SCREENING

24 PRIMARY CARE OF VETERANS WITH HIV

rectal cancer, periodic examination of the rectum may be 

considered to identify local 

recurrence. This usually is performed at 3- to 6-month intervals 

for the fi rst 2 or 3 years.

* Not including characterized familial colon cancer syndromes

Adapted from Levin et al. See References.

Abbreviations: AP = adenomatous polyp; CD = Crohn disease; UC = ulcerative colitis

Reminders

CPRS reminder defi nition and resolution options for CRC screening may differ 

among VA Medical Centers, depending on local decisions and procedure availability. An example of a typical CPRS reminder for CRC screening is shown.

What to do with a positive result

■ A positive screening result should be followed by a full colonoscopy, unless 

contraindicated.

■ Patients with negative screening but with symptoms suggestive of CRC or 

polyps should be offered a full colonoscopy.

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PRIMARY CARE OF VETERANS WITH HIV 2

Summary

Breast cancer is the most common cancer diagnosed among women in the 

United States. Incidence of breast cancer increases with age, and there is evidence 

that mammographic screening reduces mortality due to breast cancer. Most 

cases of breast cancer are detected by mammography. Whereas the benefi ts 

of starting screening for women older than 50 are well established, increasing 

evidence points to a protective effect of starting to screen women at age 40. It is 

important to note that the rate of false-positive screening tests in women 40-50 

years of age is high and that the benefi ts of screening need to be weighed against 

the potential for emotional distress and additional testing caused by false-positive 

screening results. Nevertheless, the USPSTF and VA/DoD recommend 

screening women ≥40 years of age with mammography every 1-2 years

Clinical breast examination (CBE) and breast self-examination (BSE) may be part 

of screening, depending on patient and provider preference. There is no clear 

evidence that HIV infection increases the risk of breast cancer or alters treatmen

outcomes.

Epidemiology

■ Lifetime risk of invasive breast cancer in U.S. women is approximately 12.5%; 

breast cancer is the most common cancer among women in the United 

States, and the second most common cause of cancer death among women in 

the United States (after lung cancer).

■ Women at increased risk of breast cancer are those with:

• Family history of breast cancer in a 1st degree relative

Risk higher if multiple 1st degree relatives with breast cancer _

Risk higher if affected relatives were <40 years of age when _

diagnosed

• Women with a specifi c mutation conferring risk of breast cancer, such as 

BRCA1 or BRCA2

• History of atypical hyperplasia on previous breast biopsy

• History of fi rst pregnancy after age 30

• Increased estrogen exposure

Early menarche or late menopause _

Hormone replacement therapy _

• Older age

0.4% annual incidence at age 30-39 _

1.5% annual incidence at age 40-49 _

2.8% annual incidence at age 50-59 _

3.6% annual incidence at age 60-70 _

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CANCER SCREENING

26 PRIMARY CARE OF VETERANS WITH HIV

more aggressive. Thus, screening may have less of a protective effect than 

it does for older women. The increased density of breast tissue in younger 

women also may reduce the ability of mammography to detect abnormalities.

Screening methods

■ Mammography involves low-dose radiography of the breasts. It should be 

performed at an accredited, certifi ed facility, with interpretation by an appropriately trained and certifi ed radiologist.

■ CBE involves physical examination of the breast by a health care provider for 

signs of malignancy (eg, masses, induration, discharge) or other abnormalities.

■ BSE involves monthly examination of the breast by the patient for signs such 

as redness, dimpling, or other abnormalities.

Effectiveness of screening

■ Mammography is less reliable (lower sensitivity, specifi city, and positive predictive value) in younger women than in older women.

■ Mammography is relatively sensitive for breast cancer, but sensitivity declines 

with time from mammogram:

• 71-96% sensitivity for cancers diagnosed within 1 year of screening

• 56-86% sensitivity for cancers diagnosed within 2 years of screening 

■ Specifi city of one-time mammogram is 94-97%.

■ Positive predictive value of one-time mammography: 

• 2-22% of women with an abnormal result will require further workup

• 12-78% of women with an abnormal result will require biopsy 

■ Mammography reduces breast cancer-specifi c mortality as much as 32% 

depending on the study; metaanalysis fi nds a reduction in disease-specifi c 

mortality of about 15%, including among women <50 years of age.

■ CBE has an estimated sensitivity of 40-69%, specifi city of 86-99%, and positive 

predictive value of 4-50%. There is no evidence at present that CBE reduces 

breast cancer-specifi c mortality.

■ BSE has an estimated sensitivity of 26-41%; its specifi city has not been 

defi ned. There is no evidence at present that BSE reduces breast cancerspecifi c mortality.

Recommendations for breast cancer screening

■ Screening mammography every 1-2 years for women 40-69 years of age.

■ Providers should discuss screening with women aged 70 and older, taking into 

account estimated life expectancy and presence of comorbid disease.

■ CBE and BSE may be incorporated into screening, according to patient and 

provider preference.

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PRIMARY CARE OF VETERANS WITH HIV 2

va.gov/Radiology/page.cfm?pg=3. A listing of non-VHA certifi ed mammography sites can be accessed at http://vaww1.va.gov/Radiology/page.cfm?pg=108.

■ Further information on mammography is available through the VHA Mammography Offi ce at http://vaww1.va.gov/Radiology/page.cfm?pg=1.

Reminders

CPRS reminder defi nition and resolution options for mammography may differ 

among VA Medical Centers, depending on local decisions. An example of a typica

CPRS reminder for annual mammography is shown.

What to do with a positive result

■ Results should be communicated to the patient as soon as possible. Generally, a lay summary will be sent to the patient by the interpreting radiologist. 

However, the ordering provider should ensure that results have been communicated to the patient within a reasonable time frame.

■ Patients with an abnormal result should be referred to the appropriate service (Women’s Health, Gynecology, or General Surgery, depending on the 

facility) as soon as possible for evaluation and possible biopsy.

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CANCER SCREENING

28 PRIMARY CARE OF VETERANS WITH HIV

Summary

Although there are no randomized controlled trials showing the effectiveness of 

cervical cancer screening, numerous observational studies have found an association between screening and reductions in the incidence of cervical cancer and 

disease-specifi c mortality. 

HIV-infected women are at elevated risk of cervical dysplasia and cervical cancer. 

Cervical cancer is highly associated with type 16 and 18 human papillomavirus 

(HPV) infection (high-risk subtypes). HPV prevalence is higher among HIVinfected women than among HIV-uninfected women, and HIV-infected women 

have increased persistence of HPV and greater likelihood of infection with highrisk types of HPV. Although the time between diagnosis of carcinoma in situ (CIS) 

and development of invasive disease is shorter among HIV-infected women who 

are not on ART than among HIV-uninfected women, ART has not been shown 

consistently to prevent or alter the course of cervical dysplasia in HIV-infected 

women. Women with advanced immunosuppression (CD4 count of <200 cells/

μL) are at higher risk of cervical abnormalities than women with CD4 counts of 

>200 cells/μL.

The USPSTF and VA/DoD recommend cervical cancer screening using 

Pap smear or liquid-based cytology in sexually active women with 

a cervix. Screening should be started at age 21 or within 3 years of starting 

sexual activity, whichever comes fi rst. For HIV-uninfected women, the Pap test 

should be repeated every 3 years. For HIV-infected women, most authorities 

recommend more frequent screening, typically at the time of HIV diagnosis and 

again 6 months later. Women with normal cytology and CD4 counts of >200 

cells/μL can then be screened annually, and women with CD4 counts of <200 

cells/μL are screened every 6 months.

Epidemiology/pathogenesis

■ Cervical cancer is associated with genital HPV infection; cancer is preceded 

by identifi able neoplastic changes (cervical intraepithelial neoplasia, or CIN) in 

the transformation zone of the cervix. Localized cervical cancer is highly curable (5-year survival of 92%), whereas disseminated disease is not (5-year survival of 13%). HIV-infected women progress from CIS to invasive disease faster 

than HIV-uninfected women. Cervical cancer is an AIDS-defi ning condition.

■ Women at increased risk of cervical cancer include those with:

• Immunosuppression (including HIV infection)

• Tobacco use (smoking)

• Increased risk of HPV infection, such as: 

Earlier onset of sexual intercourse _

Multiple sexual partners _

Sexual partners who have had multiple sexual partners _

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PRIMARY CARE OF VETERANS WITH HIV 2

■ Pap smear: Cervical epithelial cells, collected by brush and spatula, are 

either smeared directly on a slide and fi xed, or suspended in a liquid fi xative and spun onto a slide. The smear should be examined by an experienced 

cytopathologist.

■ Cervical detection of HPV has higher sensitivity but lower specifi city than 

traditional Pap smear for cervical cancer. The USPSTF does not currently 

recommend HPV testing as a screening method. 

Effectiveness of Screening and Screening Interval

■ Sensitivity of a single Pap smear for high-grade CIN is 60-80%; specifi city is 

approximately 98%.

■ Effectiveness of cervical cancer screening on incidence and mortality of cervical 

cancer has not been studied prospectively. Nevertheless, data from good-quality 

case-control and ecological studies show a strong association between screening 

and reductions in cervical cancer incidence and disease-specifi c mortality.

Screening recommendations

■ Screen HIV-infected women at the time of diagnosis and 6 months thereafter.

■ If initial results are normal, rescreen annually if CD4 count is >200 cells/μL or 

every 6 months if CD4 count is <200 cells/μL.

■ HIV-infected women also should be screened annually for anal carcinoma 

using Pap smears (see Anal Dysplasia, p. 83).

■ Because of the increased risk of vaginal cancer associated with HIV infection, HIV-infected women with a history of high-grade CIN or invasive cervical cancer should be screened with regular vaginal cuff Pap smear following 

hysterectomy.

Reminders

Because the frequency of recommended screening for cervical cancer differs 

between HIV-infected and HIV-uninfected women, the standard CPRS reminder 

for cervical cancer screening generally is not applicable to the former. HIV providers should work with the local Information Resource Management Service to 

construct HIV-specifi c reminders for cervical cancer screening.

What to do with a positive result

■ Most experts recommend more aggressive management of HIV-infected 

women than HIV-uninfected women, while some recommend the same management regardless of HIV serostatus.

■ The following recommendations are based largely on the 2006 consensus 

guidelines of the American College of Obstetrics and Gynecology for management of cervical abnormalities, regardless of HIV serostatus (see Table 3)

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CANCER SCREENING

30 PRIMARY CARE OF VETERANS WITH HIV

abnormality.

• CIN refers to histologic grades of cervical abnormality. CIN 2 and 

CIN 3 are considered high-grade precursors of cervical cancer.

(Table 3 refers to the management of adult women only, and not to adolescents, 

pregnant women, or the elderly.)

Table 3. Management of Women with Abnormal Cervical Cytology on 

Screening

Cytology 

Result Next Step Comments

Atypical 

Squamous Cells 

of Undetermined 

Signifi cance 

(ASCUS)

• Refer for colposcopy

Could consider:

• HPV testing for 

oncogenic subtypes

OR

• Repeat cytology 

(Pap)

There is controversy about management of ASCUS in HIV-infected women: 

• Many authorities recommend that all 

HIV-infected women with ASCUS be 

referred for colposcopy. 

• In HIV-infected women, there are 

insuffi cient data to recommend HPV 

DNA testing for oncogenic HPV 

types as part of management of 

ASCUS.

• If colposcopy is chosen, and no 

CIN is found, repeat cytology at 

12 months.

• If HPV testing is chosen, refl ex HPV 

testing of samples collected during 

cytologic screening is preferred, for 

patient’s convenience. This requires 

liquid-based cytology or samples collected specifi cally for HPV testing and 

held. Otherwise, HPV testing requires 

another Pap smear.

• If HPV negative, repeat cytology 

at 12 months.

• If HPV positive, manage as for 

LSIL (below).

• If repeat cytology is chosen, repeat at 

6-month intervals until 2 consecutive 

negative tests, then return to normal 

screening interval. If repeat shows 

ASCUS or higher, refer for colposcopy.

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PRIMARY CARE OF VETERANS WITH HIV 3

yp

Squamous Cells/

cannot exclude 

HSIL (ASC-H)

ppyppy

perform cytology at 6 and 12 months, 

or HPV testing at 12 months. If above 

are negative, return to regular cytologic 

screening schedule.

Low-Grade 

Squamous Intraepithelial Lesion 

(LSIL)

• If no CIN 2 or 3 is found on colposcopy, Refer for colposcopy

perform cytology at 6 and 12 months, 

or HPV testing at 12 months. If above 

results are negative, return to regular 

cytologic screening schedule.

High-Grade 

Squamous Intraepithelial Lesion 

(HSIL)

• Refer for colposcopy 

or loop electrosurgical procedure (LEEP)

If no CIN 2 or 3 is found, multiple 

options include: colposcopy and cytology every 6 months for 1 year as long 

as colposcopy is adequate and cytology is negative; excisional diagnostic 

procedure. 

If colposcopy is chosen, excisional 

procedure is indicated if repeat colposcopy shows HSIL or is unsatisfactory. If 

repeat colposcopies are negative, return 

to routine cytologic screening.

Adapted from Wright et al. See References. 

See also Women’s Health, p. 249.

Prostate Cancer

Summary

In contrast to screening for colorectal, breast, and cervical cancer, there is controversy over whether to screen men for prostate cancer. The VA/DoD and 

USPSTF do not recommend routine screening; the American Cancer 

Society (ACS) and the American Urological Association (AUA) favor 

annual screening for all men at age 50, and for higher-risk men at age 

45, as long as they have a life expectancy ≥10 years. Although screening is effective at detecting prostate cancer in its early stages, it is not clear that 

screening reduces disease-associated or overall mortality. Likewise, the effect of 

treating prostate cancer in its early stages on overall mortality is not clear, and 

treatment, whether by prostatectomy or radiation, carries a substantial risk of 

side effects such as urinary incontinence and sexual dysfunction (see below). 

The rate of prostate cancer increases over time in HIV-infected men, as it does 

in HIV-uninfected men. When corrected for age, HIV-infected men seem to be 

at lower risk of prostate cancer than HIV-uninfected men, for reasons that are 

unknown.

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CANCER SCREENING

32 PRIMARY CARE OF VETERANS WITH HIV

■ Lifetime risk of developing prostate cancer is 16% among men in the United 

States.

■ 10-year risk of developing prostate cancer increases with age, from 0.17% at 

age 40 to 6.46% at age 60.

■ Lifetime risk of death caused by prostate cancer is 3% among men in the 

United States.

■ Most deaths resulting from prostate cancer occur at age >65.

■ Disease confi ned to the prostate gland at diagnosis carries a better prognosis 

than disease extending beyond the gland.

■ Incidence of disease and mortality are greater among African American men 

than among white men in the United States, and among men with a 1st 

degree relative with prostate cancer.

Screening methods

■ Screening for prostate cancer includes measurement of serum prostatespecifi c antigen (PSA) combined with DRE.

■ Prognosis is associated with degree of differentiation of tumor cells (Gleason score) on biopsy and whether disease is confi ned to the gland or is 

extraprostatic. Higher Gleason scores (indicating less-differentiated cells) and 

extraprostatic disease confer a worse prognosis.

■ Elevated PSA is associated with prostate cancer, and with benign prostate 

abnormalities such as benign prostatic hyperplasia (BPH), prostatitis, and 

trauma to the gland. 

■ The higher the PSA, the higher the likelihood of prostate cancer, and the 

higher the likelihood that the cancer has spread beyond the prostate gland:

• PSA ≤4 ng/mL is classifi ed as “normal.” Although up to 27% of men 

with a PSA <4 ng/mL will have cancer, most of these will have disease 

confi ned to the gland.

• PSA >4 ng/mL is classifi ed as “elevated.” Approximately 1 in 3 men 

with elevated PSA will actually have cancer. For PSA 4-10 ng/mL, 1 in 

4 men will have cancer. Most of these cancers will be confi ned to the 

gland, but the low positive predictive value of the test means that many 

men will undergo unnecessary biopsy. For PSA >10 ng/mL, up to two 

thirds of men will have cancer and more than half of those cancers will 

be extraprostatic.

Treatment for early prostate cancer: Side effects and benefi ts 

■ Treatment consists of active surveillance (watchful waiting), prostatectomy, or 

radiation therapy.

■ Risk of persistent (at least 12 months in duration) side effects from radical 

prostatectomy:

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PRIMARY CARE OF VETERANS WITH HIV 3

• Urinary incontinence: 15-50%

■ Risk of persistent (at least 12 months in duration) side effects from externalbeam radiation therapy:

• Impaired sexual function: 20-45%

• Urinary incontinence: 2-16%

• Bowel problems: 6-25%

■ When compared with watchful waiting, radical prostatectomy following clinical detection of moderately to well-differentiated prostate cancer confi ned to 

the gland decreases disease-specifi c mortality. The effect on overall mortality 

is less clear. Whether this applies to cancer detected by screening is also not 

clear.

Effectiveness of Screening

■ When analyzed properly, the one randomized trial of screening with PSA and 

DRE vs no screening showed no mortality benefi t from screening.

■ Additional prospective trials of screening effectiveness are ongoing.

Screening recommendations

■ Patients should be counseled annually regarding the risks and benefi ts of 

screening for prostate cancer by PSA and DRE; screening may be performed 

if desired by the patient.

■ Depending on Veterans Integrated Service Network (VISN), facility, and clinician decision making, prostate cancer screening may be offered to patients 

deemed to be at increased risk.

Reminders

CPRS reminder defi nition and resolution options for prostate cancer counseling and screening may differ among VA Medical Centers, depending on local 

decisions. An example of a typical CPRS reminder for annual prostate cancer 

counseling and screening is shown.

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CANCER SCREENING

34 PRIMARY CARE OF VETERANS WITH HIV

What to do with a positive result

■ Refer to urologist for transrectal ultrasound (TRUS) and biopsy for: 

• Elevation in PSA (PSA >4 ng/mL) 

• Prostatic abnormality (asymmetry, nodule, or induration of the gland) on 

DRE

REFERENCES

Catalona WJ, Richie JP, Ahmann FR, et al. Comparison of digital rectal examination and 

serum prostate specifi c antigen in the early detection of prostate cancer: results of a 

multicenter clinical trial of 6,630 men. J Urol. 1994 May;151(5):1283-90.

Coley CM, Barry MJ, Fleming C, et al. Early detection of prostate cancer. Part I: Prior 

probability and effectiveness of tests. The American College of Physicians. Ann Intern Med. 

1997 Mar 1;126(5):394-406. 

Cooley TP. Non-AIDS-defi ning cancer in HIV-infected people. Hematol Oncol Clin North 

Am. 2003 Jun;17(3):889-99. 

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PRIMARY CARE OF VETERANS WITH HIV 3

Preventive Services Task Force. Ann Intern Med. 2002 Dec 3;137(11):917-29. 

Humphrey LL, Helfand M, Chan BK, et al. Breast cancer screening: a summary of the 

evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002 Sep 3;137(5 

Part 1):347-60. 

Levin B, Lieberman DA, McFarland B, et al; American College of Radiology Colon Cancer 

Committee. Screening and surveillance for the early detection of colorectal cancer and 

adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US 

Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. 

Gastroenterology. 2008 May;134(5):1570-95.

Loeb S, Catalona WJ. What to do with an abnormal PSA test. Oncologist. 2008 

Mar;13(3):299-305.

Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern 

Med. 2008 May 20;148(10):728-36.

U.S. Preventive Services Task Force. Screening for breast cancer: Recommendations 

and rationale. Center for Practice and Technology Assessment, Agency for Healthcare 

Research and Quality; 2002. Available at http://www.ahrq.gov/clinic/3rduspstf/breastcancer/brcanrr.pdf. Accessed November 17, 2008.

U.S. Preventive Services Task Force. Screening for cervical cancer: Recommendations 

and rationale. Center for Practice and Technology Assessment, Agency for Healthcare 

Research and Quality; 2003. Available at http://www.ahrq.gov/clinic/3rduspstf/cervcan/

cervcanrr.pdf. Accessed November 17, 2008.

U.S. Preventive Services Task Force. Screening for colorectal cancer: Recommendations 

and rationale. Center for Practice and Technology Assessment, Agency for Healthcare 

Research and Quality; 2005. Available at http://www.ahrq.gov/clinic/3rduspstf/colorectal/

colorr.pdf. Accessed November 17, 2008.

U.S. Preventive Services Task Force. Screening for prostate cancer: Recommendations 

and rationale. Center for Practice and Technology Assessment, Agency for Healthcare 

Research and Quality; 2005. Available at http://www.ahrq.gov/clinic/3rduspstf/prostatescr/

prostaterr.pdf. Accessed November 17, 2008.

Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management 

of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007 

Oct;197(4):346-55.

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PRIMARY CARE OF VETERANS WITH HIV 3

Immunizations

KEY POINTS

■ All HIV-infected patients should be offered hepatitis B, pneumococcus, 

and inactivated infl uenza vaccination as recommended.

■ Other vaccines may be indicated for some HIV-infected patients 

(see Immunization Schedule on next page).

■ Live virus vaccines should not be administered to HIV-infected 

patients, with the possible exception of MMR and varicella 

immunizations.

BACKGROUND

■ Immunization is a cost-effective, low-risk intervention to prevent morbidity 

and mortality in HIV-infected patients.

■ The current recommendations regarding immunization of HIV-infected individuals are available at http://aidsinfo.

nih.gov; the most recent schedule is 

shown on the next page.

■ All HIV-infected individuals should be 

offered 23-valent pneumococcus and 

hepatitis B vaccination (if not already 

immune to HBV); vaccination with the 

inactivated trivalent infl uenza vaccine 

should be offered annually during infl uenza season.

■ Other vaccines should be offered based on specifi c risk factors; see next 

page.

■ Live virus vaccines generally should not be administered to HIV-infected 

patients; however, administration of MMR, varicella, and zoster vaccines may 

be appropriate for some patients.

Veterans with HIV*

Infl uenza vaccination: 60% 

Pneumococcus vaccination: 68%

Hepatitis B vaccination: 40%

*Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who received the 

indicated immunizations

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IMMUNIZATIONS

38 PRIMARY CARE OF VETERANS WITH HIV

Vaccine T Age Group X 19-49 Years 50-64 Years ≥65 Years

Infl uenza (trivalent inactivated)* 1 dose annually

Pneumococcus (polysaccharide) 1 dose

Hepatitis B* 3 doses (0, 1-2, 4-6 months)

Tetanus, diphtheria, pertussis 

(Td/Tdap)*

1 dose Td booster every 10 years

Substitute 1 dose of Tdap for Td

Human papillomavirus (HPV)* For women 

aged 15-26#

HPV quadravalent vaccine 0.5 

mL IM months 

0, 2, and 6

Measles, mumps, rubella (MMR)* Do not administer to severely 

immunosuppressed persons

Varicella* Do not administer to severely 

immunosuppressed persons

Hepatitis A* 2 doses (0, 6-12 months, or 0, 6-18 months)

Meningococcus* 1 or more doses

* Covered by the Vaccine Injury Compensation Program

# Effective in preventing HPV infection and high-grade CIN associated with vaccine-related HPV types 

among young HIV-seronegative women. There are no data on the safety, tolerability, immunogenicity, 

or effi cacy in HIV-infected women, or in HIV-infected men.

 For all persons in this category who meet the age requirements and who lack 

evidence of immunity (eg, lack documentation of vaccination or have no evidence of prior infection)

 Recommended if some other risk factor is present (eg, on the basis of medical, 

occupational, lifestyle, or other indication)

Adapted from the Advisory Committee on Immunization Practices (ACIP) Adult Immunization 

Schedule. For detailed information on immunizations against infl uenza, pneumococcal disease, hepatitis B, human papillomavirus, varicella, and hepatitis A, refer to the Guidelines for Prevention and 

Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents (http://aidsinfo.nih.gov/contentfi les/Adult_OI.pdf). For information on immunizations against tetanus, diphtheria, 

pertussis, measles, mumps, rubella, and meningococcal disease, refer to recommendations of the ACIP 

(http://www.cdc.gov/vaccines/pubs/ACIP-list.htm).

REFERENCES

Adult Prevention and Treatment of Opportunistic Infections Guidelines Working 

Group. Guidelines for Prevention and Treatment of Opportunistic Infections in HIVInfected Adults and Adolescents [DRAFT]; June 18, 2008; p. 208. Available at 

http://aidsinfo.nih.gov/contentfi les/Adult_OI.pdf. Accessed December 8, 2008.

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PRIMARY CARE OF VETERANS WITH HIV 3

Prevention for Positives

KEY POINTS

■ HIV prevention should be a focus of routine HIV primary care.

■ Prevention interventions should emphasize patients’ own health 

and the health of their partners.

■ Assessment of sexual and substance-use behaviors and discussion 

of risk reduction interventions can be brief: 5-10 minutes per visit 

over a series of visits.

■ Elements of the prevention evaluation and intervention include:

• A detailed HIV transmission risk assessment, including the patient’s 

sexual practices with each partner, and needle-use practices, if 

applicable

• Screening and testing for STDs

• Pregnancy screening and testing

• Identifi cation and correction of misconceptions

• General prevention messages

• Individualized interventions 

• Referrals

• Periodic reevaluation

BACKGROUND

Basic Epidemiology of HIV Transmission in the United States: The 

Role of Prevention for Positives

There are an estimated 56,000 new HIV 

infections each year in the United States, 

almost all attributable to risky sexual and 

drug-use behaviors. Each new infection 

originates with someone already infected 

with HIV, and nearly all are preventable. 

Assessing patients’ behaviors and promoting healthy changes can decrease the 

risk of HIV transmission. This chapter will 

focus on performing sexual risk assessment 

Veterans with HIV*

Alcohol use disorder: 33%

Illicit drug use: 30%

Other and unspecifi ed drug 

use: 22%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-9 

code corresponding to these conditions

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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PREVENTION FOR POSITIVES

40 PRIMARY CARE OF VETERANS WITH HIV

turn, can protect patients and their sexual and drug-sharing partners from other 

sexually transmitted and bloodborne pathogens, and possible HIV superinfection.

Transmission route for HIV/AIDS cases diagnosed in the United 

States in 2006:

• 67% sex with other men; 16% high-risk heterosexual contact; 12% injection Men:

drug use (IDU)

• 80% heterosexual sex; 19% IDU Women:

Source: CDC, 2008. Based on data from 33 states with long-term, confi dential name-based HIV 

reporting. See References.

Helping Patients Adopt and Maintain Safer Sexual Behaviors

The HIV clinic is an important setting for prevention efforts, to help patients 

decrease the risks of:

■ Transmitting HIV to others via sexual or IDU behaviors

■ Acquiring and transmitting an STD

■ Acquiring a bloodborne infection (for injection drug users)

■ HIV superinfection (note: this appears to occur rarely, but can adversely affect 

clinical status and treatment options)

■ Unintended pregnancy

Nevertheless, studies have shown that many HIV providers do not assess transmission risks with or provide prevention messages to their patients. 

For some patients, decreasing HIV transmission risks requires them to make 

small changes in sexual and drug-use behavior; for others, signifi cant changes 

are needed. Although behavior changes can be diffi cult to make and to maintain, 

they should be encouraged. Several studies have shown that assessment of HIV 

transmission risk followed by brief prevention interventions initiated by the care 

provider can be effective, at least in the short term. Various risk reduction interventions in primary care and STD clinics have resulted in:

■ Increased condom use 

■ Safer IDU practices 

■ Fewer STDs 

As with any behavior change intervention (eg, smoking cessation, dietary modifi cation), HIV prevention interventions need to be reevaluated and reinforced 

regularly. Over time, primary care providers can have a signifi cant impact on 

their patients’ behaviors. Clinicians often underestimate how seriously patients 

take their recommendations.

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PRIMARY CARE OF VETERANS WITH HIV 4

use, can be challenging or uncomfortable for some medical providers. Learning 

how to conduct a partner-by-partner risk assessment can reduce this discomfort

Given the preventable nature of HIV infection, HIV risk assessment and the delivery of individualized prevention messages should be routine and ongoing aspects 

of HIV care that are performed at the initial evaluation and periodically thereafte

Clinicians can greatly affect patients’ risks for transmission of HIV to 

others via the following actions: 

• Performing a brief screening for HIV transmission risk behaviors 

• Communicating prevention messages 

• Discussing sexual and drug-use behavior 

• Positively reinforcing changes to safer behavior 

• Referring patients for services such as substance abuse treatment 

• Facilitating partner notifi cation, counseling, and testing 

• Identifying and treating other STDs

These measures also may decrease patients’ risks of acquiring other STDs and bloodborne infections (eg, viral hepatitis).

Adapted from CDC, HRSA, NIH, and HIVMA. See References.

Doing prevention work with HIV-infected patients can be divided into evaluation 

steps and management steps.

Evaluation:

1. Establish rapport and conduct a quick, detailed behavioral risk assessment.

2. Assess for the presence of STDs.

Management:

1. Locate patient’s risk behavior along the risk continuum.

2. Correct misinformation, answer questions, and educate.

3. Assess patient’s readiness for behavior change.

4. Work toward risk reduction with an individualized prevention message based 

on the patient’s risk behaviors and readiness to change.

5. Treat STDs and supply medications, condoms, and lubricant if needed.

6. Agree on what patient will do to reduce risk.

7. Agree to address prevention at future visits.

The rest of this chapter will focus on these steps in more detail.

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PREVENTION FOR POSITIVES

42 PRIMARY CARE OF VETERANS WITH HIV

EVALUATION

HIV transmission risk assessment should be performed at the initial evaluation and periodically thereafter. For patients with signifi cant ongoing risk factors 

for HIV transmission, it should be part of every visit, if possible.

Sexual risk assessment

■ Should include an evaluation of risks of HIV transmission and risks of acquisition and transmission of other STDs (including HBV and HCV infections).

Drug and alcohol risk assessment (see also Alcohol Misuse, p. 3; and Substance Use, p. 69)

■ Illicit drug use (particularly methamphetamine use) and alcohol misuse are 

associated with unsafe sex practices, and with STD and HIV acquisition and 

transmission.

■ Sharing of nonsterile injection equipment can itself cause transmission of HIV 

and other bloodborne pathogens (including HBV and HCV).

Mental health assessment (see also Depression, p. 271)

■ Serious mental illness, posttraumatic stress disorder, and depression increase 

the likelihood of risky sexual and drug- and alcohol-use behaviors.

STD screening/testing

■ The presence of an STD indicates risky sexual practices and increased risk of 

HIV transmission, and of acquisition of different HIV strains.

■ Coinfection with an STD (eg, gonorrhea, chlamydia, syphilis, chancroid, herpes 

simplex virus [HSV], and, in women, trichomoniasis) can increase HIV transmission risk and is deleterious to the patient’s own health.

Sexual risk assessment: In order to provide appropriate and specifi c recommendations, it is important to understand the patient’s risk behaviors and why 

he or she is engaging in them. A basic assessment should include questions about 

a variety of topics (see box below). Because a patient’s sexual activities may vary 

substantially with different partners or in different circumstances, asking follow-up 

questions to explore the circumstances of unsafe behaviors is crucial to targeting specifi c risk behaviors for intervention. One very helpful way of organizing 

an effi cient but detailed risk assessment is to ask patients to make a mental list 

of their most recent partners, and then explore their risk behaviors with each 

partner (see Table 1 below for questions to ask). 

Note: Veterans may be particularly reluctant to acknowledge same-sex sexual 

activities or IDU.

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PRIMARY CARE OF VETERANS WITH HIV 4

When interviewing patients, it is important to establish rapport in order to elicit 

truthful and complete responses and to establish a context for behavioral interventions. It often is helpful to normalize the questions as a routine part of primary 

care, and these topics should be discussed openly in a nonjudgmental manner. 

Providers often fi nd that systematically evaluating risk in a partner-by-partner fashion makes the risk assessment more clinical, less emotionally charged, and more 

comfortable for them and their patients.

Reassuring patients about the confi dentiality of their responses to questions about 

risky behavior is a key component for establishing rapport and trust and obtaining 

truthful responses. The confi dentiality of HIV-related information in the VA system 

is explicitly and specifi cally protected by federal law; for more information, see 

http://www.hiv.va.gov/vahiv?page=prtop03-ov-01; it may be helpful at a patient’s 

initial visit to clarify his or her confi dentiality rights.

Table 1. Components of a Detailed Risk Assessment

• Number of recent sex partners

• Sex of each partner

• Type of relationship with each partner 

(eg, main, casual, anonymous)

• HIV status of each partner

• Whether patient discloses his/her HIV 

status to partners or potential partners

• Type of sexual activity engaged in with 

each partner

• Safer and less-safe sexual activities 

engaged in with each partner

• Use of any risk reduction techniques 

(eg, condoms, serosorting,* disclosure)

• Consider asking questions such as: 

• “What made it more diffi cult for 

you to use condoms during this sexual encounter/with this partner?”

• “What made it easier for you to 

use condoms during this sexual 

encounter/with this partner?”

• Substance use (including alcohol) associated with sex 

• Circumstances of risky sex behaviors 

(eg, while intoxicated or high, with 

anonymous partners, in particular 

settings)

• Risky drug-use practices (eg, sharing 

injection equipment or nasal straws)

• Barriers to “safer” sex (and drug-use) 

practices

• STD symptoms 

• Women: current pregnancy, desire or 

intention for pregnancy, contraception 

• Men with female sex partners: intentions for conception or fathering, 

contraception

* Serosorting, whereby an HIV-infected person has unprotected sex only with HIV-infected partners, 

reduces HIV transmission. Serosorting does not affect the risk of acquiring other STDs, including HBV 

and HCV infections, or the risk of reinfection with drug-resistant or more pathogenic strains of HIV.

For a more complete risk assessment questionnaire, see the Risk Assessment Battery (University of 

Pennsylvania and Philadelphia Veterans Administration Medical Center), reproduced in the VA Prevention Handbook; see References.

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PREVENTION FOR POSITIVES

44 PRIMARY CARE OF VETERANS WITH HIV

Sometimes, the hardest part of doing prevention for positives is simply starting 

the conversation. The CDC HIV Prevention Guidelines present examples of 

screening and follow-up questions that may be used in interviewing patients: 

Open-end question by clinician, similar to one of the following:

• “What are you doing now that you think may present a risk of transmitting HIV 

to a partner?”

• “Tell me about the people you’ve had sex with recently.”

• “Tell me about your sex life.”

Screening questions* (checklist; should take approximately 4 minutes): 

• “Since your last checkup here,” or, if fi rst visit, “Since you found out you are 

infected with HIV ...”

• “Have you been sexually active; that is, have you had vaginal, anal, or oral sex with 

a partner?”

If yes:

“Have you had vaginal or anal intercourse without a condom with anyone?”

If yes:

“Were any of these people HIV negative, or are you unsure about their HIV status?”

“Have you had oral sex with someone?”

If yes:

(For a male patient) “Did you ejaculate into your partner’s mouth?”

• “Have you had a genital sore or discharge, discomfort when you urinate, or anal 

burning or itching?”

• “Have you been diagnosed or treated for an STD, or do you know whether any of 

your sex partners have been diagnosed or treated for an STD?”

• “Have you shared drug-injection equipment (needle, syringe, cotton, cooker, 

water) with others?”

If yes:

“Were any of these people HIV negative, or are you unsure about their HIV 

status?”

These questions may be used in a face-to-face interview, or with a self-administered 

questionnaire.

*Adapted from CDC, HRSA, NIH, and HIVMA. See References.

STD Screening

■ The presence of an STD suggests behaviors that may result in HIV transmission.

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PRIMARY CARE OF VETERANS WITH HIV 4

STD increases the risk of HIV transmission; diagnosis and treatment of STDs 

may therefore decrease HIV transmission, as well as prevent transmission of 

the STD.

■ Screen all patients at baseline and regularly thereafter, depending on their risk 

factors (eg, every 3-6 months in patients with a new sex partner or a partner 

who is an injection drug user); do specifi c tests according to sites of possible 

exposure; see below.

■ Routinely ask patients whether they have symptoms of an STD; perform diagnostic testing for all symptomatic patients, and treat as indicated. 

Table 2. Screening for STDs

STD Screening Test

Syphilis Nontreponemal tests: rapid plasma reagin (RPR); Venereal 

Disease Research Laboratory test (VDRL)

Chlamydia Urogenital infection: Nucleic acid amplifi cation test 

(NAAT) on fi rst-void urine (men and women), or cervical 

(women) or urethral (men) swab specimen

Rectal infection: NAAT of rectal swab* (for all who 

report engaging in anal receptive sex)

Gonorrhea Urogenital infection: NAAT on fi rst-void urine (men 

and women), or cervical (women) or urethral (men) swab 

specimen; culture of male urethral or female endocervical swab specimen (for men with symptoms of urethritis, 

Gram stain of urethral specimen may be done)

Pharyngeal infection: NAAT or culture of oral swab* 

(for all who report engaging in oral receptive sex)

Rectal infection: NAAT or culture of rectal swab* (for 

all who report engaging in anal receptive sex)

Trichomoniasis Wet-mount examination or culture of vaginal secretions 

(for all women)

HSV Serologic testing for HSV-2; recommended by some 

experts (for patients not previously diagnosed with HSV)

Adapted from CDC. Sexually Transmitted Disease Treatment Guidelines – 2006. See References.

* NAAT is not currently approved for this indication by the FDA. There is evidence that NAAT can 

accurately diagnose pharyngeal and rectal gonorrhea and rectal chlamydia, however, and many local 

public health departments have obtained Clinical Laboratory Improvement Amendment (CLIA) waivers to perform NAAT on pharyngeal and rectal swabs.

Pregnancy Screening

Screen all women who have a possibility of pregnancy based on sexual history, as 

well as those with missed menses or other signs or symptoms of pregnancy.

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PREVENTION FOR POSITIVES

46 PRIMARY CARE OF VETERANS WITH HIV

 MANAGEMENT

Information and education are important: Many patients have an incomplete 

or inaccurate understanding of how HIV is transmitted, the risks of various behaviors, and methods to prevent infection of sex partners or needle-sharing partners.

■ Patient education may increase knowledge and provide motivation.

■ Providers may identify and correct misconceptions. 

■ It is worth specifi cally mentioning that ART has not been proven to make 

patients noninfectious.

■ However, information alone is not adequate to change patients’ behavior.

Brief, tailored interventions and prevention messages delivered by clinicians may help patients reduce their risks of transmitting HIV. 

■ These are more effective in achieving behavior change than patient education 

alone.

There are a number of models for health behavior change and various counseling 

techniques or programs based on those models (for further information, see the 

VA HIV Prevention Handbook and References, below). Most involve:

■ Assessing the patient’s level of awareness and concern

■ Helping the patient to better understand his or her potentially harmful behavior

■ Determining the patient’s readiness for change (see Stages of Change, below)

■ Working with the patient to target a particular behavior for change 

■ Helping the patient bring about the desired change (this may require developing new skills [eg, negotiation])

■ Working toward further specifi c goals as the patient is ready

(Adapted from AIDS Institute, New York State Department of Health. HIV and Primary Care: Putting 

Prevention into Practice; 1998.)

In working with patients, it is important to assess their risk, readiness, motivation, and skills around specifi c behavioral changes and to work with them to 

prepare for these changes.

Risk Continuum

In interviewing patients, assess their positions on a continuum of risk of HIV 

transmission (see Table 3, below). Again, note that the degree or type of risk 

each person engages in may differ, depending on specifi c circumstances. Focus on 

specifi c behaviors.

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PRIMARY CARE OF VETERANS WITH HIV 4

Risk Factor

Relative Risk of 

Acquisition

Sexual Activity (some popular terms)

 Insertive fellatio (“getting head, being blown/sucked”)* 1#

 Receptive fellatio (“giving head, blowing/sucking”)* 2

 Insertive vaginal sex 10

 Insertive anal sex (“topping”) 13

 Receptive vaginal sex 20

 Receptive anal intercourse (“bottoming”) 100

Condom Use

 Yes 1

 No 20

* Best-guess estimate

# Referent category

Adapted from Varghese B, Maher JE, Peterman TA, et al. Reducing the risk of sexual transmission: 

quantifying the per-act risk for HIV infection based on choice of partner, sex act, and condom use. 

Sex Transm Dis 2002;29:38-43. Also adapted from CDC, HRSA, NIH, and HIVMA. Incorporating HIV 

Prevention into the Medical Care of Persons Living with HIV. MMWR 2003;52:RR-12.

Assess readiness for change

Using the Stages of Change model (below), identify the patient’s readiness to 

change risky sexual behaviors (for more on stages of change, see Alcohol 

Misuse, p. 3; Substance Use, p. 69; and Smoking Cessation, p. 53).

Stages of Change (Transtheoretical Model)

Contemplation

Maintenance Action

(Relapse) 

PreContemplation

Preparation

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PREVENTION FOR POSITIVES

48 PRIMARY CARE OF VETERANS WITH HIV

willing, to adopt behaviors that entirely eliminate the risk of HIV transmission 

(eg, abstinence); for most, the goal is to move from riskier activities to less-risky 

activities (see Table 3, above). Patients may do this in increments, with the support of clinicians, as they are ready and able.

Interventions may be as brief as 5-10 minutes per session. They should be 

repeated, refi ned, and reinforced at follow-up visits. For more extensive support, 

refer within and outside the VHA (eg, for counseling, psychiatric treatment, and 

substance misuse treatment).

Individualize prevention messages and interventions. Based on the risk assessment, the clinician can help patients identify behaviors that are less risky, and can 

target them for intervention. The intervention should be tailored to the individual, and the goal should be attainable. Risk reduction could include: 

■ Disclosing one’s HIV status 

■ Asking about partner’s HIV status

■ Monogamy

■ Reducing the number of sex partners 

■ Using condoms (male or female), particularly for anal or vaginal intercourse 

■ Having sex only with other HIV-infected partners (serosorting) 

■ Not having sex while intoxicated or under the infl uence of drugs or alcohol

■ Using adequate lubrication to avoid trauma to genital or rectal mucosa

■ ART with maximal suppression of HIV viremia; adherence to ART

■ Regular STD testing

■ Referring partners for HIV and STD testing and counseling

■ For drug users: using clean injection equipment; not sharing injection 

equipment

Using the risk continuum (see Table 3, above), help the patient identify ways 

toward less-risky behaviors.

An example of an intervention, based on the Stages of Change theory, is the 

following: 

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PRIMARY CARE OF VETERANS WITH HIV 4

Behavior Change, and Possible Interventions

Question: 

“How are you currently dealing with preventing HIV 

infection through sex or drug use?”

“I don't think about it.” 

“I've thought about it. I guess 

I'd like to try something.” 

“I worry about it, but I don't 

really know what to do, if 

anything.”

“I've started using condoms, but 

not all the time.”

OR 

“I've started cleaning my 

works.” 

OR 

“I'm in a treatment program.” 

OR 

“I've been clean for 3 months.” 

“I've been using a condom now 

for about 6 months, nearly all 

the time.”

OR 

“I've started using a syringe 

exchange program.” 

OR 

“I found out about a drug 

treatment program.” 

“I was really good for a long 

time, but then I started seeing 

somebody new and I just 

stopped. I'm not sure it was the 

right thing to do.” 

OR 

“I went cold turkey for a while, 

but I ran into some old friends 

who were using, and I picked up 

again.” 

Stage of Behavior 

Change Type of Answer Possible Intervention 

Precontemplative

Either unaware of risk or 

has no intention to change. 

Contemplative

Considers change but has 

no specific plan. 

Contemplation of resistance by 

the patient. Education may 

enhance such awareness. 

Education as to options. 

Assessment of barriers to 

change and discussion of 

benefits of change, resources, 

and intervention options. 

Prepared

Ready for change. 

Planning for change and 

may have taken some 

initial action. 

Action 

Initiated change. 

Maintenance 

Adopted a new behavior. 

Relapse 

Time or changing factors 

result in discontinuing 

adopted behavior. 

Discuss options for initiating 

change. 

Identify and acknowledge 

successful actions. Explore 

resources and referrals. 

Problem solve to help increase 

behavior changes. 

Evaluate factors supporting and 

potentially discouraging 

maintenance. 

Evaluate the need for 

reinitiating behavior. Discuss

factors influencing cessation 

of desired behavior. 

Reprinted with permission from AIDS Institute, New York State Department of Health. HIV and 

Primary Care: Putting Prevention into Practice; 1998. Data from Prochaska JO, DiClemente CC, 

Norcross JC. In search of how people change. Applications to addictive behavior. Am Psychol. 1992 

Sep;47(9):1102-14.

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PREVENTION FOR POSITIVES

50 PRIMARY CARE OF VETERANS WITH HIV

reduce risk. 

Practical Supports

Prescribe condoms (male and female condoms are available on the VHA 

National Formulary). Refer to drug treatment programs as needed, and needleexchange programs if available.

Refer patients, as needed, to VHA or community resources, for:

■ More intensive risk reduction counseling and intervention 

■ Instruction on practical skills (eg, correct condom use, negotiation skills)

■ Substance abuse treatment

■ Mental health treatment

■ Assistance with social problems (eg, lack of money or housing)

■ Case management, social services

■ Support around other problems that contribute to risky behaviors

Follow Up:

■ At each visit, briefl y reassess HIV transmission risks

■ Identify and correct misconceptions

■ Answer the patient’s questions

■ Reinforce focused prevention messages

■ Give encouragement and positive reinforcement for positive changes in risk 

behaviors

■ Identify next steps for further risk reduction

■ For patients who continue risky behaviors, elicit their beliefs and attitudes 

about their behaviors; offer counseling and develop further intervention, 

based on their motivation and their current stage on the change continuum

REFERENCES

Behavioral & Social Intervention Training Centers of the National Network of STD/HIV 

Prevention Training Centers – New York, Denver, Texas, California. Available at http://www.

stdhivpreventiontraining.org. Accessed December 1, 2008.

Centers for Disease Control and Prevention, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Incorporating HIV Prevention into the Medical Care of 

Persons Living with HIV. MMWR Recomm Rep. 2003 Jul 18;52(RR-12):1-24.

Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually 

transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 

4;55(RR-11):1-94.

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PRIMARY CARE OF VETERANS WITH HIV 5

Atlanta: U.S. Department of Health and Human Services, CDC; 2008.

Metsch LR, Pereyra M, del Rio C, et al. Delivery of HIV prevention counseling by 

physicians at HIV medical care settings in 4 US cities. Am J Public Health. 2004 

Jul;94(7):1186-92.

Mountain Plains AIDS Education and Training Center, Seattle STD/HIV Prevention Training 

Center. STD/HIV Risk Reduction: A Quick Reference Guide; March 2008.

National Network of STD/HIV Prevention Training Centers, AIDS Education Training Cen

ters. Facilitator’s Guide, Incorporating HIV Prevention into the Medical Care of Persons 

Living with HIV. Ask, Screen, Intervene. Adapted from Recommendations by the Centers 

for Disease Control and Prevention, the Health Resources and Services Administration, 

the National Institutes of Health, and the HIV Medicine Association of the Infectious 

Disease Society of America. Available at: http://aidsetc.org/aidsetc?page=et-pwp. Accessed 

December 1, 2008.

Varghese B, Maher JE, Peterman TA, et al. Reducing the risk of sexual transmission: quantifying the per-act risk for HIV infection based on choice of partner, sex act, and condom 

use. Sex Transm Dis 2002;29:38-43.

Veterans Health Administration, Department of Veterans Affairs. The VA HIV Prevention 

Handbook: A Guide for Clinicians. January 2002. Available at http://www.hiv.va.gov/pdf/

va01-pr/prtop-08/prevention_handbook.pdf. Accessed December 1, 2008.

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/20/09 
PRIMARY CARE OF VETERANS WITH HIV 5

Smoking Cessation

KEY POINTS

■ Smoking is the leading cause of preventable death and disease in the 

United States, accounting for approximately 440,000 deaths each 

year. It is a chronic, relapsing disorder that often requires repeated 

interventions and multiple attempts to quit. 

■ Patient interest in smoking cessation is high (>66% in most surveys). 

■ HIV-infected patients are 2-3 times more likely to be smokers than 

their age-matched HIV-uninfected counterparts.

■ HIV-infected smokers face traditional tobacco-related risks, such as 

cardiac disease, stroke, COPD, and osteoporosis. These conditions 

are likely to become more prevalent with the aging of the HIVinfected population on effective ART. Smoking and HIV infection 

substantially increase the risks of respiratory tract infection, 

including acute bronchitis, bacterial pneumonia, PCP, and TB.

■ HIV-infected smokers also are at higher risk of several tobaccorelated cancers, and may be at increased risk of poorer 

immunologic and virologic responses to ART. 

■ Asking patients about smoking is an important part of primary 

care management. Current users should be asked about smoking at 

every visit.

■ Brief (<3 min) tobacco dependence interventions are effective, and 

every tobacco user should be offered treatment.

■ Counseling and medication are effective when used by themselves 

for treating tobacco dependence. The combination of counseling 

and medication, however, is more effective than either alone.

■ Evidence-based treatment options include behavioral counseling 

and support, nicotine replacement therapy, bupropion, and 

varenicline. 

Note: Current information on VHA smoking and tobacco use cessation policy 

and tools can be found online at http://www.publichealth.va.gov/smoking/.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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SMOKING CESSATION

54 PRIMARY CARE OF VETERANS WITH HIV

BACKGROUND

■ Smoking is a cause of cancers of the 

bladder, cervix, esophagus, kidney, 

larynx, lung, oral cavity, pancreas, and 

stomach; of leukemia; of peripheral atherosclerosis, cerebrovascular disease, 

and coronary artery disease; of COPD, 

decreased lung function, and lung infections; of pregnancy complications; and 

of peptic ulcer disease. 

■ HIV-infected patients are 2-3 times more likely to be smokers than their agematched HIV-uninfected counterparts.

■ In the United States, 30-65% of patients in HIV primary care clinics are 

smokers.

■ HIV-infected smokers have higher rates of certain diseases (compared with 

HIV-uninfected smokers and HIV-infected nonsmokers), such as lung cancer, 

head and neck cancers, anal and cervical cancers, oral candidiasis, and oral 

hairy leukoplakia. 

■ HIV infection increases the risk of respiratory tract infections, and smoking 

further increases the risks of acute bronchitis, bacterial pneumonia, PCP, 

and TB.

■ Smoking may decrease the immunologic and virologic response to ART. In 

a cohort of HIV-infected women, smokers had lower CD4 cell counts and 

higher HIV viral loads compared with age-matched HIV-infected female nonsmokers after initiation of ART. 

■ Smoking is the leading cause of preventable death and disease in the United 

States. Tobacco use is a chronic, relapsing disorder that often requires 

repeated interventions and multiple attempts to quit.

■ Most smokers are interested in quitting. Surveys have found that two thirds 

of HIV-infected smokers want to quit.

■ Smoking cessation programs for HIV-infected smokers are effective. For 

example, among patients who were given a 10-week supply of nicotine 

patches, self-help booklets, and initial physician counseling plus (by randomization) 8 counseling phone calls or no calls, 37% of those in the counseling 

group were not smoking at a 3-month follow-up, compared with 10% of 

those who did not receive the counseling phone calls.

Veterans with HIV*

Tobacco Use: 38%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition 

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PRIMARY CARE OF VETERANS WITH HIV 5

EVALUATION

The 5 A’s

These strategies are designed to be brief (<3 minutes of direct clinician time). 

They need not be delivered by the same clinician; for example, a clinic nurse 

may ask about tobacco use, whereas a prescribing clinician (eg, MD, PA, or NP) 

may advise, assess, and assist, with referral to another provider for counseling 

services.

ASK ...

• All patients about tobacco use at every clinic visit:

• If a patient has never used, you do not need to ask again.

• If a patient quit years ago, congratulate and check in periodically.

• Consider making it a part of your offi ce practice to ask about and record 

tobacco use while patients are having vital signs recorded. 

▼

ADVISE ...

• Smokers with clear, strong, and personalized suggestions:

• “I think it is important that you quit smoking. I can help.” Clear:

• “Quitting smoking is one of the most important things you can do to Strong:

protect your health.”

• Associate smoking with something that is important to the Personalized:

patient, such as exposure of children to tobacco smoke, the expense of cigarettes, or pulmonary and cardiovascular comorbidities. “Remember the time you 

had that terrible pneumonia?” “Do you realize that you can save almost $2,000 a 

year on cigarette expenses if you quit?”

▼

ASSESS ...

• Smokers’ readiness to quit within 30 days: “Are you willing to give quitting a try in 

the next 30 days?” 

• If not ready, consider using motivational interviewing to increase patient’s readiness 

to quit (see the 5 R’s for Patients Unwilling to Quit, below*).

• If ready, assist and arrange (following).

▼

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SMOKING CESSATION

56 PRIMARY CARE OF VETERANS WITH HIV

• A patient’s preparations for quitting:

• etting a quit date. Ideally, the quit date should be within 2 weeks. S

• elling family, friends, and coworkers about quitting, and requesting understand- T

ing and support.

• nticipating challenges to the upcoming quit attempt, particularly during the A

critical fi rst few weeks. These include nicotine withdrawal symptoms.

• emoving tobacco products from the environment. Before quitting, avoiding R

smoking in places where a lot of time is spent (eg, work, home, car). Making the 

home smoke free.

• Offer nicotine replacement or, if appropriate, bupropion, varenicline, or other medication (see below for more details on medication options).

• Provide practical counseling (problem-solving/skills training; see below).

• Offer intensive treatment options (smoking cessation intervention programs and 

groups).

• Offer readily available counseling and support services: phone support, clinic 

counselors.

▼

ARRANGE ...

• Enrollment in a VHA-based smoking cessation clinic, if the patient wishes.

• Referral to appropriate counseling services.

• Referral to evidence-based cessation program in the community or to phone 

quit lines if VHA-based interventions are not convenient for the patient or if the 

patient is interested (800-QUIT-NOW is a national portal for state programs).

• Follow-up contact during the fi rst week after quit date (in person or by phone).

• Follow-up visit 1 month after quit date.

• Subsequent follow-up visits; congratulate upon success in quitting; anticipate 

further support with relapses (approximately 35-40% patients relapse 1-5 years 

after quitting).

Adapted from Fiore et al. See References.

* For more detailed suggestions on how to conduct motivational interviewing with smokers, 

see Fiore et al. Chapter 3, Section B (see References).

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PRIMARY CARE OF VETERANS WITH HIV 5

 MANAGEMENT

Current tobacco users who are not ready to quit:

Continue to encourage smoking cessation. 

The 5 R’s for Patients Unwilling to Quit

• Explain to patients why cessation is personally relevant (eg, comorbidi- Relevance:

ties, cost).

• Ask patients to explain their perceived potential risks of smoking; discuss Risks:

these risks with them (eg, sexual dysfunction, infertility, fetal harm, CV and pulmonary disease, malignancies, secondhand smoke). Explain that:

• 20 minutes after quitting, heart rate and blood pressure drop

• 12 hours after quitting, carbon monoxide levels drop to normal

• 2 weeks to 3 months after quitting, circulation and lung function improve

• 1 year after quitting, risk of coronary heart disease is cut in half

• 5 years after quitting, stroke risk is the same as for nonsmokers

• 10 years after quitting, lung cancer risk is cut in half

• Ask patients to explain what they might gain from cessation (eg, breath Rewards:

smells better, stained teeth get whiter, bad odor of clothes goes away, food tastes 

better, sense of smell returns to normal, everyday activities do not result in shortness of breath, skin tone gets better, health improves, worries about secondhand 

smoke lessen, respiratory symptoms improve, lung function improves).

• Ask patients to identify barriers to quitting (eg, fear of failure, weight Roadblocks:

gain, depression) and offer options to address those barriers.

• Discuss these issues with patients at each visit. Repetition:

Adapted from Fiore et al. See References.

Current tobacco users who are ready to quit:

■ Offer smoking cessation treatment at every visit to every patient who 

smokes.

■ Even minimal (<3 minute) intervention can yield benefi t, including simply 

advising a patient to quit.

■ For patients with symptoms suggestive of COPD, particularly shortness of 

breath, consider pulmonary function testing, including spirometry, lung volume, and diffusion studies, and provide medication to support a quit attempt 

(see COPD, p. 107). 

■ Patients who are informed of abnormal pulmonary function test results may 

be more likely to quit.

■ If applicable, discuss challenges patients have encountered during previous 

attempts to quit and tailor current recommendations to what patients can 

accomplish.

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SMOKING CESSATION

58 PRIMARY CARE OF VETERANS WITH HIV

(even brief sessions [<3 minutes]) and fi rst-line smoking cessation medications. Specifi cally, U.S. Public Health Service’s 2008 update of the Clinical Practice Guideline on Treating Tobacco Use and Dependence (see References,

Fiore et al.) fi nds strong evidence in favor of:

• Using medications to assist in smoking cessation

• Combining medication with behavioral counseling

• Providing multiple counseling sessions as opposed to single counseling 

sessions

■ Pharmacologic interventions included in the table below are fi rst-line therapies found to be effective by the USPHS. All were found to be more effective 

than placebo at assisting in cessation. A list of 7 monotherapies is provided, 

along with 4 combination therapies. Not all therapies listed in the Guideline 

are considered fi rst-line by the VHA (see below). Combination therapies may 

be particularly effective at blunting nicotine withdrawal symptoms, but may 

cost more and may expose the patient to a wider range of side effects.

■ Two components of counseling have been found to be particularly effective: 

working with patients to develop problem-solving skills and strategies, and 

delivering social support as part of counseling.

Examples of Problem-Solving Skills

Type of Skill Examples

Identifying situations that endanger smoking cessation• Negative stressors

• Being around smokers

• Alcohol

• Smoking cues

• Availability of cigarettes

Identifying coping skills Learning to anticipate and avoid tempt- • 

ing situations

• Cognitive strategies for improving 

mood, decreasing stress

• Changing routines that expose the 

patient to smoking cues

Identifying feelings that can threaten 

cessation 

• A single puff increases the risk of 

relapse

• Withdrawal symptoms peak 1-2 weeks 

after quitting but may persist for 

months

• Withdrawal symptoms can include negative mood, urges to smoke, diffi culty 

concentrating

Adapted from Fiore et al. See References.

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PRIMARY CARE OF VETERANS WITH HIV 5

ppp

Type of Support Examples

Encouragement to quit Effective treatments are available • 

• Half of people who have ever smoked 

have been able to quit

• Communicate belief in patient’s ability 

to quit

Communicate caring and concern Ask how patient feels about quitting • 

• Express willingness to help as often as 

needed

• Ask about patient’s fears and ambivalence about quitting

Encourage patient to talk about the quitting process• Why does patient want to quit?

• What are patient’s concerns about 

quitting?

• What success and diffi culties in quitting 

has patient had in past?

Adapted from Fiore et al. See References.

■ Continue to encourage cessation even if the patient relapses. Relapse does 

not mean that the patient will not quit successfully on a future attempt.

■ Counsel patients on potential nicotine withdrawal symptoms. Note that 25% 

of smokers who quit do not have these symptoms. Nicotine withdrawal 

symptoms include:

• Depressed mood

• Insomnia

• Irritability

• Anxiety

• Diffi culty concentrating

• Restlessness

• Decreased heart rate

• Increased appetite and weight gain (10% of patients gain >13 kg after 

smoking cessation)

Pharmacologic Interventions

Key points:

■ Nicotine replacement therapies (NRTs), such as nicotine patch, gum, and lozenges, do not interact with ARVs and have low toxicity at recommended dosages, even in patients with cardiovascular disease.

■ All forms of NRT are equally effi cacious.

■ Varenicline is not considered fi rst-line therapy for smoking cessation by the 

VHA; see the Varenicline Criteria for Prescribing at http://www.pbm.va.gov/

CriteriaForUse.aspx.

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SMOKING CESSATION

60 PRIMARY CARE OF VETERANS WITH HIV VHA Formulary Choices for Pharmacotherapy of Smoking Cessation Bupropion Nicotine Trans- dermal Patch Nicotine Polacrilex Gum Nicotine Polacrilex Lozenge Varenicline Formulations Bupropion SR 150 mg, 300 mg Bupropion IR 100 mg (Nicoderm/Habitrol) 21 mg, 14 mg, 7 mg (Nicotrol) 15 mg, 10 mg, 5 mg 2 mg, 4 mg 2 mg, 4 mg 0.5 mg, 1 mg Start instructions 1-2 weeks before quit date On quit date 1 week before quit date Recom- mended regimen Bupropion SR 150 mg QD for 3 days, then 150 mg BID (8 hours apart) Reduce dosage for patients with cirrho- sis: 150 mg QOD Bupropion IR 100 mg QD for 3 days, then 100 mg TID; reduce dosage for patients with cir- rhosis: 75 mg QD High dependence# High-dose patch for 4-6 weeks, then medium-dose patch for 2 weeks, then low-dose patch for 2 weeks Low dependence medium-dose patch for 6-8 weeks, then low-dose patch for 2 weeks High dependence# 4 mg Q1-2H for 6 weeks, then Q2-4H for 4 weeks, then Q4-6H for 2 weeks Low dependence 2 mg Q1-2H for 6 weeks, then Q2-4H for 3 weeks, then Q4-6H for 3 weeks Maximum: 24 pieces/24 hours High dependence# 4 mg Low dependence 2 mg Suck 1 lozenge Q1-2H for 6 weeks, then 1 lozenge Q2-4H for 3 weeks, then 1 lozenge Q4-8H for 3 weeks Maximum: 20 lozenges/24 hours or 5 lozenges/6 hours Initial: 0.5 mg QD on day

1-3, then 0.5 mg BID on days 4-7, then 1 mg BID for total duration of 12 weeks Reduce dosage for CrC<30: maximum dosage 0mg BID; end-stage renal disease or hemodialysis: 0.5 mg QD

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PRIMARY CARE OF VETERANS WITH HIV 6

Admin- istration comments Start 1-2 weeks • before quitting smoking (to achieve steady-state levels) Continue treat- • ment for 7-12 weeks (if no prog- ress is made by week 7, consider discontinuing therapy) If insomnia, take • evening dose in afternoon Usually worn • 16-24 hours; remove overnight Apply between • neck and waist Rotate sites • Takes 2-3 days • for effect after application of fi rst patch Chew slowly (about 10 • chews) until peppery taste is released, then “park” between teeth and gums until fl avor dissipates; repeat pro- cess on and off for 30 minutes per piece Has been studied in • combination with patch Allow lozenge to • dissolve slowly over course of 20-30 minutes, shifting in mouth occasionally Do not chew or • swallow (increased risk of GI side effects) Avoid acidic bev- • erages within 15 minutes of use (eg, citrus juices, soft drinks); these decrease absorption Start 1 week before • quit date Take drug after eating • and with 8 oz of wate

Instruct patient or • caregiver to report depression, suicidal idation, unusual changes in behavior, or worsening of preexisting psy- chiatric illness An additional 12 week

• of treatment in patien

who have successfully stopped smoking may increase likelihood of long-term abstinence 1-year abstinence rates§ 10-30% (up to 35% when combined with patch) 16-30% (dose dependent); high- dose patch: 30% 20-30% 15-20% 18.5-23% (12-week course) vs 4-10% with placebo 43.6% (with additional 12-week course) vs 37% with placebo

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SMOKING CESSATION

62 PRIMARY CARE OF VETERANS WITH HIV Bupropion Nicotine Trans- dermal Patch Nicotine Polacrilex Gum Nicotine Polacrilex Lozenge Varenicline ARV interactions Metabolized by the cytochrome P450 system; EFV and TPV may 

↓ bupropion 

levels 40-50%; when using with these ARVs, monitor for depression and titrate to clinical effect; RTV may 

↑ bupropion 

levels

None Does not interact with 

the cytochrome P450 sytem; no ARV interactions identifi ed to date

Time to peak blood concentrations 

3 hours (half life = 21 hours)

4-10 hours 15-30 minutes No data 3-4 hours

Absorption 20% 75-90% 30% 30% High; virtually complete 

absorption

Advantages (+)Disadvantages (–)

(+) Good adherence; ease of use; can be combined with patch; consistent rate of exposure; helps with withdrawal symptoms

(+) Best adherence; easy to use; consistent rate of exposure; unobtrusive

(+) Helps prevent sudden urges; can titrate to adjust for cravings; oral substitute for cigarettes; slow release of nicotine reduces addiction potential

(+) Easy to use; discreet; higher immediate levels; can titrate to adjust for cravings; reduces self-reported withdrawal symptoms

(+) Good adherence; ease of use; consistent rate of exposure; higher rate of abstinence compared with bupropion anplacebo

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PRIMARY CARE OF VETERANS WITH HIV 6

(–) Many drug interactions result- ing from metabolism by CYP 2B6; CNS side effects; must be adjusted for hepatic insuffi ciency; increased risk of seizures (–) Less effec- tive than gum for cravings; diffi cult to control titration; absorption increased at elevated tempera- tures; should abstain from smoking while using NRT (–) Diffi cult for those with poor dentition or dentures; must learn proper chewing technique; should abstain from smok- ing while using NRT; must abstain from drinking/ eating during gum use; swallowing nicotine causes GI side effects (hiccups, diarrhea or constipation, fl atulence, belching) (–) Must abstain from drinking/eating during lozenge use; should abstain from smoking while using NRT (–) Potential for serious neuropsychiatric side effects, particularly in patients with underlying psychiatric disease; dos- age adjust for renal insuf

fi ciency (CrCl <30); high incidence of nausea; not studied in patients with underlying mental illness Adverse effects Anxiety • Disturbed concen- • tration Dizziness • Insomnia • Constipation • Dry mouth • Nausea • Seizures (risk: • 1:1,000) Sleep disturbances • Local skin irrita- • tion Bone pain • Headache • Nausea • Local mouth irritation • Jaw pain • Hiccups • Dyspepsia • Rhinitis • Nausea • Local mouth irrita- • tion/tingling Heartburn, indi- • gestion, nausea (if chewed) Headache • Nausea, diarrhea • Flatulence • Dream disorders • Headache • Insomnia • Abnormal behavior • Agitation • Depressed mood • Suicidal thoughts • Constipation • Flatulence • Nausea, vomiting • Consider dosage reduc- tion for patients sensitive to adverse effects (eg, nasea, headache, insomnia)

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SMOKING CESSATION

64 PRIMARY CARE OF VETERANS WITH HIV Bupropion Nicotine Trans- dermal Patch Nicotine Polacrilex Gum Nicotine Polacrilex Lozenge Varenicline VHA National Formulary restrictions None None None Restricted to patients who cannot tolerate gum (eg, dentures, missing teeth, TMJ, previous head or neck surgery) Must meet criteria for use (http://www.pbm. va.gov/CriteriaForUse. aspx) Restricted to patients without active mental health disorders or with clinically stable mental health disorders who have had >1 relapse on NRT or bupropion VHA cost** and average cost per day based on above regimens SR: $0.48/tablet $0.96/day IR: $0.28/tablet $0.84/day 14 mg patches: $2.50/patch $2.50/day 2 mg gum: $12.62/50 pieces $20.12/110 pieces $0.18-$0.25/piece $2.20-$6/day 4 mg gum: $13.70/50 pieces $25.69/110 pieces $0.23-$0.27/piece $2-$6.50/day 2 mg or 4 mg lozenge: $29.45/72 lozenges $0.41/lozenge $5-8/day 0.5 mg and 1mg tablets: $1.17/tablet $2.34/day

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PRIMARY CARE OF VETERANS WITH HIV 6

Contraindi- cations and relative con- traindications Contraindications: History of seizures • Predisposition to • seizures (eg, severe head trauma, CNS tumor, cirrhosis) Abrupt withdrawal • from heavy, daily alcohol or other sedative MAO inhibitor • within 14 days Bulimia, anorexia • nervosa Relative contraindi- cations: Hypersensitivity • Pregnancy • category B Relative contraindications: Hypersensitivity • Pregnancy category D • Use within 14 days post MI, or in patients with serious or worsening • angina Patients should be advised not to smoke while on NRT • Relative contraindica- tions: Serious neuropsychiat

• ric disorders (includin

suicidal and homicidal ideation) History of suicidal, • homicidal, or assaultivbehavior in the past 1weeks Untreated or unstable • mental disorder such as psychotic disorder, bipolar disorder, majodepressive disorder, and PTSD Severe renal impair- • ment Pregnancy category C • 

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SMOKING CESSATION

66 PRIMARY CARE OF VETERANS WITH HIV Bupropion Nicotine Trans- dermal Patch Nicotine Polacrilex Gum Nicotine Polacrilex Lozenge Varenicline Comments Use with caution in • patients with liver, kidney failure Avoid in patients • on MAO inhibitors In combination • with behavioral program, patch doubles the quit rate Durability of • cessation is bet- ter with 21 mg patches than with 14 or 7 mg patches Using the 21 • mg patch yields roughly 40-50% the plasma nicotine levels of smoking 1.5 packs per day In combination with • an intensive behavioral program, nicotine gum can double the quit rate Using 2 mg ad lib yields • roughly 40% plasma nicotine levels of smok- ing 1 pack per day In combination • with an intensive behavioral program, nicotine lozenges can increase the quit rate Not fi rst-line ther- • apy for smoking cessation Ask patients about • any psychiatric history before pre- scribing varenicline Monitor for signs/ • symptoms of psych

atric illness during use Monitor serum crea- • tinine levels; as renal function decreases (as seen in elderly patients), dosage redutions may be necessar

* Remove nicotine patch at bedtime.# High dependence: in general, >20 cigarettes per day or use of fi rst cigarette within 30 minutes of awakening. § All NRTs have been shown to double 6- to 12-month abstinence rates compared with placebo.** Cost based on FSS or BIG4 pricing as listed on PBM website (http://www.pbm.va.gov/PBM/prices.htm).

Note: Two additional prescription products, a nicotine inhaler and nicotine nasal spray, are FDA approved for NRT; however, these products are not available on the VHA National Formulary. For more information on these products, visit the American Lung Association Smoking Cessation Support website at http://www.lungusa.org/.

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PRIMARY CARE OF VETERANS WITH HIV 6

gp

Therapy Dosage and Duration Comments

Preferred Combinations

Patch + gum Studies used patch for >14 • 

weeks

• Use standard dosages and durations of each component drug

• Coadministration with RTV 

↑ bupropion levels: use cautiously, especially at high 

dosages.

Patch + 

bupropion SR

Alternative Combinations

Patch + 

(venlafaxine or 

paroxetine or 

nortriptyline)

Studies used highest-dose patch 

(21 or 22 mg) for 6-8 weeks

plus either

Paroxetine 20 mg daily for 

9 weeks

OR

Venlafaxine 22 mg daily for 21 

weeks

OR

Nortriptyline 75-100 mg daily for 

8-52 weeks

• Nortriptyline and other 

tricyclic antidepressants are 

CYP 2D6 substrates: consider 

reducing dosage when given 

with RTV. Monitor serum 

levels. Serum levels in smoking cessation studies (in HIVuninfected patients) ranged 

from 55 ng/mL to 69 ng/mL.

• FPV and DRV decrease paroxetine levels.

Preventing or Addressing Relapse with Patients Who Have Quit

■ Congratulate patients at each visit and discuss the benefi ts and challenges of 

quitting.

■ Use open-end questions relevant to the topics below to discover whether 

the patient wishes to discuss issues related to quitting:

• The benefi ts, including potential health benefi ts, the patient may derive 

from cessation

• Any success the patient has had in quitting (eg, duration of abstinence, 

reduction in withdrawal)

• The problems encountered or anticipated threats to maintaining abstinence (eg, depression, weight gain, alcohol, other tobacco users in the 

household, signifi cant stressors)

• If the patient is still taking medication, assess effectiveness, side effects, 

and other medication issues

■ Interventions to address barriers to maintaining cessation:

• Lack of support: Refer patients to a group, schedule follow-up phone 

calls, help identify potential sources of support (individuals, community o

religious organizations).

• Prolonged withdrawal symptoms: Prolong pharmacologic interventions or consider combination therapy.

• Depressed mood: Consider using antidepressants and initiating 

psychotherapy.

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SMOKING CESSATION

68 PRIMARY CARE OF VETERANS WITH HIV

limited, encourage patients to increase exercise, counsel on a healthy diet 

(avoid strict dieting), preferentially use pharmacologic interventions that 

cause less weight gain (eg, bupropion, nicotine gum).

• Flagging motivation: Reassure patients that fl agging motivation is 

common, check to see if patients might be using tobacco periodically, 

and counsel that taking even a single puff will increase urges and make 

quitting more diffi cult.

• Smoking lapses: Suggest continued use of medications, which can 

reduce the likelihood that a lapse will lead to a full relapse. Encourage 

another quit attempt or a recommitment to total abstinence. Reassure 

that quitting may take multiple attempts, and use the lapse as a learning 

experience. Provide or refer for intensive counseling.

REFERENCES

Adeyemi O. Cardiovascular risk and risk management in HIV-infected patients. Top HIV 

Med. 2007 Nov-Dec;15(5):159-62.

Feldman JG, Minkoff H, Schneider MF. Association of cigarette smoking with HIV prognosis among women in the HAART era: a report from the women’s interagency HIV study. 

Am J Public Health. 2006 Jun;96(6):1060-5.

Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. 

Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service; May 2008. Available at http://www.ncbi.nlm.nih.gov/books/

bv.fcgi?rid=hstat2.chapter.28163. Accessed December 8, 2008.

Gritz ER, Virdrine DJ, Fingeret MC. Smoking cessation a critical component of medical 

management in chronic disease populations. Am J Prev Med. 2007 Dec;33(6 Suppl):S414-22.

VA/DoD Clinical Practice Guideline Working Group. Management of Tobacco Use. 

Washington, D.C.: Department of Veterans Affairs, Offi ce of Quality and Performance; 

2004. Available at http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. Accessed December 

18, 2008. 

VHA Pharmacy Benefi ts Management Strategic Healthcare Group and the Medical Advisory Panel. National PBM Drug Monograph on Varenicline (ChantixTM); December 2006. 

Available at http://www.pbm.va.gov/monograph/Varenicline.pdf. Accessed December 8, 

2008.

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PRIMARY CARE OF VETERANS WITH HIV 6

Substance Use

KEY POINTS

■ Substance use disorders (SUDs) are common among people who 

are HIV infected: 40% of HIV-infected individuals in the United 

States are associated with injection drug use (IDU), either directly 

or by having an IDU sex partner. 

■ Among injection drug users in the United States, 40-45% are HIV 

infected. 

■ Substance use is a signifi cant cause of morbidity and mortality in 

itself, and it is associated with HIV transmission and acquisition.

■ Ask all patients about any current or recent use of illicit drugs 

or alcohol, or misuse of prescription drugs. Ask specifi cally about 

injection drugs, opioids, methamphetamines, cocaine, and “club 

drugs.” 

■ At each visit, ask the patient directly about his or her substance use. 

Ask patients about their perceptions of IMPORTANCE of the issue 

and their CONFIDENCE in making any kind of change.

■ A comprehensive treatment program includes the care of medical 

providers, psychiatrists to assist with comorbid psychiatric 

conditions, social workers, housing counselors, case managers, and 

substance abuse counselors. Group therapy with peer support also 

may be important.

■ Treatment options exist along a continuum and include 

detoxifi cation, treatment of comorbid conditions, maintenance of 

treatment, and prevention of relapse.

BACKGROUND

■ Substances frequently abused in the 

United States include alcohol, nicotine, 

cannabis, prescription medications 

(narcotics, sedatives, and many others), 

cocaine, heroin, methamphetamines, 

tranquilizers, hallucinogens, anabolic 

steroids, inhalants, and “club drugs.”

Veterans with HIV*

Alcohol use disorder: 33%

Illicit drug use: 30%

Other drug use: 22%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-

code corresponding to these conditions

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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SUBSTANCE USE

70 PRIMARY CARE OF VETERANS WITH HIV

fl unitrazepam (Rohypnol), gamma-hydroxybutyrate (GHB), and ketamine. 

■ The focus of this chapter is on recognition and management of abuse involving heroin, other opiates, and methamphetamine. Abuse of cocaine, cannabis, 

and club drugs will be addressed briefl y.

■ Alcohol misuse and cigarette smoking are discussed in separate chapters (see 

Alcohol Misuse, p. 3 and Smoking Cessation, p. 53).

Defi nitions

Addiction: a primary, chronic, neurobiologic disease, with genetic, psychosocial, 

and environmental factors infl uencing its development and manifestations. It is 

characterized by behaviors that include one or more of the following: impaired 

control over substance use, compulsive use, continued use despite harm, and 

craving.

Physical dependence: a state of adaptation that is manifested by a drug 

class-specifi c withdrawal syndrome that can be produced by abrupt cessation, 

rapid dose reduction, decreasing blood level of the drug, or administration of an 

antagonist.

Tolerance: a state of adaptation in which exposure to a drug induces changes 

that result in a diminution of one or more of the drug’s effects over time.

Substance dependence: a maladaptive pattern of substance use, leading to 

clinically signifi cant impairment or distress, manifested as tolerance (need for 

increased amounts of the substance or decreased effect with the same amount) 

or withdrawal symptoms.

Substance abuse: a maladaptive pattern of substance use that has become 

socially, legally, or occupationally problematic for an individual. 

SUD: a more general term comprising substance dependence or abuse.

IDU: includes IV drug use, IM drug use, and skin popping. IDU can involve 

opiates, methamphetamines, cocaine, sedatives/tranquilizers, or other drugs.

Epidemiology

■ Drug abuse is closely associated with HIV infection in the United States: 

40-45% of injection drug users are HIV infected, and 25-30% of noninjection 

drug abusers are HIV infected.

■ About 40% of people who are HIV infected are associated with IDU, either 

directly or by having an IDU sex partner. 

■ In the United States, 60% of injection drug users are men, 45% are white, 43% 

have completed high school, and 53% are employed. 

■ Comorbidities are common: 30% of injection drug users in the United States 

are PPD positive, 80-90% are infected with hepatitis C, 40% are infected with 

hepatitis B, and 60% use alcohol.

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PRIMARY CARE OF VETERANS WITH HIV 7

abusers are more likely to involve themselves in prostitution and unsafe sex 

in order to obtain money for drugs. 

■ At least one third of drug abusers have an overt psychiatric comorbidity. 

Substance Abuse, HIV Infection, and ART

■ Cocaine use decreases CD4 cell production by as much as 3- to 4-fold and 

increases the rate of HIV viral replication by up to 20-fold. 

■ Methamphetamine binges are associated with interruptions in ART adherence

■ In a prospective cohort study, active drug use was strongly associated with 

underutilization of ART, nonadherence, and inferior virologic and immunologic 

responses to ART, compared with former drug use and nonuse of drugs. 

■ A recent national survey showed that 23% of health providers for HIVinfected patients have a negative attitude score toward treating HIV-infected 

IDU patients. These providers are less likely to prescribe ARVs to their IDU 

patients even when the patients meet criteria for starting ART.

EVALUATION

Although there are many reasons to identify patients who abuse substances, 

and to try motivating them toward treatment, there is little evidence from 

primary care settings that screening and brief interventions alone are effective. 

Approaches that focus on the effects of substance abuse on the patient’s own 

health (eg, in terms of poor ARV adherence, acquisition of infections) may be 

useful. See also Prevention for Positives, p. 39.

SCREENING

At initial visit and at least annually thereafter: Ask all patients about 

any current or recent use of illicit drugs (in addition to alcohol and nicotine), 

including IDU, opioids, methamphetamines, cocaine, club drugs, and illegally obtained 

prescription drugs. Check for comorbid psychiatric illnesses.

 MANAGEMENT

■ Goals for patients: Return to productive functioning.

■ Goals for providers: Reduce stigma and treatment bias.

■ Treatment includes helping the patient accept the role of having an illness, 

detoxifi cation, treatment of comorbid conditions, maintenance of treatment, 

and relapse prevention.

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SUBSTANCE USE

72 PRIMARY CARE OF VETERANS WITH HIV

tions, though many patients may not accept referral. 

■ Comprehensive treatment may reduce drug abuse by 40-60%, reduce associated crime by 40-60%, and increase employment prospects by 40%.

■ A comprehensive treatment program incorporates the expertise of medical 

providers, psychiatrists to assist with comorbid psychiatric conditions, social 

workers, housing counselors, case managers, and substance abuse counselors. Group therapy with peer support also is an important component of 

treatment.

■ Drug therapy alone for treatment of addiction is successful with only 10% of 

patients. 

■ For patients unwilling to enter treatment, continue to address their substance 

use, focusing on reducing use or increasing readiness for drug cessation.

Brief Interventions 

At each visit, ask the patient directly about substance abuse. A useful 

technique for facilitating a patient-centered conversation about the readiness to 

change is to ask questions about the patient’s perception of IMPORTANCE of 

the issue and his or her CONFIDENCE in making any kind of change.

Raise Importance

Ask: “On a scale of 1-10, how IMPORTANT is it for you to change your substance use?”

“Why did you give it (number) and not a (lower number)?”

“What would it take for you to give it a (higher number)?”

Raise Confi dence

Ask: “On a scale of 1-10, how CONFIDENT are you that you can change 

successfully?”

“Why did you give it (number) and not a (lower number)?”

“What would it take for you to give it a (higher number)?”

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PRIMARY CARE OF VETERANS WITH HIV 7

Illicit Drug Behavioral Interventions Pharmacologic Interventions

Heroin 

and other 

opioids

• In addition to brief primary 

care provider interventions 

suggested above, refer for 

specialty evaluation and 

treatment, or to substance abuse counselors in 

community-based organizations, rehabilitation facilities, 

and methadone maintenance 

sites.

• Specifi c psychosocial interventions for opioid use have 

not demonstrated consistent 

effi cacy. 

• Opioid agonist therapy is 

the gold standard for heroin 

addiction treatment. 

• If the patient is in withdrawal, or at high risk of 

withdrawal, refer for detoxifi cation or to an emergency 

department. If unstable 

(medically or psychiatrically), refer to an emergency 

department.

• For local (non-VA) substance 

abuse resources: 

800-662-HELP.

• Narcotics Anonymous 

provides group support: 

http://www.na.org.

• Counsel on safe injection 

practices, including reducing risk of transmission of 

HIV and other bloodborne 

pathogens.

• Treat comorbid psychiatric conditions.

• is a full opioid agonist Methadone

used for opioid agonist therapy in 

opioid treatment programs.

• Methadone maintenance programs 

typically start with a dose of ≤30 

mg and adjust to the lowest effective dose that suppresses withdrawal 

signs and symptoms. Typical dosage is 

between 60 mg and 120 mg QD. 

• Adverse effects include constipation, 

weight gain, drowsiness, excessive 

sweating, and changes in libido.

• Can increase QT interval, precipitating torsade de pointes and other 

arrhythmias. Avoid use in patients 

with baseline prolonged QTc; use 

with caution if coadministered with 

other medications that prolong QT.

• Methadone levels may be lowered by 

various ARVs; see Potential ARV 

Interactions, below, and Common 

Medications, p. 307.

• is a partial mu- Buprenorphine

opioid agonist and weak kappa 

antagonist with 25-50 times the 

analgesic potency of morphine. It has 

a pharmacologic “ceiling,” and lower 

risk of overdose and abuse than full 

opioid agonists.

• Buprenorphine use is controlled 

nationally and within the VHA; physicians are able to prescribe buprenorphine only with special training and 

a specifi c DEA certifi cate. See PBM 

Criteria for Use at http://www.pbm.

va.gov/criteria/Buprenorphine.pdf.

• It is administered sublingually.

• At high dosages, it may block the 

effects of full opioid agonists, leading 

to withdrawal. Therefore, patients 

should stop taking short-acting 

opioids 12-24 hours before starting 

buprenorphine and reduce their

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SUBSTANCE USE

74 PRIMARY CARE OF VETERANS WITH HIV

30-40 mg/day.

• In the United States, buprenorphine 

is coformulated with naloxone. 

Naloxone is poorly absorbed sublingually; however, if the tablet is 

crushed and injected parenterally, 

the naloxone precipitates opiate 

withdrawal.

• Buprenorphine has been approved 

for use in offi ce-based opioid dependence treatment. 

• Buprenorphine is induced over the 

fi rst 3 days of treatment, with an initial daily dosage of 4-8 mg, increased 

by 4-8 mg QD until relief from withdrawal symptoms is achieved. The 

maximum recommended dosage is 

32 mg QD.

• Side effects include disturbed sleep, 

drowsiness, sweating, headaches, 

nausea, constipation, and reduced 

libido. Mild increases in ALT have been 

reported. 

• Buprenorphine may interact with PIs 

and with EFV; see Potential ARV 

Interactions, below.

• In acute pain episodes, buprenorphine 

can be used Q8H for analgesic effects.

• opioid antagonist. Pre- Naltrexone:

cipitates opiate withdrawal; appropriate only for patients with >7 days 

of abstinence. 

• Not recommended because compliance is poor; consider as component 

of substance abuse program for 

highly motivated patients.

Methamphetamine• If unstable (medically or 

psychiatrically), refer to an 

emergency department or 

hospitalize.

• Behavioral interventions are 

the mainstay of treatment; 

no pharmacologic agents 

have proven effi cacy.

• Refer to outpatient or inpatient behavioral counseling:

• Treat comorbid psychiatric conditions.

• Dextroamphetamine “replacement 

therapy” has not shown greater effi -

cacy than placebo. 

• Ongoing studies suggest that bupropion may be useful as an adjunct to 

behavioral therapies. 

• RTV inhibits amphetamine metabolism 

and can lead to a 2- to 3-fold increase

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PRIMARY CARE OF VETERANS WITH HIV 7

g 

and cognitive-based therapy 

(eg, Matrix Model).

• Refer to harm reduction 

programs. 

• Consider referral to contingency management programs that provide vouchers 

of escalating value for successive urine samples documenting abstinence.

• For local (non-VA) substance abuse resources: 

800-662-HELP.

• Narcotics Anonymous provides methamphetaminespecifi c groups: 

http://www.na.org.

• Crystal Meth Anonymous: 

http://www.crystalmeth.org.

• Ask about ART adherence at 

each visit, as methamphetamine users frequently go 

on binges that lead to interruptions in ART adherence.

• Methamphetamine use is 

associated with unsafe sexual behaviors. Explore risk 

behaviors, screen for STDs, 

and counsel on safer sex 

options; see Prevention 

for Positives, p. 39.

• Provide written or illustrated instructions that can 

be processed visually, as 

methamphetamine users 

often have impaired auditory 

memory.

p

should be educated about this interaction.

Cocaine • Refer to cognitive-behavioral 

therapy tailored to substance abusers. 

• For local substance abuse 

resources: 800-662-HELP.

• Narcotics Anonymous also 

provides cocaine-specifi c 

groups: http://www.na.org.

• Treat comorbid psychiatric 

conditions.

• Consider the pharmacologic adjunct 

naltrexone at 50 mg QD for 12 

weeks in combination with participation in relapse prevention programs.

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SUBSTANCE USE

76 PRIMARY CARE OF VETERANS WITH HIV

g

(see below)

g

behavioral therapy tailored 

to substance abusers. 

• For local substance abuse 

resources: 800-662-HELP.

• Narcotics Anonymous also 

provides group support for 

club drug users: 

http://www.na.org.

py

• RTV increases MDMA levels 5- to 

10-fold and can increase the risk of 

fatal heatstroke and dehydration.

• RTV also increases GHB levels, leading to increased risk of seizures, 

respiratory depression, and loss of 

consciousness.

Methadone:

• The following may ↓ methadone levels. Monitor for signs of opiate withdrawal. 

Dosage adjustment of methadone may be needed.

• NRTIs: ABC

• NNRTIs: EFV, NVP

• PIs: ATV, DRV, FPV/r, LPV/r, NFV, SQV/r, TPV/r

• DLV may ↑ methadone levels. Start methadone at low dosage, monitor for 

methadone toxicity.

• Methadone may ↓ ddI levels. Dosage adjustment not established.

Buprenorphine:

• PIs: May ↑ buprenorphine levels and ↑ risk of adverse effects. 

• EFV: May ↓ buprenorphine levels; monitor for signs of opiate withdrawal. 

• Dosage adjustment of buprenorphine may be needed.

Cannabis and Club Drugs

The effects of club drugs are less well-characterized. Here is an overview of the 

effects of cannabis and some common club drugs:

Illicit Drug Effects Notes

Cannabis 

(marijuana)

Also known as chronic, 

pot, weed, grass, Mary 

Jane, spliff, ganja, hash, 

skunk, puff, herb, and 

many other names

Intoxicant, stimulant, psychedelic 

(mild hallucinogenic), relaxant 

• Very few people develop physical dependence, but psychological 

dependence is common. A chronic 

heavy user can appear apathetic 

and unmotivated, and may perform 

poorly at work or school. 

• Other health risks include increased 

incidence of respiratory infections, 

as well as toxicities from adulterants (eg, formaldehyde).

 POTENTIAL ARV INTERACTIONS !

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PRIMARY CARE OF VETERANS WITH HIV 7

Also known as ecstasy, 

E, X, XTC, rolls, beans, 

Adam

hallucinogenic 

amphetamine

pp

recreational psychoactive drugs, most 

commonly sold in the form of “ecstasy” 

tablets. It is known for its empathogenic, euphoric, and stimulant effects.

• Physical effects are similar to those 

of amphetamines.

• Between 300 and 400 deaths have 

been reported from MDMA use 

and overheating.

• Concurrent use with amphetamines, 

cocaine, or alcohol increases the 

risk of overheating.

• RTV increases MDMA levels 5- to 

10-fold and can increase the risk of 

fatal heatstroke and dehydration.

Flunitrazepam 

(Rohypnol)

Also known as roofi es, 

“date-rape” drug

Benzodiazepine 

sedative-hypnotic

• Flunitrazepam has been used in 

many “date rapes” in the United 

States, with cases also reported in 

Europe and Australia. 

• 10 times more potent in sedativehypnotic effects than diazepam.

• Causes paralysis, unconsciousness, 

and short-term amnesia.

• Onset occurs within 10 minutes 

after being taken; the effects peak in 

8 hours and last 12 hours.

• Mixing with alcohol at higher doses 

can lead to unconsciousness for 

several days.

Gammahydroxybutyrate 

(GHB)

Also known as liquid 

ecstasy, GBL (a prodrug), BDO, GBH, Blue 

Nitro, Midnight Blue, 

RenewTrient, Reviarent, SomatoPro, Serenity, Enliven

Sedative 

depressant, 

anesthetic 

• GHB is popular on the rave scene. 

It has effects of alcohol-like intoxication and sexual disinhibition. 

• Higher doses can lead to disorientation, blurred vision, nausea, vomiting, 

impaired physical coordination, and 

muscle spasms.

• Onset occurs within minutes; overdose can lead to unconsciousness 

within 30 minutes. The risk of coma 

and death is potentiated by concurrent alcohol use.

• RTV increases GHB levels, leading to increased risk of seizures, 

respiratory depression, and loss of 

consciousness.

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SUBSTANCE USE

78 PRIMARY CARE OF VETERANS WITH HIV

hydrochloride

Also known as K, 

Special K, Dorothy, 

cat tranquilizer, tekno, 

green

anesthetic, 

hallucinogenic 

(same class as 

phencyclidine, or 

PCP)

p

erinary and human anesthetic, but 

it has become popular in club and 

rave scenes.

• Initial effects are of stimulation 

and euphoria, followed by sedation and hallucination (out-of-body 

sensations). Physical effects include 

nausea and vomiting, slurred speech, 

lack of coordination, and numbness.

• Physical risks include injury resulting from the anesthetic effects. 

Overdoses can lead to respiratory 

compromise.

• Used chronically, ketamine can 

increase the risk of drug-induced 

hepatitis.

Pain Management in Patients with an SUD

■ The prevalence of self-reported pain among HIV-infected patients ranges 

from 28-97%.

■ HIV-infected patients with an SUD are more likely to be untreated or undertreated for pain.

■ Pain management in SUD patients may be complicated by opiate tolerance.

■ Clinician concerns about pain management in patients with an SUD include:

• Drug seeking by patients

• Diversion

• Relapse to substance abuse

• Legal repercussions

• Inadequate knowledge or skills on the part of the clinician 

• Unavailability of specialists

■ SUD patient concerns about pain management include:

• Relapse to substance abuse

• Anticipated physical discomforts (eg, thinking that medicines will be 

injected; fearing side effects)

• Fearing accusations of malingering

• Perceived “weakness” in taking medications for pain

■ Appropriate evaluation of pain in the HIV-infected SUD patient includes:

• An accurate and complete pain history, including results of previous 

evaluations; distinguishing between neuropathic and nonneuropathic pain 

may help guide therapy

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PRIMARY CARE OF VETERANS WITH HIV 7

therapy

• Appropriate and complete evaluation to identify correctable causes of 

pain (eg, use of ddI or other neurotoxic medication in a patient complaining of painful neuropathy)

• Accurate and complete documentation of fi ndings via CPRS

■ Principles of pain management in the HIV-infected SUD patient include:

• Having a single provider prescribe all pain medications

• Accurate and complete documentation of the rationale for the treatmen

used, including dosage, dose interval, amount prescribed, and refi ll procedures

• If a patient has an active SUD, referral to a treatment program

• Agreement with the patient on goals of therapy:

In cases of acute pain, elimination of pain is a reasonable goal, with _

agreement on when the need for therapy will end

For chronic pain, the goal should be reasonable relief of pain with a _

maximum level of functioning

• Use of specifi c rules (“contract”) that addresses reports of lost medications, missed appointments etc, to promote accountability and decrease 

the risk of diversion or drug-seeking behavior; an example of such a contract is available at http://www.painmed.org/pdf/controlled_substances_

sample_agrmt.pdf

• Pretreatment agreement to random urine toxicology screens

• Use of a stepwise approach to analgesia (see Pain Medications, p. 321)

• Use of nonpsychotropic pain medications, when possible, to achieve pain 

relief

• When opiates are indicated, use the minimum dosage needed to relieve 

pain

• Around-the-clock dosing is more effective than use as needed

• Ensuring that adequate pain relief is obtained to prevent self-medication: 

Increasing dosages may be required if the underlying cause of pain (eg, 

malignancy) progresses or tolerance develops

• Referral to a pain specialist for complex management issues or concerns 

over drug-seeking behavior

REFERENCES

AIDS Education & Training Centers National Resource Center. Recreational Drugs and 

Antiretroviral Therapy. In: Clinical Manual for Management of the HIV-Infected Adult; July 

2006. Available at http://www.aids-etc.org/aidsetc?page=cm-314_rec_drugs. Accessed 

December 10, 2008.

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SUBSTANCE USE

80 PRIMARY CARE OF VETERANS WITH HIV

Text Revision, 4th Edition. Washington D.C.: American Psychiatric Publishing; 2000.

Basu S, Bruce RD, Barry DT, et al. Pharmacological pain control for human immunodefi -

ciency virus-infected adults with a history of drug dependence. J Subst Abuse Treat. 2007 

Jun; 32(4):399-409.

Colfax G, Shoptaw S. The methamphetamine epidemic: implications for HIV prevention 

and treatment. Curr HIV/AIDS Rep. 2005 Nov;2(4):194-9. 

Erowid: a member-supported organization that provides access to diverse sources of 

information on psychoactive substances, including recreational drugs. Available at http://

www.erowid.org/. Accessed December 10, 2008.

Francis H. Substance abuse and HIV infection. Top HIV Med. 2003 Jan-Feb;11(1):20-4.

Lum PJ, Tulsky JP. The medical management of opioid dependence in HIV primary care settings. Curr HIV/AIDS Rep. 2006 Nov;3(4):195-204. 

McNicholl I. HIV InSite Database of Antiretroviral Drug Interactions. San Francisco: UCSF 

Center for HIV Information. Available at http://www.hivinsite.org/insite?page=ar-00-02. 

Accessed December 10, 2008.

National Institute on Drug Abuse (NIDA): research and policy on the prevention and 

treatment of drug abuse and addiction. Available at http://www.nida.nih.gov/. NIDA also 

has a website addressing substance abuse and HIV: http://hiv.drugabuse.gov/.

Prater CD, Zylstra RG, Miller KE. Successful pain management for the recovering addicted 

patient. Prim Care Companion J Clin Psychiatry. 2002 Aug; 4(4):125-131.

VA/DoD Evidence-Based Clinical Practice Guideline Working Group. Management of 

Substance Use Disorder in the Primary Care Setting. Washington, D.C.: Department of 

Veterans Affairs, Offi ce of Quality and Performance; September 2001. Available at 

http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. Accessed December 18, 2008.

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Organ Systems and Metaboli

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/16/09 
PRIMARY CARE OF VETERANS WITH HIV 8

Anal Dysplasia

KEY POINTS

■ HIV-infected patients are at much higher risk of developing 

squamous cell cancer of the anus (SCCA) than the general 

population and have a poorer 5-year survival rate once it is 

diagnosed.

■ At-risk populations include all HIV-infected men and women, 

particularly MSM (with or without HIV infection), any patient with 

a history of anogenital condyloma, and women with abnormal 

cervical or vulvar histology. 

■ All at-risk men and women should be screened for anal cancer at 

baseline and annually thereafter by digital rectal examination (DRE). 

Some specialists recommend an anal Pap smear, if available, at 

baseline and annually thereafter. 

■ All patients with abnormal cytology of any degree should be 

referred for high-resolution anoscopy (HRA) and biopsy. 

BACKGROUND

■ Anal dysplasia denotes precancerous 

changes in the squamous cells lining the 

anus. It is associated with human papillomavirus (HPV) infection. Neoplastic 

changes begin in the basal cell layer of 

the anal squamous epithelium, at the 

transformation zone. If untreated, anal 

dysplasia may progress over time to SCCA.

■ Anal HPV infection and dysplasia are analogous to cervical HPV infection 

and dysplasia; much of the model for evaluation and management of SCCA is 

based on cervical cancer screening and management. However, no large studies to date have shown that detection and treatment of precancerous anal 

lesions prevent anal cancer.

■ HIV infection is associated with increased rates of anal HPV infection, anal 

dysplasia, oncogenic HPV types, and SCCA. 

■ The relative risk of SCCA among HIV-infected individuals compared with the 

general population ranges from 33 to 222, depending on the cohort. 

Veterans with HIV*

Squamous cell cancer of the 

anus: 1%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-

code corresponding to this condition

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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ANAL DYSPLASIA

84 PRIMARY CARE OF VETERANS WITH HIV

fected MSM.

■ Rates of anal HPV infection and abnormal cytology increase with decreasing 

CD4 counts.

■ HIV-infected persons with SCCA are an average of 10 years younger at presentation than HIV-uninfected persons with SCCA.

■ HIV-infected persons with SCCA have poorer responses to treatment: 

the 5-year survival rate is 47-60%, compared with 70-80% in the general 

population. 

■ Studies comparing survival rates among patients with SCCA in the years 

before and after the availability of effective ART in the United States show 

confl icting results; there is no clear indication that ART improves SCCA 

outcomes. 

■ The long lead time between HPV infection and the development of cancer 

allows for screening and intervention. The value of screening and treatment of 

anal dysplasia is under investigation.

EVALUATION

Risk factors Populations of HIV-infected persons at highest risk of HPV infection 

and anal dysplasia include: 

• MSM

• Persons with a history of anal receptive intercourse

• Persons with a history of anogenital condylomas

• Women with abnormal cervical or vulvar histology 

• Smokers

Symptoms • Rectal bleeding is present in 45% of patients with SCCA.

• Sensation or pain associated with a rectal mass is present in 30% 

of patients with SCCA; pain may occur with defecation or with 

receptive anal intercourse.

• Pruritus or anal discharge is present in 25% of patients with 

SCCA.

• Approximately 20% of patients with SCCA have no tumor-related 

symptoms.

• Dysplasia usually is asymptomatic.

Physical 

examination

• Check perianal skin for external lesions.

• Conduct DRE to check for masses and other lesions.

• Check inguinal lymph nodes for enlargement suggesting spread 

(hard, fi xed, progressive).

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PRIMARY CARE OF VETERANS WITH HIV 8

SCREENING

Summary of Evaluation for Anal Dysplasia

At baseline and annually:

• Ask about symptoms (eg, mass or rectal bleeding).

• Examine perianal skin and inguinal lymph nodes.

• Screen for dysplasia: anal Pap test (where available) using smear or liquid cytology 

(see below).

• Screen for cancer: DRE

Note: Anal Pap smears should be performed before conducting DRE to avoid contamination of Pap smear with lubricant.

■ Routine screening for anal neoplasia is not yet universally adopted for a number of reasons:

• There is a lack of randomized controlled trials demonstrating that early 

diagnosis and treatment of anal intraepithelial neoplasia (AIN) leads to 

decreased rates of anal cancer.

• Infrastructure for reading anal Pap smears, and for evaluating and treating 

abnormal anal fi ndings, is not available in many clinics.

• The sensitivity and specifi city for anal Pap smears has been variable. The 

sensitivity of anal Pap smears has ranged from 69% to 93% and the specifi city has ranged from 32% to 59%, compared with diagnosis by HRAdirected biopsy samples. 

• Treatments for HIV-related anal dysplasia have shown mixed effi cacy.

■ However, accumulating evidence and clinical experience support screening fo

and treatment of precancerous lesions.

• Cohort studies show that early detection of anal dysplasia may be benefi 

cial because identifi cation and treatment of small, localized lesions lead to 

better morbidity and mortality outcomes. 

• A recent analysis of SCCA outcomes in the general population showed 

that the 5-year survival rate for patients with local disease was 78%, 

compared with 56% for those with regional disease and 18% for those 

with distant disease.

• One small study showed that early detection of anal dysplasia with anal 

Pap smears was cost-effective.

Anal Pap tests: Currently, there are no universally adopted guidelines for anal 

dysplasia screening. Many specialists recommend screening all at-risk men and 

women at baseline and (if normal) annually thereafter.

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ANAL DYSPLASIA

86 PRIMARY CARE OF VETERANS WITH HIV

Anal Pap Test Procedure

• Moisten and insert a Dacron (polyester) swab into the anal canal about 4-5 cm 

(past the anal sphincter and transformation zone), rotate around the anus to collect cells while removing the swab, while maintaining gentle pressure against the 

anal canal. Proceed to slide or liquid prep:

• Rotate the swab on labeled glass slide, apply fi xa- Glass slide prep cytology:

tive, and allow it to dry.

• Insert the swab into the liquid fi xative, swirl around Liquid prep cytology:

for 15 seconds, remove, and cap the jar. This method avoids drying artifacts.

Note: An anal Pap test must be performed before insertion of lubricant into the 

anus, because lubricating jelly interferes with smear interpretation. In addition, 

patients should refrain from using enemas or engaging in receptive anal intercourse 

for 24 hours before an anal Pap test is performed.

Anal Pap smears should be read by a pathologist trained in their interpretation. Anal cytology is generally graded using Bethesda 2001 criteria, which are 

ordered as follows: 

• Negative for intraepithelial lesion or malignancy 

• Atypical squamous cells of undetermined signifi cance (ASCUS) 

• Atypical squamous cells, cannot exclude HSIL (ASC-H) 

• Low-grade squamous intraepithelial lesion (LSIL)

• High-grade squamous intraepithelial lesion (HSIL)

• SCCA

LSIL is sometimes referred to as grade 1 anal intraepithelial neoplasia (AIN 1), 

whereas HSIL may be referred to as AIN 2 or 3, carcinoma in situ, or Bowen 

disease.

 MANAGEMENT

Management of Abnormal Pap Results

ASCUS

ASC-H

LSIL

HSIL

Referral for HRA and

biopsies to evaluate

for AIN

Consider annual

screening: DRE

and Pap

Normal cytology

Anal Pap

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PRIMARY CARE OF VETERANS WITH HIV 8

referred to GI or General Surgery for HRA and biopsy of visible lesions.

■ Note that ASCUS and LSIL fi ndings on cytology do not rule out the presence 

of HSIL or cancer; follow-up evaluation with HRA is important.

■ If HRA is not available at a local VA facility, one option is to refer the patient to a 

local non-VA provider on a fee basis; a list of anal dysplasia specialists in the United 

States can be found at http://www.analcancerinfo.ucsf.edu/resources/index.html.

• If HRA cannot be obtained, regular anoscopy can be performed to look 

for visible lesions. Biopsy should be performed on lesions to determine 

the degree of histologic changes and rule out invasive cancers. Note that 

anoscopy is likely to be insensitive.

Treatment

There currently are no consensus treatment guidelines. The treatment options 

presented here are based on expert opinion.

The focus of treatment is on high-grade, precancerous lesions, particularly HSIL. 

Lower-grade lesions typically are monitored.

Cytologic Findings Treatment Options

Condylomata, 

ASCUS, and LSIL

• Monitor via HRA every 6 months until normal twice in 

succession, then annual Pap smear

• Patients with LSIL may opt to receive topical treatment 

(see below) for symptoms such as bleeding, itching, or 

burning; or for discrete lesions

Follow-up HRA should be done every 6-12 months

HSIL, ASC-H (high 

probability of AIN 

grades 2-3)

Topical therapy

For small lesions (<1 cm2 at the base):

• Local application of bichloroacetic acid or 80-90% trichloroacetic acid (well-tolerated but occasionally painful)

• Liquid nitrogen

Other topical, self-applied options studied in small cohorts 

include:

• Topical imiquimod applied for 6-10 hours then washed off, 

TIW for 16 weeks 

• Topical 5% 5-fl uorouracil applied BID for 16 weeks

• These sometimes are used to treat diffuse lesions

Infrared coagulation (offi ce based)

• For lesions too large for topical therapy

• Followed by debridement of destroyed tissue using biopsy 

forceps

• Note: this treatment is not yet FDA approved

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ANAL DYSPLASIA

88 PRIMARY CARE OF VETERANS WITH HIV

gy 

• For large (>1 cm2) or extensive lesions, or for patients 

unable to receive infrared coagulation

• Surgical excision with a scalpel for discrete lesions with 

or without laser ablation

• Large lesions may require multiple, staged procedures to 

reduce risk of bleeding, anal stenosis, sphincter compromise, and infection 

• Referrals should be made to surgical centers with experience in treating anal dysplasia

Follow-up HRA should be done every 6 months

SCCA Full discussion of anal cancer is beyond the scope of this 

chapter, but special points are noted below:

• Clinical staging consists of physical examination and 

biopsy of the primary tumor, palpation of the groin, CT of 

the chest, and CT or MRI of the abdomen and pelvis

• Staging is based on size of tumor (T1-4) and node positivity (N0-3 for nodal metastases) and correlates with 

5-year survival rate

• First-line treatment consists of chemoradiotherapy rather 

than surgery

Prevention

The effi cacy of HPV vaccines in preventing anal HPV infection is under investigation.

REFERENCES

Berry JM, Palefsky JM, Welton ML. Anal cancer and its precursors in HIV-positive patients: 

perspectives and management. Surg Oncol Clin N Am. 2004 Apr;13(2):355-73.

Chiao EY, Giordano TP, Palefsky JM, et al. Screening HIV-infected individuals for anal cancer 

precursor lesions: a systematic review. Clin Infect Dis. 2006 Jul 15;43(2):223-33. 

Chin-Hong PV, Vittinghoff E, Cranston RD, et al. Age-specifi c prevalence of anal human 

papillomavirus infection in HIV-negative sexually active men who have sex with men: the 

EXPLORE study. J Infect Dis. 2004 Dec 15;190(12):2070-6.

Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with 

human immunodefi ciency virus infection and acquired immunodefi ciency syndrome. J Natl 

Cancer Inst. 2000 Sep 20;92(18):1500-10.

Hessol NA, Pipkin S, Schwarcz S, et al. The impact of highly active antiretroviral therapy 

on non-AIDS-defi ning cancers among adults with AIDS. Am J Epidemiol. 2007 May 

15;165(10):1143-53.

Palefsky J. Human papillomavirus infection in HIV-infected persons. Top HIV Med. 2007 

Aug-Sep;15(4):130-3.

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PRIMARY CARE OF VETERANS WITH HIV 8

Androgen Defi ciency

KEY POINTS

■ Androgen defi ciency is relatively common among HIV-infected 

individuals, although its prevalence has decreased as ART use has 

increased.

■ Symptoms of HIV-associated androgen defi ciency can include loss 

of muscle mass, fatigue, depression, decreased libido, diffi culty 

concentrating, and reduced functional status.

■ Testosterone replacement can alleviate these symptoms to varying 

degrees.

■ Men with low-normal serum testosterone but symptoms of 

androgen defi ciency may benefi t from replacement therapy.

■ Most HIV-infected men with androgen defi ciency will have the 

hypogonadotropic variant rather than testicular failure; measuring 

follicle-stimulating hormone (FSH) and luteinizing hormone (LH) 

can help distinguish the two types.

■ The use of testosterone replacement in women with HIVassociated wasting remains under study.

BACKGROUND

■ Androgen defi ciency is defi ned as subnormal testosterone production with 

associated symptoms. Hypogonadism 

is a more general term that refers to 

defi cient sex hormone production; in 

men, it refers to defective testosterone 

production, whereas in women, it refers 

to defective estrogen production.

■ This chapter will address testosterone defi ciency in HIV-infected adults; for 

information on female hypogonadism, see Women’s Health, p. 249.

■ Mechanisms may be primary (testicular) or secondary (hypothalamic/pituitary)

• Primary (hypergonadotropic) androgen defi ciency: low testosterone 

(free, bioavailable, or total) + elevated FSH and/or LH.

Veterans with HIV*

Male androgen defi ciency: 2%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-

code corresponding to this condition

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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ANDROGEN DEFICIENCY

90 PRIMARY CARE OF VETERANS WITH HIV

(free, bioavailable, or total) + low or normal FSH and/or LH.

■ Most HIV-infected men (up to 75%) with decreased testosterone levels have 

secondary (hypogonadotropic) androgen defi ciency.

■ Up to 50% of men with AIDS-related wasting had abnormally low testosterone levels in studies done before the availability of effective ART. Many 

HIV-infected women also have subnormal androgen levels (note that normal 

testosterone levels in women are approximately one tenth those in men).

■ Prevalence of androgen defi ciency has declined with the use of ART, but 

remains substantial: Up to 20% of men on ART with less-than-ideal body 

weight have abnormally low free testosterone.

■ Manifestations in men include reduced muscle mass, decreased strength, 

fatigue, depression, diffi culty concentrating, decreased libido, oligospermia, 

reduced functional status, and bone loss.

■ Manifestations in women are less studied, but include fatigue, decreased libido, 

and wasting.

■ Treatment of hypogonadal HIV-infected men with testosterone can lead to 

increased muscle mass and quality of life, and improvements in depression. 

In women, treatment has shown increase in weight and social functioning.

■ Among HIV-infected men ≥49 years of age, very low total testosterone is 

associated with viral load >10,000 copies/mL, and is inversely associated with 

African American race.

Possible causes of androgen defi ciency in HIV-infected men include:

■ HIV infection (mechanism unclear)

■ Cirrhosis

■ Medications/drugs (eg, opiates, glucocorticoids, ketoconazole, anabolic steroids, megestrol, or testosterone)

■ Tumors, infection, or infi ltration of the hypothalamus or pituitary gland

• In addition to endocrine abnormalities, symptoms may include headaches, 

seizures, visual disturbances (temporal fi eld cuts, diplopia)

• Prolactinoma

• Metastatic disease

• Granulomatous disease

• Abscess

■ Radiation therapy, chemotherapy

■ Trauma

■ Malnutrition

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PRIMARY CARE OF VETERANS WITH HIV 9

EVALUATION

Symptoms Note: Onset can be subtle and symptoms may be attributed to 

other causes (“getting older,” primary depressive disorder, anxiety, 

chronic illness)

• Loss of libido

• Weight loss, especially of lean muscle mass

• Erectile dysfunction

• Oligospermia/decreased ejaculate volume

• Depressive symptoms, poor concentration

• Fatigue

• Infertility

Physical 

examination

To include assessment of muscle mass, secondary sexual characteristics, visual fi elds. Check for:

• Small or soft testes 

(size smaller than approximately 4.5-6.5 cm long × 2.8-3.3 cm 

wide; suggests atrophy)

• Testicular masses

(roll each testicle between thumb and 1st two fi ngers, feeling for 

fi xed or fi rm masses, which may not be tender)

• Gynecomastia; suggests primary androgen defi ciency if FSH or LH 

is elevated

Laboratory 

evaluation

The measurement of testosterone is less than optimal. Total testosterone usually refl ects all circulating testosterone components: 

free (unbound) testosterone + testosterone bound (loosely) to 

albumin and (tightly) to sex hormone-binding globulin (SHBG). 

Only free testosterone and albumin-bound testosterone are 

bioavailable. SHBG can increase with old age, liver disease, and 

androgen defi ciency itself, thus increasing the total testosterone 

measured while potentially decreasing the amount of unbound 

(active) testosterone.

Initial evaluation:

• Serum testosterone: morning blood sample for total testosterone

• Average serum testosterone levels decrease with age, and 

there is no absolute cutoff dividing normal from subnormal 

serum testosterone. One approach defi nes normal as >2.5 

standard deviations below the mean serum total testosterone of healthy young males (approximately 319 ng/dL, 

per the American Association of Clinical Endocrinologists 

[AACE]).

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ANDROGEN DEFICIENCY

92 PRIMARY CARE OF VETERANS WITH HIV

authorities recommend rechecking total testosterone and 

measuring free testosterone (by equilibrium dialysis or by 

free testosterone concentration) or bioavailable testosterone. 

The analog method of measuring free testosterone is not suffi ciently accurate.

• FSH, LH to distinguish primary from secondary androgen defi ciency.

Other tests:

• Other pituitary hormone levels (prolactin, growth hormone, TSH), 

if hypopituitarism (hormone levels low) or pituitary adenoma 

(hormone levels high) is suspected.

• Sperm count and motility, if fertility is an issue.

• Consider MRI if workup suggests hypothalamic or pituitary mass 

or other abnormality (eg, abnormal pituitary hormone levels, visual 

fi eld lesions, or neurologic signs).

• Testicular ultrasound if testicular masses are detected on 

examination.

 MANAGEMENT

■ Evaluate and treat potential reversible causes of androgen defi ciency (see 

above).

■ Testosterone is the preferred treatment for men with documented androgen 

defi ciency (signs and symptoms with abnormal total testosterone usually 

<200-320 ng/dL, or free testosterone usually <6.5 ng/dL).

■ Some authorities recommend testosterone replacement therapy in men with 

symptoms of androgen defi ciency (see Symptoms, above), but low-normal 

testosterone levels.

■ Typical recommended dosages for men (note that testosterone is classifi ed as 

a Schedule III drug by the U.S. Drug Enforcement Agency):

• IM testosterone (cypionate or enanthate):

100 mg IM every 7 days _

200 mg IM every 14 days _

300 mg IM every 21 days _

Longer dosing intervals with higher dosages are more convenient, but _

risk higher peak levels and greater fl uctuations in testosterone level.

• Transdermal (patch) testosterone:1 patch (5 mg) applied daily

• Testosterone gel: 5 mg applied daily to trunk and shoulders

• Transscrotal testosterone: 6 mg patch applied daily

■ For women with HIV-associated wasting and subnormal serum testosterone, 

twice weekly transdermal testosterone (5 mg twice weekly) for 6 months has 

been studied as a treatment. This treatment resulted in an increase in muscle 

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PRIMARY CARE OF VETERANS WITH HIV 9

terone use in women.

■ Testosterone is absolutely contraindicated in men with prostate 

cancer; it should be used with extreme caution in men with benign prostatic 

hypertrophy, and only after urologic consultation.

■ Testosterone is absolutely contraindicated in pregnant women 

because of adverse effects on the fetus.

■ Testosterone therapy usually is well tolerated. Potential adverse effects of 

testosterone therapy include: 

• Testicular atrophy

• Hirsutism 

• Gynecomastia 

• Prostatic enlargement 

• Acne 

• Mood swings (especially with high doses of IM testosterone) 

• Polycythemia (more common with IM testosterone) 

• Elevations in ALT, AST

• Dyslipidemia

• Skin irritation at patch site 

• Sleep apnea (rare)

• In women, testosterone may also cause virilization; start with low doses 

and monitor closely for adverse effects

■ Follow up 2-3 months after starting replacement: 

• Measure serum testosterone response to check for effi cacy of dosage: 

IM testosterone: measure serum testosterone at midpoint between _

doses

Patch: measure 4-8 hours after application _

Gel: timing not critical, as blood levels are constant _

• Assess for side effects and check hepatic transaminases and hemoglobin/

hematocrit. 

• In case of adverse effects, discontinue or lower the dosage of testosterone.

With the IM formulation, may consider switching to a transdermal _

formulation, which gives more even dosing and avoids high peak 

testosterone levels. May also consider switching from high-dose/lessfrequent administration to lower-dose/more-frequent administration.

• Testosterone therapy may unmask cryptic prostate cancer. Examine the 

prostate every 6-12 months, looking for prostatic enlargement; check 

serum prostate-specifi c antigen (PSA) in older men.

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ANDROGEN DEFICIENCY

94 PRIMARY CARE OF VETERANS WITH HIV

are detected, or PSA becomes abnormally elevated, discontinue 

testosterone and refer to Urology for evaluation.

Note: Other anabolic steroids such as oxandrolone, an orally available alkylated 

androgen, are not recommended in place of testosterone, as they do not have 

the same effects in the body and may convey higher risk of adverse effects, such 

as hepatic toxicities (peliosis hepatis, hepatoma, cholestatic jaundice) and lipid 

derangements. Nandrolone, a parenteral androgen with more anabolic properties than testosterone, is no longer available in the United States. 

WHEN TO REFER

Endocrinology • Lack of symptomatic improvement

• Diagnostic uncertainty, especially if secondary androgen defi -

ciency remains in the differential diagnosis

• Evidence of hypothalamic or pituitary mass

Urology • Testicular masses

• Prostatic enlargement, masses, or nodules, or elevated PSA

REFERENCES

American Association of Clinical Endocrinologists. American Association of Clinical 

Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients—2002 update. Endocr Pract. 2002 NovDec;8(6):440-56.

Corcoran C, Grinspoon S. Treatments for wasting in patients with the acquired immunodefi ciency syndrome. N Engl J Med. 1999 Jun 3;340(22):1740-50. 

Dobs AS, Dempsey MA, Ladenson PW, et al. Endocrine disorders in men infected with 

human immunodefi ciency virus. Am J Med 1988 Mar;84(3 Pt 2):611-6. 

Grinspoon S. Androgen defi ciency and HIV infection. Clin Infect Dis. 2005 Dec 

15;41(12):1804-5. 

Klein RS, Lo Y, Santoro N, et al. Androgen levels in older men who have or who are at risk 

of acquiring HIV infection. Clin Infect Dis. 2005 Dec 15;41(12):1794-803. 

Miller K, Corcoran C, Armstrong C, et al. Transdermal testosterone administration in 

women with acquired immunodefi ciency syndrome wasting: A pilot study. J Clin Endocrinol Metab. 1998 Aug;83(8):2717-25.

Mylonakis E, Koutkia P, Grinspoon S. Diagnosis and treatment of androgen defi ciency 

in human immunodefi ciency virus-infected men and women. Clin Infect Dis. 2001 Sep 

15;33(6):857-64. 

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PRIMARY CARE OF VETERANS WITH HIV 9

weight loss related to human immunodefi ciency virus infection who were receiving highly 

active antiretroviral therapy. Clin Infect Dis. 2000 Nov;31(5):1240-4. 

Rosner W, Auchus RJ, Azziz R, et al. Position statement: Utility, limitations, and pitfalls 

in measuring testosterone: An Endocrine Society position statement. J Clin Endocrinol 

Metab. 2007 Feb;92(2):405-13.

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/26/09 
PRIMARY CARE OF VETERANS WITH HIV 9

Asthma

KEY POINTS

■ Asthma is characterized by airway hyperresponsiveness, infl ammation, 

and reversible obstruction.

■ Stepwise, multimodal treatment of asthma may decrease symptoms.

■ Patients should know their baseline peak expiratory fl ow rate (PEFR) 

measurements and their PEFR thresholds for seeking medical care.

■ Drug-drug interactions between PIs and certain medications may affect 

treatment.

BACKGROUND

■ Asthma is a chronic infl ammatory disorder of the airways that causes recurrent 

episodes of wheezing, breathlessness, chest tightness, and cough, particularly at 

night and in the early morning. 

■ These symptoms are associated with airfl ow limitation that typically is revers

ible and responsive to bronchodilator therapy, unlike chronic obstructive pulmonary disease (COPD) (see COPD, p. 107).

■ In asthma, airfl ow limitation is secondary to airway hyperresponsiveness and 

narrowing (increased resistance to fl ow) caused by infl ammation and edema. 

In contrast, in COPD (particularly in the case of emphysema), airfl ow limitation is primarily caused by lung tissue destruction and loss of recoil, and is 

largely irreversible.

■ Asthma is best distinguished from COPD (emphysema and chronic bronchitis) by clinical features such as: 

• Marked variability in symptoms 

• No history of cigarette smoking (although some asthmatics may smoke)

• Onset early in life (although asthma may present in adulthood)

• History of allergies such as hay fever

Because COPD may demonstrate partially reversible airfl ow obstruction, the 

response to a bronchodilator, particularly a single administration in the pulmonary function laboratory, may not reliably distinguish asthma and COPD. 

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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ASTHMA

98 PRIMARY CARE OF VETERANS WITH HIV

■ The prevalence of asthma in the 

United States is approximately 6-11%, 

depending on the population surveyed 

(higher prevalence among people living 

in the inner city).

■ 75% of patients with asthma are 

diagnosed before the age of 7, although asthma may develop at any age.

■ A small cross-sectional study of 83 HIV-infected children and young adults 

showed that 34% of the subjects carried a clinical diagnosis of asthma, and 

42% were using rescue bronchodilators.

EVALUATION

Clinical Signs and Symptoms

Risk factors • Atopy

• Passive smoking

• Upper respiratory tract infections

• Beta-blockers (including ophthalmic formulations)

History

Favoring diagnosis of asthma

Favoring other 

diagnosis (especially 

COPD)

• Wheezing

• Cough often worse at night

• Shortness of breath

• Chest tightness

• Episodic symptoms: hours to days

• Triggers: exercise (after 10-15 minutes), cold air, exposure to allergens 

(dust, molds, furry animals, cockroaches, pollens), GERD, aspirin or 

NSAIDs

• Personal or family history of atopy 

(including allergic rhinitis)

• Asthmatic symptoms as a child

• Onset of symptoms at 

age >50 

• History of cigarette 

smoking

• Sputum production

• Lack of marked 

improvement after 

beta-agonist inhaler or 

oral steroids

Physical 

examination

• Normal between exacerbations

• Wheezes (nonspecifi c, and may not be present)

• Rhonchi

• Prolonged expiration

Asthma: 6% 

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition

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PRIMARY CARE OF VETERANS WITH HIV 9

()

• Use of accessory muscles

• Tachypnea

• Tachycardia

• Prolonged expiratory phase

• Disappearance of wheezing as airfl ow diminishes (suggests 

impending respiratory arrest)

Imaging • Chest X ray usually normal; may show hyperinfl ation in severe 

disease

Pulmonary 

function 

tests

• Spirometry (see below)

• Peak fl ow rate assessment (see below)

Differential 

diagnosis 

• COPD

• Diffuse bronchiectasis

• Allergic bronchopulmonary aspergillosis

• Constrictive bronchiolitis

• Eosinophilic bronchitis

• Postviral bronchiolitis (usually reversible with time but not 

bronchodilators)

• Upper airway obstruction (tumors)

• Congestive heart failure

Pulmonary Function Testing

Defi nitions

• Irreversible airfl ow obstruction: a post-bronchodilator forced expiratory volume in 1 second (FEV1

) to forced vital capacity (FVC) ratio of 

<0.70 (note: may be less specifi c in older people).

• Reversible airfl ow obstruction: increase in post-bronchodilator FEV1

of ≥200 mL or >12% of predicted value.

• Partially reversible airfl ow obstruction: post-bronchodilator FEV1

/

FVC <70% of predicted value despite signifi cant bronchodilator responsiveness.

■ Spirometry: Measure FEV1, FVC, and bronchodilator response.

■ PEFR: Measure brief, forceful exhalation on a peak fl ow meter. Peak fl ow 

meters are inexpensive, provide objective, reproducible assessments of airfl ow, and may be ordered through a facility’s Prosthetics Service for home use 

by patients. 

The test can be performed with the patient sitting or standing. Instruct the 

patient to breathe in maximally, put meter to mouth, seal lips around mouthpiece, and blow as hard and as fast as possible into meter.

• Record patients’ personal best PEFR when they feel well and have had a 

number of good trials on the meter.

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ASTHMA

100 PRIMARY CARE OF VETERANS WITH HIV

• Normal variability in PEFR is 15-20%. Unchanged PEFR in the presence of 

symptoms suggests a diagnosis other than asthma.

• Average PEFRs vary by age, sex, and height.

If initial pulmonary function test (PFT) results are normal or unobtainable, but 

asthma is still suspected:

■ Have the patient record serial PEFR measurements and symptoms in a diary 

to determine whether there is evidence of intermittent airfl ow limitation that 

correlates with symptoms such as dyspnea, chest tightness, or cough.

■ Repeat evaluation when patient is symptomatic. 

■ Consider performing serial measurements before and after bronchodilator 

treatment (this is helpful only if there is baseline airfl ow limitation at the time 

of testing).

■ To diagnose occupational asthma, test before and after occupational exposures; this can be done with spirometry or PEFR. Taking repeated PEFR measurements and keeping a symptom diary are simple to do and may provide 

more useful information.

■ Consider performing bronchoprovocation testing (methacholine or exercise 

challenge) for patients with atypical symptoms, such as chronic (rather than 

intermittent) cough or with normal baseline pulmonary function. Provocative 

testing should not be performed in patients who have typical asthma symptoms.

 MANAGEMENT

Chronic Asthma

Goals

■ ≤2 episodes/week of symptoms requiring treatment with short-acting betaagonist (SABA) medication

■ Prevent exacerbations and need for emergency department visits

■ Minimize limitations on activity

■ Minimize toxicities

Monitoring and Intervention

■ Patients with asthma who use tobacco should be counseled to stop. 

(See Smoking Cessation, p. 53.)

■ At each visit, ask patients whether asthma has woken them from sleep, necessitated more rescue bronchodilator use than usual, necessitated urgent care 

or emergency room visits, or limited participation in usual activities.

■ Ask about control of triggers.

■ Instruct patients to perform serial PEFR measurements at home and workplace. 

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PRIMARY CARE OF VETERANS WITH HIV 10

■ Determine each patient’s PEFR threshold and symptom threshold for escalating therapy or seeking medical evaluation; see Acute Asthma Exacerbation, below. Patients should know their baseline PEFRs and their PEFR 

thresholds. Written plans based on symptoms or PEFR thresholds improve 

disease control.

■ Review and instruct on correct use of inhalers with spacers. Patients who are 

unable to use spacers properly may need a nebulized formulation of a SABA.

■ Use of SABA >2 times per week generally indicates inadequate chronic control and may necessitate a “step-up” in treatment. See below.

Maintenance Treatment according to Severity of Symptoms

Severity Classifi cation Criteria Treatment

Intermittent • Symptoms ≤2 days/week

• Nighttime awakenings ≤2/

month

• SABA use ≤2 days/week

• No interference with normal 

activity

• FEV1

 >80% predicted or 

PEFR >80% personal best; 

FEV1

/FVC normal

• 0-1 exacerbations requiring 

oral steroids per year

Step 1:

• SABA, as needed

Mild Persistent • Symptoms >2 days/week

• Nighttime awakenings 3-4/

month

• SABA >2 days/week but not 

daily

• Minor limitation with normal 

activity

• FEV1

 or PEFR ≥80%; FEV1/

FVC normal

• ≥2 exacerbations requiring 

oral steroids per year

Step 2:

• Low-dose inhaled corticosteroid (ICS)*

• SABA, as needed

Alternatives: cromolyn, leukotriene receptor antagonist 

(montelukast, zafi rlukast), 

nedocromil, theophylline

Moderate 

Persistent

• Symptoms daily

• Nighttime awakenings >1/

week but not daily

• SABA daily

• Some limitation with normal 

activity

• FEV1

 or PEFR >60% and <80%, 

or FEV1

/FVC reduced 5%

Step 3:

• Low-dose ICS* and longacting beta-agonist (LABA) 

(eg, salmeterol or formoterol)

OR

• Medium-dose ICS*

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ASTHMA

102 PRIMARY CARE OF VETERANS WITH HIV

qg 

oral steroids per yearoral steroids (eg, prednisone 

40 mg QD for 5 days) when 

initiating treatment

• SABA, as needed

Alternatives: low-dose ICS* 

with leukotriene receptor 

antagonist, theophylline, or 

zileuton

Severe 

Persistent

• Symptoms throughout the 

day

• Nighttime awakenings daily

• SABA several times per day

• Extreme limitation with normal activity

• FEV1

 or PEFR <60%, or FEV1/

FVC reduced >5%

• ≥2 exacerbations requiring 

oral steroids per year

Step 4:

• High-dose ICS* and LABA

Step 5 (add to above):

• Consider omalizumab for 

patients with allergies, as 

evaluated by an immunologist

* There are important interactions between some inhaled corticosteroids and certain ARVs. See 

Potential ARV Interactions below. 

WHEN TO REFER

• Disease severity moderate persistent or greater: refer to Pulmonary 

• Atypical symptoms: refer to Pulmonary

• Elevated IgE levels: refer to Pulmonary or Allergy/Immunology

Acute Asthma Exacerbation

Treatment according to Severity of Symptoms

Severity Signs and Symptoms Treatment

Mild • Dyspnea with activity

or

• PEFR ≥70% personal best/

predicted

• Can be managed at home 

• SABA 

• Possible short course of oral 

systemic corticosteroids 

(5 days)

Moderate • Dyspnea limits usual activity

or

• Usually requires emergency 

department or offi ce visit 

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PRIMARY CARE OF VETERANS WITH HIV 10

p

predicted

q

• Oral steroids (40-80 mg QD) 

until PEFR >70% personal best/

predicted

Severe • Dyspnea at rest, or lack or 

response to treatments for 

moderate-severity acute 

asthma

or

• PEFR <40% personal best/

predicted

• Usually requires emergency 

department or offi ce visit 

• Frequent nebulized SABA

• Oral steroids (40-80 mg QD) 

until PEFR >70% personal best/

predicted

Life 

Threatening

• Too dyspneic to speak

or

• PEFR <25% personal best/

predicted

• Requires emergency department visit, usually hospitalization 

• Nebulized SABA and ipratropium hourly or continuous

• PO or IV steroids 

• Consider magnesium sulfate 

infusion (2 g), heliox delivered 

albuterol

• Consider intubation in patients 

with persistent hypercapnia, 

exhaustion, depressed mental 

status 

Medications and Other Therapies

For acute symptoms and exacerbations

SABA (eg, albuterol, levalbuterol)• Mainstay of therapy for intermittent disease

• Via nebulizer (eg, 0.083% albuterol solution) or 

metered-dose inhaler (MDI) (90 mcg/puff) 

• For symptoms: PRN 

• For exacerbation: 4-8 puffs every 20 min × 3, then 

Q1-4H PRN

Anticholinergic bronchodilators 

(eg, ipratropium)

• Adjunct to beta-agonists

• Via nebulizer (0.03% solution), or MDI (18 mcg/puff, 

2 puffs), 4-8 puffs every 20 minutes for up to 3 hours

Systemic corticosteroids 

(prednisone or equivalent)

• For mild exacerbation, prednisone 40-60 mg QD for 

5-10 days

• For more severe exacerbations, prednisone 40-80 mg 

QD until PEFR reaches 70% personal best/predicted

• Methylprednisolone 60-125 mg IV Q6-12H for severe 

exacerbations

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ASTHMA

104 PRIMARY CARE OF VETERANS WITH HIV

g

Inhaled corticosteroids (ICS); 

in order of increasing potency 

(on mg per mg basis): 

• Triamcinolone = fl unisolide

• Beclomethasone = budesonide

• Fluticasone

• Mainstay of therapy for mild disease or greater

• www.pbm.va.gov/reviews/ See http://

oralinhaledsteroids.pdf for dosing summary

• Start with beclomethasone 200 mcg BID or 

equivalent

• Use lowest dose consistent with disease control

• Adding LABA is superior to doubling ICS dose

LABA (eg, formoterol, 

salmeterol)

• Not appropriate for monotherapy; may mask 

exacerbation

• Administer via dry powder inhaler (DPI)

• Dosage: formoterol 12 mcg Q12H; salmeterol 

50 mcg Q12H

Leukotriene receptor 

antagonists (eg, montelukast, 

zafi rlukast)

• Potential alternative to low-dose ICS for patients 

with mild asthma unable to use MDI or DPI, or as 

adjunct to ICS for patients with moderate persistent asthma

• Montelukast has not been shown to inhibit CYP 

3A4, whereas zafi rlukast may inhibit CYP 3A4 and 

2C9, potentially interacting with PIs

Mast cell inhibitors (cromolyn, 

nedocromil)

• Potential alternative to low-dose ICS for patients 

with mild asthma unable to use MDI or DPI, or as 

adjunct for ICS in patients with moderate persistent asthma

• Dosage: 2 puffs QID

Theophylline Use discouraged because of drug-drug interac- • 

tions and narrow therapeutic index

• Use only with patients who show clinical benefi t

• Dose using extended-release form; follow levels 

closely (target level 5-15 mcg/mL)

• Initial dosage: 300 mg QD in 2-3 divided doses; a 

dose increase of 1 mg/kg will increase levels by 

2 mcg/mL

• Decrease by 50% in patients with liver dysfunction

Omalizumab Reserved for patients with elevated serum IgE • 

• Use restricted to Pulmonary or Allergy/Immunology services

Oral corticosteroids 7.5-60 mg QD (or dosed QOD to decrease • 

adrenal suppression)

For prevention of exercise-induced bronchospasm

• Use SABA just before exercise; alternatively, use LABA 15 minutes (formoterol) or 

30 minutes (salmeterol) before exercise

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PRIMARY CARE OF VETERANS WITH HIV 10

POTENTIAL ARV INTERACTIONS !

Inhaled Corticosteroids

Fluticasone: 

• caution: PIs: ↑ serum fl uticasone levels; can cause systemic corticosteroid side 

effects, including Cushing syndrome

• Avoid (or limit) use with RTV, particularly in the LPV/r, ATV/r, and DRV/r 

combinations

• Even boosting dosages of RTV (eg, 100 mg BID) may ↑ serum fl uticasone 

Cmax by 2,500% 

• ATV: can ↑ fl uticasone levels – use with caution 

• It is unclear whether signifi cant interactions occur between other inhaled 

steroids and PIs

• no signifi cant interactions expected NRTIs, NNRTIs: 

Long-Acting Beta Agonists

• CYP 3A4 inhibitors such as RTV may ↑ salmeterol levels

Theophylline

• RTV: ↓ theophylline AUC

• IDV: small ↑ in theophylline AUC

• Monitor and adjust theophylline dosing as needed

Leukotriene receptor antagonists 

• Zafi rlukast may inhibit CYP 3A4 and 2C9, potentially interacting with PIs (no formal studies); monitor clinically for adverse effects. Montelukast has not been shown 

to inhibit CYP 3A4. 

REFERENCES

Foster SB, Paul ME, Kozinetz CA, et al. Prevalence of asthma in children and young adults 

with HIV infection. J Allergy Clin Immunol. 2007 Mar;119(3):750-2. 

GINA: Global Strategy for Asthma Management and Prevention. Global Initiative for 

Asthma; 2007. Available at http://www.ginasthma.org. Accessed November 1, 2008.

National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. National Heart, Lung and Blood 

Institute; 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/. Accessed 

November 1, 2008.

!

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/20/09 
PRIMARY CARE OF VETERANS WITH HIV 10

Chronic Obstructive Pulmonary 

Disease (COPD) 

KEY POINTS

■ COPD comprises emphysema, chronic bronchitis, or a combination 

of the two.

■ COPD is a common cause of morbidity in HIV-infected veterans.

■ Multimodal treatment may decrease symptoms and slow 

progression.

■ For smokers, smoking cessation should be emphasized.

■ Drug-drug interactions between PIs and inhaled corticosteroids 

may affect treatment.

BACKGROUND

COPD is:

■ A general term that applies to individuals with emphysema, chronic bronchitis, 

or as is common clinically, a combination of the two.

■ Characterized by airfl ow limitation 

that is not fully reversible. 

■ Usually progressive; it is associated 

with abnormal infl ammatory response 

of the lung to irritants.

■ Preventable and treatable.

■ Diagnostically defi ned as a post-bronchodilator forced expiratory volume in 

second (FEV1) to forced vital capacity (FVC) ratio of <0.70, and lack of alternative explanation for the symptoms and airfl ow obstruction. 

Epidemiology

■ COPD is the fourth leading cause of chronic morbidity and mortality in the 

United States.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Veterans with HIV*

COPD: 11%

Emphysema: 2%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to these

conditions

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

108 PRIMARY CARE OF VETERANS WITH HIV

tions from COPD. 

■ Underdiagnosed: Approximately 50% of patients with COPD have not been 

diagnosed.

■ Only 15-20% of individuals with a signifi cant smoking history are ever diagnosed with COPD. This refl ects underdiagnosis as well as variability in susceptibility of smokers to the disease.

■ HIV-infected subjects were 50-60% more likely than HIV-uninfected subjects 

to have COPD in a prospective observational study done at VA medical 

centers.

■ After adjustment for age, race, ethnicity, pack-years of smoking, and history 

of intravenous drug and alcohol abuse, HIV infection has been identifi ed as an 

independent risk factor for COPD.

Types of COPD

Emphysema • Abnormal and permanent enlargement of the airspaces 

that are distal to the terminal bronchioles

• Usual onset in mid-life; largely irreversible,* often progressive (particularly in smokers who continue to smoke)

Chronic bronchitis • Productive cough for 3 months in each of 2 successive 

years in a patient for whom other causes of cough have 

been excluded

• Usual onset in mid-life; largely irreversible; often progressive (particularly in smokers who continue to smoke)

* Irreversible airfl ow obstruction = post-bronchodilator FEV1/FVC <70%

EVALUATION

Risk factors • Pack-years of smoking

• Increasing age

• History of bacterial or Pneumocystis jiroveci pneumonia 

• History of recurrent respiratory infections

• Exposure to occupational or other dust and chemicals

• Exposure to environmental (secondhand) tobacco smoke

• Exposure to indoor and outdoor air pollution

• Low socioeconomic status

History Dyspnea

• With exertion

• Progressive

• Persistent

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PRIMARY CARE OF VETERANS WITH HIV 10

g gpgy 

breathing”

Chronic cough (may not be present)

• Intermittent or persistent

• Productive or nonproductive

Chronic sputum production

• If present, any pattern of chronic sputum production (even of 

small amounts) can suggest COPD 

Physical 

examination

Note: Physical examination has low sensitivity and specifi city. 

• Vital signs, including respiratory rate (may be elevated), O2 saturation (may be low), blood pressure, heart rate, temperature (all 

may be elevated in exacerbations)

• Observation: tachypnea, dyspnea, accessory muscle use, hyperinfl ation, pursed lips

• Lungs: prolonged expiratory phase, decreased lung sounds, 

basilar crackles, wheezes may be present (usually during an 

exacerbation)

• CV: distant heart sounds due to hyperinfl ation

• Extremities: clubbing, cyanosis

Imaging Chest X rays • have low sensitivity for COPD (50%) but may 

establish alternative diagnoses; radiographic features associated 

with COPD include fl attened diaphragm, increased radiolucency 

of the lung, long heart shadow, bullae, prominent hilar vasculature suggestive of pulmonary hypertension and cor pulmonale 

Pulmonary 

function tests 

(PFTs), including spirometry

PFTs and spirometry are the diagnostic tests of choice. Order:

• Spirometry: airfl ow loops and measurements

• Lung volume (increased in COPD)

• Diffusing capacity of the lung for carbon monoxide (DLCO) 

(reduced in COPD; normal in asthma)

• Consider arterial blood gas (ABG) test for patients with <50% 

of predicted FEV1, severe symptoms, and documented or suspected hypoxemia (O2 saturation by pulse oximetry <88%)

• Consider bronchodilator reversibility testing for diagnosis of 

airway obstruction, particularly if history of asthma symptoms; 

may see partial but not full reversibility in COPD 

• Repeat spirometry if there is an increase in symptoms, or a 

complication

Other 

evaluation

• `1-antitrypsin defi ciency screening: patients of Caucasian 

descent who develop COPD before age 45 or have a strong 

family history of early COPD 

• may give useful information; most COPD Exercise tolerance

patients can walk 500-600 meters over a 6-minute period; 

increases of >50 meters indicate clinically signifi cant response 

to rehabilitation

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

110 PRIMARY CARE OF VETERANS WITH HIV

diagnosis

(keep in mind 

that patients may 

have multiple 

conditions affecting pulmonary 

function, eg, 

COPD plus 

congestive heart 

failure)

(p) 

• Reversible airway obstruction, without other features of COPD 

(see Asthma for distinction between reversible and irreversible airfl ow obstruction)

• Chronic infl ammatory disorder; recurrent episodes of wheezing, 

breathlessness, chest tightness, and coughing 

• Onset usually in childhood; symptoms vary daily

Heart failure 

• Orthopnea, crackles, elevated jugular venous pulse (JVP), S3 gallop, volume restriction rather than airfl ow limitation on PFTs

Bronchiectasis 

• Large volumes of purulent sputum, bronchial dilation, and wall 

thickening on chest X ray; high resolution CT scan is diagnostic 

test of choice

Tuberculosis 

• Exposure risk, subacute fevers, weight loss, infi ltrate on chest 

X ray

Bronchiolitis obliterans 

• Younger age, nonsmoker, fume exposure, hypodense areas on 

CT scan

Diffuse panbronchiolitis 

• Male, nonsmoker, chronic sinusitis, diffuse small centrilobular 

nodular opacities on CT scan

 MANAGEMENT

Smoking Cessation: Prevention and Treatment

• is the single most effective and cost-effi cient intervention Smoking cessation

for most people to reduce the risk of developing COPD and limit its progression.

• Brief, 3-minute periods of counseling from a provider to urge a smoker to quit 

result in smoking cessation rates of 5-10%. 

• , try to incorporate the 5 A’s of brief cessation counseling at For all smokers

each visit:

• sk about tobacco use A

• dvise to quit A

• ssess willingness to make a quit attempt within the next 30 days A

• ssist patients in quitting if they are ready A

• rrange follow-up A

See Smoking Cessation, p. 53, for more information.

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PRIMARY CARE OF VETERANS WITH HIV 11

Goals: prevent progression, relieve symptoms, improve exercise tolerance, 

improve health status, prevent and treat complications, prevent and treat exacerbations, reduce mortality

Remember: Counsel for smoking cessation at all stages!

All Patients:

■ Avoid triggers and exposures 

■ Receive annual infl uenza vaccine

■ Receive pneumococcal vaccine every 5 years

Other Treatments according to Stage:

Stage Spirometric 

Classifi cation Treatment

I: Mild FEV1/FVC <0.70

FEV1 ≥80% predicted

• Short-acting bronchodilator as needed: 

beta-agonists such as albuterol, levalbuterol, and pirbuterol, and/or anticholinergics such as ipratropium

II: Moderate FEV1/FVC <0.70

FEV1 50-79% predicted

Short-acting bronchodilator, plus:

• Long-acting bronchodilator (fi xed dosing schedule): beta-agonists (eg, salmeterol, formoterol, arformoterol) and/or 

anticholinergics (eg, tiotropium)

• Pulmonary rehabilitation

III: Severe FEV1/FVC <0.70

FEV1 30-49% predicted

Each of the above, plus:

• Inhaled corticosteroid* for repeated 

exacerbations (steroid in order of 

increasing potency: triamcinolone, fl unisolide, beclomethasone, budesonide, 

fl uticasone)

• For patients with signifi cant symptoms, 

consider addition of theophylline: may 

improve symptom control

IV: Very 

Severe

FEV1/FVC <0.70

FEV1 <30% predicted

Each of the above, plus:

• Oxygen supplementation if PaO2 <60

• Consider surgical procedures

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

112 PRIMARY CARE OF VETERANS WITH HIV

py 

Failure

2 

g 

or without PaCO2

>50 mmHg

y 

* There are important interactions between some inhaled corticosteroids and certain ARVs. See 

Potential ARV Interactions below. 

WHEN TO REFER

■ Pulmonary rehabilitation (stage II and greater) – refer to Pulmonary or 

Physical Therapy, depending on facility practice

■ Lung volume reduction (stage IV) – refer to Thoracic Surgery

Acute Exacerbations of COPD

This refers to acute increases in symptoms beyond normal daily variation, including 1 or more of the following symptoms:

• Cough: ↑ severity and frequency

• Sputum production: ↑ in volume or changes in character

• Dyspnea: ↑

■ Among patients with an acute exacerbation of COPD and a PaCO2 of >50 

mmHg, the 6-month mortality rate is 33%. 

■ Precipitants include bacterial or viral infection (50-60%), air pollution exposure (10%), and temperature changes. 

■ In patients with COPD and advanced HIV infection, consider evaluation for 

respiratory opportunistic infections (eg, P jiroveci pneumonia) in the setting of 

an exacerbation.

Medications and Other Therapies

Beta-adrenergic agonists 

(albuterol, levalbuterol, pirbuterol)

• Mainstay of therapy

• eg, albuterol via nebulizer (2.5 mg) or metereddose inhaler (MDI) (180 mcg [2 puffs]) Q2H

Anticholinergic bronchodilators 

(ipratropium, glycopyrrolate)

• In addition to beta-agonists

• eg, ipratropium via nebulizer (500 mcg) or MDI 

(34 mcg [2 puffs]) Q4H

Glucocorticoids Methylprednisolone 60-125 mg IV Q6-12H, or • 

prednisone 40 mg PO QD

• Treat for up to 14 days; studies show good outcomes with 9 days of treatment

• Studies show no difference in outcomes 

between taper vs abrupt cessation of steroids 

in courses up to 14 days

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PRIMARY CARE OF VETERANS WITH HIV 11

g 

benefi t over placebo

• May consider for patients with increased sputum purulence AND increased sputum volume 

OR for patients with increased dyspnea alone

• For patients with severe exacerbations 

requiring mechanical ventilation (invasive or 

noninvasive)

• Predominant bacteria include Haemophilus infl uenza, Streptococcus pneumoniae, and Moraxella 

catarrhalis

• For uncomplicated patients (FEV1 >50%, no 

antibiotics in past 3 months, <3 exacerbations 

in last year): doxycycline, TMP-SMX, 2nd or 

3rd generation cephalosporin, or extendedspectrum macrolide

• For complicated patients (cardiac disease, FEV1

<50%, antibiotics in past 3 months, ≥3 exacerbations in past year): amoxicillin + clavulanate 

or fl uoroquinolone 

• Treat for 7-10 days

Theophylline Initial dosage of 400-600 mg/day (long- • 

acting formulation), with target blood level of 

5-12 mcg/mL

Oxygen therapy By nasal cannulae, Venturi masks, non- • 

rebreather masks

• Titrate to target pulse oxygen >90% or PaO2

>60-65 mmHg

Noninvasive positive pressure 

ventilation (NIPPV) in hospitalized 

patients

• Such as bilevel positive airway pressure

• Improves respiratory acidosis, decreases respiratory rate, severity of breathlessness, and 

length of hospital stay

• Studies suggest that NIPPV may reduce mortality and the need for invasive ventilation

• Consider in moderate to severe exacerbations 

with acidemia (pH ≤7.35) and increased work 

of breathing (eg, RR >25); also in patients with 

PaCO2 above baseline (note that patients with 

COPD may have stable chronic elevation in 

PaCO2); compare acute value with baseline 

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

114 PRIMARY CARE OF VETERANS WITH HIV

!

ARVs and inhaled corticosteroids 

Fluticasone: 

■ PIs: Caution: ↑ serum fl uticasone levels; can cause systemic corticosteroid side 

effects, including Cushing syndrome

• Avoid (or limit) use with RTV, particularly in the LPV/r, ATV/r, and DRV/r 

combinations

• Even boosting doses (eg, 100 mg BID) of RTV may ↑ fl uticasone 

Cmax by 2,500%

• ATV: can ↑ fl uticasone levels – use with caution 

■ It is unclear whether signifi cant interactions occur between other inhaled steroids 

and PIs 

■ NRTIs, NNRTIs: no signifi cant interactions expected

ARVs and theophylline 

■ RTV: ↓ theophylline AUC

■ IDV: small ↑ in theophylline AUC

■ Monitor and adjust theophylline dosage as needed

REFERENCES

Crothers K. Chronic obstructive pulmonary disease in patients who have HIV infection. 

Clin Chest Med. 2007 Sep;28(3):575-87, vi. 

Crothers K, Butt A, Gibert C, et al. Increased COPD among HIV-positive compared to 

HIV-negative veterans. Chest. 2006 Nov;130(5):1326-33.

Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir 

Crit Care Med. 2007 Sep 15;176(6):532-55.

VA/DoD Clinical Practice Guideline Working Group. Management of Chronic Obstructive 

Pulmonary Disease. Washington, D.C.: Department of Veterans Affairs, Offi ce of Quality 

and Performance; 2007. Available at http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. 

Accessed December 18, 2008.

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PRIMARY CARE OF VETERANS WITH HIV 11

Dermatologic Conditions

This chapter will focus on the diagnosis and treatment of some of the most 

common dermatological diseases in HIV-infected adults: seborrheic dermatitis, 

folliculitis, onychomycosis, psoriasis, and HPV-associated warts.

KEY POINTS

■ Immunologic status strongly infl uences the incidence and clinical 

presentation of many dermatologic conditions.

■ At CD4 counts of <50 cells/μL, patterns in skin fi ndings can 

become atypical and bizarre.

■ In the absence of effective ART, up to 40% of HIV-infected patients 

and 80% of those with AIDS have seborrheic dermatitis; this 

condition usually improves with ART.

■ Eosinophilic folliculitis is seen more commonly in patients with 

CD4 counts of <200 cells/μL, and during immune reconstitution. It 

usually improves after 6 months on ART. 

■ Staphylococcal folliculitis is seen more commonly in patients with 

CD4 counts of <200 cells/μL. Presumptive treatment should include 

coverage for MRSA.

■ Onychomycosis should be confi rmed by KOH preparations of nail 

clippings before treatment. Oral antifungals interact with many 

ARVs; consult dosing information before prescribing.

■ Psoriasis can be severe (>50% of the body surface area) in patients 

with CD4 counts of <200 cells/μL, particularly those not on 

effective ART. 

■ HPV-associated warts are diffi cult to treat, require multiple treatments, 

and may recur despite immune reconstitution with ARVs. 

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

BACKGROUND

Epidemiology

■ Dermatological diseases are common among HIV-infected persons.

■ In one large population study, 69% of HIV-infected patients had cutaneous 

disease. 

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DERMATOLOGIC CONDITIONS

116 PRIMARY CARE OF VETERANS WITH HIV

mon dermatologic diagnosis.

■ At CD4 counts of <50 cells/μL, 

patterns in skin fi ndings can be atypical 

and bizarre.

■ Skin fi ndings may represent opportunistic infections or other illnesses.

Dermatologic Conditions according to Clinical Status

Clinical Status Associated Dermatological Diseases

Most common at CD4 counts of 

<200 cells/μL in patients who are not 

on effective ART 

• Severe psoriasis (>50% body)

• Extreme photodermatitis 

• Prurigo nodularis

• Molluscum contagiosum (see photo at 

end of chapter)

• Adverse drug reactions

• Mycobacteria: tuberculosis, kansasii, MAC 

• Fungal infections (eg, cryptococcus, 

aspergillosis)

• Herpes zoster

• Eosinophilic folliculitis

• Bacillary angiomatosis (Bartonella)

• Kaposi sarcoma

• Lichenifi cation 

• Diffuse seborrheic dermatitis

May occur at any CD4 count despite 

ART

• Eczema

• Xerosis

• HPV-associated warts 

• Kaposi sarcoma (less common at higher 

CD4 count and with ART)

• Staphylococcal and streptococcal skin 

infections

• Drug reactions

May emerge or worsen with immune 

reconstitution on ART

• Acne

• Erythema nodosum

Associated with HIV/HCV 

coinfection

• Lichen planus

• Xerosis

• Leukocytoclastic vasculitis

• Pruritus without apparent rash

Number of visits to 

dermatology clinic: 7,098

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007

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PRIMARY CARE OF VETERANS WITH HIV 11

EVALUATION AND MANAGEMENT

Seborrheic Dermatitis*

Etiology Findings/

Distribution Diagnostic Clues Management

May be related to 

skin-surface yeasts 

(Malassezia furfur)

and environmental 

factors

Erythematous scaly 

plaques on the 

central face, scalp, 

behind ears

Can be pruritic

Can affect sternum, 

axillae, and genital 

region

More severe, atypical, and diffuse in 

patients with low 

CD4 count nadirs

Common in 

patients who are 

not on ART: up to 

40% of HIV-infected 

patients and 80% 

of AIDS patients 

have seborrheic 

dermatitis

Should improve 

with immune 

reconstitution on 

ART

Hydrocortisone 

1% ointment mixed 

with ketoconazole 

or econazole 

applied BID to 

affected area

If very itchy: triamcinolone 0.5% ointment in nonfacial 

areas 

Scalp: ketoconazole, tar (T-Gel), 

selenium sulfide 

(Selsun), or zinc 

pyrithione (eg, 

Head & Shoulders) shampoo 

twice weekly; 

leave lather on 

for 5 minutes 

before rinsing

* See photo at end of chapter.

Folliculitis

Etiology Findings/

Distribution Diagnostic Clues Management

Eosinophilic 

folliculitis (see 

photo at end of 

chapter)

Numerous, 

extremely itchy 

pustules on the 

face, neck, scalp, 

and trunk

Mainly seen in 

patients with CD4 

counts of <200 

cells/μL

Can be seen during 

immune reconstitution in the fi rst 3-6 

months on ART

Itraconazole* 200-

400 mg daily (for 

anti-eosinophilic 

effect)

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DERMATOLOGIC CONDITIONS

118 PRIMAR Y CARE OF VETERANS WITH 

cially on facecan be used every 

other day from the 

waist up (for dryin

eect) 

Should resolve 

after 6 months on 

ART

Pityrosporum

folliculitis (see 

photo at end of 

chapter)

Erythematous 

papules and tiny 

pustules along hair 

follicles

Looks like a milder 

version of bacterial 

folliculitis with 

much smaller 

lesions 

Lesions are smaller 

and less pruritic 

than eosinophilic 

folliculitis

Commonly excoriated

Less likely to form 

large pustules

Overgrowth of 

tinea

Ketoconazole* 200 

mg PO QD for 

3 weeks

Follow with maintenance therapy 

using ketoconazol

2% shampoo twice 

weekly

Staphylococcus 

folliculitis

Erythematous papules and pustules 

along hair follicles

Often excoriated 

Often draining pus

Presents as an eryMRSA common;

consider culture to 

guide treatment

Presumptive treatment for MRSA:

• TMP-SMX DS 

BID,or doxycycline, or clindamycin;treat fo

10-14 days

• dicloxacillin or 

cephalexin

Pseudomonal 

folliculitis

Papular lesions 

appear within 

8-48 hours after 

exposure

Associated with 

use of hot tub and 

wet suit/swimwear 

(lesions may be 

concentrated in 

areas covered by 

swimwear)

In immunocompe tent persons,

self-limited to 

7-14 days

For immunosuppressed persons 

or those with 

prolonged or 

severe cases, consider treating with 

oxation for 

10 days

*See PotentialARV Interactions, below.

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PRIMARY CARE OF VETERANS WITH HIV 11

Be sure to differentiate folliculitis and acne.

• Acne presents with red papules and pustules on face, neck, arms, and back. 

• It is associated with exogenous testosterone and other systemic steroids, isoniazid, lithium, and antiseizure medications.

• Management: Stop the offending drug, if possible. 

• Treat cystic acne with tetracycline, doxycycline, or minocycline. If severe and 

unresponsive to these antibiotics, consider isotretinoin. Because of its toxicity and 

teratogenicity, isotretinoin use is restricted in the United States; see VA Criteria 

for Use at http://www.pbm.va.gov/criteria/HighlyTeratogenicRetinoidsAndHighDoseVitaminACFU.pdf

Onychomycosis

■ Refers to invasion of nails by dermatophytes (tinea unguium; with 3 subtypes)

yeast, or molds.

■ Dermatophytes cause more toenail infections, yeast cause more fi ngernail 

infections, and molds cause <10% of toenail infections.

■ Prevalence in the general population is approximately 8%.

■ Increased prevalence among patients with HIV infection, with more severe 

disease if CD4 count is <400 cells/μL.

■ Thought to be the cause of 50-60% of abnormal-looking nails.

■ Differential diagnosis includes psoriasis, eczematous conditions, senile ischemia, trauma, and lichen planus.

■ Poor response to treatment: Before starting treatment, inform patients about 

high rates of treatment failure (25-50%) and recurrence (20-50%).

Type Findings/

Distribution

Diagnostic 

Clues Management

Distal subungual onychomycosis (see 

photo at end of 

chapter)

Infection with 

Trichophyton 

rubrum in vast 

majority of 

cases

Affects great toe 

fi rst; can affect all 

toes

Begins with 

discoloration 

of distal corner 

of nail, spreads 

across nail, then 

extends toward 

cuticle

Culture: most 

sensitive and 

specifi c 

KOH preparation: clip or fi le 

nail-plate and 

collect scales 

from most 

proximal area

Indications for treatment: 

cellulitis, pain, patient desire 

for treatment

Oral therapies* (in order of 

decreasing effi cacy), pulse 

dosing: 

• Terbinafine 250 mg QD for 

1 week each month

• Itraconazole 200 mg QD for 

1 week each month 

• Fluconazole 150 mg once 

weekly

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DERMATOLOGIC CONDITIONS

120 PRIMAR Y CARE OF VETERANS WITH 

can break o,

becoming heaped 

and irregular

hyphae and 

arthrospores

Low sensitivity 

but up to 100% 

sensitive if >2 

preparations 

examined

If negative, consider biopsy for 

histopathology

months(toenails)

Fluconazole 400 mg once 

weekly for 6 months has 

nocompromised patients;

drug interactions than 

itraconazole

Cure rates range from 76% 

Topical therapies generally 

ineective; ciclopirox topica

nail lacquer can be used wit

patients who cannot safely 

take oral therapy; trials show 

7% cure rate

Surgery:removal of nail in 

isolated nail infection or 

dermatophytoma

See PotentialARV Interactions, below, andCommon 

Medications ,p. 307.

Proximal 

subungual 

onychomycosis

Trichophyton 

rubrum most 

common

Marker of 

HIV infection,

immunocompromised state

Discoloration 

begins at cuticle 

and extends 

distally

Same as above Same as above

White supercial onychomycosis

Trichophytonmentagrophytes 

most common

Starts as dull 

white spots,

then spreads 

centrifugally 

White areas are 

soft and can be 

scraped with 

a curette for 

culture or KOH 

slide

Same as above 

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PRIMARY CARE OF VETERANS WITH HIV 12

y

chomycosis

Candida albicans

More common 

in patients with 

HIV infection

of fi ngernail 

infection

Often in previously damaged 

nails 

Rarely in toenails

Nail thickening 

and discoloration

Can lead to 

onycholysis

gp

ing should be 

sent for culture 

of yeast

p(

decreasing effi cacy), pulse 

dosing:

• Itraconazole 200 mg QD 

for 1 week each month

• Terbinafi ne 250 mg QD 

for 1 week each month

Treat 2 months (fi ngernails), 

3 months (toenails)

Mold

(eg, Aspergillus, 

Scopulariopsis)

Rare cause of 

toenail infection

Consider when 

dermatophyte 

infection is 

ruled out

Oral therapies (in order of 

decreasing effi cacy), pulse 

dosing:

• Itraconazole 200 mg QD 

for 1 week each month

• Terbinafi ne 250 mg QD 

for 1 week each month

Treat 2 months (fi ngernails), 

3 months (toenails) 

* See Potential ARV Interactions, below, and Common Medications, p. 307.

Antifungal safety monitoring:

Terbinafi ne, itraconazole, and fl uconazole can cause hepatotoxicity.

■ Obtain pretreatment liver function values.

■ Monitor the development of hepatic symptoms.

■ Monitor liver function in patients with underlying liver disease.

POTENTIAL ARV INTERACTIONS !

Pharmacokinetic interactions between many ARVs (PIs, NNRTIs, and maraviroc) and antifungal medications may signifi cantly affect serum levels of the 

ARV or the antifungal medication. Some of these require dosage adjustment 

or careful monitoring, and some combinations are contraindicated. See 

Common Medications, p. 307 for further information.

UCS-PCM-08-0701-Dermatology.indd 121 CS-PCM-08-0701-Dermatology.indd 121 3/17/09 1/17/09 1
DERMATOLOGIC CONDITIONS

122 PRIMARY CARE OF VETERANS WITH HIV

(see photo at end of chapter)

Etiology Findings/

Distribution Diagnostic Clues Management

Activation of lymphocytes causes 

shortened epidermal life cycle (10 

times shorter than 

normal), leading to 

epidermal hyperproliferation

Silvery scales on 

red plaques 

More common on 

extensor surfaces

In HIV infection, 

can have unusual 

distribution, such 

as inverse psoriasis on palms and 

on soles of feet

More severe and 

more diffi cult to treat 

in patients with low 

CD4 cell counts

Patients with CD4 

counts of <200 cells/

μL not on ART can 

have lesions on >50% 

of body

May see unusual presentations of inverse 

and diffuse psoriasis

Biopsy shows epidermal hyperplasia, 

parakeratosis, neutrophils, diminished 

granulosum layer

Clobetasol 0.05% 

ointment BID

OR

Calcipotriene topical 0.005% ointment 

BID

Ultraviolet light

Acitretin 10-25 mg 

daily; avoid during 

pregnancy; can cause 

dyslipidemia

Interactions: acitretin + tetracycline 

carries risk of 

pseudotumor 

cerebri; avoid 

combination

In cases of extensive psoriasis, 

consider initiating 

ART (or maximizing 

effi cacy of ART)

Topical steroid relative potency (1 = least potent; 10 = most potent)

1 4 7 10

Hydrocortisone 

1% cream/lotion/

ointment

Triamcinolone (TAC) 

0.1% cream/ointment 

Alclometasone 0.05% 

cream/ ointment 

Desonide 0.05% 

cream/lotion/

ointment

Fluocinonide (Lidex) 

0.05% cream/gel/

lotion/ointment

Clobetasol 

0.05% cream/gel/

ointment/

solution

UCS-PCM-08-0701-Dermatology.indd 122 CS-PCM-08-0701-Dermatology.indd 122 3/17/09 1/17/09 1
PRIMARY CARE OF VETERANS WITH HIV 12

(see photo at end of chapter)

Etiology Findings/

Distribution

Diagnostic 

Clues Management

Human papillomavirus; 

most common 

subtypes 6, 11; 

also associated 

with dysplastic 

subtypes 16, 18, 

31, 33, 35

Worse and more 

diffi cult to treat 

in patients with 

low CD4 nadirs

Condyloma 

acuminata: soft, 

skin-colored 

fl eshy warts

Perianal lesions 

can be rough and 

caulifl ower-like 

In and around 

genitalia and anus, 

around mouth, 

palmar surface of 

hands, on feet

Can recur 

despite effective 

ART

Can recede on their 

own in 3 months with 

or without ART

Start with liquid nitrogen (10-second bursts 

with 30-second thaw), 

podophyllin (for genital 

warts), or paring (for 

large lesions) every 

3 weeks for 12 sessions

Patients can be 

instructed to use duct 

tape and other exfoliative techniques at 

home between offi ce 

treatment sessions 

(eg, for lesions on the 

extremities, apply duct 

tape nightly and pull off 

during the day; use pumice stone daily to sand 

down lesions)

For genital warts, may 

add imiquimod if initial 

treatment is not 

effective

Consider laser 

treatment, surgical 

excision (and send for 

pathology)

Repeat treatments are 

usually required

Can recur after any of 

the treatment modalities; none is 100% 

effective

For anal lesions, see 

Anal Dysplasia, p. 83. 

UCS-PCM-08-0701-Dermatology.indd 123 CS-PCM-08-0701-Dermatology.indd 123 3/17/09 1/17/09 1
DERMATOLOGIC CONDITIONS

124 PRIMARY CARE OF VETERANS WITH HIV

Primary Lesions

Macule: circumscribed area of skin, up to 1 cm in diameter, with a change from 

normal skin color, which is neither raised above nor depressed below the surrounding skin. Many use the term for lesions much larger than 1 cm. Term does 

not include purpura.

Patch: a fl at, circumscribed, discoloration of skin or mucous membrane >1 cm 

in diameter. 

Papule: discrete solid area of skin that is elevated by palpation above the surrounding skin and <1 cm in diameter. Variations include accuminate, keratotic, 

fl at-topped, follicular, umbilicated, pedunculated, and necrotic.

Plaque: similar to a papule but >1 cm in diameter. Often formed by the confl uence or coalescence of papules. Secondary features may include, among others, 

atrophy, lichenifi cation, and hyperkeratosis. 

Nodule: discrete, solid, palpable, round or oval (ellipsoidal) lesion of the skin 

measuring ≤1 cm in diameter (or long axis). Applies to processes involving any or 

all levels of the skin, and is a general term for any mass, benign or malignant. 

Tumor: a term used by some for a “nodule” >1 cm in diameter. Applies to processes involving any or all levels of the skin, and is a general term for any mass, 

benign or malignant. 

Vesicle: a circumscribed fl uid-fi lled lesion <1 cm in diameter that usually is 

elevated above the surrounding skin. May be described as solitary, grouped, 

umbilicated, dyshidrotic, spongiotic, multilocular, or unilocular. 

Bulla: a circumscribed fl uid-fi lled lesion >1 cm in diameter that usually is 

elevated above the surrounding skin. May attain diameters of several cm and are 

described as tense or fl accid. 

Pustule: discrete elevated vesicle or bulla of skin, usually small, containing 

purulent exudate composed of infl ammatory leukocytes (pus), with or without 

cellular debris. May be superfi cial, deep-seated, follicular, grouped, etc, and may 

arise secondarily from a vesicle. 

Wheal: an evanescent, round or irregular, often fl at-topped elevation of skin 

with a pale red color, arising from edema in the superfi cial dermis. May vary from 

2-3 mm to 10 or more cm in diameter, with round or arcuate confi gurations. 

Should be distinguished from angioedema, a massive edema involving the entire 

dermis and subcutaneous tissues. 

Secondary Lesions

Scar: a hard plaque of dense fi brotic tissue covered by a thin epidermis. A mark 

of injury from any sort of process (physical or pathologic). 

UCS-PCM-08-0701-Dermatology.indd 124 CS-PCM-08-0701-Dermatology.indd 124 3/17/09 1/17/09 1
PRIMARY CARE OF VETERANS WITH HIV 12

or shiny surface. Atrophy also may apply to thinning of dermal or subcutaneous 

tissue, with or without changes in the epidermis. 

Ulcer: loss of skin tissue or substance from the surface downward, leaving an 

uncovered or denuded wound that is slow to heal. 

Erosion: a superfi cial denudation of the skin, usually implying the loss of the 

epidermis. 

Fissure: a vertical splitting or separation of the skin. 

Crust: dried surface fl uid, often serous (inspissated serum), with or without 

tissue debris; includes the term “scab.” 

Excoriation: a scratch mark, often with denudation of the skin to form a small 

ulcer. Exposure of the corium by mechanical removal of the epidermis.

Scale: a thin fl ake of epithelium (mostly composed of corneocytes) that is separated from the underlying intact skin proper. 

Lichenifi cation: a thickening of the skin surface and an increase of skin markings, usually seen with chronic coalescence of papular lesions, especially atopic 

eczema. 

Vegetating: a lushly growing, proliferating process, usually with elevated or 

exophytic features. 

Linear/Figurate: technically not secondary features, but included here for 

convenience. These are confi gurations that skin lesions may assume, and the 

descriptors aid in their diagnostic identifi cation. Figurate includes geometrical 

shapes (eg, annular, arciform, cyclic). 

REFERENCES

Maurer TA. Dermatologic manifestations of HIV infection. Top HIV Med. 2005 Dec-2006 

Jan;13(5):149-54.

Maurer T, Leslie K. Common Skin Diseases in HIV-Infected Patients in the Antiretroviral 

Era. International AIDS Society – USA Resource Card 2007. Available at http://www.

iasusa.org/dermatology/index.html. Accessed November 20, 2008.

Muñoz-Pérez MA, Rodriguez-Pichardo A, Camacho F, et al. Dermatological fi ndings correlated with CD4 lymphocyte counts in a prospective 3 year study of 1161 patients with 

human immunodefi ciency virus disease predominantly acquired through intravenous drug 

abuse. Br J Dermatol. 1998 Jul;139(1):33-9.

UCS-PCM-08-0701-Dermatology.indd 125 CS-PCM-08-0701-Dermatology.indd 125 3/17/09 1/17/09 1
UCS-PCM-08-0701-Dermatology.indd 126 3/17/09 

DERMATOLOGIC CONDITIONS

126 PRIMAR Y CARE OF VETERANS WITH 

Molluscum Contagiosum

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-280318089

Seborrheic Dermatitis

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-586555642

Eosinophilic Folliculitis 

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1059415431

Pityrosporum Folliculitis 

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=1689503733

Onychomycosis, Distal 

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-1998842971

Psoriasis

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=77950693

HPV-Associated Warts

http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=197153797
PRIMARY CARE OF VETERANS WITH HIV 12

Diabetes

KEY POINTS

■ Diabetes is an independent risk factor for CAD and signifi cantly 

increases the risk of stroke, peripheral vascular disease, retinopathy, 

chronic kidney disease, and dementia. 

■ Preventive health care is critical for patients with diabetes to 

reduce the risks of CV and cerebrovascular disease, limb loss, vision 

loss, and renal damage.

■ The risk of diabetes for HIV-infected patients consists primarily of 

traditional factors, with some added risk from the use of PIs and 

NRTIs, which may exacerbate underlying diabetes risk. 

■ Primary prevention:

• Screen for diabetes and impaired fasting glucose with a fasting 

glucose test before starting ARVs, and 3 months after starting or 

changing ARVs. If initial screening results are normal, check fasting 

glucose annually. If impaired fasting glucose is present, check every 

3-6 months. 

• Encourage weight loss for patients who are overweight, and exercise 

for all.

■ Secondary prevention: 

• For treatment of Type 2 diabetes, start with monotherapy 

(metformin is preferred for obese patients); sequentially add other 

classes of oral agents. If the HbA1c goal has not been reached with 

use of ≥2 oral agents, add insulin. 

• Reduce CV risks by controlling blood pressure and lipid levels, 

counseling on smoking cessation, and initiating antiplatelet therapy.

■ Tertiary prevention:

• Screen annually for:

Renal disease _

Retinopathy (dilated eye examination) _

Lower extremity complications _

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

UCS-PCM-08-0701-Diabetes.indd 127 CS-PCM-08-0701-Diabetes.indd 127 3/30/09 /30/09 
128 PRIMARY CARE OF VETERANS WITH HIV

DIABETES

BACKGROUND

■ Diabetes is an independent risk factor for the development of CAD and 

is considered a CAD risk equivalent 

for the purposes of lipid management 

and antiplatelet therapy (see Dyslipidemia, p. 143). 

■ Diabetes signifi cantly increases the risk 

of stroke, peripheral vascular disease, 

retinopathy, chronic kidney disease, and 

HIV dementia.

■ Risk of diabetes for HIV-infected patients consists primarily of traditional factors (see Evaluation, below).

■ PIs and some NRTIs confer added risk of Type 2 diabetes, and these medications may exacerbate underlying diabetes risk. 

■ New-onset diabetes is estimated to occur in 1-6% of HIV-infected patients on 

PIs. In one study, 7% of patients on PIs were diagnosed with diabetes using the 

oral glucose tolerance test (OGTT).

■ The same study showed that an additional 16% of patients had impaired glucose tolerance (IGT). 

■ The pathogenesis of insulin resistance among patients on PIs is not fully 

understood. It is hypothesized that inhibition of the GLUT-4 insulin-stimulated 

glucose-transport system by some PIs plays a role.

■ NRTIs that affect fat distribution can cause an increase in lipolysis, which can 

lead to a higher risk of insulin resistance.

■ Increased insulin resistance is seen among patients who have developed lipohypertrophy, with a dorsocervical fat pad (“buffalo hump”) or increased upper 

chest fat or intraabdominal fat.

■ Obesity is a major risk factor for Type 2 diabetes in HIV-infected persons and 

in the general population. 

Defi nitions 

State Defi nition/Diagnosis

Insulin resistance • Failure of target tissues to respond appropriately to insulin 

• This leads to decreased muscle uptake 

of glucose and sometimes to increased 

hepatic gluconeogenesis. Insulin production 

is increased to overcome the insulin resistance and maintain glucose homeostasis. 

Over time, even high levels of endogenous 

insulin may not control serum glucose levels, resulting in IGT, followed by diabetes.

Veterans with HIV*

• Diabetes, Type 2: 15% 

• Diabetes, Type 1: 3%

• Ischemic heart disease: 11%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to these 

conditions

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PRIMARY CARE OF VETERANS WITH HIV 12

pg gg g() (

fast) = 100-125 mg/dL

IGT • Serum glucose ≥140-199 mg/dL on 2-hour 

OGTT (serum glucose 2 hours after intake 

of 75 g oral glucose)

Diabetes mellitus • FBG ≥126 mg/dL, or

• Random glucose ≥200 mg/dL + symptoms, 

or

• 2-hour OGTT ≥200 mg/dL

• Results must be confi rmed by retesting (any 

method) on a different day

EVALUATION

History

Risk factors include: Medications that increase diabetes 

risk include:

• Family history of diabetes

• Increasing age

• Obesity

• Fat redistribution

• Hepatitis C

• Medications (see list at right)

• PIs: Most (except unboosted ATV) 

have been implicated, particularly: 

• IDV

• RTV

• LPV/r

• NRTIs: d4T, ddI

• Pentamidine 

• Niacin

• Human growth hormone

• Corticosteroids

• Antipsychotics: including olanzapine, 

quetiapine, ziprasidone

SCREENING

■ Fasting glucose (and fasting lipid panel) before starting ARVs

■ Fasting glucose

• 3 months after starting or changing ARVs 

• Every 3-6 months for patients with IGT, to screen for diabetes and 

need for treatment

• Annually, if initial glucose measures are within normal limits

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130 PRIMARY CARE OF VETERANS WITH HIV

DIABETES

■ Consider 2-hour OGTT for patients with impaired fasting glucose or 

signifi cant risk factors (eg, family history, obesity, fat redistribution)

Initial Evaluation of Newly Diagnosed Diabetic Patients

Physical 

examination

• Blood pressure

• Weight, height, and BMI (BMI is available through the Vitals section of the CPRS Cover Sheet; see Dyslipidemia, p. 146, for 

BMI formula)

• Retinal eye examination (refer to Ophthalmology for dilated 

examination)

• Foot risk assessment:

• Visual inspection of feet for breaks in skin, erythema, trauma, 

pallor on elevation, dependent rubor, changes in size/shape 

of foot, nail deformities, extensive callus, tinea pedis, edema

• Neurologic examination: 

Monofi lament test for decreased sensation _

Vibratory sense at great toe IP joint, pinprick sensation _

over hallux, ankle refl exes (for peripheral neuropathy)

• Peripheral pulses, presence of foot hair

• Limb-threatening conditions: acute ischemia, foot ulceration, 

puncture wound, ingrown toenail, signs of systemic infection

Laboratory 

evaluation

• Glycosylated hemoglobin (HbA1c): refl ects glycemia over 

previous 3-month period

• Fasting lipid panel

• Electrolytes, BUN, creatinine (assess for renal function and 

metabolic acidosis)

• Urine albumin/creatinine ratio (microalbuminuria: 30-299 mcg/mg; 

macroalbuminuria: ≥300 mcg/mg; see Renal Disease, p. 211) 

• LFTs

• TSH

 MANAGEMENT

Basic Concepts

■ Standards of treatment and management of diabetes for patients with HIV 

generally are the same as those for diabetic patients without HIV; see below.

■ Emphasize behavior modifi cation in all patients with IGT and Type 2 diabetes; 

see below. This includes:

• Avoiding obesity

• Weight loss for those who are overweight

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PRIMARY CARE OF VETERANS WITH HIV 13

• Exercise

• Minimizing alcohol intake

■ Refer all patients for basic diabetes education.

■ Treatment goals:

• HbA1c <7%, while avoiding hypoglycemia.

Less-stringent goals may be appropriate for patients with advanced _

microvascular disease, comorbidities, or short life expectancy.

Note: _ Recent studies in HIV-uninfected patients with Type 2 diabete

have failed to prove that patients with tighter glucose control (HbA1c

<6.5%) have better CV outcomes than patients with somewhat 

higher HbA1c levels, and in one study, more-intensive glycemic 

control was associated with more CV events. 

• Reduce other CV risks by controlling blood pressure and lipid levels, 

counseling on smoking cessation, and initiating antiplatelet therapy. 

Glycemic control may reduce microvascular disease but may not _

reduce risk of macrovascular events, including MI. Controlling other 

CV risk factors in diabetic patients is critical.

• Reduce risks of limb loss, vision loss, and renal injury.

■ For Type 2 diabetes, start with monotherapy (metformin is preferred for 

obese patients). Sequentially add other classes of oral agents if needed. If 

the HbA1c goal has not been reached on ≥2 oral agents, add insulin. Oral 

sulfonylurea should be stopped if the patient is taking insulin more than 

once a day. 

■ Note that PI-related diabetes tends to be nonketotic and usually responds to 

oral agents.

■ Self-monitoring of blood glucose (SMBG) is critical for maintaining glycemic 

control; glucometers and test strips can be ordered through the Prosthetics 

Service at the local VA Medical Center.

Switching ART Regimens

• For patients who are taking ARV agents that may be causing or exacerbating hyperglycemia, consider discontinuing the problematic ARVs if safe and effective alternatives are available.

• For example, substitute ATV or an NNRTI in place of a PI, or an unboosted PI 

(eg, ATV or FPV) for an RTV-boosted PI.

• Replace d4T with another agent.

• Before making ARV substitutions, carefully consider the possible effect on HIV virologic control and the potential adverse effects of new ARVs.

• In some cases, antidiabetic agents may still be necessary after ARV substitution. 

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132 PRIMARY CARE OF VETERANS WITH HIV

DIABETES

At diagnosis: 

Lifestyle 

+ 

Metformin

Lifestyle + Metformin 

+ 

Basal insulin

Lifestyle + Metformin 

+ 

Pioglitazone 

No hypoglycemia 

Oedema/CHF

Bone loss

Lifestyle + Metformin 

+ 

Intensive insulin

Lifestyle + Metformin 

+ 

Sulfonylureaa

Lifestyle + Metformin 

+ 

GLP-1 agonistb

No hypoglycemia 

Weight loss 

Nausea/vomiting

Lifestyle + Metformin 

+ 

Pioglitazone 

+ 

Sulfonylureaa

Lifestyle + Metformin 

+ 

Basal insulin

Tier 1: Well-validated core therapies

Tier 2: Less well-validated therapies

STEP 1 STEP 2 STEP 3

aSulfonylureas other than glybenclamide (glyburide) or chlorpropamide. 

b

Insufficient clinical use to be confident regarding safety. CHF,

congestive heart failure.

Copyright © 2009 American Diabetes Association, Diabetes Care®,

Vol. 32, 2009; 193-203. Reprinted with permission from The American 

Diabetes Association.

■ Reinforce lifestyle interventions at every visit.

■ Check HbA1c every 3 months until the goal is reached and then at least every 

6 months. The interventions should be changed if HbA1c is above goal.

■ Thiazolidinediones are nonformulary within the VHA; see PBM Criteria for 

Use at http://www.pbm.va.gov/criteria/TZD%20criteria.pdf.

Management of Diabetes Mellitus

Intervention Dosage Comments

Behavior

modifi cation

Reinforce at 

every visit

• Institute for all patients

• Weight loss for overweight or obese patients, 

avoiding overweight for others

• Limit alcohol use (no more than 2 standard 

drinks/day for men, 1 standard drink/day for 

women; see Alcohol Misuse, p. 3)

• Balanced American Diabetes Association diet 

(see http://www.diabetes.org/home.jsp for further information)

• Daily exercise; at least 2.5 hours per week

• For further resources, see MOVE!

(http://www.move.va.gov), the VA NCP weight 

management program (http://www.diabetes.org), 

and the VA Obesity Clinical Practice Guidelines 

(http://vaww.oqp.med.va.gov/CPGintra/cpg/

cpg.htm)

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PRIMARY CARE OF VETERANS WITH HIV 13

y

(preferably complex)

• 10-20% protein

• <30% fats (<7% 

saturated fats)

• <300 mg/day of 

cholesterol 

• Limit trans fats

p

• Refer for dietary counseling and 

diabetes education as needed

• For further resources, see 

MOVE! (http://www.move.

va.gov), the VA NCP weight 

management program 

(http://www.diabetes.org), and 

the VA Obesity Clinical Practice 

Guidelines (http://vaww.oqp.med.

va.gov/CPGintra/cpg/cpg.htm)

Education • Refer all patients for diabetes As needed • 

education

Medications

Oral agents

Biguanide: 

metformin 

• Start with 500 mg BID 

or 850 mg daily

• Increase as needed to 

850 mg TID or 1,000 

mg BID (maximum of 

2,550 mg/day divided 

into 2-3 doses)

• Preferred fi rst-line treatment for 

most patients, especially those 

with BMI >25

• Insulin sensitizer 

• May promote weight loss, which 

is useful for overweight patients

• Potential adverse effects: nausea, 

diarrhea, gas, abdominal pain 

(take with food to reduce GI 

effects), lactic acidosis 

• Contraindicated in renal insuffi ciency (men: Cr level >1.5 mg/

dL; women: Cr level >1.4 mg/

dL), CHF

• For patients on NRTIs, especially 

d4T and ddI, there may be compounded risk of lactic acidosis

• May improve lipoaccumulation 

(mixed results in studies) but 

may worsen lipoatrophy

Sulfonylureas: 

glyburide, 

glipizide

• Glyburide: start with 

1.25-2.5 mg QAM or 

BID (maximum of 20 

mg/day, may be divided 

into 2 doses)

OR

• Glipizide: start with 

2.5-5 mg QAM; maximum of 40 mg/day 

(divided into 2 doses)

• Increase insulin secretion

• Dose cautiously in patients with 

renal insuffi ciency: glyburide 

is 50% renally cleared and has 

T1⁄2 of 10 hours; glipizide is 80% 

renally cleared and has T1⁄2 of 

2-5 hours; start at low dosage, 

increase slowly; decrease dosage 

or discontinue if renal function 

worsens

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134 PRIMARY CARE OF VETERANS WITH HIV

DIABETES

• Glipizide XL 5-10 mg 

QAM

• Take 30 minutes 

before a meal

p

metabolite; use preferentially in 

chronic renal failure

• Potential adverse effects: hypoglycemia, weight gain (approx. 

4-5 lb in the fi rst year), rash, 

elevation of serum transaminase 

levels

Thiazolidinedione: 

pioglitazone

rosiglitazone

• Start with 15 mg QD

• Increase as needed, up 

to 45 mg QD

• Only for combination therapy 

in selected patients; see PBM 

Criteria for Use at http://www.

pbm.va.gov/criteria/TZD%20

criteria.pdf

• Not recommended for monotherapy unless:

• Patient is intolerant of or 

has contraindications to 

both sulfonylureas and 

metformin; and 

• 1c is likely to be Target HbA

attained

• Absolute contraindications:

• Type 1 diabetes or prediabetes

• CHF: NYHA Class III or IV 

• Active liver disease or ALT 

>2.5 times upper limit of 

normal

• Jaundice or CHF on another 

thiazolidinedione 

• Currently not on VHA formulary; pioglitazone is the preferred agent for nonformulary 

use

• Monitor fl uid/volume status

• Potential adverse effects: weight 

gain (~10 lb in fi rst year of treatment), edema, CHF; reduction in 

bone mineral density in women; 

possible increased risk of MI; 

caution in patients with high risk 

of CV events (particularly with 

rosiglitazone)

• Rosiglitazone: studies confl ict, 

but possible increased risk of MI 

and CV death

UCS-PCM-08-0701-Diabetes.indd 134 CS-PCM-08-0701-Diabetes.indd 134 3/30/09 /30/09 
PRIMARY CARE OF VETERANS WITH HIV 13

y p

hepatic steatosis

• May improve lipoatrophy (mixed 

results in studies)

Sitagliptin • 100 mg QD

• Reduce to 50 mg 

QD for patients 

with CrCl 30-50 

mL/min

• Reduce to 25 mg 

QD for patients 

with CrCl <30 

mL/min and ESRD

• Nonformulary in VHA

• Only for patients who meet 

specifi c criteria; see PBM Criteria for Use at http://www.pbm.

va.gov/criteria/Sitagliptin.doc

• Potential serious adverse effects 

include anaphylaxis, angioedema, 

and Stevens-Johnson syndrome

Exenatide • Nonformulary; restricted to 5 mcg SQ BID • 

diabetes specialists in VHA

Insulin See below for formulations and dosing; potential adverse 

effects: weight gain, hypoglycemia

Onset Peak (hours) Duration (hours)

Rapid acting

Insulin lispro 10-15 min 1-2 3-5

Insulin aspart 10-15 min 1-2 3-5

Short-acting: regular 0.5-1 h 2-4 4-8

Intermediate acting

NPH 1-3 h 4-10 10-18

Lente 2-4 h 4-12 12-20

Long acting

Insulin detemir 2-3 h None Up to 24

Insulin glargine 2-3 h None 24+

Premixed insulins

70/30 (70% N + 

30% R)

0.5-1 h 2-10 10-18

75% NPL + 25% 

lispro

10-15 min 1-3 10-16

70% NPA + 30% 

aspart

10-15 min 1-3 10-16

Abbreviations: N = NPH; NPA = neutral protamine aspart; NPH = neutral protamine Hagedorn; 

NPL = neutral protamine lispro; R = regular

Note: Glargine cannot be diluted or mixed with other insulins.

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136 PRIMARY CARE OF VETERANS WITH HIV

DIABETES

■ Optimal insulin dosing mimics physiologic insulin release and consists of a 

basal component along with a prandial component, which is used to metabolize ingested carbohydrates.

■ Individualization of insulin therapy is critical for ensuring optimal glycemic 

control.

■ SMBG is critical to successful glycemic control with insulin.

■ Patients should be educated regarding symptoms of hypoglycemia (eg, sweating, anxiety, disorientation, tachycardia) and instructed to ingest hard candy, 

juice, or another rapidly absorbed glucose source if symptoms occur.

■ Insulin dosing for Type 1 diabetes

• First choice: glargine + premeal regular insulin (rapid-acting analogues 

[lispro and aspart] are preferred because of improved glycemic control 

and decreased risk of hypoglycemia; administer 10-15 minutes before or 

immediately after meals)

• Second choice: NPH or detemir 2 times per day + premeal regular insulin (lispro or aspart preferred)

• Third choice: NPH 2 times per day or at night + regular insulin (lispro or 

aspart) TID; the patient must not miss meals

• Starting basal dosage is 0.6 units/kg per day, given as 1 dose of glargine or 

divided as 2 doses of NPH or detemir; adjust dosage based on SMBG

• Starting prandial dosage is 5-10 units given 10-15 minutes before or 

immediately after meals; adjust dosage based on SMBG

■ Insulin dosing for Type 2 diabetes (see Figure 2)

UCS-PCM-08-0701-Diabetes.indd 136 CS-PCM-08-0701-Diabetes.indd 136 3/30/09 /30/09 
PRIMARY CARE OF VETERANS WITH HIV 13

Insulin regimens should be designed taking lifestyle and meal schedule into account. The algorithm 

can only provide basic guidelines for initiation and adjustment of insulin.

aPremixed insulins not recommended during adjustment of doses; however, they can be used 

conveniently, usually before breakfast and/or dinner, if proportion of rapid- and intermediate-acting 

insulins is similar to the fi xed proportions available. bg, blood glucose

Copyright © 2009 American Diabetes Association, Diabetes Care®, Vol. 32, 2009; 193–203. Reprinted 

with permission from The American Diabetes Association

Yes

Yes

No

No

Start with bedtime intermediate-acting insulin 

or bedtime or morning long-acting insulin (can 

initiate with 10 units or 0.2 units per kg)

Check fasting glucose (fingerstick) usually daily and 

increase dose, typically by 2 units every 3 days until 

fasting levels are consistently in target range (3.9-7.2 

mmol/l [70-130 mg/dl]). Can increase dose in larger 

increments, e.g., by 4 units every 3 days, if fasting 

glucose is >10 mmol/l (180 mg/dl)

If fasting bg is in target range (3.9-7.2 

mmol/l [70-130 mg/dl]), check bg 

before lunch, dinner, and bed. 

Depending on bg results, add second 

injection as below. Can usually begin 

with ~4 units and adjust by 2 units 

every 3 days until bg is in range

If hypoglycemia occurs, or 

fasting glucose level <3.9 

mmol/l (70 mg/dl), reduce 

bedtime dose by 4 units or 

10%–whichever is greater

Continue 

regimen. Check 

A1C every 3 mo

Pre-lunch bg 

out of range. 

Add 

rapid-acting 

insulin at 

breakfasta

Pre-bed bg 

out of range. 

Add 

rapid-acting 

insulin at 

dinnera

Pre-dinner bg out 

of range. Add 

NPH insulin at 

breakfast or 

rapid-acting at 

lunch

A1C ≥7% after 3 months

A1C ≥7% after 2-3 months

Recheck pre-meal bg levels and if out of range, may need to add 

another injection. If A1C continues to be out of range, check 2 h 

postprandial levels and adjust preprandial rapid-acting insulin

UCS-PCM-08-0701-Diabetes.indd 137 CS-PCM-08-0701-Diabetes.indd 137 3/30/09 /30/09 
DIABETES

138 PRIMARY CARE OF VETERANS WITH HIV

Other Therapies

Important for reduction of macrovascular disease, including CV events

Intervention Dosage Comments

Aspirin 81 mg daily Consider for patients aged >40 years, • 

with other CV risks, or history of CV 

disease

Smoking cessation N/A Assess readiness at each visit • 

• Refer to cessation programs when 

patient is ready

• Offer adjuncts as needed (eg, nicotine 

patches, bupropion)

• See Smoking Cessation, p. 53

ACE inhibitor or ARB Varies by 

agent 

• For treatment of microalbuminuria and 

hypertension in diabetic patients

Hydrochlorothiazide 25 mg daily For treatment of hypertension • 

Monitoring and Other Prevention Strategies

Method Goal Comments

HbA1c • <7%; less-stringent control 

may be appropriate for 

patients with advanced 

microvascular disease, 

comorbidities, or short life 

expectancy

• Every 3 months if not at goal 

or after change of medication 

or dosage

• Every 6 months if at goal

SMBG • Postprandial goal: <180 mg/

dL (for type 2 diabetes)

• Fasting goal: 90-130 mg/dL

• Patients on insulin: measure 

3 times daily before meals until 

glucose is controlled; then 

measure once daily alternating 

prebreakfast, lunch, supper, and 

bedtime

• Midnight SMBG may be helpful 

to detect hypoglycemia if FBG 

is persistently elevated (from 

the dawn phenomenon [Somogyi effect])

• Patients not on insulin: if unstable or in poor glycemic control, 

measure fasting glucose several 

times per week, or on specifi ed 

timeline; if controlled, measure 

2 times/week

• Patients should be educated 

regarding symptoms of hypoglycemia (eg, sweating, anxiety,

UCS-PCM-08-0701-Diabetes.indd 138 CS-PCM-08-0701-Diabetes.indd 138 3/30/09 /30/09 
PRIMARY CARE OF VETERANS WITH HIV 13

y) 

instructed to ingest hard candy, 

juice, or other rapidly absorbed 

glucose source if symptoms 

occur

• Note: SMBG has no benefi t if 

not used to guide therapy

Blood pressure • SBP: <130 mmHg

• DBP: <80 mmHg

• At each offi ce visit. Treat if 

elevated. (see Hypertension, 

p. 171)

Fasting lipids • LDL: <100 mg/dL

• HDL: >40 mg/dL

• TG: <150 mg/dL

• Every 3-6 months if adjusting 

medications

• Annually if stable and at goal

• Use statins or other lipidlowering agents as indicated

• Be aware of possible interactions between PIs and statins 

(see Dyslipidemia, p. 143; 

and Lipid-Lowering Medications, p. 315) 

• With most PIs, rosuvastatin 

or pravastatin is preferred; 

alternatively, low dosage of 

atorvastatin

• May need to increase dosage 

when using statins with NNRTIs

LFTs • ALT <2.5 times upper limit 

of normal

• Monitor every 6 months in 

patients on sulfonylureas or 

statins

Urine albumin/

Cr ratio

• Slow progression of renal 

injury

• Albumin/Cr ratio <30 mg/g

• Treat albuminuria with ACE 

inhibitor or ARB (see Renal 

Disease, p. 211)

Foot 

examination

• Prevention of ulcers, 

infections

• Detection of neuropathy

• Early intervention

• Perform foot risk assessment 

annually (see Initial 

Evaluation, above) 

• Educate patient about 

preventive foot care

• Refer to Podiatry as needed for 

lesions and protective footwear

• Refer to Vascular Surgery for 

evaluation of arterial insuffi ciency

Retinal eye 

examination

• Vision maintenance; early 

diagnosis of retinopathy 

• Annually, by an ophthalmologist

• Laser therapy available for diabetic retinopathy 

UCS-PCM-08-0701-Diabetes.indd 139 CS-PCM-08-0701-Diabetes.indd 139 3/30/09 /30/09 
DIABETES

140 PRIMARY CARE OF VETERANS WITH HIV

vaccine

y 

Pneumococcus 

vaccine

• Every 5 years Decreased risk of infection • 

Counseling on 

diet, weight 

loss, and 

exercise 

• On diagnosis and at every visit Improved glycemic control • 

WHEN TO REFER

■ Refer all patients with diabetes for education.

■ All patients with Type 1 diabetes:

• Should be referred to a diabetes clinic with multidisciplinary 

resources (eg, diabetologist, diabetes nurse, educator/manager, and 

registered dietitian) for institution and adjustment of insulin therapy.

• If expeditious referral is not possible, the primary care provider 

should institute “survival” insulin therapy: see Insulin dosing for 

Type 1 diabetes, p. 136.

■ Refer to Podiatry for foot lesions, ingrown toenails, foot deformities, or 

protective footwear.

■ Refer to Vascular Surgery for evaluation of arterial insuffi ciency.

■ Refer to Endocrinology for recurrent hypoglycemia or refractory hyperglycemia.

■ Refer to an emergency department for patients suspected of diabetic 

ketoacidosis or nonketotic hyperglycemia based on orthostatic hypotension, tachycardia, disorientation, or ketotic breath.

REFERENCES

American Diabetes Association Position Paper. Standards of Medical Care in Diabetes – 

2007. Diabetes Care. 2007 Jan;30 Suppl 1:S4-S41.

Boulton AJ, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk 

assessment: a report of the task force of the foot care interest group of the American 

Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care. 2008 Aug;31(8):1679-85.

Dubé MP. Disorders of glucose metabolism in patients infected with human immunodefi -

ciency virus. Clin Infect Dis. 2000 Dec;31(6):1467-75. 

Gerstein HC, Miller ME, Byington RP, et al; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 

2008 Jun 12;358(24):2545-59.

UCS-PCM-08-0701-Diabetes.indd 140 CS-PCM-08-0701-Diabetes.indd 140 3/30/09 /30/09 
PRIMARY CARE OF VETERANS WITH HIV 14

insulin therapy. Ann Intern Med. 2006 Jul 18;145(2):125-34.

Nathan D, Buse J, Davidson MB, et al. Medical management of hyperglycemia in type 2 

diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus 

statement from the American Diabetes Association and the European 

Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. 

Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes

a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the 

European Association for the Study of Diabetes. Diabetes Care. 2008 Jan;31(1):173-5.

Patel A, MacMahon S, Chalmers J, et al; ADVANCE Collaborative Group. Intensive blood 

glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 

2008 Jun 12;358(24):2560-72.

Schambelan M, Benson CA, Carr A, et al. Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: Recommendations of an International 

AIDS Society-USA Panel. JAIDS. 2002; 31:257-275. 

VA/DoD Clinical Practice Guideline Working Group. Management of Patients with Diabetes Mellitus in the Primary Care Setting. Washington, D.C.: Department of Veterans Affairs

Offi ce of Quality and Performance; 2003. Available at http://vaww.oqp.med.va.gov/CPG

intra/cpg/cpg.htm. Accessed December 15, 2008. 

Wohl DA, McComsey G, Tebas P, et al. Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy. Clin Infect Dis. 2006 Sep 

1;43(5):645-53.

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UCS-PCM-08-0701-Diabetes.indd 142 CS-PCM-08-0701-Diabetes.indd 142 3/30/09 

/30/09 
PRIMARY CARE OF VETERANS WITH HIV 14

Dyslipidemia

KEY POINTS

■ Dyslipidemia is a well-described risk factor for CV disease, and 

occurs in a high proportion of patients with HIV infection.

■ Both HIV infection itself and ARV medications may cause lipid 

abnormalities.

■ Other risk factors for CV disease are common in HIV-infected 

populations:

• Other metabolic abnormalities (eg, insulin resistance and 

diabetes, which may be caused or exacerbated by ARV 

medications)

• Hypertension

• Smoking

• Inactivity

■ Patients should be treated for dyslipidemia based on their lipid 

levels and other risk factors for CV disease.

■ LDL cholesterol is the primary target for lipid-lowering therapy.

■ Some lipid-lowering medications are contraindicated for use with 

ARV medications, and others require dosage adjustment.

BACKGROUND

■ Dyslipidemia is an important risk factor for CV disease, and occurs in a 

high proportion of people with HIV 

infection. As advances in ART extend 

the life spans of people with HIV infection, it is likely that morbidity and mortality from CV disease will increase. It 

is important to identify patients’ CV 

risk factors and to reduce those that 

are modifi able.

■ CV risk is associated with:

• Elevated LDL and TC 

Veterans with HIV*

Dyslipidemia: 38%

Ischemic heart disease: 11%

Hypertension: 45%

Diabetes, Type 2: 15%

Tobacco use: 38%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to these 

conditions

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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DYSLIPIDEMIA

144 PRIMARY CARE OF VETERANS WITH HIV

• Elevated TG 

Of these, elevated LDL is most closely linked to CV risk, and usually is the 

primary target of therapeutic interventions. 

■ Dyslipidemia is associated both with HIV infection itself and with ARV medications. It is not yet clear whether HIV infection or ARV medications increase 

the risk of CV disease, independent of their effects on lipids.

■ Patients with untreated HIV infection commonly show:

• ↓ TC 

• ↓ LDL cholesterol 

• ↓ HDL cholesterol 

• ↓ TG 

■ Patients treated with ARV medications commonly show:

• ↑ TC, LDL, and TG levels

• Low HDL

■ Dyslipidemia among patients taking ARV medications probably is related to 

multiple factors, including:

• Individual patient characteristics

• HIV infection itself

• ARV medications

■ Certain agents in each of the 3 major classes of ARVs may cause lipid 

abnormalities.

• PIs: may markedly ↑ TC, LDL, and TG levels (particularly RTV and RTVboosted PIs; unboosted ATV does not typically affect lipids)

• NNRTIs: effects are more variable, particularly with EFV; NVP is less 

likely to cause abnormalities; NNRTIs may ↑ TC, LDL, and TG

• NRTIs: d4T may ↑ TC and TG

• Fusion inhibitors, CCR5 antagonists, integrase inhibitors: not associated 

with dyslipidemia

■ For patients with CHD or CHD risk equivalents (see below), if possible, 

select ARV regimen to minimize the risk of dyslipidemia.

SCREENING

■ Check fasting lipids before starting ART.

■ Check fasting lipids ≤3-6 months after starting or changing ARVs.

If normal: screen at least once per year

If abnormal: monitor closely until LDL goal is achieved

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PRIMARY CARE OF VETERANS WITH HIV 14

EVALUATION

Note: The following recommendations are based on National Cholesterol 

Education Program (NCEP) guidelines for the evaluation and management 

of dyslipidemia. These are widely used, but have not been validated in HIVinfected patients.

History 

The need for lipid management is based on lipid levels and on risk factors for 

coronary artery disease events. In the history, focus on factors that suggest CHD

CHD equivalents, or CV risk.

■ CHD risk equivalent: considered equal in risk to known CHD

■ CHD risk factor: a condition associated with greater risk of serious cardiac 

events 

CHD CHD Risk Equivalents CHD Risk Factors

• History of MI

• Unstable angina

• Stable angina 

• CHD procedures 

• Evidence of clinically 

signifi cant myocardial 

ischemia 

• Diabetes mellitus

• Peripheral vascular 

disease

• Carotid artery disease

• Abdominal aortic 

aneurysm 

• Transient ischemic 

attacks 

• 2 or more CHD risk 

factors with a 10-year 

risk of CHD >20% (see 

the 10-year cardiac 

event risk calculator 

online at http://hin.nhlbi.

nih.gov/atpiii/calculator.

asp) 

• Male sex

• Cigarette smoking 

• Hypertension (systolic 

blood pressure ≥140 

mmHg or taking 

anti hypertensive 

medication) 

• HDL <40 mg/dL (if HDL 

is ≥60 mg/dL, subtract 

1 risk factor) 

• Patient age ≥45 (men) 

or ≥55 (women)

• Family history of 

premature CHD in 

fi rst-degree relatives 

aged <55 (men) or <65 

(women)

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DYSLIPIDEMIA

146 PRIMARY CARE OF VETERANS WITH HIV

History • Factors that contribute to dyslipidemia:

• Obesity, chronic liver disease, alcohol consumption, high-fat or 

high-carbohydrate diet, genetic disorders of lipid metabolism, 

chronic kidney disease, and prothrombotic or proinfl ammatory states

• Factors that contribute to hypertriglyceridemia: 

• Genetic disorders, obesity, diabetes, alcohol consumption, 

hypothyroidism, nephritic syndrome, chronic kidney disease

• Causes of secondary dyslipidemia, including diabetes, hypothyroidism, nephrotic syndrome, liver diseases

• Family history of obesity, diabetes, and lipid abnormalities

• Medications

• ARVs, especially those known to increase cholesterol or TG 

levels (eg, RTV and RTV-boosted PIs, EFV, d4T)

• Other medications that may cause lipid abnormalities (eg, 

corticosteroids, anabolic steroids, progestins, beta-blockers, 

thiazide diuretics, quetiapine)

Physical 

examination

• Blood pressure

• Weight, height, and waist circumference (for patients of European 

descent, abnormal is >40 inches [men] or >35 inches [women])

• Obtain BMI: normally available in the Vitals section of the CPRS 

Cover Sheet; otherwise BMI = weight (kg)/height (m2 ); calculator 

available online: http://www.nhlbisupport.com/bmi/.

• Underweight: BMI <18.5

• Normal weight: 18.5-24.9 

• Overweight: 25-29.9 

• Obese: ≥30 

• Cardiovascular examination: murmurs, gallops

• Stigmata of hyperlipidemia and hypertriglyceridemia: xanthelasma 

and tendon xanthomas, which are associated with extremely 

elevated LDL levels; eruptive xanthomas and hepatomegaly, which 

may be present in the setting of extremely elevated TG levels 

(chylomicronemia)

Laboratory 

evaluation 

• Fasting (8- to 12-hour fast) lipid panel: measured TC, LDL, HDL, 

and TG levels; calculated non-HDL, and TC/HDL ratio

• Fasting glucose

Assessment Tools

Determine whether intervention is needed according to the patient’s lipid values 

and CHD risks, following these 3 steps. Note that for most patients, LDL is 

the main indicator of need for lipid-lowering therapy.

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PRIMARY CARE OF VETERANS WITH HIV 14

2. Determine risk category, LDL goal, and LDL threshold for treatment using 

Table 1. 

• The NCEP also recommends estimating the patient’s 10-year risk of MI 

using the assessment tool derived from the Framingham Heart Study 

(http://hin.nhlbi.nih.gov/atpiii/calculator.asp). Note that this tool does not 

estimate lifetime risk of MI, which for many patients is substantially higher 

than their 10-year risk. Intervention to treat lipid abnormalities may be 

warranted even in patients with a low 10-year risk, to prevent CV events 

later in life.

3. Assess TG risk level using Table 2; determine whether TG-lowering treatment is needed.

Table 1. LDL Cholesterol Goals and Thresholds for Treatment* 

Risk Category LDL Goal*

LDL Threshold to 

Initiate Therapeutic Lifestyle 

Changes

Consider Drug 

Therapy

Lower risk: 

No CHD or CHD 

equivalents and 0-1 

risk factor

<160 mg/dL ≥160 mg/dL ≥190 mg/dL (at 

160-189 mg/dL, 

drug therapy 

optional)

Moderate risk:

No CHD or CHD 

equivalents; ≥2 risk 

factors and 10-year 

estimated risk 

<10%

<130 mg/dL ≥130 mg/dL ≥160 mg/dL

Moderately high 

risk:

No CHD or CHD 

equivalents; ≥2 risk 

factors and 10-year 

estimated risk 

10-20%

<130 mg/dL

(optional goal: 

<100 mg/dL)

≥130 mg/dL ≥130 mg/dL

High risk:

CHD or CHD 

equivalent

<100 mg/dL

(optional goal: <70 

mg/dL)

≥100 mg/dL ≥100 mg/dL

* Non-HDL cholesterol target levels are 30 mg/dL higher than corresponding LDL cholesterol levels

Adapted from NCEP, et al. See References.

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DYSLIPIDEMIA

148 PRIMARY CARE OF VETERANS WITH HIV

■ Consider drug therapy to decrease LDL (or non-HDL) if TC is >240 mg/dL 

or HDL cholesterol is <35 mg/dL. 

■ If TG is >400 mg/dL, the LDL cholesterol calculation is unreliable. Use nonHDL cholesterol as a surrogate target of therapy (non-HDL = TC – HDL); 

the non-HDL goal is 30 mg/dL higher than the LDL goal. 

■ If TG is 200-500 mg/dL, LDL is the primary target of initial therapy (see 

Table 1 for LDL intervention levels); if TG is ≥500 mg/dL, TG may be the 

initial target of therapy (see below).

Hypertriglyceridemia is associated with CAD risk, but it is unclear whether 

it is an independent risk factor; hence indications for treatment are less certain 

than those for cholesterol abnormalities.

Table 2. Classifi cation of Triglyceride Levels 

Risk Category Triglyceride 

Measurement Initiate Therapy

Normal <150 mg/dL

Borderline High 150-199 mg/dL

High 200-499 mg/dL TLC • 

• Consider drug therapy for those with 

CHD, CHD equivalents, high risk of 

CHD

Very High ≥500 mg/dL Low-fat diet (<15% of caloric intake); • 

pharmacologic therapy probably will 

be required

• Consider drug therapy 

• If severe (>1,000 mg/dL), treat to 

decrease risk of pancreatitis

Adapted from NCEP, et al. See References below.

 MANAGEMENT

The primary goal of lipid-lowering therapy for most patients is to 

lower LDL to target levels. The potential benefi ts of lipid-lowering therapy 

for HIV-infected patients should be balanced against drug toxicities, as well as the 

risk of CV mortality relative to HIV-associated mortality.

■ If the TG level is very high, it may have to be reduced before LDL is treated 

directly (see below). 

■ Low HDL is not usually a primary target of therapy; data are confl icting as to 

whether raising HDL confers CV benefi ts.

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PRIMARY CARE OF VETERANS WITH HIV 14

■ Lifestyle modifi cation

■ Lipid-modifying medication

■ Changes in ARV medication (or other exacerbating medication), if possible

■ Management of associated conditions (eg, diabetes)

See Table 1 for LDL levels at which either TLC or drug therapy should be initiated, and for the target goals for LDL cholesterol. 

Lifestyle Modifi cation

Lifestyle modifi cation is fundamental to the management of dyslipidemia and 

should be initiated in all patients with dyslipidemia. Behavioral changes may be 

diffi cult for patients, but can yield signifi cant results in improving lipid values and 

reducing CHD risk. 

Encourage patients to:

■ Reduce dietary cholesterol and saturated fat (all patients)

■ If overweight, lose weight

■ Maintain or increase aerobic exercise (all patients) 

■ Reduce alcohol consumption (especially for those with high TGs)

■ Stop smoking, and reduce other CHD risk factors 

Medication

See Table 3 and Characteristics of Lipid-Lowering Medications, below, for 

information about lipid-lowering medications. Therapies should be intensifi ed or 

augmented until lipid targets are met. 

Table 3. Suggested Drug Treatments for Lipid Abnormalities 

Lipid 

Abnormality First Choice Second Choice Comments

Isolated high 

LDL, non-HDL 

cholesterol

Statin Niacin 

(time-release 

formulation)

• Be aware of possible 

statin-ARV interactions (see 

below and Lipid-Lowering Medications, p. 315); 

use pravastatin, fl uvastatin, 

rosuvastatin, or atorvastatin 

for most patients taking PIs

• Patients taking PIs may have 

increased risk of myopathy

• Start with low statin 

dosages

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DYSLIPIDEMIA

150 PRIMARY CARE OF VETERANS WITH HIV

(reserve for 

patients intolerant of other 

agents who have 

high LDL, low 

HDL)

Ezetimibe (third 

choice)*

pp

statin, consider:

• Increasing statin dosage

• Switching to more 

potent statin (rosuvastatin or atorvastatin)

• Adding niacin (timerelease formulation)

• Adding ezetimibe

• Bile acid sequestrants 

in general should be 

avoided unless there 

are no other options; 

may interfere with 

absorption of ARVs and 

other medications

• Ezetimibe should used 

as monotherapy only for 

patients unable to tolerate 

statins who do not respond 

to other agents

• Avoid combining statin and 

fi brate: increased risk of 

myopathy

• Triple therapy with statins, 

niacin, and ezetimibe is not 

recommended

Isolated high 

TG

N-3 fatty acid

Niacin (time-release formulation)

Fibrate

• Fibrates are most effective 

in lowering TG

• If response is inadequate, 

add second agent

• Atorvastatin may lower TG 

(as well as LDL)

High LDL + 

high TG

Statin + N-3 

fatty acid or niacin (time-release 

formulation)

Fibrate Dual therapy likely to be • 

most effective

• Could start with single 

agent (eg, niacin) and add 

second agent if response is 

inadequate

• Avoid combination of statin 

and fi brate: increased risk 

of myopathy

Isolated low 

HDL

Niacin 

(time-release 

formulation)

Fibrate Initiate CV exercise • 

* See PBM Criteria for Use at http://www.pbm.va.gov/criteria/Ezetimibe.

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PRIMARY CARE OF VETERANS WITH HIV 15

pg 

Statins (HMG-CoA reductase inhibitors): Decrease TC, LDL, and nonHDL cholesterol levels; atorvastatin also decreases TG levels. There is substantial evidence that statins reduce CV events. First-line treatment for most 

patients with hypercholesterolemia or combined hypercholesterolemia + 

hypertriglyceridemia (see Table 3).

Many have signifi cant drug interactions with PIs and NNRTIs; some combinations are contraindicated (see Lipid-Lowering Medications, p. 315). Possible 

adverse effects include, GI disturbance, myopathy, rhabdomyolysis, liver toxicity 

(check LFTs 1 month after initiating, then every 3 months). Contraindicated 

in women who are pregnant or nursing; use caution in patients with active or 

chronic liver disease.

Recommended starting dosages of statins for patients taking PIs:

Pravastatin: 20 mg PO QD

Fluvastatin: 20 mg PO QD

Atorvastatin: 10 mg PO QD

Rosuvastatin: 5-10 mg PO QD

When given concomitantly, statins and fi brates increase the risk of rhabdomyolysis; in general, this combination should be avoided.

Fibrates: Decrease TG and increase HDL; modestly decrease LDL. Gemfi brozil has been shown to reduce risk of CV events (in HIV-uninfected individuals); 

fenofi brate has not. In one study, clofi brate was associated with increased risk 

of noncardiac mortality. An option for initial treatment of isolated hypertriglyceridemia and an alternative treatment for combined hypertriglyceridemia and 

hypercholesterolemia. 

Not metabolized by the cytochrome P450 hepatic enzyme system; no signifi cant drug interactions with ARVs. Contraindicated in severe renal or 

hepatic disease. Fibrates generally should not be used with statins because 

of increased risk of myositis. Other possible adverse effects: GI disturbance, 

gallstones, dizziness. Recommended dosages:

Fenofi brate: 50-200 mg PO QD

Gemfi brozil: 600 mg PO BID, 30 minutes before meals

N-3 (omega-3) polyunsaturated fatty acids: Decrease TG levels. May be 

effective as initial or adjunctive therapy. Limited data suggest CV benefi t. Usual 

dosage 2-6 grams daily. Possible adverse effects: fi shy taste, GI disturbance.

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DYSLIPIDEMIA

152 PRIMARY CARE OF VETERANS WITH HIV

y 

adjunctive therapy, but may worsen insulin resistance. Other possible adverse 

effects include elevated serum transaminase levels, fl ushing (to decrease fl ushing, premedicate with aspirin; titrate dosage slowly, use time-release formulations [eg, Niaspan]). Contraindicated in chronic liver disease and severe gout; 

relatively contraindicated in diabetes, peptic ulcer disease, and hyperuricemia.

Bile acid sequestrants: Generally should be avoided unless no other 

options; may interfere with the absorption of other drugs (including ARVs), 

and may increase TG levels.

Ezetimibe: Has not been studied thoroughly in HIV-infected individuals, but 

appears to be effective in lowering TC and LDL. However, because of lack of 

data showing that ezetimibe decreases CV events, it should not be used as 

monotherapy except in well-defi ned circumstances (see PBM Criteria for Use 

at http://www.pbm.va.gov/criteria/Ezetimibe). Usually used in combination with 

statins if LDL is not controlled adequately with a statin alone. Contraindicated 

in patients with liver disease.

Switching ARVs 

■ For patients with CHD or CHD equivalents, try to select ARV medications 

associated with the lowest risk of dyslipidemia.

■ For patients with dyslipidemia caused by ARV agents, consider discontinuing 

lipogenic ARVs if safe and effective alternatives exist.

• For example, substitute ATV or NVP in place of a lipogenic PI or substitute an unboosted PI (eg, ATV or FPV) for a RTV-boosted PI.

• Replace d4T with TDF, or perhaps ABC*. 

■ Before making ARV substitutions, consider the possible effect on HIV virologic control and the potential adverse effects of new ARVs.

■ In some cases, antihyperlipidemic agents may still be necessary after ARV substitution. 

* Recent data from the D:A:D observational study associated ABC with increased risk of MI. There 

were insuffi cient data to analyze the effect of TDF. See References.

POTENTIAL ARV INTERACTIONS !

Interactions with ARVs: Most PIs inhibit the metabolism of most statins 

and can signifi cantly increase serum statin levels, thus increasing the risk of 

toxicity, including rhabdomyolysis. Some combinations are contraindicated. 

Of the statin drugs, pravastatin is the least affected by most PIs (DRV is an 

exception). Atorvastatin, if used, must be initiated cautiously and at a low 

dose. EFV can induce the metabolism of some statins, causing therapeutically 

signifi cant decreases in their concentrations. See Lipid-Lowering Medications, p. 315, for further information.

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PRIMARY CARE OF VETERANS WITH HIV 15

REFERENCES

AIDS Education and Training Centers. Dyslipidemia. Clinical Manual for Management of 

the HIV-Infected Adult; July 2006. Available at http://www.hiv.va.gov/vahiv?page=cm-309_

dyslip. Accessed December 10, 2008.

Brunzell JD. Clinical practice. Hypertriglyceridemia. N Engl J Med. 2007;357:1009-17.

D:A:D Study Group, Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in 

the D:A:D study: a multi-cohort collaboration. Lancet. 2008 Apr 26;371(9622):1417-26. 

Lloyd-Jones DM, Leip EP, Larson MG. Prediction of lifetime risk for cardiovascular disease 

by risk factor burden at 50 years of age. Circulation. 2006 Feb 14;113(6):791-8. 

National Cholesterol Education Program (NCEP), National Heart, Lung, and Blood 

Institute, National Institutes of Health. Detection, Evaluation, and Treatment of High Blood 

Cholesterol in Adults (Adult Treatment Panel III). NIH Publication No. 02-5215. September 2002. Available online at http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm. 

Accessed December 10, 2008.

Schambelan M, Benson CA, Carr A, et al. Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International 

AIDS Society-USA panel. J Acquir Immune Defi c Syndr. 2002 Nov 1;31(3):257-75. 

VA/DoD Clinical Practice Guideline Working Group. Management of Dyslipidemia in the 

Primary Care Setting. Washington, D.C.: Department of Veterans Affairs, Offi ce of Quality 

and Performance; 2006. Available at http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. 

Accessed December 15, 2008.

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/20/09 
PRIMARY CARE OF VETERANS WITH HIV 15

Gastroesophageal Refl ux Disease 

(GERD)

KEY POINTS

■ Typical symptoms of GERD are heartburn and regurgitation.

■ Less common GERD symptoms (eg, cough) may mimic other 

conditions.

■ Evaluation of GERD in patients with HIV depends on the stage of 

infection.

■ In patients with a CD4 count of >350 cells/μL with typical GERD 

symptoms, a trial of empiric acid suppression therapy may be 

undertaken in lieu of other diagnostic testing.

■ In patients with more advanced HIV infection, evaluation for OIs 

affecting the esophagus should be considered, along with empiric 

GERD therapy.

■ Patients with GERD symptoms lasting >5 years should be evaluated 

by endoscopy for Barrett esophagus because of the increased risk 

of esophageal carcinoma.

■ Patients with alarm symptoms (eg, unexplained dysphagia or 

weight loss, hematemesis) should be evaluated by endoscopy for 

malignancy or other GERD complications.

BACKGROUND

■ GERD is defi ned by the American 

College of Gastroenterology as “symptoms or mucosal damage produced by 

the abnormal refl ux of gastric contents 

into the esophagus.” However, there 

is no universally accepted defi nition of 

the condition, and no gold standard for 

its diagnosis.

■ Uncomplicated GERD is characterized by typical symptoms of heartburn, 

regurgitation, or both.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Veterans with HIV*

Esophageal disease: 19%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition 

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GASTROESOPHAGEAL REFLUX DISEASE (GERD)

156 PRIMARY CARE OF VETERANS WITH HIV

strictures, hemorrhage or perforation, and extraesophageal complications 

such as aspiration, asthma, chronic coughing, chest pain, and 

laryngopharyngitis. 

■ Etiology involves lower esophageal sphincter (LES) dysfunction with refl ux 

of acidic gastric contents into the esophagus, often resulting in damage to 

esophageal mucosa. Decreased esophageal motility and abdominal distention 

also may play a role.

■ Symptoms of heartburn are common in Western countries: 25% of the general population is reported to have heartburn at least once a month, 12% has 

heartburn at least weekly. GERD can have a very negative impact on quality of 

life. 

■ There is no reported association of GERD with HIV infection. For HIVinfected patients, however, the differential diagnosis of GERD symptoms 

includes several HIV-related conditions (see Partial differential diagnosis, 

p. 161).

■ Diagnosis usually depends on the presence of symptoms and/or the confi rmation of esophagitis with esophagogastroduodenoscopy (EGD) or other 

testing. 

■ Esophagitis (esophageal erosions or other mucosal damage) is seen on EGD 

or histology in <50% of patients. The majority of patients with GERD symptoms have no evidence of esophagitis on EGD (ie, nonerosive refl ux disease, 

or NERD).

■ The severity and course of symptoms of esophagitis and NERD are similar.

■ The condition is often chronic, with remissions and relapses, but usually not 

progressive. Possible complications include:

• Esophageal stricture 

• Esophageal ulcers

• Barrett esophagus

• Adenocarcinoma

• Bleeding

• Perforation

• Aspiration

■ The symptoms and esophageal mucosal injuries caused by GERD usually 

respond to acid-suppressive treatment, though some complications (eg, Barrett esophagus) may not improve with treatment. 

EVALUATION

■ There is no gold standard for diagnosis of GERD.

■ Uncomplicated GERD may be diagnosed by clinical symptoms alone.

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PRIMARY CARE OF VETERANS WITH HIV 15

complicated GERD (extraesophageal or alarm symptoms; see below) and 

those at risk of Barrett esophagus (see below).

■ The differential diagnosis of symptoms referable to the esophagus in patients 

with HIV depends on the stage of infection.

• In patients with CD4 counts of <350 cells/mL, the differential diagnosis 

should include esophageal OIs, such as candidiasis and CMV infection.

• In patients with higher CD4 counts, evaluation should focus on GERD, 

and on Barrett esophagus and alarm symptoms that suggest malignancy 

or other conditions (see below); however, the possibility of OIs should 

be considered as well.

■ Patients with symptoms lasting for >5 years should be evaluated for Barrett 

esophagus because of the associated increase in risk of esophageal 

adenocarcinoma.

Check for alarm symptoms:

• Dysphagia

• Odynophagia

• Unexplained weight loss

• GI bleeding (hematemesis, melena, bloody stool)

• Anemia

• Chest pain

• Choking/dysphagia

• Failure to improve with therapy

In HIV-infected patients with relatively high CD4 counts, these suggest malignancy, 

ulceration, or stricture. If present, refer for immediate evaluation via EGD. Consider starting trial of acid suppression therapy while awaiting further evaluation.

Barrett Esophagus

• Metaplasia, with replacement of esophageal squamous epithelium by abnormal 

columnar epithelium 

• Associated with severe GERD, but may occur in asymptomatic patients 

• Increases risk of esophageal adenocarcinoma 50-fold compared with GERD alone

• Unclear whether acid suppression prevents progression of Barrett esophagus or 

development of adenocarcinoma

• Patients with a history of GERD symptoms for >5 years, especially those ≥50 

years of age, should be evaluated for Barrett esophagus by EGD

• Refl ux symptoms should be controlled before EGD to maximize sensitivity and 

specifi city of EGD

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GASTROESOPHAGEAL REFLUX DISEASE (GERD)

158 PRIMARY CARE OF VETERANS WITH HIV

• The surveillance interval for Barrett esophagus is determined by the grade of dysplasia at initial EGD

• For low-grade dysplasia, EGD should be repeated within 6 months to exclude 

higher-grade dysplasia

• For high-grade dysplasia, EGD should be repeated within 3 months

Risk factors • Obesity: 1.5- to 2-fold risk of GERD, increasing with higher BMI

• Pregnancy

• Fatty foods

• Hiatal hernia

• Stress

• Medications: beta-blockers, calcium channel blockers, anticholinergics (LES relaxation), NSAIDs, aspirin (mucosal injury)

• Lifestyle factors: Many of these cause relaxation of the LES, but 

there is little evidence that GERD results. Associations, if true, 

appear to be weak, though some patients may be sensitive to 

these factors.

• Diet: carbonated sodas, caffeinated beverages, chocolate, saturated fats, peppermint, acidic foods, low fi ber

• Alcohol use

• Smoking

History History is usually the basis of GERD diagnosis; however:

• Patients may have atypical symptoms or be asymptomatic.

• Severity of symptoms does not predict severity (or presence) of 

mucosal damage; conversely, severity of esophagitis does not 

predict severity of symptoms. 

• There may be great variability in symptoms and fi ndings upon 

diagnostic testing, and the two may not correlate.

• Absence of symptoms does not rule out GERD.

Symptoms:

• retrosternal burning pain (because of potential for Heartburn: 

misunderstanding, it may be helpful to avoid the term 

“heartburn” and instead ask patients about “a burning feeling 

rising from the stomach or lower chest up toward the neck”)

• refl ux of gastric contents (acid, with or without Regurgitation:

food); very specifi c for GERD

• Dysphagia

• Odynophagia

• Symptoms of “extraesophageal” GERD:

• Cough

• Asthma

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PRIMARY CARE OF VETERANS WITH HIV 15

p

• Hoarseness/voice changes

(Note: GERD is a common cause of chronic cough, wheezing, and 

chest pain.)

Associated factors:

• Ask about risk factors, above.

• Duration of symptoms; patients with a long history of GERD 

symptoms should be evaluated for Barrett esophagus (see above).

• Symptoms after meals (symptoms after a large or fatty meal: 

highly specifi c for GERD)

• Symptoms with recumbency (particularly after a meal)

• Nocturnal symptoms

• Treatments tried and symptom response (improvement with 

acid-lowering medications supports the diagnosis)

Physical 

examination

• Performed mostly to evaluate for other causes (infections, 

asthma, cardiac disease, cancer)

• Vital signs; O2

 saturation

• Inspection of oropharynx (ulcerations, candidiasis, lesions, 

masses), neck (nodes, masses), and lungs (wheezes, crackles)

• Absence of oropharyngeal candidiasis does not exclude 

esophageal candidiasis.

• Abdomen: masses, tenderness

• Evaluation for malignancy and infection if history and 

examination suggest these diagnoses

Diagnostic 

tests

• Diagnosis of GERD usually is made on the basis of clinical evaluation; in patients with symptoms consistent with GERD, history 

usually is suffi cient to move to a trial of empiric acid-lowering 

therapy (4-8 weeks) without further evaluation.

• Exceptions require immediate and appropriate evaluation:

• Chest pain (rule out cardiac origin)

• Other alarm symptoms (see above)

• Other atypical symptoms or fi ndings; high suspicion of an 

alternative diagnosis

• Hematocrit and fecal occult blood testing may be indicated if 

anemia caused by an upper GI source is suspected.

• testing is of little value in evaluation of GERD. Helicobacter pylori

• Empiric

proton 

pump 

inhibitor 

(PPI) 

therapy

• Response to acid-lowering therapy (typically PPI therapy) 

supports a diagnosis of GERD, though studies of correlation 

show varying results, and symptom improvement may not correlate with fi ndings on EGD or pH monitoring. Sensitivity 78% and 

specifi city 54% for GERD; use of high dosages of PPI may improve 

sensitivity. 

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GASTROESOPHAGEAL REFLUX DISEASE (GERD)

160 PRIMARY CARE OF VETERANS WITH HIV

p

or other testing as below.

• (Note that a small number of patients have GERD symptoms that 

are not related to gastric acid.)

• EGD • Useful for diagnosing esophagitis and complications (eg, strictures, 

Barrett esophagus), but is normal in >50% of patients with symptoms: high specifi city (>90%) but low sensitivity (50%) (ie, normal 

endoscopy does not exclude GERD). Severity of mucosal injury 

does not necessarily correlate with symptoms.

• The role of EGD in the initial evaluation of patients with 

uncomplicated GERD is somewhat controversial. The VHA 

Pharmacy Benefi ts Management Strategic Healthcare Group and 

the American College of Gastroenterology propose that a trial 

of therapy is preferable to EGD for most patients.

• Perform EGD as part of initial evaluation for complicated GERD 

(eg, if alarm symptoms or other concerning symptoms are present), or if alternative diagnoses are likely (eg, candidiasis or CMV 

esophagitis, esophageal cancer, gastritis, and peptic ulcer disease), 

or if patient is at risk of Barrett esophagus (see above).

• Consider trial of acid-lowering therapy while awaiting EGD; 

may result in partial (or full) remission of GERD; will improve 

sensitivity for detection of Barrett esophagus.

• Perform EGD for patients whose symptoms persist despite 

therapy; consider for patients with long duration of symptoms (eg, 

>5 years). 

• The surveillance interval for Barrett esophagus is determined by 

the grade of dysplasia at initial EGD (see Barrett Esophagus, 

p. 157).

• Ambulatory 

pH monitoring

• Presence of acid in the esophagus does not correlate well with 

symptoms.

• Does not detect nonacid refl ux.

• Limited availability, uncomfortable for patients. 

• Consider for patients with persistent symptoms if the EGD is 

negative for mucosal damage and for those with unusual, extraesophageal, or refractory symptoms.

• Can monitor control of refl ux in patients on acid-reducing medications (eg, for patients who are considering surgery).

• Barium

esophagram

• Detects severe esophagitis and strictures reliably, but is not sensitive or specifi c for milder or nonerosive disease. 

• Not sensitive for detection of Barrett esophagus.

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PRIMARY CARE OF VETERANS WITH HIV 16

differential 

diagnosis

pg(ypy ypg

dysphagia)

• Candidiasis

• CMV

• Herpes simplex virus

• Dyspepsia 

• Peptic ulcer disease

• Gastritis

• “Pill esophagitis”

• Stricture

• Hiatal hernia

• Esophageal dysmotility

• Cancer (esophageal, gastric)

• Gastroparesis

• Coronary artery disease

 MANAGEMENT

Acute/Initial Treatment 

Goals of therapy: 

■ Symptom relief

■ Healing of esophageal erosions (if present) 

■ Prevention of complications (data demonstrate reduction in esophageal strictures, but do not clearly show that treatment prevents or slows development 

of Barrett esophagus or adenocarcinoma)

As discussed in the Evaluation section, empiric acid-suppressing treatment may 

be initiated on the basis of GERD symptoms. The rate of symptom response to 

adequate therapy is high (>80%), so patients whose symptoms do not improve 

should be evaluated for other causes.

Medications

Acid-suppressive agents

■ Mainstay of GERD treatment.

■ Primary acid-suppressive treatments are PPIs and H2 receptor antagonists 

(H2RAs).

■ For symptom control and healing of esophagitis, the order of effi cacy is: highdose PPI > standard-dose PPI > half-dose PPI > high-dose H2RA > standarddose H2RA. 

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GASTROESOPHAGEAL REFLUX DISEASE (GERD)

162 PRIMARY CARE OF VETERANS WITH HIV

failure to respond to H2RAs should be started on standard-dose PPI rather 

than an H2RA.

■ For patients with NERD, the optimal initial treatment strategy has not been 

defi ned. Some authorities prefer to start with PPIs at maximal doses and step 

down to less-intensive therapy after symptom remission; others prefer to 

start with less-intensive therapy and step up if symptom relief or esophageal 

healing is incomplete.

■ PPIs and H2RAs may affect serum levels of some ARVs; these drug-drug interactions may infl uence which type of medication is selected for initial treatment of GERD (see Potential ARV Interactions below).

■ Most GERD patients (>60%) gain symptom relief, and approximately 80% 

have healing of esophagitis at 8-12 weeks.

Antacids

■ No role as primary therapy (typically, patients have self-treated with antacids 

without symptom relief). 

■ May be helpful for some patients as supplement to PPI therapy, to be used as 

needed for breakthrough symptoms.

Prokinetic agents

■ Metoclopramide is the only prokinetic agent available in the United States.

■ Increases LES resting tone, esophageal peristalsis, and gastric emptying.

■ Less effective than PPIs; similar to but perhaps less effective than H2RAs.

■ Associated with CNS adverse effects (eg, irreversible tardive dyskinesia).

■ Should be used only as adjunct to acid suppression, not monotherapy.

Dietary and Lifestyle Modifi cation

■ Generally aimed at avoiding decreases in LES function, or increases in abdominal pressure or position, which promote refl ux of acid above the LES.

■ Adjunct to acid suppression in selected patients; not suitable for sole therapy.

■ Limited data on effi cacy from randomized controlled trials for most measures.

■ Specifi c modifi cations should be based on individual circumstances and identifi ed triggers.

Initial Interventions for GERD

PPIs

• Available PPIs have comparable effi cacy at equivalent dosages.

• Greater effi cacy and more rapid symptom control than H2RAs.

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PRIMARY CARE OF VETERANS WITH HIV 16

pg gpg

ages and step down to less-intensive therapy after symptom remission, others prefer 

to start at lower dosages and increase treatment intensity if needed.

• Should be taken a half hour before breakfast (or dinner).

• Usually well tolerated. Potential adverse effects include GI symptoms (abdominal 

pain, diarrhea, nausea), headache, rash, and liver toxicity.

• No dosage adjustment needed for renal impairment.

• May require lower dosage in hepatic impairment; dosage not defi ned.

• Decrease absorption of drugs with pH-dependent bioavailability, particularly ATV. 

(See Potential ARV Interactions below.)

Generic Drug Name Dosage Range Comments

Esomeprazole 20-40 mg QD If diffi culty swallowing, can 

open capsule and sprinkle 

contents on applesauce

Lansoprazole 15-30 mg QD or 

30 mg BID

If diffi culty swallowing, can 

open capsule and sprinkle 

contents on applesauce

Omeprazole 20-40 mg QD If diffi culty swallowing, can 

open capsule and sprinkle 

contents on applesauce; 

immediate-release form 

contraindicated with 

hypocalcemia or alkalosis

Pantoprazole 40 mg QD or 40 mg BID No dosage adjustment 

needed for hepatic impairment; may cause falsepositive THC result on 

urine toxicology screen

Rabeprazole 20 mg QD or 20 mg BID Delayed-release tablet

H2RAs

• Less effective than PPIs for acid suppression, relief of symptoms, and healing of 

esophagitis; approximately 40% of patients gain symptom relief. Treatment with 

H2RAs may be adequate for some patients.

• Potential adverse effects vary somewhat according to the specifi c H2RA. They 

include cytopenias, rash, GI intolerance, and arrhythmias. 

• Dosage adjustment is required for patients with renal insuffi ciency. 

• Cimetidine interacts signifi cantly with many other drugs. 

• See Potential ARV Interactions below. 

Cimetidine 800 mg BID or 800 mg TID Multiple drug interactions (see Potential ARV 

Interactions below)

Famotidine 20 mg BID or 40 mg BID May decrease ATV 

absorption

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GASTROESOPHAGEAL REFLUX DISEASE (GERD)

164 PRIMARY CARE OF VETERANS WITH HIV

g g y 

absorption

Ranitidine 150 mg BID or 150 mg 

QID

May decrease ATV 

absorption; may decrease 

FPV, LPV, RTV levels

Antacids

• Typically contain aluminum hydroxide, magnesium hydroxide, calcium carbonate, 

sodium bicarbonate, or combinations of these compounds.

• Liquid formulation is preferable to tablets because of more rapid action.

• Usual dosage is 15-30 mL QID (after meals and at bedtime).

• If tablets are used, they should be thoroughly chewed and followed by full glass of 

water.

• Antacids combined with alginic acid (eg, Gaviscon) may be superior to antacids alone.

• Adverse events:

• Antacids containing magnesium: diarrhea

• Antacids containing aluminum or calcium: constipation

• Hypophosphatemia with chronic use

• Magnesium and/or aluminum retention in chronic renal failure

• Multiple drug interactions caused by binding to form insoluble complexes, including 

PIs and integrase inhibitors. (See Potential ARV Interactions below.)

Prokinetic Agents

Metoclopramide 10-15 mg QID (after meals 

and at bedtime)

Associated with irreversible tardive dyskinesia, 

other CNS effects; may 

consider metoclopramide 

as adjunctive therapy 

(add-on to PPI)

Dietary and Lifestyle Modifi cation

Dietary In most patients, avoiding the following is useful: • 

• Carbonated beverages

• Voluminous meals

• In selected patients, avoiding the following triggers may 

be useful:

• Fatty meals

• Sweets, including chocolate

• Spicy foods/raw onions

• Caffeinated beverages

• Citrus products/juices

Lifestyle In most patients, the following are useful: • 

• Weight loss

• Smoking cessation

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PRIMARY CARE OF VETERANS WITH HIV 16

yg pg

• Avoiding excessive physical activity (running)

• In selected patients, the following may be useful:

• Avoiding alcohol

• Elevating head of bed (for nocturnal symptoms)

Evaluate Treatment Response (after 4-8 weeks):

Possible responses to treatment Options for treatment 

and evaluation

Adequate control of symptoms • Preferred: Step-down (decrease 

in intensity) of therapy (eg, from 

high-dose PPI to standard-dose PPI, 

or from PPI to H2RA), with goal 

of eventually discontinuing therapy; 

monitor symptoms

• Discontinue therapy and monitor 

symptoms

• Continue current therapy

Partial control of symptoms • Increase intensity of therapy (eg, to 

high-dose PPI)

• Extend the course of treatment 

(reevaluate after additional 4-8 

weeks) 

• Refer to GI for further evaluation

Lack of response • Increase intensity of therapy

• Consider alternative diagnosis

• Refer to GI for evaluation

More than 60% of patients respond to adequate therapy. Most authorities 

recommend that all patients who do not respond to a trial of PPI therapy be 

referred for further evaluation. In patients with low CD4 counts, consider 

candidiasis or CMV esophagitis, and other HIV-associated conditions.

Relapse of GERD Symptoms

■ Restart the medication at the dosage that was effective in controlling the 

patient’s symptoms.

■ If relapse occurs on H2RA, step up therapy to PPI.

■ Consider referral for further diagnostic testing.

Chronic GERD Symptoms

■ Goals: Suppress symptoms, prevent relapses.

• Limited data on optimal strategy for long-term acid suppression

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GASTROESOPHAGEAL REFLUX DISEASE (GERD)

166 PRIMARY CARE OF VETERANS WITH HIV

disease

– Episodic treatment as needed for relapses: consider for patients with 

mild GERD

• It is rational to use the lowest possible dosage of PPI or H2RA that controls symptoms, but recurrences are common with decreased intensity 

or discontinuation of medications; some data suggest that effi cacy of 

H2RAs may decline over time.

• Chronic PPI therapy appears to be safe, but data from controlled trials 

are not available and risks are not fully known.

– May decease absorption of vitamin B12; use with caution for patients 

with risk factors for B12 defi ciency.

Surgery and Endoscopic Treatments

Most surgical and endoscopic therapies (eg, fundoplication) alter LES function, 

and have variable success. Criteria for selecting patients are not completely 

defi ned, but usually include those with large-volume refl ux, good responses to 

medical therapy, or intolerance to medical treatment. Following surgery, a high 

proportion of patients continue to require acid-lowering medications for control 

of symptoms. Refer to GI for evaluation. 

WHEN TO REFER

Gastroenterology • Severe symptoms

• Atypical symptoms

• Screening for Barrett esophagus

• Alarm symptoms suggesting malignancy, ulceration, or 

stricture

• Failure to improve, incomplete response, or relapse on 

empiric acid-suppression therapy

• Consider for chronic symptoms requiring continuous 

therapy

• Evaluation for OIs by EGD

Surgery • Evaluation for fundoplication for:

• Large-volume refl ux

• Long-term control of symptoms

• Intolerance to medical therapy

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PRIMARY CARE OF VETERANS WITH HIV 16

POTENTIAL ARV INTERACTIONS !

Acid-lowering medications have interactions with various ARVs. Consult 

dosing information, as certain combinations require specifi c dosing strategies, 

and some are contraindicated.

PPIs: interactions with ARVs are incompletely studied

■ All PPIs: 

• ↓ ATV levels (ATV requires an acidic GI environment for absorption); 

see specifi c dosing recommendations below

• ↓ IDV (predicted)

■ Omeprazole (in addition to All PPIs, above):

• ↓ NFV, ETV

• ↓ SQV

H2RAs: 

■ All H2RAs:

• ↓ ATV levels (ATV requires an acidic GI environment for absorption); 

see specifi c dosing recommendations below 

■ Cimetidine (in addition to All H2RAs, above): 

• ↓ NVP levels; dosage adjustment not established 

• May ↑ FPV levels; consider alternative agents 

• May ↓ DRV levels

■ Ranitidine

• May ↓ FPV and LPV/r levels; dosage adjustments not established 

Antacids

■ Maalox, Mylanta, Tums, milk of magnesia, others

• May ↓ levels of ATV, FPV, TPV; separate dosing by 2 hours

■ Calcium (eg, Tums, Mylanta)

• May bind integrase inhibitors and interfere with their activity (until 

further information is available, separate dosing by at least 2 hours)

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GASTROESOPHAGEAL REFLUX DISEASE (GERD)

168 PRIMARY CARE OF VETERANS WITH HIV

ARV-Naive Patients ARV-Experienced Patients

PPI • ATV/r 300/100 mg QD; PPI 

dosage not to exceed the 

equivalent of omeprazole 

20 mg QD, with the PPI to be 

taken approximately 12 hours 

before ATV/r.

• Unboosted ATV is not 

recommended.

• PPIs are not recommended.

H2RA • ATV/r 300/100 mg QD; H2RA 

dosage not to exceed the 

equivalent of famotidine 40 

mg BID; give ATV/r with the 

H2RA and/or ≥10 hours after 

the H2RA.

• Unboosted ATV is not recommended; if used with H2RA, 

H2RA should not exceed the 

equivalent of famotidine 20 

mg per dose or daily total of 

40 mg; give ≥2 hours after 

and/or ≥10 hours before 

ATV/r.

• ATV/r 300/100 mg QD; H2RA 

dosage not to exceed the 

equivalent of famotidine 20 mg 

BID; give ATV/r with the H2RA 

and/or ≥10 hours after the 

H2RA.

• If TDF is used in the regimen, 

give ATV/r 400/100 mg QD. 

Administer H2RA as described 

above.

• Unboosted ATV is not recommended.

Source: Reyataz package label

REFERENCES

DeVault KR, Castel DO; American College of Gastroenterology. Updated guidelines for 

the diagnosis and treatment of gastroesophageal refl ux disease. Am J Gastroenterol. 2005 

Jan;100(1):190-200.

Ip S, Bonis P, Tatsioni A, et al. Comparative Effectiveness of Management Strategies for Gastroesophageal Refl ux Disease. Evidence Report/Technology Assessment No. 1. (Prepared 

by Tufts-New England Medical Center. Evidence-based Practice Center under Contract 

No. 290-02-0022.) Rockville, MD: Agency for Healthcare Research and Quality; December 

2005. Available at http://www.effectivehealthcare.ahrq.gov/reports/fi nal.cfm. Accessed 

November 6, 2008.

Moayyedi P, Talley NJ. Gastro-oesophageal refl ux disease. Lancet. 2006 Jun 

24;367(9528):2086-100. 

van Pinxteren B, Numans ME, Bonis PA, et al. Short-term treatment with proton pump 

inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal refl ux diseaselike symptoms and endoscopy negative refl ux disease. Cochrane Database Syst Rev. 2006 

Jul 19;3:CD002095. 

UCS-PCM-08-0701-GERD.indd 168 CS-PCM-08-0701-GERD.indd 168 3/16/09 /16/09 
PRIMARY CARE OF VETERANS WITH HIV 16

for gastroesophageal refl ux disease: follow-up of a randomized controlled trial. JAMA. 

2001 May 9;285(18):2331-8. 

VA/DoD Clinical Practice Guideline Working Group. Management of Adults with Gastroe

sophageal Refl ux Disease in Primary Care Practice. Washington, D.C.: Pharmacy Benefi ts 

Management Strategic Healthcare Group and the Medical Advisory Panel, Veterans Health 

Administration, Department of Veterans Affairs, and the Pharmacoeconomic Center, 

Department of Defense; March 12, 2003. Available at http://vaww.oqp.med.va.gov/

CPGintra/cpg/cpg.htm. Accessed November 6, 2008.

Wang KK, Sampliner RE; Practice Parameters Committee of the American College of 

Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of 

Barrett esophagus. Am J Gastroenterol. 2008 Mar;103(3):788-97. 

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/16/09 
PRIMARY CARE OF VETERANS WITH HIV 17

Hypertension

KEY POINTS

■ Hypertension is an independent, reversible risk factor for 

cardiovascular, cerebrovascular, and renal disease that is 

underdiagnosed and undertreated.

■ HIV-infected patients have a high prevalence of hypertension and 

other cardiovascular risk factors.

■ In most cases, the treatment of hypertension should start with 

lifestyle modifi cation and a thiazide diuretic. Other antihypertensive 

drugs may be useful, depending on the patient’s additional 

comorbidities.

Note: This chapter does not address hypertensive emergency or urgency in detai

BACKGROUND

Rationale for Detecting and Treating High Blood Pressure

■ Elevated blood pressure (BP) is an 

independent risk factor for myocardial 

infarction (MI), stroke, heart failure, and 

kidney disease.

■ The relationship between BP and these 

disease events is continuous; the risk 

of cardiovascular disease doubles for 

every 20 mmHg increase in systolic BP or 10 mmHg increase in diastolic BP. 

This effect applies across the spectrum of BP, from normal to severely elevated

■ In clinical trials, treatment of hypertension is associated with substantial 

reductions in the incidence of MI, stroke, and heart failure.

■ “Prehypertension” (as defi ned in the Seventh Report of the Joint National 

Committee on Prevention, Detection, Evaluation, and Treatment of High 

Blood Pressure [JNC 7], see Table 1 below) confers an increased risk 

of developing hypertension and often warrants therapeutic intervention. 

Because the short-term pharmaceutical treatment of prehypertension has 

not been shown to forestall the development of hypertension, some experts 

have questioned the benefi t of labeling patients with this diagnosis.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Veterans with HIV*

Hypertension: 45%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition

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HYPERTENSION

172 PRIMARY CARE OF VETERANS WITH HIV

of lifestyle changes and pharmaceutical therapy, hypertension remains poorly 

controlled for many patients. 

Special Considerations regarding Hypertension and ART

Although a relationship between ART and other components of the metabolic 

syndrome, such as hyperlipidemia and elevated blood glucose, has been established, it is not clear whether HIV or specifi c ARVs are independent risk factors 

for hypertension.

Some early studies suggested a link between PI-based ART and elevated BP. More 

recent and larger studies, including the D:A:D study, found that this relationship was accounted for by other factors, such as age, race, and, in particular, 

increases in BMI that occurred after initiation of ARVs. Another study suggests a 

link between the duration of ART and BP. Prolonged ART, defi ned as 2-5 years in 

duration, was independently associated with development of hypertension in the 

MACS study, whereas ART of <2 years in duration was not. 

Treatment Goals (see Table 1)

■ Current VA recommendations are to lower BP to a target of <140/90 

(<140/80 for patients with diabetes) to reduce the risk of cardiovascular 

events and other end-organ damage. 

■ JNC 7 and the American Heart Association (AHA) recommend a target BP of 

<130/80 for patients with:

• Diabetes 

• Chronic kidney disease (CKD) 

■ AHA also recommends a target BP of:

• <130/80 for patients with:

Coronary artery disease (CAD) or its equivalents _

CAD equivalents: carotid or peripheral arterial disease, abdominal _

aortic aneurysm

10-year Framingham Risk Score ≥10% _

• <120/80 for patients with left-side heart failure

EVALUATION

SCREENING

■ Although an optimal screening interval has not been defi ned, the current 

VA/DoD guidelines recommend annual BP screening. JNC 7 recommends 

screening for hypertension every 2 years for patients with BP <130/85, and 

more frequently for patients with BP >130/85.

■ Checking BP at all clinic visits should be encouraged.

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PRIMARY CARE OF VETERANS WITH HIV 17

■ The patient should be seated in a chair for 5 minutes, feet on the fl oor, with 

arm at heart level.

■ The patient should not have smoked, had caffeine, or exercised within 30 min

utes before BP measurement.

■ Cuff bladder should encircle ≥80% of arm.

■ The average of at least 2 measurements per offi ce visit should be recorded.

■ The diagnosis of prehypertension or hypertension (see Table 1) is based 

on the presence of an elevated BP taken on at least 2 offi ce visits over a 

2-month period. For Stage 2 hypertension, evaluation or referral should be 

performed within 1 month of the initial measurement.

Table 1. Defi nition and Treatment of High Blood Pressure

Blood Pressure

(mmHg) Classifi cation Treatment(associated tables in bold)

<120/80 Normal No treatment indicated.

Encourage lifestyle measures as shown 

in Table 3.

Systolic: 120-139

or

Diastolic: 80-89

Prehypertension Lifestyle modifi cation (Table 3) and

Treat comorbidity,* if present and 

appropriate.

If diabetic, treat to target BP of 

<140/80.#§

Systolic: 140-159

or

Diastolic: 90-99

Stage 1 

hypertension

Goal: BP <140/90 (140/80 if diabetic)#§

Lifestyle modifi cation (Table 3) and

Start medication 

• If no comorbidity,* use thiazide 

(preferred) or angiotensin-converting 

enzyme inhibitor (ACEI), angiotensin 

receptor blocker (ARB), beta-blocker 

(BB), calcium channel blocker (CCB), 

or fi xed-dose combination (FDC) of 

agents. 

• If comorbidity,* choose from table 

of disease-specifi c antihypertensives (Table 4).

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HYPERTENSION

174 PRIMARY CARE OF VETERANS WITH HIV

y

or

Diastolic: >99

g

hypertension

()

Lifestyle modifi cation (Table 3) and

Start 2 medications 

• If no comorbidity,* use thiazide plus

ACEI, ARB, BB, or CCB, dosed separately or as an FDC.

• If comorbidity,* choose from table 

of disease-specifi c antihypertensives (Table 4).

Consider gradual BP reduction starting 

with 1 agent for patients at risk of 

postural hypotension (eg, elderly).

* Comorbidities include diabetes, CAD, peripheral vascular disease, cerebrovascular disease, heart 

failure, or renal disease defi ned as a reduced GFR (CrCl <60 mL/min/1.75 m2) or albuminuria 

(>300 mg/dL).

# The JNC 7 Report recommends a target BP of <130/80 for diabetic patients. AHA 2007 

guidelines recommend a target BP of <130/80 for patients with diabetes, CKD, known CAD, or 

CAD equivalents (carotid or peripheral arterial disease, abdominal aortic aneurysm), or 10-year 

Framingham Risk Score ≥10%.

§

 VA/DoD guidelines recommend a target BP of <140/90 for patients with renal disease; some 

authorities recommend a target BP of <130/80.

Adapted from VA/DoD Guidelines, JNC 7 Report, and AHA Guidelines. See References, VA/DoD, 

Chobanian, Rosendorff.

Offi ce Evaluation of the Hypertensive Patient

Specifi c fi ndings of end-organ damage or cardiovascular comorbidities should 

guide the choice or intensity of therapy and prompt possible additional workup. 

The basic evaluation of the hypertensive patient, adapted from the JNC 7, is 

shown in Table 2. Although <5% of patients have secondary hypertension, clinicians should be alert to possible underlying causes such as Cushing syndrome 

or sleep apnea. Workup of secondary hypertension is addressed in VA/DoD 

guidelines at http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm.

Table 2. Evaluation of Hypertensive Patients for End-Organ Damage 

and Treatable Comorbidities

Component Evaluation Possible Findings

History • Review of systems 

• Past medical history 

• Health-related behavior

• Family history

• Dyspnea, chest pain, edema, 

polyuria/polydipsia

• CAD, CHF, diabetes, renal disease

• Tobacco use, physical activity

• Early CAD, diabetes

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PRIMARY CARE OF VETERANS WITH HIV 17

y

examination

g

• Ophthalmologic 

examination

• Peripheral circulation

• Cardiac examination

• Respiratory examination

• Arteriovenous nicking, papilledema (hypertensive retinopathy)

• Diabetic retinopathy

• Bruits: carotid, abdominal, or femoral (peripheral vascular disease)

• Decreased peripheral pulses

• LVH, S3, S4, distended neck veins 

(hypertrophy, failure)

• Crackles/wheezes

Studies • Electrolytes, BUN, Cr, glucose, Ca2+

• Fasting lipids

• Urinalysis

• ECG

• Spot urine protein/Cr ratio

• Decreased renal function, diabetes, hyperaldosteronism

• Hyperlipidemia

• Proteinuria, glycosuria, hematuria

• LVH, CAD

 MANAGEMENT

Initial Management

Lifestyle modifi cation

■ All hypertensive patients should be encouraged to attempt lifestyle 

modifi cation (see Table 3).

■ Whenever possible, tobacco use should be addressed (see Smoking Cessation, p. 53).

Table 3. Lifestyle Modifi cations Shown to Reduce Blood Pressure

Area to 

Modify Goals Anticipated SBP Reduction

Diet DASH (Dietary Approaches to Stop Hypertension) diet:

• in fruit/vegetables, lean protein, low-fat HIGH

dairy products, nuts, fi ber, K+, Mg+ Ca+, whole 

grains (risk of hyperkalemia in patients with 

renal disease)

• in lean red meat, sugars LOW

For specifi c dietary recommendations, including 

serving sizes and ingredients, see the DHHS online 

DASH diet guide: http://www.nhlbi.nih.gov/health/

public/heart/hbp/dash/new_dash.pdf

Low sodium diet: ≤2.4 g/day

8-14 mmHg

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HYPERTENSION

176 PRIMARY CARE OF VETERANS WITH HIV

y

• Aerobic activity = brisk walking

g

Alcohol ≤2 alcoholic drinks/day (men) or ≤1 drink/day 

(women)

• 1 drink = 0.4 oz (12 g) of ethanol: 12 oz beer, 

5 oz wine, or 1.5 oz 80-proof (40%) liquor

See Alcohol Misuse, p. 3

2-4 mmHg

Weight Maintain BMI 18.5-24.9

• BMI = weight (kg)/height (m2

)

• U.S. DHHS BMI calculator: http://nhlbisupport.

com/bmi/

5-20 mmHg per 

10 kg weight loss

Resources

Diet: The HealthierUS Veterans program has useful dietary resources at http://vaww.

prevention.va.gov/HealthierUSVeterans_Toolkit.asp. Nutritional information is available 

from the Veterans Canteen Service at http://vaww.vcscanteen.aac.va.gov/NutritionalInfo.asp.

Exercise and weight loss: The VHA MOVE program is a national weight management program for veterans; for further details, see http://vaww.move.med.va.gov/.

Alcohol misuse: See Alcohol Misuse, p. 3. Also, VA resources for reducing alcohol 

use are available at http://vaww.hepatitis.va.gov/vahep?page=prtop03-wp-01-res.

Adapted from JNC 7 Report. See References, Chobanian.

Medications

■ Many patients will require pharmacologic therapy.

■ Considerations in choosing antihypertensive medication:

• Thiazide diuretics have been shown to prevent cardiovascular events 

related to hypertension and are recommended as fi rst-line therapy for 

most patients. For patients with renal or cardiovascular comorbidity, other 

agents may offer additional benefi t (see Table 4 and Table 5, below).

• BBs, ACEIs, ARBs, and long-acting CCBs also have been shown to reduce 

the cardiovascular complications of hypertension. 

• Many patients require 2 agents for suffi cient control. Add a second agent 

if upward titration of the initial agent does not adequately control BP.

• Patients with Stage 2 hypertension generally should be started on 

2 drugs, including a thiazide diuretic.

• Patients with renal or cardiovascular comorbidities may gain particular 

benefi t from specifi c types of antihypertensive drugs (see Table 4 and 

Table 5).

• Many antihypertensive drugs that are commonly prescribed together are 

marketed as single-tablet FDCs. These can be useful if the patient tolerates the same dosage of each drug given separately.

• Whenever possible, use medications that can be given once daily to promote adherence.

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PRIMARY CARE OF VETERANS WITH HIV 17

Comorbidities

Comorbidity Diuretic BB ACEI ARB CCB Aldosterone 

Antagonist

CHF × × × × ×

Post-MI × × ×

High risk of CAD × × × ×

Diabetes × × × × ×

CKD × ×

Prevention of 

recurrent stroke

 × ×

Adapted from JNC 7 Report. See References, Chobanian.

Evaluation of Treatment Response

■ Home BP monitoring can provide extremely useful information on BP control; BP cuffs for home use can be ordered through the local Prosthetics 

Service. Devices with a memory function are preferable to patient recall or 

diary-keeping.

■ Patients should be seen within 1 month after initiating therapy to assess effi -

cacy, adherence, and toxicity. (Patients requiring blood tests, those at high risk 

of end-organ damage, and those at risk of postural hypotension should be 

seen earlier.)

■ If BP is controlled to the target range, adequacy of control should be reevaluated at least every 3-6 months.

■ If BP is not controlled:

• Explore adherence to regimen and educate patients about the importance of controlling hypertension.

• Be alert to use of concomitant medications that may increase BP (eg, 

NSAIDs, decongestants, erythropoietin, cyclosporine) and to substance 

use (eg, alcohol, methamphetamine, cocaine).

• Consider titration of initial drug regimen (usually doubling of dosage; see 

Table 5).

• Add an agent from a second class. Agents shown to decrease morbidity 

and mortality are preferred (ACEI, ARB, BB, long-acting CCB).

• If a thiazide diuretic was not the initial drug chosen, it should be used as 

part of combination therapy unless contraindicated or not tolerated.

• Consider joint care management with a clinical pharmacist.

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HYPERTENSION

178 PRIMARY CARE OF VETERANS WITH HIV

WHEN TO REFER

Hypertension Clinic, 

Cardiology, or Renal

• Failure to achieve target BP after addition of second 

drug class

• Workup indicating secondary hypertension

Emergency Department • Hypertensive emergency: BP >180/120 complicated 

by:

• Hypertensive encephalopathy

• Intracranial hemorrhage

• Acute MI or unstable angina

• Dissecting aortic aneurysm

• Acute heart failure with pulmonary edema

• Hypertensive urgency: BP >180/120 without target 

organ dysfunction. May see:

• Headache

• Epistaxis

• Shortness of breath

• Severe anxiety

Table 5. Antihypertensives: Drug Dosing and Interactions with ARVs

Notes

1. Dosages listed here are for hypertension only. Many of these agents (eg, 

ACEIs) have additional indications, such as for congestive heart failure, for 

which lower dosages may be appropriate.

2. “Divided” means “1/X of the daily dosage, given X times per day.” 

Therefore, “100 mg daily, divided BID” means 50 mg BID. It does not mean 

100 mg BID.

3. Drugs listed are representative of their respective classes only; other drugs 

within each class are also used, and specifi c dosing information should be 

followed. 

Generic Drug Name Usual Starting Dosage/

Dosage Titration

Comments/Drug 

Interactions

Thiazide Diuretics

Pros: Cardioprotective in ALLHAT study; fi rst-line therapy in JNC 7, VA/DoD guidelines. Thiazide diuretics and CCBs may be more effective than other antihypertensives 

for African American patients.

Cons: Risk of hypokalemia. Monitor electrolytes periodically. Other potential adverse 

effects include rash, hyperglycemia, sexual dysfunction, and frequent urination. Should 

not be given to patients with a history of gout, as they may trigger attacks. 

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PRIMARY CARE OF VETERANS WITH HIV 17

g 

may increase up to 50 

mg QD; dosages higher 

than 50 mg carry risk 

of hypokalemia without 

added benefi t

Hydrochlorothiazide 

(HCTZ)

Start at 12.5-25 mg QD; 

may increase up to 50 mg 

QD, though dosages higher 

than 25 mg carry risk 

of hypokalemia without 

added benefi t

Beta-Blockers (BBs)

Pros: Useful for patients with concomitant CAD, CHF, previous MI.

Cons: When discontinuing, taper over course of 14 days to avoid rebound hypertension, angina, MI, or arrhythmia. May be less effective for patients without CAD, 

especially elderly patients. Use with caution in patients with reactive airway disease. 

Potential adverse effects include bradycardia, hypotension, fatigue, and sexual 

dysfunction.

Atenolol Start at 25-50 mg QD or 

divided BID; maximum 100 

mg per day

ATV may ↑ atenolol 

concentrations; no dosage 

adjustment appears to be 

necessary.

Metoprolol Start at 50 mg BID; maximum 225 mg BIDCYP 2D6 substrate; PIs 

may ↑ metoprolol levels. 

Metoprolol Extended 

Release 

Start at 50-100 mg QD; 

maximum 400 mg QD

CYP 2D6 substrate; PIs 

may ↑ metoprolol levels. 

Propranolol Start at 20 mg BID; maximum 640 mg per day in 

divided doses

Propranolol Extended 

Release 

Start at 60 mg QD; maximum 640 mg QDExtended-release formulation cannot be substituted 

for immediate-release 

form on a mg per mg 

basis; may require dosage 

change.

Mixed Alpha-/Beta-Blockers

Pros: Cardioprotective.

Cons: Same as for BBs. Avoid in patients with decompensated heart failure who are 

dependent on sympathetic stimulation.

Carvedilol Start at 6.25 mg BID; 

titrate slowly; usual dosage: 

12.5-50 mg/day, divided BID

CYP 2D6 substrate; PIs 

may ↑ carvedilol levels.

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HYPERTENSION

180 PRIMARY CARE OF VETERANS WITH HIV

gg

day, divided BID

yp

sive emergencies.

ACE Inhibitors

Pros: Cardioprotective, renal protective.

Cons: Avoid during pregnancy; use with caution in patients who are elderly, are 

fl uid depleted, or have renal insuffi ciency. Risk of hyperkalemia. Check electrolytes 1 

week after starting ACEI. Other potential adverse effects include angioedema, cough, 

renal insuffi ciency, and sexual dysfunction.

Benazepril Start at 10 mg QD; maximum 80 mg per day; usual 

dosage: 20-40 mg QD or 

divided BID; may need BID 

dosing for continuous BP 

control

Start at 5 mg QD if 

patient is elderly, has renal 

insuffi ciency, or is taking a 

diuretic.

Fosinopril Start at 10 mg QD; maximum 80 mg per day, but 

no additional effect over 

40 mg per day; usual 

dosage: 10-40 mg QD or 

divided BID; BID dosing 

may be needed for 

continuous BP control

Start at 5 mg QD if 

patient is elderly, has renal 

insuffi ciency, or is taking a 

diuretic.

Lisinopril Start at 10 mg QD; maximum 80 mg QD but no 

additional effect over 

40 mg per day; usual 

dosage: 20-40 mg QD

Start at 2.5-5 mg QD if 

patient is elderly, has renal 

insuffi ciency, or is taking a 

diuretic.

Ramipril Start at 2.5 mg QD; 

maximum 20 mg QD; usual 

dosage: 2.5-20 mg QD or 

divided BID; may need BID 

dosing for continuous BP 

control

Start at 1.25 mg QD if 

patient is elderly, has renal 

insuffi ciency, or is taking a 

diuretic.

Angiotensin Receptor Blockers (ARBs)

Pros: Cardioprotective, renal protective.

Cons: Avoid during pregnancy; use with caution in patients who are elderly, are 

fl uid depleted, or have renal insuffi ciency. Risk of hyperkalemia. Other potential adverse 

effects include angioedema and renal dysfunction.

Candesartan Usual starting dosage: 

16 mg QD, may be divided 

BID; maximum 32 mg per 

day

Start at lower dosage in 

patients with moderate or 

worse hepatic impairment, 

volume depletion.

Irbesartan Start at 150 mg QD; maximum 300 mg QDStart at 75 mg QD for 

patients with volume 

depletion.

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PRIMARY CARE OF VETERANS WITH HIV 18

g 

maximum 100 mg QD or 

divided BID

g 

patients with volume 

depletion or hepatic 

insuffi ciency.

Telmisartan Usual starting dosage: 40 

mg QD; maximum 80 mg 

QD

Start at 20 mg QD in 

elderly, patients with 

hepatic impairment or 

volume depletion; monitor 

closely.

Valsartan Start at 80 mg QD; maximum 320 mg QD

Calcium Channel Blockers (CCBs)

Pros: CCBs and thiazide diuretics may be more effective than other antihypertensives 

for African American patients.

Cons: Metabolism of CCBs is inhibited by PIs; if CCBs must be used with PIs, reduce 

initial dosage and titrate up while monitoring for side effects (eg, hypotension, conduction block, bradycardia, and peripheral edema). Metabolism of CCBs may be induced by 

the NNRTIs EFV and NVP, leading to blunted antihypertensive effect.

Avoid immediate-release forms. Avoid in patients with CHF. 

Amlodipine Start at 2.5 mg QD; maximum 10 mg daily

See Cons above.

Diltiazem Sustained 

Release

Start at 60 mg BID; maximum 360 mg per day in 

divided doses

Diltiazem Extended 

Release 

Start at 120 mg QD; maximum 540 mg QD

Nifedipine Extended 

Release 

Start at 30 mg QD; maximum 120 mg QD

Verapamil Sustained 

Release

Start at 120 mg QD; maximum 480 mg per day, but 

divide BID if using >240 

mg per day

Immediate-release formulation is not recommended for treatment of 

hypertension.

Verapamil Extended 

Release 

Covera HS: Start at 

180 mg QHS; maximum 

480 mg QHS

Verelan PM: start at 

100 mg QHS; maximum 

400 mg QHS

Immediate-release 

formulation is not recommended for treatment of 

hypertension.

Potassium-Sparing Diuretics and Aldosterone Antagonists

Pros: May be useful in patients with hypokalemia; often combined with a thiazide 

diuretic.

Cons: may cause hyperkalemia: monitor K+

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HYPERTENSION

182 PRIMARY CARE OF VETERANS WITH HIV

pgg 

100 mg QD or divided 

BID

yp

check K+ 1 week after 

starting spironolactone. 

Potential adverse effects 

include liver toxicity, 

gynecomastia, and sexual 

dysfunction.

Triamterene Start at 100 mg BID; 

maximum daily dosage is 

300 mg

Monitor for hyperkalemia; 

check K+ 1 week after 

starting triamterene.

Direct Vasodilators and Anti-Adrenergic Agents

(Note: Alpha-blockers used for treatment of benign prostatic hypertrophy are not 

recommended as monotherapy for hypertension; however, these may cause hypotension especially in patients who are taking other antihypertensive medications.)

Clonidine PO: Start at 0.1 mg BID; 

increase to usual maintenance dosage of 0.2-1.2 mg 

divided BID to TID; maximum 2.4 mg in divided 

doses

Patch: Start at 0.1 mg/24-

hour patch, increasing to 

desired effect; maximum 

dosage is 0.6 mg/24-hour 

patch

Possible adverse effects 

include bradycardia, 

sedation. Risk of rebound 

hypertension upon discontinuation: taper over 

course of 7 days.

Hydralazine Start at 10 mg QID; 

increase by 10-25 mg/dose 

to effective dosage; may 

divide effective daily dosage BID; maximum 300 mg 

per day in divided doses

Possible adverse effects 

include lupus-like syndrome, requiring discontinuation. May cause refl ex 

tachycardia; use with caution in patients with CAD.

Doxazosin Start at 1 mg QHS; maximum 16 mg per dayNot a fi rst-line agent. 

Possible adverse effects 

include risk of CHF, dizziness, postural hypotension, 

drowsiness, and syncope; 

all more likely if doxazosin 

is given with other vasodilators, including PDE-5 

inhibitors. Risk of syncope 

with initial dosages; start at 

lowest dose QHS. If drug 

is interrupted, restart at 

1 mg QHS dosing.

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PRIMARY CARE OF VETERANS WITH HIV 18

g 

usual maintenance dosage 

20 mg/day divided BID 

or TID; maximum 40 mg 

divided BID or TID

g

Possible adverse effects 

include risk of CHF, dizziness, postural hypotension, 

drowsiness, and syncope; 

all more likely if prazosin is 

given with other vasodilators, including PDE-5 

inhibitors. Risk of syncope 

with initial dosages; start at 

lowest dose QHS. If drug 

is interrupted, restart at 

1 mg QHS.

Terazosin Start at 1 mg QHS; usual 

daily dosage 1-5 mg QD 

or divided BID; maximum 

20 mg per day

Not a fi rst-line agent. 

Possible adverse effects 

include risk of CHF, dizziness, postural hypotension, 

drowsiness, and syncope; 

all more likely if terazosin 

is given with other vasodilators, including PDE-5 

inhibitors. Risk of syncope 

with initial dosages; start 

at lowest dosage QHS. If 

drug is interrupted, restart 

at 1 mg QHS dosing.

REFERENCES

Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute 

Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High 

Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, 

Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 

21;289(19):2560-72. 

Crane HM, Van Rompaey SE, Kitahata MM. Antiretroviral medications associated with 

elevated blood pressure among patients receiving highly active antiretroviral therapy. 

AIDS. 2006 Apr 24;20(7):1019-26.

Friis-Møller N, Weber R, Reiss P, et al. Cardiovascular disease risk factors in HIV 

patients--association with antiretroviral therapy. Results from the DAD study. AIDS. 

2003 May 23;17(8):1179-93.

Lawes CM, Bennett DA, Lewington S, et al. Blood pressure and coronary heart disease: 

a review of the evidence. Semin Vasc Med. 2002 Nov;2(4):355-68. Semin Vasc Med. 2002; 

2:355-68.

Rosendorff C, Black HR, Cannon CP, et al; American Heart Association Council for High 

Blood Pressure Research; American Heart Association Council on Clinical Cardiology; 

American Heart Association Council on Epidemiology and Prevention. Treatment of 

UCS-PCM-08-0701-Hypertension.indd 183 CS-PCM-08-0701-Hypertension.indd 183 3/20/09 /20/09 
HYPERTENSION

184 PRIMARY CARE OF VETERANS WITH HIV

tifi c Statement from the American Heart Association Council for High Blood Pressure 

Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. 

Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease. 

Circulation. 2007 May 29;115(21):2761-88.

Seaberg EC, Muñoz A, Lu M, et al. Association between highly active antiretroviral 

therapy and hypertension in a large cohort of men followed from 1984 to 2003. AIDS. 

2005 Jun 10;19(9):953-60. 

Triant VA, Lee H, Hadigan C, et al. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodefi ciency virus disease. J Clin 

Endocrinol Metab. 2007 Jul;92(7):2506-12.

VA/DoD Clinical Practice Guideline Working Group. Management of Hypertension in 

Primary Care. Washington, D.C.: Department of Veterans Affairs, Offi ce of Quality and 

Performance; 2004. Available at http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. 

Accessed December 18, 2008.

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PRIMARY CARE OF VETERANS WITH HIV 18

Liver Disease and Cirrhosis

KEY POINTS

■ Chronic liver disease is common among HIV-infected patients, and 

is increasingly a cause of mortality and morbidity as effective ART 

allows persons with HIV to live longer.

■ HIV infection may accelerate liver damage caused by HCV or HBV 

infection. HCV infection is particularly common among HIV-infected 

patients, especially those who acquired HIV through injection drug 

use (IDU). 

■ Long-term complications of HBV and HCV infection include 

cirrhosis, end-stage liver disease (ESLD), and hepatocellular 

carcinoma (HCC).

■ It is essential that providers working with HIV patients be able to 

identify liver disease and determine whether cirrhosis has developed. 

■ Long-term management of cirrhosis is important to providing 

optimal prevention and treatment of complications.

■ Some ARVs may cause liver toxicity (hepatotoxicity) but most 

can be used safely by patients with liver disease, with proper 

monitoring. Patients should not be undertreated for HIV because of 

concurrent liver disease. 

Note: Current information on VHA policy, guidelines, and tools related to liver 

disease can be found online at http://www.hepatitis.va.gov/.

BACKGROUND

Any disease or injury that chronically 

affects the liver can cause fi brosis (scarring); this process ultimately may progress 

to cirrhosis.

Cirrhosis is characterized by diffuse interlacing bands of fi brous tissue dividing the 

hepatic parenchyma into micronodular or 

macronodular areas.

Veterans with HIV*

Cirrhosis: 2%

Decompensated liver disease: 1%

HCC: 0.3%

HCV: 28% 

HBV: 11% 

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-

code corresponding to these conditions

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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LIVER DISEASE AND CIRRHOSIS

186 PRIMARY CARE OF VETERANS WITH HIV

■ High morbidity and mortality: In the U.S. general population, cirrhosis 

accounts for 40,000 deaths per year and for the loss of more than 228,000 

years of potential life. 

■ As HIV patients with access to ART survive longer, comorbidities such as 

chronic liver disease have become leading causes of illness and death. ESLD 

is now a leading cause of death in patients with HIV/HCV or HIV/HBV 

coinfection. 

■ HIV infection accelerates progression of liver disease associated with HCV or 

HBV. 

■ Other factors that cause more severe liver disease, including alcohol misuse, 

drug-associated hepatotoxicity, male gender, and fatty liver (steatosis), are also 

more common in the HIV-infected population. 

Potential Causes of Liver Disease, Especially among HIV-Infected 

Patients

Common

• Alcoholic hepatitis

• Alcoholic cirrhosis

• Chronic hepatitis B

• Chronic hepatitis C

• Nonalcoholic fatty liver disease

Less Common

• Drug-induced liver injury 

• Autoimmune hepatitis

• Primary biliary cirrhosis

• Primary sclerosing cholangitis

• Hemochromatosis

• Wilson disease

• Alpha-1 antitrypsin defi ciency

■ Prevalence of viral hepatitis among HIV-infected individuals in the 

United States

• 30-40% coinfected with HCV

9-27% of heterosexuals _

1-12% of men who have sex with men _

72-95% of injection drug users _

28% of veterans _

• 6-14% coinfected with HBV

4-6% of heterosexuals _

9-17% of men who have sex with men _

7-10% of injection drug users _

11% of veterans _

■ Risk factors for liver diseases other than viral hepatitis are common in the 

HIV-infected population.

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PRIMARY CARE OF VETERANS WITH HIV 18

sons, even in the absence of HCV or HBV infection.

• Cross-sectional studies have shown a high prevalence of elevated AST 

(20%), ALT (15%), and alkaline phosphatase (43%).

■ Alcohol consumption is common among people with HIV infection. 

• Rates of heavy drinking among people with HIV are almost twice those 

found in the general population. Approximately 8% of persons with HIV 

report heavy drinking in the past month.

• Alcohol use disorders were diagnosed in 33% of HIV-infected veterans in 

VA care in 2007.

■ Other comorbidities associated with liver disease:

• Diabetes mellitus

• Hyperlipidemia

• Obesity

• Hemophilia

• Ulcerative colitis

EVALUATION

■ At initial assessment, HIV-infected patients should be evaluated for clinical, 

biochemical, and virologic evidence of chronic liver disease.

■ Frequency of reassessments depends on the presence and severity of existing 

disease, risk factors for liver disease (eg, IDU, alcohol misuse), and prescription of potentially hepatotoxic medications (eg, NVP).

Clinical Features of Liver Diseases

(see below for features of decompensated cirrhosis)

History More than 40% of patients with cirrhosis are asymptomatic.

• Fatigue

• Weight loss

• Inability to concentrate

• Decreased libido

• Pruritus (in cholestatic liver diseases)

Physical 

examination

Perform a thorough physical examination with special attention to 

the abdomen, skin, and neurologic system. Note that patients may 

display no abnormalities. Abnormal fi ndings include:

• Jaundice

• Spider angiomata

• Palmar erythema

• Caput medusa

• Asterixis

• Gynecomastia

• Testicular atrophy

• Temporal wasting

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LIVER DISEASE AND CIRRHOSIS

188 PRIMARY CARE OF VETERANS WITH HIV

pgy (pp)

• Splenomegaly

• Ascites

• Clubbing

ypp

osteoarthropathy

• Dupuytren contracture

• Fetor hepaticus

ARVs and Hepatotoxicity

Many ARVs may cause liver damage, particularly in patients with preexisting liver 

disease. These include:

• NVP* 

• Most PIs, particularly DRV, TPV

• d4T, ddI

Note: ATV and IDV may cause isolated hyperbilirubinemia through inhibition of 

uridine diphosphate-glucuronosyltransferase (UGT) activity; this does not indicate 

liver disease.

* Increased risk if NVP is initiated in men with CD4 counts >400 cells/μL or in women with 

CD4 counts >250 cells/μL. 

Biochemical Features of Liver Disease and Common Causes

Elevated aminotransferases (AST, ALT)

Elevated alkaline phosphatase (with or without bilirubin elevation)Elevated bilirubin 

(without increase in 

alkaline phosphatase)

• Chronic HCV

• Chronic HBV

• Autoimmune hepatitis

• Nonalcoholic steatohepatitis (NASH)

• Drug effect/

hepatotoxicity

• Alcohol

• Primary biliary cirrhosis

• Sclerosing cholangitis

• Drug-induced liver 

injury

• Infi ltrative liver disease

• Sarcoidosis

• Granulomatous hepatitis

• Cirrhosis

• Drug effect (eg, ATV and 

IDV commonly cause 

isolated elevation of 

unconjugated bilirubin)

(Note: A Web-based course on liver function test abnormalities is available at http://www.hepatitis.

va.gov/vahep?page=prtop02-ed-01.)

Laboratory Findings and Specifi c Liver Diseases

Disease Typical Findings (may not be present)

Alcoholic liver disease History of alcohol abuse • 

• AST/ALT ratio often >2:1 

• AST and ALT both <500 IU/mL (if no other injurious 

processes) 

• GGT may be ↑

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PRIMARY CARE OF VETERANS WITH HIV 18

p() 

• HCV RNA +

• AST, ALT may be ↑ or normal

Chronic hepatitis B HBsAg + (in some cases may be –) • 

• HBV DNA + (usually; may be undetectable in patients 

who take ARVs with activity against HBV)

• HBeAg may be + or –

• AST, ALT usually ↑; may be normal

Primary biliary cirrhosis Antimitochondrial antibodies + • 

Primary sclerosing 

cholangitis

• History of infl ammatory bowel disease

• ANA often +

• ASMA often +

Autoimmune hepatitis ANA often + • 

• ASMA often +

• Anti-LKM-1 often +

• Hypergammaglobulinemia

Steatohepatitis/Nonalcoholic fatty liver disease 

(NAFLD)

• History of diabetes mellitus

• History of metabolic syndrome (obesity, dyslipidemia, 

diabetes mellitus)

• AST and/or ALT ↑

• Fatty infi ltration of liver on imaging

Abbreviations: ANA = antinuclear antibodies; ASMA = antismooth muscle antibodies; GGT = gamma

glutamyltransferase; LKM = liver/kidney microsomes

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LIVER DISEASE AND CIRRHOSIS

190 PRIMARY CARE OF VETERANS WITH HIV Virologic Features of Liver Disease HBV Diagnostic Tests and Interpretation Acute Hepatitis B Recovery from Acute Hepatitis B Chronic HBeAg+ Disease Chronic HBeAg- Disease Successful Vaccination Recovery from Acut

Hepatitis B with Lo

of HBsAb HBsAg + (may clear) – + +– – Anti-HBs – + – –+ – Anti-HBc IgM

+

(may be only marker 

during window 

period)

– – –– –

Anti-HBc + + + +– +

(also termed 

“isolated HBcAb+”)

HBeAg + – + –– –Anti-HBe – +

(in some cases)

– +– +

(in some cases)

DNA (PCR if required)

+ – + +– –

(in rare cases may be +

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PRIMARY CARE OF VETERANS WITH HIV 19

HCV Diagnostic Tests and Interpretation Acute Hepatitis C Spontaneously Resolved or Successfully Treated Hepatitis C Chronic Hepatitis C Low-Level Chronic Hepatitis C False-Positiv

Hepatitis C Anti-HCV – or + + + ++ HCV RIBA – or + + + + – HCV RNA Quantitative + – + –– HCV RNA Qualitative + (may be only marker during window period) – + +– HCV Genotype + – + + or – –

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LIVER DISEASE AND CIRRHOSIS

192 PRIMARY CARE OF VETERANS WITH HIV

Defi nitions:

Compensated cirrhosis: Cirrhosis is present but patient is without any specifi c clinical complication of cirrhosis.

Decompensated cirrhosis: Patient develops at least 1 complication of cirrhosis, such as ascites, jaundice, encephalopathy, or variceal hemorrhage.

Signs/Symptoms of Cirrhotic 

Decompensation Causes

Upper GI bleeding Variceal hemorrhage

Confusion Encephalopathy

Abdominal distention Ascites

Edema Hypoalbuminemia

Leg and muscle cramps Reduced circulating plasma volume

Jaundice Hyperbilirubinemia (liver insuffi ciency)

Dyspnea Pleural effusion (hydrothorax), 

hepatopulmonary syndrome

Diagnostic Tests for Cirrhosis 

Liver biopsy (“gold standard”): histological diagnosis made by liver biopsy 

or at autopsy.

Alternatives to liver biopsy: 

■ Diagnosis can be made clinically, using available clinical and laboratory data 

but without obtaining a liver biopsy. 

■ Diagnosis may be made radiologically.

Potential Laboratory Findings in Patients with Cirrhosis

Indicators of liver insuffi ciency

↑ Bilirubin 

↑ Prothrombin time or INR

↓ Albumin

Indicators of portal hypertension

↓ Platelets (earliest fi nding)

↓ Leukocytes and neutrophils

↑ Globulins 

Role of abdominal imaging in liver disease 

■ Radiological imaging can sometimes detect fi ndings of cirrhosis and may obviate the need for liver biopsy. Findings that suggest the presence of cirrhosis 

include: 

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PRIMARY CARE OF VETERANS WITH HIV 19

• Surface nodularity, increased echogenicity of liver

• Splenomegaly

• Ascites

• Collateral veins (the most important fi nding indicative of cirrhosis)

• (See Management of Complications of Cirrhosis and Chronic 

Liver Disease, p. 195)

■ The major use of abdominal imaging is for detecting complications of cirrhosis (eg, ascites, HCC, and hepatic or portal vein thrombosis) in cirrhotic 

patients.

■ In patients with chronic liver disease but without cirrhosis, abdominal imaging 

can be completely normal or can show fatty liver, a nonspecifi c fi nding.

■ Useful radiology studies include abdominal ultrasound, abdominal CT scan, 

and abdominal MRI.

Staging and Classifi cation of Cirrhosis

Child-Turcotte-Pugh Score

■ Originally developed to estimate the risk of death after portacaval shunt 

surgery; this modifi ed version was intended to assess the risk of nonshunt 

operations.

■ The score is determined by assessing clinical (subjective) complications of cirrhosis and laboratory (objective) abnormalities indicative of liver dysfunction.

Child-Turcotte-Pugh Classifi cation of Liver Disease

Points Assigned

Parameter 1 2 3

Ascites Absent Slight (or diuretic 

responsive)

Moderate/Tense (or 

refractory to diuretics)

Encephalopathy None Grade 1-2 (or 

precipitant induced)

Grade 3-4 (or chronic)

Bilirubin (mg/dL) <2 2-3 >3

Albumin (mg/dL) >3.5 2.8-3.5 <2.8

Prothrombin 

time (seconds 

over control) or 

INR

PT: 1-3

or

INR: <1.7

PT: 4-6

or

INR: 1.7-2.3

PT: >6

or

INR: >2.3

Grade A = Total score 5-6

Grade B = Total score 7-9

Grade C = Total score 10-15

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LIVER DISEASE AND CIRRHOSIS

194 PRIMARY CARE OF VETERANS WITH HIV

■ The MELD score is a newer method for predicting 3-month survival. It is 

used for liver allocation (transplant) by the United Network for Organ Sharing (UNOS) and has been adopted for use in the nontransplant setting.

■ It is used to determine how urgently a patient needs a liver transplant within 

the coming 3 months.

■ It is the strongest predictor of mortality in HIV-infected patients with ESLD.

• Used for patients ≥12 years of age 

• Expressed on a numerical scale, ranging from 6 to 40

• Computed using 3 routine laboratory test results: bilirubin, INR, and 

CrCl:

MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum 

creatinine (mg/dL)] + 6.43

A calculator for determining MELD scores is available on the Mayo Clinic 

website: http://www.mayoclinic.org/meld/mayomodel6.html

• HCC and other complications of cirrhosis are ascribed additional MELD 

points.

 MANAGEMENT

Goals: prevention of further liver damage, slowing progression of liver disease, 

management of cirrhotic complications

Prevention of further insults to the liver:

■ HAV vaccination

■ HBV vaccination

■ Pneumococcus vaccination

■ Infl uenza vaccination

■ Avoid or minimize hepatotoxic drugs

■ Maintain normal BMI (avoid obesity)

■ For hepatically metabolized drugs, adjust dosages according to package insert 

instructions

Slow progression of liver disease:

■ Abstinence from alcohol use for all, regardless of underlying disease process: 

counsel or refer for treatment, as appropriate (see Alcohol Misuse, p. 3)

■ Avoidance of hepatotoxic or nephrotoxic medications (eg, NVP, ddI, NSAIDs, 

aminoglycosides)

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PRIMARY CARE OF VETERANS WITH HIV 19

slow progression of HBV and HCV

■ Treatment of chronic HCV, if eligible: pegylated interferon-alfa in combination 

with ribavirin

■ Treatment of chronic HBV, if eligible: currently FDA-approved medications for 

treatment of HBV include 3TC, TDF, telbivudine, entecavir, adefovir, and pegylated interferon-alfa. Another ARV, FTC, is also active against HBV, but is not 

approved for treatment of HBV.

• It is very important to note that, when using HBV antiviral agents that 

are also active against HIV (eg, 3TC, FTC, TDF, or entecavir) in a patient 

coinfected with HIV and HBV, these agents should not be used as monotherapy. In coinfected patients, the HBV medications must be used as 

combination therapy within a multidrug, fully suppressive HIV regimen to 

avoid development of HIV resistance. 

■ Treatment of autoimmune hepatitis: can include prednisone or immunosuppressive agents

Management of Complications of Cirrhosis and Chronic Liver Disease

Detection, Prevention, Treatment

(Note: Patients with cirrhosis are best managed in collaboration with a GI specialist, particularly those with severe or recurrent complications. A summary of 

VA Hepatitis C Resource Center recommendations on management of cirrhosis 

can be found at http://www.hepatitis.va.gov/doc/va01-pr/prtop08/prtop08-01-

quicknotes.doc.) 

Ascites

Overview:

• The most common complication of cirrhosis

• 30% of patients with compensated cirrhosis develop ascites within 5 years

• 2-year survival rate of patients with ascites is 50% 

Primary prophylaxis: none recommended, other a than low-salt diet (1-2 g 

Na/day); may liberalize salt intake if salt restriction results in poor food intake

Treatment: Diuretics (eg, spironolactone alone or together with furosemide) 

• Start with spironolactone 50-100 mg daily, then add furosemide 20-40 mg 

daily and sequentially increase as necessary and tolerated to maximum 

dosage of spironolactone 400 mg daily and furosemide 160 mg daily

• Avoid NSAIDs because of risk of hepatorenal syndrome

• Patients with massive ascites may require therapeutic large-volume paracenteses, often with albumin supplementation; should be treated in consultation 

with a GI/hepatology specialist

• Refractory ascites may require placement of a transjugular intrahepatic 

portosystemic shunt (TIPS)

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LIVER DISEASE AND CIRRHOSIS

196 PRIMARY CARE OF VETERANS WITH HIV

p()

Overview:

• Bacterial infection of ascitic fl uid that occurs in the absence of an intraabdominal source of infection 

• Diagnosis: Polymorphonuclear leukocyte (PMN) count of >250 cells/μL in the 

ascitic fl uid, obtained via paracentesis

• Patients may be asymptomatic, may have very subtle clinical fi ndings, or may 

have fever, abdominal pain, and altered mental status

Primary prophylaxis: Fluoroquinolone may be initiated in the hospitalized patient 

with severe liver disease and renal dysfunction 

Treatment: Third-generation cephalosporin, ampicillin/sulbactam, or fl uoroquinolone, given IV for initial occurrence; avoid aminoglycosides

Secondary prophylaxis: Fluoroquinolone or TMP-SMX

Variceal Hemorrhage/GI Bleeding

Overview:

• ~25% of patients with cirrhosis and varices experience hemorrhage from 

gastroesophageal varices in the fi rst year after diagnosis

• The bleeding-related mortality is around 30%

Screening: Upper endoscopy (EGD) is recommended for every patient with 

cirrhosis

Primary prophylaxis: Nonselective beta-blockers or endoscopic variceal ligation 

are recommended for prophylaxis in patients with medium or large varices, to prevent the fi rst episode of variceal hemorrhage

• Recommendation: Propranolol; start 10-20 mg PO BID, increase as tolerated 

(goal is to titrate to a heart rate of 50-60 bpm, if tolerable)

• Starting beta-blockers is not recommended unless varices have been 

documented

Treatment: When a variceal bleed occurs, immediate hospitalization and GI consultation are needed for treatment

Secondary prophylaxis: After a variceal bleed, the combination of nonselective 

beta-blockers and endoscopic variceal ligation are recommended to decrease the 

risk of another bleed

Hepatic Encephalopathy

Overview:

• Variable abnormalities of neurological and psychiatric function, including 

insomnia, hypersomnia, irritability, confusion, disorientation, hyperactive deep 

tendon refl exes, and asterixis

• Diagnosis: Based on clinical picture rather than laboratory or imaging results

Primary prophylaxis: None

Treatment: Mainly consists of identifi cation and treatment of precipitating factors 

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PRIMARY CARE OF VETERANS WITH HIV 19

• Lactulose: start at 30 cc PO every 1-2 hours until bowel evacuation, titrate to 

2-3 soft bowel movements per day, but avoid diarrhea as it will lead to volume 

depletion and dehydration 

• Rifaximin: 400 mg PO TID is an alternative for patients who cannot tolerate 

lactulose

Secondary prophylaxis: None; once precipitating factors are eliminated, lactulose 

can be discontinued; in patients with chronic encephalopathy, chronic treatment with 

lactulose is warranted 

• Sedatives and tranquilizers should not be used 

• Constipation should be avoided

Hepatocellular Carcinoma (HCC)

Overview:

• Incidence varies widely according to geographic location, as well as among 

various ethnic groups within the same country

• In the United States, the incidence of HCC is rising and has almost doubled 

during the past 2-3 decades, chiefl y among patients with cirrhosis secondary 

to HCV; in the VHA, the number of HCC cases nearly doubled between 2004 

and 2007

• A study of 384 patients with HCV and compensated cirrhosis found that 1.4% 

per year developed HCC 

• 20-56% of patients who develop HCC have previously undiagnosed cirrhosis

• In chronic HBV, HCC can occur before the development of cirrhosis, but 

in other chronic liver diseases, HCC typically does not occur until there is 

cirrhosis

Risk factors:

• Age 

• Duration of liver disease

• Male sex

• HBV (can occur in patients with inactive, carrier HBV [HBsAg+, normal 

ALT, undetectable or low-level HBV DNA] and in those with chronic HBV 

[HBsAg+, elevated ALT, high HBV DNA])

• Chronic HCV with cirrhosis 

• Hereditary hemochromatosis with cirrhosis, alcoholic cirrhosis

• Cirrhosis of almost any other cause

Screening: See below

Treatment: Potential indication for liver transplant; other treatment options 

include tumor resection, radiofrequency tumor ablation, transarterial chemoembolization, or chemotherapy; refer to Hepatology or Oncology

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LIVER DISEASE AND CIRRHOSIS

198 PRIMARY CARE OF VETERANS WITH HIV

SCREENING

Screening for Hepatocellular Carcinoma

(based on American Association for the Study of Liver Diseases [AASLD] 2005 

guidelines for screening of HCC) 

Patients who should be screened for HCC:

(Note that some patients with chronic HBV are at increased risk even in the 

absence of cirrhosis)

■ HBsAg+ Asian males ≥40 years of age

■ HBsAg+ Asian females ≥50 years of age

■ HBsAg+ and cirrhosis of any gender/age

■ HBsAg+ Africans ≥20 years of age

■ HBsAg+ with a family history of HCC

■ Cirrhosis resulting from alcohol use

■ Cirrhosis resulting from HCV

■ Cirrhosis resulting from hemochromatosis

■ Cirrhosis resulting from primary biliary cirrhosis

■ Patients on transplant waiting list

■ Patients with cirrhosis resulting from NAFLD, autoimmune hepatitis, or 

alpha-1 antitrypsin defi ciency: few data, no recommendations 

Recommended technique and time intervals for HCC screening 

■ Surveillance should be performed every 6-12 months using ultrasound. 

Because ultrasound is particularly operator dependent, some centers 

where ultrasound reliability is low may choose to use either CT or MRI for 

surveillance imaging.

■ Alpha-fetoprotein (AFP) should not be used alone as a screening 

tool for HCC unless ultrasound is not available: it has poor sensitivity and 

specifi city. 

• AFP measurement is recommended if a focal hepatic mass is detected 

with ultrasound or other abdominal imaging.

• AFP level does not correlate well with other clinical features of HCC, 

such as size, stage, or prognosis.

• Based on a systematic review, with a cutoff of 20 mcg/L, AFP has 

sensitivity of 41-65% and specifi city of 80-94%.

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PRIMARY CARE OF VETERANS WITH HIV 19

■ For a mass <1 cm in diameter found on ultrasound in a cirrhotic liver: repeat 

ultrasound in 3-4 months to look for stability versus a change in size.

■ For a mass ≥1 cm in diameter found on ultrasound in a cirrhotic liver: CT 

scan with dynamic vascular imaging.

■ For evaluation, see Figure 1 below.

Figure 1. AASLD algorithm for evaluation of liver mass found on 

screening ultrasound

Mass on surveillance 

ultrasound in a cirrhotic liver

<1 cm 1-2 cm >1 cm

Repeat US at 3-4 

month intervals

Return to standard 

surveillance protocol 

(6-12 monthly)

Coincidental 

typical vascular 

pattern on 

dynamic imaging

Stable over 

18-24 

months

Diagnostic 

of HCC

Nondiagnostic

Repeat biopsy or 

imaging follow-up

Change in 

size/profile

Repeat imaging 

and/or biopsy

Other 

diagnosis

Atypical 

vascular pattern 

with both 

techniques

Typical vascular 

pattern on 

dynamic imaging 

or AFP >200 

ng/mL

Atypical 

vascular 

pattern

Typical vascular 

pattern with 

one technique

Two dynamic 

imaging studies

One dynamic 

imaging technique

Biopsy

Enlarging

Positive Negative

Treat as hepatocellular carcinoma

Source: Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of 

Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005 Nov;42(5):1208-36. 

Reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.

Proceed 

according to 

lesion size

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LIVER DISEASE AND CIRRHOSIS

200 PRIMARY CARE OF VETERANS WITH HIV

Note: Current information on VA transplantation policy and procedures can be 

found at the website for the VA National Transplant Program at www.va.gov/

transplant. Resources for providers can be found at http://www.hepatitis.va.gov/

vahep?page=prtop08-03-rr.

Background

■ Chronic hepatitis C with progression to ESLD or HCC is the most common 

reason for liver transplantation, both within the VA system and in the United 

States general patient population.

■ VA patients may be referred for liver transplantation within the VA system or 

at affi liated academic medical centers.

■ Currently, approximately 100 liver transplants are performed annually within 

the VA system, with survival rates that meet or exceed UNOS averages.

■ HIV-infected patients are eligible for consideration for liver transplantation at 

selected VA transplant centers.

■ Referral for liver transplantation involves submission of a transplantation 

package to the VA Central Offi ce; if approved, the package is forwarded to 

one of the national VA liver transplant centers for further evaluation.

■ For HIV-infected transplant candidates, the application package must contain 

an infectious disease evaluation using a template specifi ed by the VA National 

Transplant Program.

■ In cases of fulminant hepatic failure or other critical situations, emergency 

applications may be made by contacting the VA National Transplant Program.

Transplant referral

■ The local VA Medical Center Transplant Referral Coordinator should be consulted as soon as referral for liver transplantation is under consideration.

■ Update Child-Turcotte-Pugh and MELD scores regularly. For purposes of 

ESLD follow-up, patients should be seen as follows based on MELD scores 

(note: other factors may indicate more frequent follow-up): 

• ≤10: at least every 6-12 months

• 11-18: at least every 3 months

• 19-24: at least every month

• ≥25: at least every week

■ Refer for transplant evaluation if:

• Child-Turcotte-Pugh score is ≥7 or MELD score is ≥15

• MELD score is 11-13 and patient has refractory ascites or 

hyponatremia

• Meets HCC criteria for transplantation (≤3 masses, all ≤3 cm in diameter; WHO performance status <3; Child-Turcotte-Pugh score ≤9)

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PRIMARY CARE OF VETERANS WITH HIV 20

substance use of any kind, or <6 months’ sobriety, is the most common 

reason for rejection or deferral of patients for listing for transplantation; 

see Alcohol Misuse, p. 3; Substance Use, p. 69; and Smoking Cessation

p. 53.

■ Patients also must have documented adequate social support for care during 

the peritransplant and posttransplant periods.

Posttransplant care

■ Patients who have received liver transplants (whether inside or outside the 

VA system) will return to the referring VA Medical Center for care.

■ 1-year survival rates are typically >80%.

■ The major clinical issues in the posttransplant period are management of 

and toxicities from immunosuppressive agents required to prevent 

transplant rejection, drug interactions, and infectious complications of 

immunosuppression.

■ See http://www.hepatitis.va.gov/vahep?page=prtop08-03-cs-01#S7X for more 

information on posttransplant care.

REFERENCES

Bruix J, Sherman M; Practice Guidelines Committee, American Association for the 

Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005 

Nov;42(5):1208-36. 

Castellares C, Barreiro P, Martín-Carbonero L, et al. Liver cirrhosis in HIV-infected 

patients: prevalence, aetiology and clinical outcome. J Viral Hepat. 2008 Mar;15(3):165-72.

Galvan FH, Bing EG, Fleishman JA, et al. The prevalence of alcohol consumption and heavy 

drinking among people with HIV in the United States: results from the HIV Cost and 

Services Utilization Study. J Stud Alcohol. 2002 Mar;63(2):179-86.

Hooshyar D, Hanson DL, Wolfe M, et al. Trends in perimortal conditions and mortality 

rates among HIV-infected patients. AIDS. 2007 Oct 1;21(15):2093-100.

Merriman RB. Nonalcoholic fatty liver disease and HIV infection. Curr HIV/AIDS Rep. 

2006 Sep;3(3):113-7.

Rockstroh JK. Infl uence of viral hepatitis on HIV infection. J Hepatol. 2006;44(1 Suppl):S25-7

Sterling RK, Chiu S, Snider K, et al. The prevalence and risk factors for abnormal liver 

enzymes in HIV-positive patients without hepatitis B or C coinfections. Dig Dis Sci. 2008 

May;53(5):1375-82.

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/26/09 
PRIMARY CARE OF VETERANS WITH HIV 20

Osteoarthritis

KEY POINTS

■ Osteoarthritis (OA) is a joint disorder caused by the progressive 

breakdown and eventual loss of cartilage of one or more joints.

■ Typical symptoms include joint pain exacerbated by activity and 

relieved by rest, morning stiffness, or stiffness after periods of 

inactivity.

■ Evaluation of OA includes plain X rays; distinction from other 

arthritides may include ESR and rheumatoid factor (RF) 

determinations and synovial fl uid examination to rule out infection 

or crystal disease.

■ The goals of treatment are pain reduction, improvement of joint 

mobility, and prevention of functional impairment.

■ All patients should receive nonpharmacologic interventions, 

including weight loss counseling as indicated. Pharmacologic 

interventions should start with the lowest-risk intervention for 

the level of impairment (acetaminophen, NSAIDs, or injections) 

and proceed along the analgesic ladder and levels of intervention 

(opioids, arthroscopy, or other surgical procedures). 

BACKGROUND

OA is the most common form of arthritis 

in the United States. Risk factors include 

age, obesity, and history of joint trauma. 

Recreational running does not increase 

the risk of developing OA.

Defi nitions and Classifi cation

■ OA (also called degenerative joint disease) is a disorder caused by the 

progressive breakdown and eventual loss of cartilage of ≥1 joints. OA usually 

affects weight-bearing joints.

■ OA can be idiopathic or secondary:

• Idiopathic OA does not have a specifi c inciting cause, and typically 

involves the hands, feet, knees, hips, or spine.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Veterans with HIV*

Osteoarthritis: 14%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition

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OSTEOARTHRITIS

204 PRIMARY CARE OF VETERANS WITH HIV

trauma, calcium pyrophosphate dehydrate deposition disease (CPPD), or 

other bone or joint disorders such as osteonecrosis, rheumatoid arthritis, gout, septic arthritis, or Paget disease. This form of OA can present 

with atypical joint involvement.

■ Treatment of OA depends on whether it is noninfl ammatory or infl ammatory. Symptoms of infl ammatory OA include swelling, morning stiffness 

lasting >30 minutes, and night pain.

Diagnostic criteria for OA depend on the joint affected:

■ Knee osteoarthritis = knee pain + ≥3 of the following:

1. Age >50

2. Morning stiffness for <30 minutes

3. Crepitus on active motion of the knee (see Evaluation below)

4. Bony tenderness

5. Bony enlargement

6. No palpable warmth

• Other characteristics that add to the accuracy of the diagnosis: ESR <40 

mm/hour, RF <1:40, synovial fl uid with clear fl uid and white blood cell 

(WBC) count of <2,000 cells/μL, and X rays showing osteophytes

■ Hand osteoarthritis = hand pain + ≥3 of the following:

1. Bony enlargement of ≥2 of the following joints: 2nd or 3rd distal interphalangeal (DIP) joint or proximal interphalangeal (PIP) joint, 1st carpometacarpal (CMC, base of thumbs) of either hand

2. Bony enlargement of ≥2 DIP joints

3. Swelling of <3 metacarpophalangeal (MCP) joints

4. Deformity of at least 1 of the joints listed in #1

■ Hip osteoarthritis = hip pain and ≥2 of the following:

1. ESR <20 mm/hour

2. Femoral or acetabular osteophytes on radiography

3. Joint space narrowing on radiography

• Other characteristics that add to the accuracy of the diagnosis: 

internal rotation of <15o, pain on internal rotation, morning stiffness, 

fl exion <115o

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PRIMARY CARE OF VETERANS WITH HIV 20

EVALUATION

Risk factors • Age >40 years

• Obesity

History Ask about history of:

• Trauma

• CPPD

• Osteonecrosis

• Rheumatoid arthritis

• Gout

• Septic arthritis

• Paget disease

• Reactive arthritis

Differential 

diagnosis

(Partial. Note 

that these may 

be superimposed on OA.)

• Typically affects knees, wrists, MCP joints, hips; check CPPD:

synovial fl uid.

• Typically affects great toes, ankles, knees, wrists; acute onset Gout:

with intense swelling and pain; check synovial fl uid.

• MCP and PIP joint involvement typically Rheumatoid arthritis:

prominent; stiffness is worse after resting the joint; check RF.

• typically affects a single Infectious monoarticular disease:

joint; check synovial fl uid. Common organisms include Staphylococcus aureus, Streptococcus organisms, Neisseria gonorrhoeae, Borrelia 

burgdorferi. In immunocompromised patients, etiologies include 

gram-negative bacteria, mycobacteria, fungi, and mycoplasma. 

• Typically Osteonecrosis or avascular necrosis (AVN):

involves the femoral or humeral heads; patients with HIV are at 

increased risk of AVN (4% of HIV-infected patients had AVN in 

one study). Patients typically present with pain, particularly with 

weight-bearing and motion. Groin pain is seen with femoral head 

involvement, shoulder pain with humeral head involvement. AVN 

has been associated with corticosteroids, testosterone, statins, 

weight training, alcohol consumption, tobacco smoking, and presence of anticardiolipin antibodies. Magnetic resonance imaging 

(MRI) is the most sensitive test for early diagnosis; plain X rays will 

show changes after months to 5 years from onset.

• Frequently secondary to trauma; does not limit motion Bursitis:

unless joint is involved. Most common sites include prepatellar, 

olecranon, trochanteric, and bursae. Consider bursal fl uid aspiration to rule out infection.

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OSTEOARTHRITIS

206 PRIMARY CARE OF VETERANS WITH HIV

ypJpy y y 

• Morning stiffness or stiffness after periods of inactivity

• Advanced disease: pain may be present with progressively less 

activity, eventually during rest and at night

• Episodic fl ares: increases in pain and infl ammation that may result 

from crystal disease 

Physical 

examination

Examination with particular attention to joints:

• Tenderness on palpation, usually without warmth or signifi cant 

erythema

• Effusions occasionally present

• Crepitus: disruption of normally smooth surfaces of joints

[Place hand on a joint, ask the patient to move that joint. If crepitus is present, bumps and cracks will be felt.]

• Osteophytes: palpable bony enlargements along the joint 

periphery 

Typical joints affected:

• DIP and PIP with Heberden nodes (bony enlargements) Hands:

• especially the great toe Feet:

• osteophytes, effusions, crepitus, limited range of motion Knees:

• pain and limited range of motion Hips:

• C5, T8, L3; can lead to spondylosis (osteophytes from the Spine:

vertebral body impinging on the spinal canal)

• anterior shoulder pain at the glenohumeral joint Shoulders:

Imaging • Obtain plain X rays for patients with suspected OA

• Radiographic changes in OA are insensitive in early disease and 

correlate poorly with symptoms; however, the following changes 

are fairly specifi c and make further imaging unnecessary:

• Joint space narrowing

• Osteophytes

• Subchondral sclerosis

• Subchondral cysts 

• Consider MRI of the knee in patients with knee locking, popping, 

or instability suggestive of meniscal or ligamentous damage (can 

be treated surgically).

• Consider MRI if trying to rule out AVN

Diagnostic 

testing

• Joint aspiration: When the patient has a joint with signifi cant effusion or presence of warmth and erythema, obtain synovial fl uid 

for examination (refer to Rheumatology or Orthopedic Surgery if 

needed). Request cell count, crystal analysis, Gram stain, and culture. In OA, the synovial fl uid typically has mild pleocytosis, normal 

viscosity, and modestly elevated protein. 

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PRIMARY CARE OF VETERANS WITH HIV 20

py y(

cells/μL and polymorphonuclear leukocytes [PMNs] >75% but 

no crystals and a negative culture), consider checking ESR (or 

C-reactive protein [CRP]), RF, and anti-cyclic citrullinated peptide 

(CCP) antibodies. Positive results can suggest a diagnosis of rheumatic disorder. 

Diagnostic 

criteria

See diagnostic criteria above for specifi c joints.

 MANAGEMENT

■ The goals of treatment are pain reduction, improvement of joint mobility, and 

prevention of functional impairment.

■ All patients with OA should receive nonpharmacologic interventions in addition to analgesics, as indicated. Depending on noninfl ammatory vs infl ammatory OA, advance up the analgesic and intervention “ladder”: 

• acetaminophen or NSAIDs +/– adjuvants →

• weak opioids +/– adjuvants →

• strong opioids +/– adjuvants.

■ Obesity is the most important modifi able contributor to OA; all overweight 

patients should be encouraged to lose weight.

Intervention Comments

Nonpharmacologic

• Weight-loss programs as indicated

• For acute fl ares, short periods of rest only (12-24 

hours), followed by passive joint exercises

• Range of motion and strengthening exercises that target 

weak muscle groups

• Exercise programs involving exercises such as swimming, 

biking, walking, yoga, and tai chi 

• Knee OA: simple elastic sleeve brace or wedged shoe 

insoles to help reduce joint impact

• Psychoeducation and cognitive-behavioral therapy (CBT) 

coping skills training

Pharmacologic 

(for dosages and additional information, see Pain Medications, p. 321)

Capsaicin • Topical medication, for noninfl ammatory and 

infl ammatory OA

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OSTEOARTHRITIS

208 PRIMARY CARE OF VETERANS WITH HIV

pgy 

• Possible adverse effects: hepatotoxicity (especially 

if taken with alcohol), nephrotoxicity (with chronic 

overdose)

• Safer but less effective than NSAIDs for chronic OA

NSAIDs

(eg, ibuprofen, naproxen)

• For persistent noninfl ammatory and infl ammatory OA

• Avoid in patients with peptic ulcer disease or cirrhosis

• To minimize risks, use the lowest effective dosage and 

try to use for short periods of time

• Avoid indomethacin: associated with increased joint 

destruction

Intraarticular corticosteroid injection• For moderate, persistent symptoms

• Triamcinolone or methylprednisolone suspensions

Finger or toe joints: 10 mg

Wrists, elbows, ankles: 20 mg

Shoulder, knee, hip: 40 mg

• Refer to rheumatologist or orthopedic surgeon if expertise is not available in clinic

• Do not inject the joint if there is any suspicion of joint 

infection (clues include rapid onset of a large effusion, 

fever, leukocytosis) 

• Ensure aseptic technique

• Possible adverse effects: tendon rupture (particularly 

with undiluted glucocorticoids in the shoulder), nerve 

atrophy if glucocorticoids enter the nerve sheath, skin 

changes, iatrogenic infection (rare) 

• Can repeat every 3 months for up to 2 years if effective

• Hip injections are technically diffi cult and should be 

done under fl uoroscopic guidance by a rheumatologist, 

orthopedist, or interventional radiologist

Colchicine • Consider for patients with refractory infl ammatory OA: 

many have calcium pyrophosphate crystals in the synovial fl uid 

• Use in conjunction with NSAIDs

• Avoid use for patients with renal or hepatic disease

Opiate analgesics

Options include:

• Use opioids for patients who have pain refractory to the 

interventions listed above (nonpharmacologic, capsaicin, 

acetaminophen, ibuprofen, injections, colchicine) or who 

cannot receive those interventions 

• Start with weak opioids and assess safety, effi cacy, and 

usage; titrate up and move to stronger opioids as needed

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PRIMARY CARE OF VETERANS WITH HIV 20

(not a typical opiate; 

exact mechanism of 

action is unknown; acts 

in part as a central opioid agonist) 

Weak opioids

• Codeine

• Hydrocodone + 

acetaminophen

• Oxycodone + 

acetaminophen

Strong opioids

• Morphine 

• Oxycodone

• Hydromorphone

• Fentanyl transdermal

py y p

• Opioid therapy for chronic pain should follow a fi xeddose schedule, not PRN dosing

• Risk of dependence, overdose: monitor closely

• Chronic opioid therapy should incorporate an opioid 

use agreement that includes functional goals for outcome, not reduced pain intensity alone

• Note that tramadol 37.5 mg + acetaminophen 325 mg 

has shown pain relief equivalent to codeine 30 mg + 

acetaminophen 325 mg but with fewer adverse effects 

(major adverse effect: headache)

Surgical 

Arthroscopic irrigation or debridement• For moderate persistent symptoms

• Referral to an orthopedic surgeon

• Irrigation with sterile saline

• Suction of debris and blood

• Removal of fl oating cartilage

• Debridement of excess tissue or bone

• Repair of tears as needed and to extent possible

Arthroscopic 

synovectomy 

• For infl ammatory OA with profound impairment

• Referral to an orthopedic surgeon

• Arthroscopic removal of involved synovial tissue

Major surgical 

procedure 

• For end-stage OA, profound impairment

• Referral to an orthopedic surgeon

• Includes total joint replacement

REFERENCES

Altman R, Asch E, Bloch D, et al. Development of criteria for the classifi cation and report

ing of osteoarthritis. Classifi cation of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 

Aug;29(8):1039-49.

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OSTEOARTHRITIS

210 PRIMARY CARE OF VETERANS WITH HIV

2000 update. American College of Rheumatology Subcommittee on Osteoarthritis 

Guidelines. Arthritis Rheum. 2000 Sep;43(9):1905-15. Available at http://www.

rheumatology.org/publications/guidelines/oa-mgmt/oa-mgmt.asp. Accessed August 14, 

2008.

World Health Organization. Treatment and Care of Injecting Drug Users; Module 10: Managing Pain in HIV-Infected Injecting Drug Users, 2007. Jakarta: ASEAN Secretariat; 2007. 

Available at www.searo.who.int/LinkFiles/Publications_Module_10_Treatment_&_Care_

for_HIV_positive_IDUs.pdf. Accessed August 14, 2008. [Page 13 has useful charts on the 

WHO analgesic ladder and equivalent opiate doses.]

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PRIMARY CARE OF VETERANS WITH HIV 21

Renal Disease

KEY POINTS

■ At the time of HIV diagnosis, all patients should be screened for 

renal dysfunction with a urinalysis (UA) and a calculated estimate of 

renal function.

■ Elevated risk of developing kidney disease: African American race, 

hypertension, diabetes, family history, CD4 count <200 cells/μL, 

unsuppressed viral load, hepatitis C virus (HCV) infection. Persons 

meeting any of these criteria should be screened annually.

■ Chronic kidney disease (CKD) increases the risk of developing 

cardiovascular disease.

■ Acute renal failure (ARF) usually is attributable to prerenal causes 

or medication toxicity leading to acute tubular necrosis (ATN) (see 

Table 5).

■ Patients with CKD should be referred to a nephrologist for 

evaluation and possible renal biopsy.

■ HIV-infected persons with CKD are less likely to receive ART, even 

when ART is indicated.

■ HIV-associated nephropathy (HIVAN) is an indication to start ART.

■ Dosage of most NRTIs should be adjusted for impaired renal 

function (see Table 4). 

BACKGROUND

■ There is a high prevalence (30%) 

of abnormal renal function among 

patients with HIV disease. 

■ CKD is increasingly a cause of morbidity among people with HIV infection.

■ Risk factors for CKD include African 

American race, hypertension, diabetes, 

family history of CKD, CD4 count 

<200 cells/μL, unsuppressed viral load, and HCV infection.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Veterans with HIV*

Renal failure, acute: 7%

Renal failure, chronic: 6% 

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 with an ICD-9 

code corresponding to these conditions

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RENAL DISEASE

212 PRIMARY CARE OF VETERANS WITH HIV

and family history of CKD. Prevalence of HIVAN is 3.5% among HIV-infected 

African American patients.

■ African Americans are disproportionately affected by kidney disease.

■ HIV-infected persons with CKD are less likely to receive ART, even when ART 

is indicated.

■ ART should be given to patients with renal disease, if indicated, though most 

NRTIs must be dosed according to renal function and some ARVs should be 

avoided (see Table 4 and Table 5).

SCREENING

■ All HIV-infected patients should be screened for kidney disease at the 

time of HIV diagnosis or entry into care. 

■ Patients with additional risk factors or exposure to nephrotoxic medications should be screened annually.

■ Individuals without risk factors may be rescreened based on clinical signs 

and symptoms.

■ Screening tests: calculated estimate of renal function, UA, and quantitative 

spot measurement of proteinuria.

■ If screening shows creatinine clearance (CrCl) or estimated GFR (eGFR) 

<60 mL/min/1.73 m2,or proteinuria ≥1+ on urine dipstick analysis, calculate spot urine albumin-to-Cr ratio or spot urinary protein-to-Cr 

(described below), obtain renal ultrasound to look for anatomic abnormalities (including size), and refer to nephrologist for management and 

possible biopsy. 

1. Estimate renal function:

• The fi rst evidence of renal dysfunction may be an elevated serum Cr 

(SCr) level. Increases in SCr from baseline should prompt an evaluation.

• In many patients, SCr may not be an accurate measure of renal function:

May be deceptively low in the elderly and persons with low muscle mass _

May be deceptively high in African Americans and persons with high _

muscle mass

• A calculated estimate of renal function is a better measure because it 

corrects for these variations.

• The simplifi ed Modifi cation of Diet in Renal Disease (MDRD) 

Study equation for eGFR is thought to yield a more accurate estimate 

of renal function than the Cockcroft-Gault equation, which measures 

CrCl, a proxy for GFR.

• CrCl typically is used to determine medication dosage adjustments in 

patients with renal insuffi ciency.

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PRIMARY CARE OF VETERANS WITH HIV 21

Simplifi ed MDRD Equation for Estimating Renal Function

GFR (mL/min/1.73 m2) 186  [serum creatinine (mg/dL)]–1.154 

[age (years)]–0.203  [0.742 if female]  [1.212 if African American]

Normal GFR: ≥90 mL/min/1.73 m2

CKD: GFR <60 mL/min/1.73 m2

Online calculator available at:

http://www.nkdep.nih.gov/professionals/gfr_calculators/orig_con.htm

2. Perform urinalysis (dipstick or formal); look especially for proteinuria 

and hematuria (see Urology, p. 227, for evaluation of isolated hematuria).

Table 1. Dipstick Interpretation in Setting of Abnormal eGFR

Protein Blood Consider

Negative Negative False negative

Microalbuminuria (see below), multiple myeloma and 

other paraproteinemias, prerenal causes (see Table 3), 

postrenal causes (see Table 3), ischemic nephropathy

Positive Negative False positive 

Benign or orthostatic proteinuria, hypertension, nephrosclerosis, diabetes, tubulointerstitial diseases, polycystic 

kidney disease (PCKD), nephrotic syndrome, glomerulonephritis (GN)

Positive Positive UTI, pyelonephritis, rapidly progressive GN, other GN, 

HIV-associated vasculitis, pulmonary-kidney syndrome, 

hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, malignant hypertension, nephrotic syndrome, nephrolithiasis with obstruction, atypical diabetes, 

PCKD

3. Quantitate proteinuria:

• Evaluate patients with ≥1+ protein on dipstick or GFR <60 mL/min/1.73 m2

• Dipstick UA is insensitive for microalbuminuria (albuminuria below level 

detected by conventional dipsticks).

• Microalbuminuria may be the fi rst indication of renal dysfunction; if 

detected, treatment to slow progression of renal disease should be 

started (see below).

• Timed (ie, 24-hour) collections have largely been replaced by:

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RENAL DISEASE

214 PRIMARY CARE OF VETERANS WITH HIV

 AlbuminUrine [mg/dL] / CrUrine [mg/dL] 

 Highly sensitive for microalbuminuria; normal is <0.03. 

Should be used at initial screening and for follow-up, if 

microalbuminuria is diagnosed. 

2. The random urinary protein-to-Cr ratio:

ProteinUrine [mg/dL] / CrUrine [mg/dL] 

 Highly sensitive for proteinuria, but not for microalbuminuria; normal is <0.15. 

Used to estimate 24-hour urine protein excretion (the 

ratio corresponds to grams of urinary protein excreted per 

24 hours; eg, ratio of 0.15 corresponds to 0.15 g [150 mg] 

of proteinuria per 24 hours). Can be used to grade degree 

of proteinuria (see box below); can be monitored over time.

 Note: these estimates may be inaccurate in muscular or 

cachectic patients.

Degree of Proteinuria Based on Spot Urinary Protein-to-Cr Ratio

Normal:

Trace proteinuria:

Mild proteinuria:

Moderate proteinuria:

Nephrotic range proteinuria:

<150 mg/24 hours

150-500 mg/24 hours

500 mg to 1 g/24 hours

1-3 g/24 hours

>3 g/24 hours

• Patients with signifi cant proteinuria should be referred for further 

evaluation

Types of Proteinuria

Overfl ow proteinuria: Trace or negative dipstick protein but disproportionately 

larger amount on 24-hour test. Suggests light-chain disease, paraproteinemia, lymphoproliferative process, or hemolysis (if dipstick is also positive for blood).

Tubular protein: 500-2,000 mg/24 hours

Differentiate from glomerular causes by UPEP +/– IEP.

• UPEP: albumin > globulin suggests glomerular proteinuria; globulin > albumin 

suggests light chains or paraproteinemia

Common causes include analgesic nephropathy, focal glomerular sclerosis (recurrent UTI, refl ux), collagen vascular diseases (Sjögren syndrome, lupus), hepatitis, 

HIVAN (see below), PCKD, heavy metal toxicity, interstitial nephritis (drugs or 

infectious), granulomatous diseases.

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PRIMARY CARE OF VETERANS WITH HIV 21

Glomerular protein, suggested by moderate to heavy proteinuria: 

Suggests a more serious disorder. Rule out HIVAN, diabetes progression, hepatitis, 

vasculitis, malignancy, GN. Signifi cant glomerular damage with proteinuria of >3 g: 

refer to nephrologist. 

Massive proteinuria: >6 g/24 hours

Focus evaluation on HIVAN, hepatitis-associated nephropathy, severe focal glomerulosclerosis. Refer to nephrologist.

Chronic Kidney Disease 

EVALUATION

■ CKD is characterized by the presence for ≥3 months of either of the 

following:

• Structural or functional kidney abnormalities, with or without decreased 

GFR, as diagnosed by abnormal pathology or abnormal markers. Markers 

can include blood or urine abnormalities (urinary protein, red blood cells

white blood cells, casts, fat) or abnormalities on imaging studies.

• GFR <60 mL/min/1.73 m2

, with or without other evidence of kidney 

damage (see simplifi ed MDRD equation, above).

■ Proteinuria and eGFR <60 mL/min/1.73 m2 are associated with increased cardiovascular disease and increased all-cause mortality.

■ Treatment of early-stage CKD in HIV-noninfected persons slows progression 

of kidney disease.

■ CKD has 5 stages, based on estimated renal function (see Table 2).

Table 2. National Kidney Foundation Stages of Chronic Kidney 

Disease (based on eGFR)

Stage Defi nition eGFR

(mL/min/1.73 m2) Recommendations

1 Kidney damage with 

normal eGFR

≥90 Treat comorbid conditions; slow progression 

of CKD; reduce cardiovascular risk factors 

2 Kidney damage with 

mildly decreased eGFR

60-89 Estimate progression 

of CKD

3 Kidney damage with moderately decreased eGFR30-59 Evaluate and treat 

complications of CKD

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RENAL DISEASE

216 PRIMARY CARE OF VETERANS WITH HIV

Evaluation of CKD

Risk factors • Diabetes

• Hypertension

• Toxic insults (including medications)

• Autoimmune disease

• HCV infection

• PCKD) Inherited kidney disease (eg, 

• HIVAN (see below)

• Chronic urinary tract obstruction

• Paraproteinemias

• ARF

History • Chronic medical problems: diabetes, hypertension, prior kidney 

disease, collagen vascular disease, hepatitis, kidney stones, prostate 

disease

• Symptoms associated with kidney disease, such as: decreased 

attentiveness, nausea, vomiting, anorexia, weight change, dyspnea, orthopnea, leg swelling, fatigue, muscle cramps, restless legs, 

peripheral neuropathy, pruritus, urinary urgency or frequency, 

nocturia, dysuria, oliguria

• Medications and over-the-counter products: NSAIDs, ACE 

inhibitors (ACEIs), angiotensin receptor blockers (ARBs), diuretics, 

analgesics, antibiotics, antiviral agents, lithium

Physical 

examination

• Height, weight

• Vital signs including orthostatic blood pressure

• Volume assessment (rales, jugular venous distention, peripheral 

edema) 

• Cardiac exam (S3, S4, heave, murmur, rub)

• Vascular exam (pulses, bruits)

• Abdominal fi ndings (mass, bruit, palpable bladder, fl ank tenderness)

• Digital rectal exam (prostate) in men

• Neurological exam, including mental status

• Integument (rash, stigmata of embolic disease or ischemia)

• Joints (arthritis)

y g

severely decreased 

eGFR

p

replacement therapy 

(RRT; dialysis)

5 Kidney failure* <15* RRT, if uremia present*

* Dialysis usually is initiated when eGFR falls below 10 mL/min/1.73 m2.

UCS-PCM-08-0701-Renal.indd 216 CS-PCM-08-0701-Renal.indd 216 3/20/09 /20/09 
PRIMARY CARE OF VETERANS WITH HIV 21

g

testing

yp

protein-to-Cr ratio, as above

• Renal ultrasound

• Basic workup for non-HIV-related causes:

• Hepatitis B and C serologies

• Cryoglobulins

• SPEP/UPEP

• Fasting blood glucose

• Complement levels

• Antinuclear antibodies and antineutrophil cytoplasmic 

antibodies

(Note: signifi cant false-positive rates in HIV-infected persons)

WHEN TO REFER

■ Refer promptly to nephrologist for possible biopsy and for directing appropriate therapy, particularly if HIVAN is suspected

■ HIVAN can progress rapidly from proteinuria to end-stage renal disease 

(ESRD), and requires biopsy for unequivocal diagnosis (see HIV-Associated 

Nephropathy, below)

■ Biopsy also can distinguish HIVAN from other HIV-related causes of CKD, 

such as immune complex disease and thrombotic angiopathy, as well as 

non-HIV-related causes of CKD

 MANAGEMENT

Goals: 

• Slow progression of CKD

• Address metabolic and hematologic abnormalities

■ Determine whether patient has signs/symptoms of ARF (see below).

■ Maintain blood pressure at ≤130/80 mmHg. 

■ Initiate ACEIs or ARBs for patients with hypertension or proteinuria (see 

Hypertension, p. 171, for dosing information).

• Closely monitor patients on ACEIs and ARBs for hyperkalemia.

■ ART: 

• Initiate or maximize effi cacy of ART if diagnosis of HIVAN is established 

(see below).

• Avoid ARVs with signifi cant renal toxicity (see below).

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RENAL DISEASE

218 PRIMARY CARE OF VETERANS WITH HIV

receptor antagonists) for renal function, as needed.

■ Avoid NSAIDs and other nephrotoxic medications. 

■ Screen for and/or maximize treatment for diabetes and dyslipidemia (see 

Diabetes, p. 127, and Dyslipidemia, p. 143).

■ Screen for and treat hematologic abnormalities (eg, anemia).

■ Advise on protein- and salt-restricted diet; refer to renal dietitian to avoid 

malnutrition.

■ Refer for substance abuse counseling, when appropriate, to decrease risk of 

nephropathy associated with use of heroin or other illicit substances.

■ Monitor renal function; consult Nephrology regarding other care.

■ Refer patients with moderate to advanced CKD for RRT (ie, dialysis) or kidney transplantation.

• Early referral and counseling for RRT improve outcomes.

• HIV-infected and HIV-uninfected ESRD patients have similar outcomes.

• Refer before Cr rises to 4 or eGFR falls below 25 mL/min.

• Refer at least 6 months before anticipated need for RRT (plot inverse of 

Cr vs time to defi ne likely rate of progression).

• Referral for transplantation may be made to the VA National Transplant 

Program (http://www.va.gov/transplant).

HIV-Associated Nephropathy

EVALUATION

■ Occurs almost exclusively in persons of African descent. Other risk factors 

include low CD4 cell count, high HIV RNA.

■ Much less common since the advent of combination ART.

■ Among African American men, between 1995 and 1999, incidence of HIVAN 

decreased whereas prevalence and survival increased, which is consistent 

with a benefi cial effect of ART on preventing and treating HIVAN. 

■ Most often presents as nephrotic syndrome, with proteinuria and decreased 

GFR. May progress rapidly to ESRD, often over the course of several weeks 

to months (especially in patients not on ART). 

■ Peripheral edema may be present. 

■ Imaging typically shows large echogenic kidneys. 

■ Biopsy shows collapsing focal segmental glomerulosclerosis with tubular and 

interstitial damage.

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PRIMARY CARE OF VETERANS WITH HIV 21

 MANAGEMENT

Goal: 

• Slow progression of HIVAN

■ All patients with HIVAN should be started on ART regardless of CD4 count.

■ Refer immediately to a nephrologist for evaluation (including biopsy) and 

possible treatment. 

■ For patients with hypertension or proteinuria, treat with ACEIs or possibly 

ARBs to reduce blood pressure to <125/75 mmHg, and to eliminate or 

decrease proteinuria as much as possible.

■ Closely monitor patients on ACEIs and ARBs for hyperkalemia.

■ Consider adding corticosteroids if renal function fails to improve on ART 

(consult with nephrologist). Recommended prednisone dosage is 1 mg/kg/day

to a maximum dosage of 80 mg/day. Treatment duration is 2 months, with a 

2-4 month taper. 

■ Refer patients with progressive disease for dialysis or transplantation.

Acute Renal Failure

EVALUATION

■ Defi nition of ARF: 

• Decrease in eGFR of ≥25% over the course of days to weeks.

■ In a prospective cohort of HIV-infected outpatients, incidence of ARF was 5.9 

cases per 100 person-years. The most common causes of ARF were a prerenal state and acute tubular necrosis (ATN). 

Risk factors • Male sex 

• HCV coinfection 

• HIV viral load of >10,000 copies/mL 

• CD4 count of <200 cells/μL

• Presence of an opportunistic infection 

• History of an AIDS diagnosis

• Current or prior ART 

■ May be asymptomatic, or may present with volume overload (dyspnea, 

orthopnea), hypertension, metabolic abnormalities, decreased urine output, 

anorexia, nausea, vomiting, or encephalopathy.

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RENAL DISEASE

220 PRIMARY CARE OF VETERANS WITH HIV

Prerenal Causes

• Hypovolemia: hemorrhage, dehydration attributable to diarrhea, vomiting, or inadequate fl uid intake

• Hypoperfusion: ischemia (septic shock, heart failure, cardiogenic shock); reduced 

oncotic pressure (hypoalbuminemia, anemia)

Intrinsic Renal Causes

• Glomerulonephritis (any type)

• ATN resulting from prolonged prerenal injury

• ATN resulting from toxins, including nephrotoxic medications: IV radiographic 

contrast dye, pentamidine, amphotericin B, foscarnet, cidofovir, high-dose acyclovir, 

aminoglycosides, TDF

• ATN resulting from rhabdomyolysis (crush injury, statins [including in association 

with PIs], fi brate derivatives, cocaine)

• Acute interstitial nephritis (AIN) resulting from medications: TMP-SMX and other 

sulfa-containing compounds, beta-lactam antibiotics, rifampin, IDV, NSAIDs, salicylates, many other medications

• AIN resulting from infection: streptococcus, cytomegalovirus (rare)

Postrenal Causes

• External obstruction: retroperitoneal masses; ureteral compression, urethral compression or blockage (eg, severe benign prostatic hypertrophy)

• Internal obstruction: crystal deposition, nephrolithiasis, clot

 MANAGEMENT

■ Assess volume status and metabolic abnormalities.

■ Provide supportive care (dialysis if necessary) and treat the underlying processes causing ARF. 

■ Dialysis is indicated for uremic pericarditis, encephalopathy, volume overload 

with pulmonary edema, hyperkalemia, or metabolic acidosis.

Selecting ARVs for Patients with Kidney Disease

■ ART generally should not be avoided because of kidney disease.

■ ART is indicated in patients with HIVAN.

■ Accumulating evidence suggests ART decreases the risk of kidney disease 

in HIV-infected patients.

■ NRTIs, except for ABC, are excreted renally; dosage should be based on 

steady-state CrCl or eGFR (see Table 4).

■ TDF has been associated with rare cases of ARF and Fanconi syndrome.

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PRIMARY CARE OF VETERANS WITH HIV 22

ypy 

patients with preexisting renal insuffi ciency (see Table 5).

■ Agents from other classes (NNRTI, PI, fusion inhibitor, integrase inhibitor, 

chemokine coreceptor antagonist) do not undergo signifi cant renal 

excretion and do not require dosage adjustment in patients with renal 

insuffi ciency. 

■ Serum levels of ATV, for unclear reasons, are substantially decreased in 

patients on hemodialysis; thus ATV should not be given to HIV treatmentexperienced patients undergoing hemodialysis.

■ IDV and (rarely) ATV have been associated with nephrolithiasis 

(see Table 5).

■ Note that other medications commonly given to HIV-infected patients may 

also cause renal dysfunction (see Table 5).

Table 4. NRTI Dosing for Patients with Decreased Renal Function 

(based on CrCl)

Drug Standard 

Dosage Adjusted Dosage/Notes

ABC 300 mg PO BID Dosage adjustment for renal insuffi ciency does not appear 

necessary 

ddI 250-400 mg PO 

QD, depending 

on weight

CrCl (mL/min) Weight ≥60 kg Weight <60 kg

≥60 400 mg QD 250 mg QD 

30-59 200 mg QD 125 mg QD 

10-29 125 mg QD 125 mg QD

<10 125 mg QD formulation not suitable 

Hemodialysis 125 mg QD formulation not suitable 

FTC 200 mg PO QD CrCl (mL/min) 

≥50 200 mg QD 

30-49 200 mg Q48H 

15-29 200 mg Q72H 

<15 200 mg Q96H 

Hemodialysis 200 mg Q96H, give after dialysis 

3TC 150 mg PO BID 

or 300 mg PO 

QD 

CrCl (mL/min) 

≥50 150 mg BID or 300 mg QD 

30-49 150 mg QD 

15-29 150 mg fi rst dose, then 100 mg QD 

5-14 150 mg fi rst dose, then 50 mg QD 

<5 50 mg fi rst dose, then 25 mg QD 

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RENAL DISEASE

222 PRIMARY CARE OF VETERANS WITH HIV

PO BID, depending on weight

>50 40 mg BID 30 mg BID 

26-50 20 mg BID 15 mg BID 

10-25 20 mg QD 15 mg QD

Hemodialysis 20 mg QD 15 mg QD

TDF 300 mg PO QD Experience in patients with CrCl <60 mL/min is limited. 

Preliminary data suggest: 

CrCl (mL/min) 

≥50 300 mg QD

30-49 300 mg Q48H

10-29 300 mg twice weekly

Hemodialysis 300 mg weekly

ZDV 300 mg PO BID CrCl (mL/min)

<15 100 mg Q6-8H

Hemodialysis 100 mg TID

Adapted from McNicholl IR, Rodriguez RA. Dosing of Antiretroviral Drugs in Adults with Renal Insuffi ciency and Hemodialysis. San Francisco: University of California San Francisco, Center for HIV Information; 2008. Available at: http://hivinsite.ucsf.edu/InSite?page=md-rr-18. Accessed November 1, 2008.

ARV and Other Medications Associated with Renal Dysfunction 

A number of medications commonly prescribed for treatment of HIV infection or opportunistic illnesses may cause acute or chronic renal disease (see 

Table 5). Some of these should be avoided in patients with renal insuffi ciency.

Table 5. Renal Adverse Effects of Medications Commonly Taken by 

HIV-Infected Persons

Drug Disorder/

Pathology Findings Comments/Suggestions

TDF TDF-associated 

renal insuffi ciency 

↑ Cr, usually 

small; slight (4% 

vs other NRTIs) 

decrease in 

eGFR over time

• Of unclear clinical signifi -

cance, but warrants monitoring of renal function.

• May be associated with 

duration of HIV infection, 

concomitant RTV-boosted 

PIs (which boost TDF levels), 

preexisting renal dysfunction, 

or diabetes.

• Check serum and urine 

electrolytes, eGFR, UA before 

starting therapy and every 6 

months on therapy, 

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PRIMARY CARE OF VETERANS WITH HIV 22

injury (ATN)

y

drome (metabolic acidosis, 

↑ Cr, ↓ serum 

K+ and phosphate, ↑ urine 

bicarbonate, 

phosphate, and 

glucose)

py p

eGFR ≤90 mL/min/1.73 

m2

, renally secreted drugs, 

RTV-boosted PIs, diabetes, or 

hypertension.

• Adjust TDF dosage based on 

steady-state CrCl.

• Rare, usually resolves with 

discontinuation of TDF, but 

can lead to permanent damage, ESRD.

• May be more likely in patients 

with preexisting renal disease.

• Check serum and urine electrolytes, eGFR, UA before 

starting therapy and every 

6 months on therapy, especially in patients with eGFR 

≤90 mL/min/1.73 m2

, renally 

secreted drugs, RTV-boosted 

PIs (which boost TDF levels), 

diabetes, or hypertension. 

ATV Nephrolithiasis Symptoms of 

renal colic, dysuria, urgency; 

mild ↑ Cr; 

ATV-containing 

stones 

• Case reports.

• Treat with hydration; if symptoms do not resolve, or if 

symptoms recur, may need to 

discontinue drug.

IDV AIN ↑ Cr, pyuria • Usually resolves with drug 

discontinuation; may require 

steroids.

Crystalluria Asymptomatic, 

or symptoms 

of renal colic, 

dysuria, urgency; 

crystals on UA; 

mild ↑ Cr

• Treat with hydration.

• If manifestations do not 

resolve, may need to discontinue drug.

• Not necessary to discontinue 

for asymptomatic crystalluria.

Nephrolithiasis Renal colic, dysuria, urgency; mild 

↑ Cr; crystals on 

UA; stones or 

fi lling defects on 

radiography

• Risk reduced by drinking 

1.5-2 liters of liquids per day. 

• Treat with hydration; if symptoms do not resolve, or if 

symptoms recur, may need to 

discontinue drug.

Acyclovir Crystalluria May precipitate 

ARF

• Treat with hydration; avoid 

rapid intravenous bolus; adjust 

dosage for renal function.

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RENAL DISEASE

224 PRIMARY CARE OF VETERANS WITH HIV

p

tericin Bpermeability and/

or renal vasoconstriction

, 

K+ and Mg++, ↓

urine bicarbonate; distal renal 

tubular acidosis; 

non-aniongap metabolic 

acidosis

likely with concurrent nephrotoxins (aminoglycosides, 

foscarnet), diuretic use, hypovolemia, chronic renal failure.

• Hydration with normal saline 

is somewhat protective.

• Switch to lipid formulation 

of amphotericin B for rise 

in Cr of >2.5 mg/dL while 

on conventional amphotericin B; continue to monitor 

electrolytes.

Cidofovir Proximal tubular 

injury

(See TDF, above) Incidence reduced with • 

hydration (normal saline) and 

probenecid, which blocks 

absorption of drug by tubular 

epithelial cells.

• Check Cr and urine protein 

within 48 hours before each 

dose and reduce dosage for 

decreased CrCl or eGFR.

• Discontinue drug for either 

Cr ≥0.5 mg/dL above baseline 

or proteinuria ≥3+ on 

dipstick analysis. 

Foscarnet ATN

Crystal deposition

↑ Cr, ↓ serum 

Ca++, Mg++, 

phosphorus; 

sometimes ↑

serum Ca++ and 

phosphorus

• Cr generally increases after 

1-2 weeks of foscarnet 

therapy.

• Renal toxicity is reduced 

with infusion of 0.5-1 liter of 

normal saline with or before 

foscarnet.

• Toxicity is more likely with 

concomitant nephrotoxins.

Pentamidine (IV, 

rarely 

aerosolized)

Tubular toxicity 

(ATN)

↑ Cr, ↑ serum 

K+; ↓ serum 

Mg++ and Ca++

• Discontinuation of pentamidine reverses toxicity, 

although that process can 

take several weeks.

TMPSMXHyperkalemia 

caused by blockage of Na+ channel in collecting 

tubule

↑ Serum K+ • Usually seen with high-dose 

therapy (eg, PCP treatment), 

but sometimes seen with 

lower dosages.

• Hyperkalemia more common 

with preexisting renal insuffi ciency.

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PRIMARY CARE OF VETERANS WITH HIV 22

secretion of Cr

after 1 week of therapy.

• Consider monitoring serum 

K+, especially with high-dose 

therapy.

REFERENCES

Choi AI, Rodriguez RA. Renal Manifestations of HIV. In: Coffey S, Bacon O, Volberding PA, 

eds. HIV InSite Knowledge Base [online textbook]. San Francisco: UCSF Center for HIV 

Information; 2006. Available at http://hivinsite.ucsf.edu/InSite?page=kb-04-01-10. Accessed 

November 1, 2008.

Franceschini N, Napravnik S, Eron JJ Jr, et al. Incidence and etiology of acute renal failure 

among ambulatory HIV-infected patients. Kidney Int. 2005 Apr;67(4):1526-31.

Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney 

disease in HIV-infected patients: recommendations of the HIV Medicine Association of the 

Infectious Diseases Society of America. Clin Infect Dis. 2005 Jun 1;40(11):1559-85. 

Mehta RI, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to 

improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.

National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney 

Disease: Evaluation, Classifi cation, and Stratifi cation. New York: National Kidney Foundation; 2002. Available at http://www.kidney.org/professionals/kdoqi/index.cfm. Accessed 

November 1, 2008. 

VA/DoD Evidence-Based Clinical Practice Guideline Working Group. Management of 

Chronic Kidney Disease and Pre-ESRD in the Primary Care Setting. Washington, D.C.: 

Department of Veterans Affairs, Offi ce of Quality and Performance; November 2000. 

Available at http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. Accessed December 

18, 2008.

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/20/09 
PRIMARY CARE OF VETERANS WITH HIV 22

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Urology: 

Benign Prostatic Hypertrophy, Erectile 

Dysfunction, Epididymitis, Nephrolithiasis

KEY POINTS

Benign Prostatic Hypertrophy (BPH)

■ Approximately 19% of men aged >38 have symptoms related to 

BPH; the proportion increases with age.

■ Treat mild to moderate BPH with alpha-adrenergic antagonist 

monotherapy. Treat moderate to severe BPH with combination 

alpha-adrenergic antagonist and 5-alpha-reductase inhibitor 

therapy.

Erectile Dysfunction (ED) 

■ HIV-infected men are more likely than age-matched HIVuninfected men to have ED. Some studies have found the 

prevalence of ED among HIV-infected men to be as high as 70%.

■ First-line therapy: Phosphodiesterase 5 (PDE5) inhibitors. Note: 

serum levels of PDE5 inhibitors are increased signifi cantly in the 

presence of CYP 3A4 inhibitors such as PIs. PDE5 inhibitors are 

contraindicated for use with patients receiving nitrates.

Epididymitis 

■ Among sexually active men aged <35, acute epididymitis is 

most frequently caused by Chlamydia trachomatis and Neisseria 

gonorrhoeae. Escherichia coli, and other enteric organisms 

are common causes among men who practice insertive anal 

intercourse.

■ Among HIV-infected men, especially those with advanced 

immunosuppression, fungi and mycobacteria can cause acute 

epididymitis and should be considered in the differential diagnosis 

when symptoms do not respond to fi rst-line treatment.

Nephrolithiasis 

■ Formation of renal stones is infl uenced by diet, metabolism, 

comorbid conditions, and drugs. 

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UROLOGY

228 PRIMARY CARE OF VETERANS WITH HIV

pp

the urinary tract to form stones. ATV and NFV also have been 

reported to form stones. 

■ Diagnosis relies on imaging, although IDV-containing stones may 

be radiolucent on both plain X rays and CT.

■ The majority of patients can be managed with hydration and 

analgesics. The underlying cause should be defi ned in order to 

determine therapy to prevent recurrences.

Benign Prostatic Hypertrophy

BACKGROUND

BPH is a nonmalignant overgrowth of prostate tissue (stromal components > 

epithelial cells), usually originating in the 

central/transitional zone of the prostate.

■ BPH may cause symptoms of urinary 

obstruction, which vary widely in 

degree of severity.

■ Symptoms typically appear slowly and 

progress gradually over the course of several years.

■ Overall prevalence of BPH symptoms in men aged >38 is 19%; the prevalence 

increases with age.

■ Approximately 40% of men will have pathologic evidence of BPH by age 60, 

increasing to 90% by age 90.

■ Men with symptomatic BPH who are not treated have a 2.5% per-year risk of 

developing acute urinary retention.

EVALUATION

■ There are no consensus diagnostic criteria for BPH. Generally, diagnosis is 

made clinically on the basis of lower urinary tract symptoms (LUTS). The 

American Urological Association (AUA) has created the International Prostate Symptoms Score (IPSS) to evaluate LUTS. See AUA IPSS chart, below. 

History • Symptoms:

• Increased frequency of urination

• Nocturia

• Hesitancy

Veterans with HIV*

BPH: 8%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-9 

code corresponding to this condition

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PRIMARY CARE OF VETERANS WITH HIV 22

gy

• Weak urinary stream

• Family history of BPH or prostate cancer

• Medications that can impair bladder function, especially:

• Anticholinergics and antihistamines

• Medications that can increase outfl ow resistance:

• Sympathomimetics

• Type 2 diabetes, which increases risk of BPH

• Sexual dysfunction, which occurs in about 62% of men with LUTS

• Gross hematuria, which may signify calculi or bladder tumor 

• History of urethral trauma, urethritis, or urethral instrumentation, 

which can lead to a urethral stricture 

• Use the AUA IPSS chart, below, to score symptoms

Differential 

diagnosis 

(partial)

• Urinary tract infection (UTI), prostatitis

• Neurogenic bladder

• Prostate cancer

• Bladder calculi

• Bladder cancer

• Urethral stricture

• Bladder neck contracture

• Medication adverse effects

Physical 

examination, 

laboratory 

tests, 

imaging

• Digital rectal examination to assess prostate size and detect 

nodules

• Urinalysis: white blood cells (WBCs) (suggest infection), and red 

blood cells (suggest calculi or tumor)

• To screen for prostate cancer: digital rectal examination and serum 

prostate-specifi c antigen (PSA) (Note: elevated PSA is not specifi c 

for cancer; may indicate prostate infl ammation or large prostate 

resulting from BPH) 

• Optional: postvoid residual urine volume (>50 mL is abnormal, 

measured by straight catheter or bladder scanner); maximal 

urinary fl ow rate (<15 mL/sec is abnormal, measured in 

Urology Clinic)

• If signs of signifi cant obstruction, check serum creatinine; if 

creatinine level is high, obtain ultrasound of the bladder, ureters, 

and kidneys to check for hydronephrosis

• Suspected bladder calculi or tumor: refer to Urology Clinic for 

urethrocystoscopy

IPSS: AUA Symptom Index + Quality-of-Life Question

The International Prostate Symptom Score uses the 7 questions of the AUA Symptom 

Index (presented below) plus a disease-specifi c quality-of-life question (bother score).

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UROLOGY

230 PRIMARY CARE OF VETERANS WITH HIV Patient name: _____________ DOB: __________ ID: _________ Date of assessment: ___________ Initial Assessment ( ) Monitor during: ________ Therapy ( ) after: __________ Therapy/surgery ( ) ________ AUA BPH Symptom Score Not at all Less than 1 time in 5 Less than half the time About half the time More than half the time Almost always 1. Over the past month, how often have you had a sensation of not emptying your bladder completely after you fi nished urinating? 01 2 3 4 5 2. Over the past month, how often have you had to urinate again less than 2 hours after you fi nished urinating? 01 2 3 4 5 3. Over the past month, how often have you found you stopped and started again several times when you urinated? 01 2 3 4 5 4. Over the past month, how often have you found it diffi cult to postpone urination? 01 2 3 4 5 5. Over the past month, how often have you had a weak urinary stream? 01 2 3 4 5 6. Over the past month, how often have you had to push or strain to begin urination? 01 2 3 4 5 None 1 time 2 times 3 times 4 times 5 or more times 7. Over the past month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning? 01 2 3 4 5 Total Symptom Score: The AUA Symptom Index for BHP and the Disease-Specifi c Quality-of-Life Question

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PRIMARY CARE OF VETERANS WITH HIV 23

0-7 Mild symptoms

8-19 Moderate symptoms

20-35 Severe symptoms

The Disease-Specifi c Quality-of-Life Question (bother score):

“If you were to spend the rest of your life with your urinary condition just the 

way it is now, how would you feel about that?”

Delighted (0); Pleased (1); Mostly satisfi ed (2); Mixed (3); Mostly disappointed (4)

Unhappy (5); Terrible (6)

Treatment Decisions:

IPSS ≤7, or no bothersome symptoms: watchful waiting

IPSS ≥8: discuss treatment options; consider referral to Urology for further 

testing

Reprinted from the Journal of Urology (1992), 148(5), Barry, M. J., Fowler Jr, F. J., 

O’Leary, M. P., Bruskewitz, R. C., Holtgrewe, H. L., Mebust, W. K. and Cockett, A. T. 

(The Measurement Committee of the American Urological Association), ‘The 

American Urological Association Symptom Index for Benign Prostatic Hyperplasia’, pp. 1549-1557. (c) American Urological Association, 1992. Reproduced with 

permission.

 MANAGEMENT

■ Behavior modifi cations:

• Avoid drinking fl uids before bedtime and before going out.

• Avoid or reduce diuretics, including caffeine and alcohol.

• Void twice in order to empty the bladder more completely.

■ Avoid use of antihistamine, anticholinergic, and sympathomimetic agents.

■ Medical treatment (for patients who have symptoms that are signifi cant 

enough to create desire for therapy).

• Mild to moderate BPH by AUA IPSS score: alpha-adrenergic 

antagonist monotherapy

Terazosin: _ 1 mg QHS; if tolerated, titrate upward every 5-7 days 

to effect (eg, increase to 2 mg, then 5 mg, 10 mg, 20 mg [maximum]). 

Usual dose is 10 mg; patient should experience clinical effect within 

4-6 weeks.

Doxazosin: _ 1 mg QHS; if tolerated, titrate upward every 5-7 days 

to effect (eg, increase to 2 mg, then 4 mg, 8 mg, 16 mg [maximum]). 

Usual dose is 8 mg; patient should experience clinical effect within 

4-6 weeks.

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UROLOGY

232 PRIMARY CARE OF VETERANS WITH HIV

asthenia, and nasal congestion

• Terazosin and doxazosin lower blood pressure more signifi -

cantly than the other agents and therefore should be taken at 

bedtime; caution for additive hypotension if used concurrently 

with antihypertensives or sildenafi l or vardenafi l (for more 

details, see http://www.pbm.va.gov/CriteriaForUse.aspx).

Uroselective alpha-adrenergic antagonists: _

• Not currently listed on the VHA National Formulary, but may be 

considered for patients who have signifi cant orthostatic or postural hypotension on a nonselective alpha-adrenergic antagonist 

(see PBM Criteria for Use for these agents at http://www.pbm.

va.gov/CriteriaForUse.aspx); tamsulosin is the preferred nonformulary uroselective agent:

• Tamsulosin: 0.4 mg QD, can increase to 0.8 mg QD after 2-4 

weeks

• Alfuzosin: 10 mg QD

■ Patients with hypertension should not, in general, be treated with an alphaadrenergic antagonist as monotherapy for hypertension (see Hypertension, 

p. 171, as well as table of blood pressure changes expected with these agents 

at http://www.pbm.va.gov/CriteriaForUse.aspx).

POTENTIAL ARV AND OTHER DRUG INTERACTIONS !

■ Alfuzosin: Avoid use with patients who are taking P450 inhibitors. 

• PIs such as RTV, SQV, IDV, and NFV ↑ serum alfuzosin concentrations. 

• EFV also has been shown to ↑ alfuzosin concentrations.

• Other P450 inhibitors including azole antifungals (eg, ketoconazole, 

voriconazole, posaconazole, and itraconazole) can ↑ alfuzosin concentrations to toxic levels. Concurrent use of alfuzosin and azoles 

can increase the risk of QTc prolongation. 

■ Moderate to severe BPH by AUA score, or BPH not controlled by 

an alpha-adrenergic antagonist alone: Combination therapy with 5-alphareductase inhibitor and maximum tolerated dosage of an alpha-adrenergic 

antagonist may be of benefi t.

• Combination therapy can reduce the size of the prostate gland over a 

6- to 12-month period. Used alone, 5-alpha-reductase inhibitors have not 

shown effi cacy for BPH treatment. Consider for patients who are on a 

maintenance dosage of an alpha-adrenergic antagonist (eg, terazosin 10 

mg QD), or on the highest tolerated dosage if a maintenance dosage was 

not achieved; who have a large prostate (>40 mL, the size of a golf ball), 

and who show clinical progression of BPH symptoms as suggested by:

An increase in the AUA score ≥4 points from baseline, or _

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PRIMARY CARE OF VETERANS WITH HIV 23

Persistently bothersome symptoms despite adequate alpha- _

adrenergic antagonist therapy, as above

• Consider for patients who have not tried alpha-adrenergic antagonist 

therapy but who have an AUA score >12 and are at high risk of urinary 

retention or require an intervention.

• See PBM Criteria for Use at http://www.pbm.va.gov/CriteriaForUse.aspx.

■ 5-alpha-reductase inhibitors

• Finasteride: 5 mg QD. (Note: Finasteride has been associated with 

development of higher-grade prostate cancer in patients diagnosed with 

prostate cancer while on this agent.)

• Dutasteride: 0.5 mg QD (may be more potent than fi nasteride).

• Possible adverse effects: decreased libido, ejaculatory dysfunction, ED.

• Note: These medications can cause PSA levels to decrease by 50%. This 

should be taken into account if PSA levels are being followed to track 

other diseases.

WHEN TO REFER

Refer to Urology for evaluation or possible surgical interventions for 

patients who develop: 

• Hydronephrosis

• Urinary retention

• Bladder stones

• Renal dysfunction

• Recurrent infection

• Severe symptoms that do not respond well to medical therapy

• Elevated serum PSA or microscopic or gross hematuria

Erectile Dysfunction

BACKGROUND

■ ED is the inability to achieve or maintain 

penile erection suffi cient for satisfactory 

sexual performance (National Institutes 

of Health Consensus Panel defi nition).

■ HIV-infected men have a higher prevalence of ED than age-matched HIVuninfected men. 

Veterans with HIV*

Erectile dysfunction: 18% (fi lled 

prescriptions for ED drugs)

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition

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UROLOGY

234 PRIMARY CARE OF VETERANS WITH HIV

high as 70%.

■ Sexual dysfunction also occurs in women, but is less well studied. 

■ Sexual dysfunction often is multifactorial in etiology; causes can include: 

• Medication effects (see below)

• Psychological: depression, stress

• Endocrine: androgen defi ciency, thyroid disease, diabetes mellitus

• Neurologic: stroke, spinal cord or back injury, prostate surgery, pelvic 

trauma, multiple sclerosis, or dementia

• Vascular: cardiovascular disease, hypertension 

• Metabolic and diet-related: obesity, dyslipidemia

• Substance use: alcohol, tobacco; methamphetamine, cocaine, and heroin can 

initially increase libido but over time can cause inability to sustain an erection

■ Among HIV-infected men, ED has been associated with:

• Age >40

• Depression, anxiety, posttraumatic stress disorder

• Use of antidepressants (although the effect of these medications is 

diffi cult to separate from the effect of underlying depression)

• Use of psychotropic medications (although the effect is diffi cult to 

separate from that of underlying psychiatric disease)

• Duration of ART (higher prevalence of ED with longer duration of ART, 

regardless of regimen)

• Presence of peripheral neuropathy

• Hypogonadism

Up to 20% of HIV-infected men have low testosterone levels (see _

Androgen Defi ciency, p. 89)

• Heterosexual orientation

• Nonuse of alcohol

Medications Commonly Associated with ED

• Antidepressants (particularly SSRI, serotonin-norepinephrine reuptake inhibitor 

[SNRI] classes)

• Bupropion, mirtazapine, and nefazodone confer lower risk of ED

• Spironolactone

• Thiazide diuretics

• Beta-blockers (not clearly associated; mixed data)

• Clonidine

• Methyldopa

• Ketoconazole

• Cimetidine

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PRIMARY CARE OF VETERANS WITH HIV 23

EVALUATION

■ The abridged International Index of Erectile Function (IIEF-5) is a validated 

question set used to diagnose the presence and severity of ED. 

■ The sensitivity of the IIEF-5 is 98% and the specifi city is 88%, using a cutoff 

score of 21. 

The IIEF-5 Questionnaire

Over the past 6 

months:

1. How do you rate 

your confi -

dence that you 

could get and 

keep an erection?

Very low

1

Low

2

Moderate

3

High

4

Very high

5

2. When you had 

erections with 

sexual stimulation, how often

were your 

erections hard 

enough for 

penetration?

Almost 

never/

never

1

A few 

times

(much less 

than half 

the time)

2

Sometimes

(about half 

the time)

3

Most 

times

(much 

more than 

half the 

time)

4

Almost 

always/

always

5

3. During sexual 

intercourse, how 

often were you 

able to maintain 

your erection 

after you had 

penetrated 

(entered) your 

partner?

Almost 

never/

never

1

A few 

times

(much less 

than half 

the time)

2

Sometimes

(about half 

the time)

3

Most 

times

(much 

more than 

half the 

time)

4

Almost 

always/

always

5

4. During sexual 

intercourse, how 

diffi cult was 

it to maintain 

your erection to 

completion of 

intercourse?

Extremely 

diffi cult

1

Very 

diffi cult

2

Diffi cult

3

Slightly 

diffi cult

4

Not 

diffi cult

5

5. When you 

attempted sexual 

intercourse, how 

often was it 

satisfactory for 

you?

Almost 

never/

never

1

A few 

times

(much less 

than half 

the time)

2

Sometimes

(about half 

the time)

3

Most 

times

(much 

more than 

half the 

time)

4

Almost 

always/

always

5

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UROLOGY

236 PRIMARY CARE OF VETERANS WITH HIV

The IIEF-5 score is the sum of the ordinal responses to the 5 items.

22-25 No erectile dysfunction

17-21 Mild erectile dysfunction

12-16 Mild to moderate erectile dysfunction

 8-11 Moderate erectile dysfunction

 5-7 Severe erectile dysfunction

Reprinted by permission from Macmillan Publishers Ltd: Rosen RC, Cappelleri 

JC, Smith MD, et al. Development and evaluation of an abridged, 5-item version 

of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for 

erectile dysfunction. Int J Impot Res. 1999 Dec;11(6):319-26. © 1999

History • Rapidity of onset: sudden onset points to psychogenic causes

• Presence or absence of spontaneous erections: absence suggests 

vascular or neurogenic causes

• Screen for depression, anxiety, and posttraumatic stress disorder 

(including rape, sexual assault, and military sexual trauma)

• Screen for interpersonal confl ict with sex partner(s)

Physical 

examination

• Penis: corporal plaques associated with Peyronie disease (buildup 

of scar tissue in erectile tissues can cause pain or bending with 

erections)

• Testes: size, symmetry, consistency, masses

• Epididymis and vas deferens: swelling or varicoceles

• If patient is aged >50, consider digital rectal examination and PSA 

for prostate cancer screening

• Cardiovascular system (heart, femoral, and peripheral pulses): 

vascular health

• Secondary sexual characteristics, gynecomastia: endocrine health

• Neurologic screen: sensorimotor examination of S2-S4. Rapid screen: 

• Anal wink test: anal sphincter contracts when perianal skin is 

stroked

• Bulbocavernosus refl ex test: anal sphincter contracts when the 

glans penis is squeezed 

• Anal sphincter tone: digital rectal examination; 

ask patient to contract the sphincter during the examination

Laboratory 

evaluations 

and other 

studies

• Testosterone: to evaluate for hypogonadism (see Androgen 

Defi ciency, p. 89)

• Fasting glucose, HbA1c: screen for diabetes

• Fasting lipid panel: screen for hyperlipidemia and underlying vascular disease

• TSH to evaluate for hypothyroidism

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PRIMARY CARE OF VETERANS WITH HIV 23

gy p

(NPT) testing, which is a home test of number of nocturnal erections and level of penile rigidity a man experiences during sleep; a 

normal NPT measurement suggests psychogenic ED

 MANAGEMENT

■ It is critical that management of ED be accompanied by discussions 

regarding sexual health and practice of safer sex (see Prevention for 

Positives, p. 39).

■ Obese patients: Weight loss and increased physical activity are associated with 

improvement in erectile function in one third of patients. 

■ Psychotherapy with or without psychoactive medications is indicated for men 

with depression or anxiety (avoid antidepressant medications that may cause 

ED, if possible; see Medications Commonly Associated with ED, above)

■ Men with hypogonadism: androgen replacement (testosterone); see 

Androgen Defi ciency, p. 89.

Note: Testosterone preparations are classifi ed as Schedule III controlled 

substances.

• Intramuscular testosterone (eg, cypionate): 200 mg IM every 2 

weeks

• Transdermal patch: 5 mg QD

• Gel: 1% gel, 5-10 mg QD

• Buccal: 30 mg BID

• Possible adverse effects (particularly with IM testosterone) include mood 

swings, gynecomastia, testicular atrophy, acne, erythrocytosis, dyslipidemia, and elevation of serum transaminase levels. Also, pain and irritation at injection or application sites, local pruritus and erythema with 

patches (which can be relieved by topical steroids); bitter taste with the 

buccal delivery method.

• Contraindications: prostate cancer.

• Monitoring (particularly important with IM testosterone): testosterone 

levels 1-2 months after initiation. (Note: For patients on IM testosterone, check testosterone level at nadir, just before scheduled injection.); 

PSA every 6-12 months; hemoglobin and liver function tests every 3-6 

months.

■ PDE5 inhibitors

• A summary of information on PDE5 inhibitors from the VA PBM can be 

found at http://www.pbm.va.gov/DrugClassReviews.aspx.

• PDE5 inhibitors interact with PIs and often require dosage adjustment; 

see below.

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UROLOGY

238 PRIMARY CARE OF VETERANS WITH HIV

• Vardenafi l is currently the PDE5 inhibitor on the VHA National Formulary. For information on obtaining another PDE5 inhibitor for a patient in 

whom vardenafi l has been ineffective, see http://www.pbm.va.gov/CriteriaForUse.aspx.

• Tadalafi l has a longer duration of action than sildenafi l or vardenafi l, up to 

36 hours.

• If tolerated, titrate to effect.

POTENTIAL ARV INTERACTIONS !

Serum levels of all PDE5 inhibitors are signifi cantly increased in the presence of 

CYP 3A4 inhibitors such as PIs. See Recommended Dosing below.

Recommended Dosing of PDE5 Inhibitors

PDE5 

Inhibitor

Dosing 

Instructions

Patients on PIs and 

Other Strong CYP 

3A4 Inhibitors

Patients Not on 

Interacting Drugs

Vardenafi l 

(Levitra)

Take on empty 

stomach 1 hour 

before sexual 

activity

Start: 2.5 mg per day

Maximum: 2.5 mg per 

72 hrs (ATV, DRV, RTV, 

TPV); 2.5 mg per 24 

hours (other PIs)

Start: 2.5-10 mg per 

day (≤5 mg if age >65)

Maximum: 20 mg 

every 24 hours

Sildenafi l

(Viagra)

Take on empty 

stomach 0.5-4 

hours before sexual 

activity

Start: 25 mg per day

Maximum: 25 mg 

every 48 hours

Start: 25-50 mg per 

day (25 mg if age >65)

Maximum: 100 mg 

every 24 hours 

Tadalafi l 

(Cialis)

Take with or without food, before 

sexual activity

Start: 5-10 mg per day

Maximum: 10 mg 

every 72 hours

Start: 5-10 mg per day

Maximum: 20 mg 

every 24 hours

• Use low dosages or avoid for patients with signifi cant liver disease. 

• Possible adverse effects: (common) headache, fl ushing, dizziness, nasal 

congestion; (<2% but serious) hypotension, cardiac arrest, cerebrovascular hemorrhage, ischemic optic neuropathy, vision loss, priapism.

• All PDE5 inhibitors are contraindicated for use by patients who take 

nitrate drugs.

• Exercise caution if using PDE5 inhibitors concurrently with alpha-adrenergic antagonists (eg, terazosin) because of risk of hypotension, although 

tamsulosin 0.4 mg QD seems to be safe with tadalafi l use (for more 

details, see http://www.pbm.va.gov/CriteriaForUse.aspx).

• Patients on a stable alpha-adrenergic antagonist regimen should start the 

PDE5 inhibitor at the lowest possible dosage.

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PRIMARY CARE OF VETERANS WITH HIV 23

indicated (eg, patients on nitrate drugs), not tolerated, or not effective. 

• Yohimbine hydrochloride, an alpha2

-adrenergic antagonist. Starting 

dosage is 5.4 mg (may be increased to 10.8 mg) PO TID. Side effects 

include nausea, dizziness, and nervousness. No data on ARV interactions 

are available.

The following require referral to a urologist and instruction on proper use: 

• Penile self-injectable drugs (eg, intracavernous alprostadil, papaverine

phentolamine)

Override sympathetic inhibition and encourage relaxation of the _

penile smooth muscle. 

Require injection with an insulin syringe through the shaft of the _

penis into a corporeal body a few minutes before sexual activity. 

• Intraurethral alprostadil

Alprostadil is instilled into the urethra, followed by penile massage _

for 1 minute to distribute the medication into the corpora 

cavernosae.

• Vacuum devices

Mechanical devices increase arterial infl ow, and occlusive rings _

decrease venous outfl ow from the corpora cavernosae.

■ Refractory ED: For patients who are refractory to or unable to use PDE5 

inhibitors, injectables, intraurethrals, or vacuum devices, options include:

• Referral for surgical implantation of penile prosthesis, including malleable 

rods and infl atable prostheses

Epididymitis

■ Acute epididymitis is a syndrome consisting of pain, swelling, and infl amma

tion of the epididymis lasting <6 weeks.

■ Chronic epididymitis lasts ≥3 months and consists of pain in the scrotum, 

testicle, or epididymis, localized on physical examination. 

■ Testicular pain and swelling (orchitis) also may be present.

■ It is often accompanied by dysuria, urinary frequency, and urgency.

■ Among sexually active men aged <35, acute epididymitis is most frequently 

caused by infection, particularly by C trachomatis and N gonorrhoeae. E coli

and other enteric organisms are common causes among men who practice 

insertive anal sex.

BACKGROUND

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UROLOGY

240 PRIMARY CARE OF VETERANS WITH HIV

fungi and mycobacteria cause acute epididymitis more frequently than they 

do among HIV-uninfected men. These should be considered in the differential 

diagnosis when symptoms do not respond to fi rst-line treatment.

■ Other causes include lower urinary tract obstruction (eg, BPH, occlusive 

sexual enhancement aids), surgical instrumentation. 

EVALUATION

Symptoms • Unilateral testicular pain, with or without swelling

Differential 

diagnosis

• Urethritis without epididymitis

• UTI

• Testicular abscess

• Testicular tumor

• Infarction

• Testicular torsion

Note: Testicular torsion is a surgical emergency, because testicular 

viability is at risk:

It is important to differentiate torsion and epididymitis.

Torsion involves sudden and severe onset of pain, generally without 

evidence of infl ammation or infection. Obtain urgent testicular ultrasound, urologic consultation, or both if torsion is suspected.

Physical 

examination

• Examine testes and epididymis: exquisite tenderness and palpable 

swelling of the epididymis (usually begins at the tail and spreads to 

the rest of the epididymis and testicle), hydrocele, mass.

• Spermatic cord: usually tender and swollen.

Laboratory 

evaluation 

and imaging

• If urethritis: Gram stain of urethral secretions; ≥5 WBC per oil 

immersion fi eld indicates infection. Presence of gram-negative 

diplococci is diagnostic for gonococcal infection. 

• First-void urine: ≥10 WBC per high-powered fi eld on microscopy 

indicates infection. Send urine for nucleic acid amplifi cation tests 

(NAAT) for C trachomatis and N gonorrhoeae. Send urine culture if 

infection with other organisms (eg, E coli) is suspected.

• Testicular/scrotal ultrasound: Radiologic evaluation is not routinely 

necessary, but is important if other testicular conditions such as 

torsion, mass, and abscess are suspected. Doppler ultrasonography 

is 70% sensitive and 88% specifi c in diagnosing acute epididymitis.

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PRIMARY CARE OF VETERANS WITH HIV 24

 MANAGEMENT

■ Consider hospitalization for patients who are febrile and for those with 

severe pain that suggests other diagnoses (eg, torsion, testicular infarction, 

and abscess) that require more complicated evaluation.

■ Acute epididymitis:

• Begin empiric antibiotic treatment based on suspected cause.

• C trachomatis or N gonorrhoeae confi rmed or suspected:

Ceftriaxone 125 mg or 250 mg IM, or cefi xime 400 mg PO for single _

dose

Plus

Doxycycline 100 mg BID for 10 days _

Note: _ Fluoroquinolones are not recommended for treatment of 

confi rmed or suspected N gonorrhoeae because of high rates of 

resistance.

• Enteric organisms confi rmed or suspected; or, patient is allergic to cepha

losporins or tetracyclines:

Ofl oxacin 300 mg BID for 10 days _

Levofl oxacin 500 mg QD for 10 days _

■ Management of sex partners: 

• Refer sex partners for evaluation if the patient has confi rmed or suspected C trachomatis or N gonorrhoeae epididymitis and sexual contact 

has occurred within 60 days from onset of symptoms. 

• At the current time, VA facilities are not authorized to evaluate or treat 

nonveteran sex partners. 

• VA facilities are strongly encouraged to report notifi able STDs to the 

local public health department, in accordance with established VA policies 

and procedures.

• Patients should avoid sexual contact until they and their sex partners 

have completed therapy and no longer have symptoms.

■ Follow-up: Symptoms should improve within 3 days of initiating therapy. If 

there is no improvement or if the symptoms persist after completion of antibiotics, reevaluate for the following:

• Other causes of epididymitis (eg, fungi, mycobacteria)

• Testicular abscess

• Testicular infarction

• Testicular tumor

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Nephrolithiasis

BACKGROUND

■ Renal calculi are common in the general population, affecting 12% of men and 

5% of women.

■ Stones result from supersaturation of urine with a normally soluble compound, with subsequent nucleation, crystal aggregation, and stone formation.

■ Stones typically result from a combination of dietary, metabolic, genetic, and 

medical factors.

■ Calculi most often are composed of calcium, but may form from uric acid or 

cystine.

■ Stones also may be composed of drugs; IDV in particular may cause nephrolithiasis. Among HIV-infected patients who receive IDV, 5-15% develop stones. 

Other PIs (ATV, NFV) also have been reported as causes of stones.

■ 50% of patients will have a recurrence within 10 years. It is important to 

defi ne the underlying cause in order to determine preventive therapy.

EVALUATION

History Symptoms 

• Flank pain, frequently severe, radiating to groin

• Undulating cramps

• Gross hematuria

• Nausea, vomiting

Ask about:

• Duration, characteristics, location of pain

• History of renal stones

• UTIs

• Family history of renal stones

• Solitary or transplanted kidney

• Medications: IDV, sulfa drugs, penicillins, quinolones

• Presence of metabolic syndrome, diabetes mellitus

Differential 

diagnosis 

(partial)

• Appendicitis

• Biliary colic

• Diverticulitis

• Pancreatitis

• Lumbar disc disease

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PRIMARY CARE OF VETERANS WITH HIV 24

• Ectopic pregnancy

• Abdominal abscess

• Aortic aneurysm

• Bowel ischemia

Physical 

examination, 

laboratory 

evaluation, 

imaging

• On physical examination, look for:

• Costovertebral tenderness

• Absence of peritoneal signs

• Laboratory studies

• Urinalysis (85% of patients will have hematuria)

• CBC, electrolytes, creatinine, calcium, uric acid, phosphorus, 

parathyroid hormone levels (if serum calcium is elevated)

• 24-hour urine collection for patients <30 years of age, multiple 

calculi, renal failure, renal transplant, family history of calculi, 

recurrent calculi; analyze for pH, calcium, oxalate, uric acid, 

sodium, phosphorus, citrate, magnesium, creatinine, total volume

• Stone analysis (size, morphology, composition); if IDV or ATV 

suspected, may need to order specifi c testing

• Imaging studies:

• Abdominal X ray (calcium-containing stones are radiopaque; 

IDV stones are radiolucent)

• Renal ultrasound

• Intravenous urography (may be the only way to detect IDVcontaining stones)

• Helical CT without contrast (will not demonstrate IDV 

stones)

 MANAGEMENT

Acute

■ In the absence of infection, most (80%) patients can be managed medically.

• Stones <5 mm in diameter typically pass spontaneously. 

• Hydration and analgesia (see Pain Medications, p. 321) should be instituted promptly.

• Consider use of medications that relax ureteral smooth muscle (eg, terazosin; nifedipine [use caution regarding interactions with PIs; see Hypertension, p. 171]).

• For patients suspected of having an IDV stone, it is reasonable to discontinue IDV temporarily to lower urinary concentrations and allow dissolu

tion. (To avoid the development of virologic failure and HIV resistance, 

IDV should be replaced by another appropriate ARV, or all ARVs should 

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UROLOGY

244 PRIMARY CARE OF VETERANS WITH HIV

dissolution.

• Indications for hospitalization include infection with concurrent obstruction, patients with a solitary or transplanted kidney, uncontrolled pain, 

intractable emesis, or comorbidities (eg, coronary artery disease) that 

may complicate management.

• If infection is suspected, consult a urologist regarding drainage via nephrostomy tube placement.

• Passed stones should be analyzed to determine their composition in 

order to design a preventive therapy regimen.

■ Larger (>10 mm) stones and those located more proximally are less likely to 

pass spontaneously and frequently require surgical therapy; consult a urologist for percutaneous nephrostolithotomy, ureterorenoscopy, or shock wave 

lithotripsy. 

• IDV stones typically are gelatinous and thus not amenable to lithotripsy; 

endoscopic stent placement is the procedure of choice for patients who 

do not respond to medical therapy alone.

Prevention

■ All patients with a history of nephrolithiasis should maintain a daily fl uid 

intake >2 L and restrict sodium intake.

■ Targeted preventive therapy depends on identifi ed metabolic abnormalities 

and stone analysis:

• If hyperparathyroidism has been excluded, patients with hypercalciuria 

should restrict dietary calcium to 600-800 mg/day; consider use of a 

thiazide diuretic to decrease urinary calcium excretion.

• Patients with hyperoxaluria should increase daily intake of calcium to 

1-4 g (calcium citrate is the preferred agent) and avoid foods high in 

oxalate (chocolate, spinach, rhubarb, beets).

• Patients with hyperuricosuria should be treated with potassium citrate 

(60-80 mEq/day), along with allopurinol 100-300 mg/day to decrease uric 

acid excretion.

• Patients with recurrent UTI resulting from struvite stones should 

undergo stone removal.

• Patients with IDV stones should maintain an adequate fl uid intake 

(>1.5 L/day) if continued on IDV.

REFERENCES

Benign Prostatic Hyperplasia: Diagnosis and Treatment (Clinical Practice Guideline). Publication No. AHCPR 94-0582. Rockville, MD: Agency for Health Care Policy and Research, 

Public Health Service, U.S. Department of Health and Human Services, February 1994. 

Available at http://www.ahrq.gov/clinic/medtep/bphguide.htm. Accessed December 8, 2008.

UCS-PCM-08-0701-Urology.indd 244 CS-PCM-08-0701-Urology.indd 244 3/20/09 /20/09 
PRIMARY CARE OF VETERANS WITH HIV 24

Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006

MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94.

Centers for Disease Control and Prevention. Sexually transmitted diseases treatment 

guidelines 2006. MMWR 2006;55: epididymitis chapter updated April 2007. Available at 

http://www.cdc.gov/std/Treatment/2006/updated-regimens.htm. Accessed December 8, 

2008.

Crum NF, Furtek KJ, Olson PE, et al. A review of hypogonadism and erectile dysfunction 

among HIV-infected men during the pre- and post-HAART eras: diagnosis, pathogenesis, 

and management. AIDS Patient Care STDS. 2005 Oct;19(10):655-71. 

Daudon M, Jungers P. Drug-induced renal calculi: epidemiology, prevention and management. Drugs. 2004;64(3):245-75. 

Lebovitch S, Mydlo JH. HIV-AIDS: urologic considerations. Urol Clin N Am. 2008 

Feb;35(1):59-68; vi. 

Roehrborn CG, McConnell JD, Barry MJ, et al. AUA Guideline on the Management of 

Benign Prostatic Hyperplasia. American Urological Association Education and Research, 

Inc; 2003. Available at http://www.auanet.org/guidelines/bph.cfm. Accessed December 8, 

2008.

Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an abridged, 

5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool 

for erectile dysfunction. Int J Impot Res. 1999 Dec;11(6):319-26. 

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Women’s Health

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PRIMARY CARE OF VETERANS WITH HIV 24

Womens Health

KEY POINTS

■ A Women Veterans Program Manager is available at every VA 

Medical Center to assist in providing care for women veterans.

■ Nearly one third of people living with HIV in the United States are 

women.

■ In the United States, HIV-infected women are less likely than HIVinfected men to receive ART.

■ General preventive strategies and health maintenance are all part of 

routine care for HIV-infected women.

■ Women should receive reproductive counseling. 

■ For pregnant women and women who may become pregnant, avoid 

use of EFV.

■ Women with HIV have increased risk of developing abnormal 

cervical, vaginal, vulvar, and anal cytology, with possible progression 

to squamous carcinoma, especially if the CD4 count is <200 cells/μL.

■ Women with HIV have higher rates of persistence and recurrence 

of herpes simplex virus, human papillomavirus (HPV), bacterial 

vaginosis, and candidal genital tract infections compared with their 

HIV-uninfected counterparts.

■ Women with HIV are at increased risk of neuropsychiatric disease 

and should be screened accordingly.

■ All women veterans, including those with HIV, should be screened 

for military sexual trauma and exposure to domestic violence.

■ All women veterans, including those with HIV, should be screened 

for breast cancer and osteoporosis.

BACKGROUND

Epidemiology

■ One half of the people living with HIV 

worldwide are women.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Veterans with HIV*

Women: 3% 

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007

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WOMEN’S HEALTH

250 PRIMARY CARE OF VETERANS WITH HIV

• Nearly one third of people living with HIV are women.

• Heterosexual transmission is the main mode of HIV acquisition among 

women (80% in recent years), followed by injection drug use.

• Rates of HIV infection are increasing in rural and small metropolitan 

areas. 

• Women of color are disproportionately infected with HIV. 

– In 2005, the diagnosis rate of both HIV/AIDS and AIDS 

was 20 times higher for non-Hispanic black women than for 

non-Hispanic white women; 60% of HIV-infected women are African 

American.

– The rate of both HIV/AIDS and AIDS was >5 times higher among 

Hispanic women than among non-Hispanic white women.

• HIV-infected women are less likely than their male counterparts to be on 

ART, largely because of decreased access to health care and because of 

other priorities that compete for their attention.

Natural History

■ Women generally have lower viral loads than men at the time of 

seroconversion.

■ On average, HIV RNA levels are at least 50% lower in women than in men 

with the same CD4 cell counts and duration of HIV infection.

■ From seroconversion, the time to the development of AIDS and overall 

mortality are the same for women and men despite the difference in HIV 

RNA levels. 

■ Virologic and CD4 responses to ART are the same for women and men. 

Risks for Women with HIV

■ Women tend to be diagnosed later in the course of HIV infection than men, 

and they tend to seek care at more advanced disease stages.

■ Barriers to care include: 

• Child care or family care obligations, transportation limitations, lack of 

insurance, fear of disclosure (particularly to male partners, also to community and social networks), denial, and cultural mistrust of the health 

care system

• Perception of their own need for medical care as being of 

low priority

■ Depression: A prospective cohort study showed that women who selfreported chronic depressive symptoms were twice as likely to have CD4 

declines and to die than women with mild or no depressive symptoms.

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PRIMARY CARE OF VETERANS WITH HIV 25

Pharmacologic Considerations for Women with HIV

■ Limited pharmacokinetic studies show differences in ARV metabolism 

between women and men.

• Women often have higher serum drug levels of certain ARVs, including EFV, NVP, IDV, LPV, and SQV.

• Women have higher rates of adverse effects from certain ARVs, 

including: 

– Hepatotoxicity related to NVP, especially when NVP is initiated 

at CD4 counts of >250 cells/μL or during pregnancy

– Rash related to NNRTIs and the PIs DRV and TPV

– Nausea and vomiting related to PIs 

– ABC hypersensitivity (odds ratio: 1:4) 

■ There is little information on dosage adjustment of ARVs for women 

(pregnant or nonpregnant).

■ Metabolism of ARVs may be altered during pregnancy.

■ Some ARVs should not be used by pregnant women or those who may 

become pregnant, because of potential teratogenicity or other toxicity.

■ Some ARVs have signifi cant interactions with certain hormonal contraceptives; ARVs and contraceptives should be selected with this in 

mind (see Potential ARV Interactions, below).

Health maintenance: With prolonged survival in the era of ART, preventive 

strategies and health maintenance measures such as control of hypertension, 

smoking cessation, minimizing cardiovascular risk factors, and routine screening 

for osteoporosis and cancer (cervical, breast, and colon) are all part of routine 

care for HIV-infected women. See Evaluation and Management, below, 

as well as Hypertension (p. 171), Dyslipidemia (p. 143), and Smoking 

Cessation (p. 53) for further information on these topics.

This chapter will address these commonly encountered issues for HIV-infected 

women:

■ Reproductive and hormonal issues

■ Interactions of ARVs with hormonal contraceptives

■ Screening for neuropsychiatric disorders 

■ Screening for military sexual trauma and domestic violence

■ Screening for cancer, osteoporosis, and STD

■ Cervical dysplasia

■ Osteoporosis

■ Genital tract infections

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WOMEN’S HEALTH

252 PRIMARY CARE OF VETERANS WITH HIV

 EVALUATION AND MANAGEMENT

Note: A Women Veterans Program Manager is available at every VA Medical 

Center to assist in providing care for women veterans, including those with HIV 

infection.

HIV Prevention (see also Prevention for Positives, p. 39)

Recommendations Comments

Prevention 

of HIV 

transmission

• Evaluate each patient’s need for HIV 

prevention strategies on a regular 

basis

• Evaluate patient for high-risk behaviors (eg, alcohol misuse, substance 

use disorders) that may predispose 

to high-risk behaviors

• Encourage use of condoms (male or 

female) during all sexual encounters

• Other barriers: diaphragm, cervical 

cap (limited effi cacy in preventing 

HIV transmission)

• Screen regularly for STDs, and treat 

as needed

• Use of nonoxynol-9 is not recommended: increased risk of HIV 

transmission resulting from vaginal 

irritation; lack of prevention of 

STDs 

• If used correctly and 

consistently, condoms 

are effective for preventing transmission of 

HIV and other STDs, 

including HPV.

• Condoms may also be 

effective for contraception, but only if used 

optimally (see below).

• In some women, HIV 

viral load may be substantially higher in vaginal secretions than in 

blood; thus risk of sexual transmission of HIV 

may not be predicted 

by plasma viral load.

Reproductive and Hormonal Issues

Issue Recommendations Comments

Contrace ption• Condoms (male or female) during 

all sexual encounters; high failure 

rate if used suboptimally (consider 

second contraceptive method); if 

used correctly and consistently, 

effective also for prevention of HIV 

transmission

• Other barriers: diaphragm, cervical 

cap

• Spermicides (eg, nonoxynol-9) are 

not recommended: increased risk 

of HIV transmission resulting from 

vaginal irritation

• 50% of pregnancies in 

the United States are 

unplanned.

• On a regular basis, 

evaluate each woman’s 

pregnancy intent and 

need for contraceptive information and 

methods. 

• For women who intend 

or desire pregnancy, 

provide preconception 

counseling (see below).

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PRIMARY CARE OF VETERANS WITH HIV 25

p

drug-drug interactions with some 

ARVs (see Potential ARV Interactions, below)

• Injectable contraceptives (medroxyprogesterone [DMPA, DepoProvera]): appear to be safe and 

effective for women on ARVs (however, see Potential ARV Interactions, below)

• Transdermal/patch: little information 

on interactions with ARVs 

• Intravaginal ring (NuvaRing): possibly 

improved contraceptive compliance; 

little information on interactions 

with ARVs

• Intrauterine devices (IUDs), particularly the Mirena levonorgestrelreleasing (LNG) device and 

copper-T devices have been shown 

to be safe for use by HIV-infected 

women and do not increase HIV 

viral shedding 

women who use inadequate or inconsistent 

contraception (risk of 

teratogenicity).

• Interactions between 

oral hormonal agents 

and many ARVs may 

decrease contraceptive 

effi cacy (see Potential 

ARV Interactions, 

below). Fewer data are 

available for drug-drug 

interactions with other 

formulations.

• Possible adverse 

effects of hormonal 

contraceptives include 

thrombosis, myocardial 

infarction (estrogen/

progesterone), stroke, 

menstrual irregularities, breast tenderness, 

weight gain, mood 

changes, loss of 

bone mineral density 

(DMPA), increased risk 

of breast cancer.

• For women in whom 

hormonal methods are 

contraindicated (eg, 

history of thrombosis, 

thrombophilia, or cancer), the copper-T IUD 

may be safe and effective.

Preconce ptionPreconception counseling is needed 

for all women who intend to become 

or who may become pregnant; preconception counseling and care includes:

• Education regarding HIV and pregnancy, risk of transmission (to fetus 

or uninfected partners), measures 

to reduce this risk

• Initiation of folate supplementation 

(higher dosage required for women 

who take TMP-SMX; see Pregnancy, below)

• Many HIV-infected 

women become pregnant, intentionally or 

unintentionally. It is 

important to discuss 

each patient’s intentions and desire to bear 

children at entry to 

care and periodically 

thereafter.

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WOMEN’S HEALTH

254 PRIMARY CARE OF VETERANS WITH HIV

g 

cella titers in patients with no varicella history, HBV serologies, HCV 

antibody, Toxoplasma immunoglobulin G, cytomegalovirus, tuberculosis 

screening (purifi ed protein derivative 

or Quantiferon), complete blood 

count; consider fasting glucose

• Vaccinations as appropriate

• Pap smear, STD screening (gonorrhea, 

chlamydia, syphilis, trichomoniasis)

• Nutrition evaluation 

• Substance abuse and mental health 

screening and treatment as indicated

• Referral to reproductive health 

specialist with experience in working with HIV-infected women (see 

Pregnancy, below)

• Referral for prenatal genetic counseling 

Assist women to become pregnant 

in ways that have lowest risk of HIV 

infection for partner (if HIV uninfected) and for fetus. Note that VA 

does not provide in vitro fertilization or other assisted reproduction services; patients must be 

referred to a non-VA provider for 

such services, which cannot be 

covered by VA on a fee basis.

• For an HIV-infected woman with an 

HIV-uninfected male partner, advise 

methods of conception that avoid 

risk of HIV transmission to the 

partner (eg, home or offi ce artifi cial 

insemination using partner’s semen)

• For an HIV-uninfected woman with 

an HIV-infected male partner, consider sperm washing, in vitro fertilization (IVF), intracytoplasmic sperm 

injection (ICSI); full disclosure of 

genetic and other risks of assisted 

reproduction should occur

• Sperm washing results in sperm that 

is reported to be >99.9% free of 

HIV virus 

tion have been noted 

to have increased rates 

of infertility compared 

with non-HIV infected 

women.

• Tubal infertility is 

more common 

among women with 

HIV.

• For women with 

diffi culty conceiving, 

referral for evaluation of possible etiologies for infertility 

(including evaluation of endocrine, 

uterine, tubal, and 

male factors) should 

occur in advance of 

referral for assisted 

reproduction.

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PRIMARY CARE OF VETERANS WITH HIV 25

g

states may limit access to reproductive services 

• Maximize ART effi cacy, selecting 

ARVs that are appropriate for use 

during pregnancy (see below)

• Avoid potential teratogens, including 

EFV, ribavirin, hydroxyurea, thalidomide, some antiepileptic drugs 

• Optimize control of other medical 

conditions (eg, hypertension, diabetes)

Pregnancy • Detailed information on care of 

HIV-infected pregnant veterans is 

available at http://www.hiv.va.gov/

vahiv?page=cm-306_pg_tx

• Refer to an obstetrician who has 

expertise working with HIV-infected 

women; for centers that do not have 

such expertise available, consultation 

is available through the National Perinatal HIV Consultation and Referral 

Service (http://www.ucsf.edu/hivcntr/

Hotlines/Perinatal.html; the number 

of the hotline for the service is 888-

448-8765)

• For pregnant women or women 

who may become pregnant, give 

folate (folate dosage should be 

4-5 mg QD for women who take 

TMP-SMX, to overcome the folateantagonist effects of TMP-SMX)

• ART during pregnancy:

• Test for HIV resistance before 

initiating ART

• Give combination ART with goal 

of maximal virologic suppression

• Recommended agents for use 

during pregnancy*:

• ZDV + 3TC, combined with 

NVP or LPV/r

• Alternative ARVs during pregnancy:

• NRTIs: ABC,# ddI, FTC, d4T

• NNRTIs: none

• PIs: IDV/r, NFV, RTV, SQV/r

• Goals include maximal 

suppression of HIV 

RNA to prevent HIV 

transmission and to 

optimize the patient’s 

health.

• Higher risk of perinatal 

transmission with: 

• High viral load

• Low CD4 count

• Advanced HIV 

infection

• Poor nutrition

• Drug use 

• STD

• Vaginal delivery (if 

HIV RNA >1,000 

copies/mL)

• Invasive monitoring

• Prolonged rupture 

of membranes

• Chorioamnionitis

• Without ART, risk of 

transmission is 25%; 

with PI-based ART, risk 

of transmission is 1% in 

the United States.

• Pharmacokinetic changes 

during pregnancy may 

alter serum levels of 

some ARVs; check 

USPHSTF guidelines for 

recommended dosage 

adjustments; consult 

with pharmacologist.

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WOMEN’S HEALTH

256 PRIMARY CARE OF VETERANS WITH HIV

FPV, TPV, ENF, RTV, MVC

• Avoid use of EFV, DLV: risk of 

teratogenicity, especially during fi rst 

trimester) 

y p

ommend increase 

in LPV/r dosage to 

600/150 mg BID 

during 3rd trimester.

• Some evidence suggests 

ART may increase rates 

of preeclampsia.

• Consider scheduled 

cesarean section delivery if HIV viral load is 

>1,000 copies/mL near 

time of delivery.

Breastfeeding• Breast-feeding is not recommended in 

the United States (to avoid risk of HIV 

transmission through breast milk).

Menstrual 

irregularities 

and menopause

• Evaluate menstrual irregularities 

as in HIV-uninfected women. Initial 

considerations include:

• For abnormal bleeding, seek to 

determine source of bleeding 

(bladder, urethra, vagina, uterus), 

with further evaluation depending on source

• Pregnancy test

• Consider polycystic ovarian syndrome (PCOS) in women with 

amenorrhea or hypomenorrhea 

and features suggestive of PCOS 

(clinical or serum hyperandrogenism, glucose intolerance, 

obesity)

• Consider menopause (check 

follicle-stimulating hormone 

[FSH] to confi rm)

• Consider checking FSH and 

prolactin for secondary causes 

of amenorrhea

• Consider hypothyroidism (check 

TSH)

• For intermenstrual bleeding, 

evaluate for estrogen or progestin breakthrough on hormonal 

contraceptives, complications of 

intrauterine device, polyps, genital tract cancers, genital tract 

infections such as endometritis

• HIV-infected women 

more commonly experience irregular cycles 

and amenorrhea, but 

it is not entirely clear 

whether this is associated with HIV infection 

itself. Some research 

suggests associations 

between CD4 count 

and ovulatory status.

• Confounders include 

weight loss, psychiatric 

medications, hormonal 

treatments, substance 

abuse, stress, and 

chronic disease. 

• Prolonged amenorrhea 

without ovarian failure 

in HIV-infected women 

is associated with low 

body mass index and 

low serum albumin.

• Combined analysis of 

data from the HERS 

and WIHS cohorts 

showed that women on 

ART with good CD4 

response had lower 

rates of menstrual 

irregularities than HIVuninfected women.

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PRIMARY CARE OF VETERANS WITH HIV 25

pg

for cervical malignancies and 

lesions, also for STDs

• Treatment of menopausal symptoms: consider hormonal therapy 

as for HIV-uninfected women; keep 

in mind potential adverse effects, 

as well as drug-drug interactions 

between estrogens and some ARVs 

(see Potential ARV Interactions

below)

y

average age at onset 

of menopause was 48 

for both HIV-infected 

women and HIVuninfected women of 

similar demographics. 

• There is a blunted 

CD4 recovery to ART 

among postmenopausal 

women with HIV. This 

is postulated to be 

related to lower levels 

of estrogen and with 

decrease in thymic volume (associated with 

aging).

Sexual 

function

Evaluate women’s perceived 

level of and satisfaction with sexual 

function 

Evaluate for factors related to 

perceptions of suboptimal sexual 

function:

• Physical, sexual, emotional abuse

• Relational problems

• Depression

• STDs

• Medications

• Pelvic pain

• Constitutional symptoms

• Peripheral and autonomic 

neuropathy 

• Hypogonadism 

• Other medical and psychiatric 

comorbidities

Sexual function in HIVinfected women is a 

neglected area of study. 

Discuss patient’s concerns 

candidly.

• Patient-reported sexual 

dysfunction is associated with nonadherence to ART.

• Sexual dysfunction may 

be a marker for depression, worsening health 

status including pain 

syndromes, or intimate 

partner violence.

• A wide variety of 

medications, especially 

psychiatric, antiepileptic, and cardiovascular 

drugs, are associated 

with sexual dysfunction.

Abbreviations: HERS = Heart and Estrogen/Progestin Replacement Study; USPHSTF = U.S. Public 

Health Services Task Force; WIHS = Women’s Interagency HIV Study

* Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant 

HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in 

the United States; November 2, 2007.

# If possible, check for HLA-B*5701 before treatment with ABC.

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WOMEN’S HEALTH

258 PRIMARY CARE OF VETERANS WITH HIV

! POTENTIAL ARV INTERACTIONS

Hormonal Contraception and ARVs

Drug interactions between oral contraceptive agents and many PIs and NNRTIs 

may affect the serum levels of either the hormonal agent or the ARV. In some cases, 

contraceptive effi cacy or the potential for side effects may be affected signifi cantly. 

Dosage adjustments may be required, and some combinations are contraindicated. 

See table below for details. 

There are very few data on potential interactions between ARVs and nonoral 

hormonal contraceptives. Transdermal (patch) and transvaginal (intravaginal ring) 

contraceptive devices contain ethinyl estradiol (EE); thus caution should be used 

on a theoretical basis with ARVs that increase the serum estradiol levels. DMPA 

(Depo-Provera) is a progestin; thus, its interactions with ARVs may mirror those of 

norethindrone (NE). This may be cause for concern if DMPA is used with ARVs that 

increase NE levels, because DMPA is long-acting and has sustained serum levels. 

There are no signifi cant known interactions between hormonal contraceptives and 

NRTIs, integrase inhibitors, or CCR5 antagonists.

Potential Interactions between Oral Contraceptives and PIs or 

NNRTIs

Decreased EE or NE levels

PIs:

• ATV/r

• DRV/r

• LPV/r

• NFV

• RTV

• TPV/r

Risk of contraceptive failure; use alternative (or additional) 

contraceptive method

(If oral contraceptive used with ATV/r, it should contain ≥35 

mcg of EE.)

NNRTIs: 

• NVP

Risk of contraceptive failure; use alternative (or additional) 

contraceptive method.

Increased EE or NE levels

PIs (without RTV): 

• ATV 

• FPV

• IDV

• ATV: Risk of EE or NE adverse effects (eg, deep vein 

thrombosis). Use alternative method of contraception 

or lowest effective dosage with careful monitoring for 

adverse effects. If given concurrently, oral contraceptive 

should contain ≤30 mcg of EE; however, doses <25 mcg 

have not been studied.

• FPV: Risk of EE or NE adverse effects; also, ↓ FPV levels; 

avoid, or use lowest effective dosage of EE/NE with careful 

monitoring for adverse effects and for ARV effi cacy.

• IDV: No dosage adjustment.

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PRIMARY CARE OF VETERANS WITH HIV 25

EFV

p

method is recommended.

No data

PIs: 

• SQV

Alternative method of contraception is recommended.

Mixed effects

NNRTIs:

• ETR

↑ EE, ↓ NE; no dosage adjustment.

Neuropsychiatric Disorders 

Recommendations Comments

Screen for neuropsychiatric disorders in HIV-infected women

• Depression

• Dementia

• Posttraumatic stress disorder 

(PTSD)

• Personality disorders

Perform neuropsychiatric testing 

as needed

Neuropsychiatric disorders are common in HIVinfected individuals:

• Direct effects of HIV on neuronal function

• Underlying psychiatric disease

• Affective disorders

• Prior trauma

• Social comorbidities

• Personality disorders

Women with HIV are at increased risk of 

HIV- associated psychiatric disease, especially 

HIV- related dementia, but also at risk of underdiagnosis and undertreatment of depression.

Neuropsychiatric testing is recommended to 

establish diagnosis.

Owing to increased rates of depression and PTSD 

in women veterans, aggressive screening and 

treatment of depression in HIV-infected women is 

recommended.

Substance abuse is often comorbid with PTSD 

and depression.

For women with HIV infection, especially those 

with multiple responsibilities, psychosocial needs 

may be complex, requiring multidisciplinary team 

care. Research suggests that case management 

can improve outcomes, care, and treatment 

adherence.

For further information, see Depression, p. 271.

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WOMEN’S HEALTH

260 PRIMARY CARE OF VETERANS WITH HIV

Issue Recommendations Comments

Military sexual 

trauma (MST)

• Screen all veterans, including 

female veterans, for MST.

• Refer veterans with MST to 

the designated MST Counselor 

or team; referral to a local Vet 

Center may be an appropriate 

alternative based on available 

services.

• All VA Medical Centers 

have designated MST 

Coordinators.

• 30-45% of female veterans 

have been exposed to MST.

• Effects of MST include:

• Avoidance of places 

or objects that recall 

memories of the traumatic incident

• Anxiety

• Depression

• Suicidal thoughts

• Misuse of alcohol and 

other substance

• Recurring and intrusive 

thoughts and dreams 

about the trauma 

incident

• Nonspecifi c health 

problems

• Problems with interpersonal relationships

Domestic 

violence

• Consider screening with the 

HITS scale:

• urt: How often does your H

partner physically hurt you?

• nsult: How often does your I

partner insult or talk down 

to you?

• hreaten: How often does T

your partner threaten you 

with physical harm?

• cream: How often does S

your partner scream or 

curse at you?

Each question is answered on a 

5-point scale: 1 = never; 2 = rarely; 

3 = sometimes; 4 = fairly often; 5 = 

frequently. The score ranges from 4 

to a maximum of 20. A score of ≥10 

is considered diagnostic of abuse.

• Domestic violence is prevalent among both female 

veterans and women living 

with HIV infection.

• Screening instruments 

such as the HITS scale 

have been validated.

• There is weak evidence 

for the effi cacy of interventions in the health care 

setting.

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PRIMARY CARE OF VETERANS WITH HIV 26

py

abuse (bruises, fractures, injuries 

accompanied by implausible 

explanation).

• If abuse is documented or 

suspected:

• Consult Social Work Service

• Refer the patient to community domestic violence 

agencies

• Work with the patient to develop 

an emergency safety plan.

Screening: Cancer, Osteoporosis, and STDs

Note: For other routine cancer screening, see Cancer Screening, p. 17.

Test Recommendations Comments

Cervical cancer 

screening:

• Cervical Pap test 

(smear or liquid 

cytology) 

• Baseline 

• Repeat in 6 months

• If both Pap results are 

normal and CD4 count 

is >200 cells/μL, repeat 

annually 

• If both Pap results are 

normal and CD4 count 

is <200 cells/μL, repeat 

every 6 months

• If any Pap smear result 

is abnormal, additional 

testing should be done; 

see Cervical Dysplasia and Management 

of Abnormal Pap 

Smear Results, below 

• HIV-infected women are more 

likely than HIV-uninfected women 

to be infected with HPV, especially with oncogenic HPV types. 

• Dysplasia may involve the cervix, vulva, vagina, or anus.

• Abnormalities on cervical 

colposcopy are seen in 64% 

of women with CD4 counts 

of <200 cells/μL and 34% of 

those with CD4 counts of 

>400 cells/μL.

• HIV-infected women have 

decreased rates of clearance of 

HPV; as a result, they have an 

increased risk of disease progression and recurrence.

• For management of abnormal 

results, see Cervical Dysplasia and Management 

of Abnormal Pap Smear 

Results, below.

Vulvar and vaginal 

cancer screening:

• Visual and manual 

inspection

• Evaluate at times of 

cervical Pap test

• Suspicious lesions: colposcopy; biopsy

• HIV-infected women have 

elevated rates of vulvar and 

vaginal neoplasia.

• Lesions may be multifocal, 

extensive, and recurrent, and 

may have an unusual appearance; 

sometimes progressing rapidly, 

especially in women with CD4 

counts of <200 cells/μL.

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WOMEN’S HEALTH

262 PRIMARY CARE OF VETERANS WITH HIV

are resistant to treatment and 

unusual vulvar lesions should 

be referred for biopsy; also 

check RPR.

Anal cancer 

screening: 

• Digital rectal 

examination 

(DRE)

• Anal Pap test

No national guidelines 

for anal cancer screening; 

consider:

• Baseline

• Annual DRE and anal 

Pap screening if patient 

is sexually active and 

baseline result was 

normal

• Use polyester swab and 

liquid cytology method, 

if available 

• Anal dysplasia and anal cancer rates among HIV-infected 

women are not fully known but 

appear to be higher than those 

for HIV-uninfected women.

• Anal dysplasia is seen in 

women with and without a history of receptive anal sex.

• ART has not been shown to 

prevent or alter the course of 

anal dysplasia.

• ASCUS, LSIL, HSIL: Refer for 

high-resolution anoscopy with 

biopsy.

• Screening was cost-effective 

in a small study; no large-scale 

clinical trials on cost-effectiveness have been conducted.

• See Anal Dysplasia, p. 83. 

Breast cancer 

screening:

• Mammogram 

• Age 40-69: every 

1-2 years

• Age ≥70: discuss and 

take into account estimated life expectancy 

and presence of comorbid disease

• HIV-infected women do not 

appear to have elevated risk of 

breast cancer.

• see Cancer Screening, p. 17.

Osteoporosis/

osteopenia 

screening:

• Dual-energy X-ray 

absorptiometry 

(DEXA) bone 

densitometry 

• Baseline for patients at 

risk and all women >65 

years of age

• Also consider for thin 

female smokers >40 

years of age 

• Every 1-2 years for 

patients with osteoporosis who are treated 

with bisphosphonates

• Age and previous fracture are 

the most signifi cant risk factors.

• See Osteoporosis, below, for 

more information and treatment recommendations.

STD screening:

• RPR, VDRL

• Cervical GC and 

CT (NAAT or culture of fi rst-void 

urine or cervical 

specimen)

• Perform at baseline, 

repeat according to 

risks or exposures (eg, 

every 3-6 months for 

women with new sex 

partners since previous 

examination)

• STDs should be treated to 

prevent health complications 

for the patient, and also to prevent perinatal transmission or 

transmission to sex partners.

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PRIMARY CARE OF VETERANS WITH HIV 26

p

ryngeal testing 

for GC and CT, 

based on possible 

risks or exposures 

(NAAT or culture 

of swab)

• (wet- Trichomonas

mount examination or culture of 

vaginal secretions)

• HBV, HCV

• HSV IgG (type 

specifi c)

y y 

increase risk of HIV transmission to uninfected sex 

partners.

• See Prevention for 

Positives, p. 39.

Abbreviations: ASCUS = atypical squamous cells of undetermined signifi cance; CT = Chlamydia 

trachomatis; GC = Neisseria gonorrhea; HSIL = high-grade squamous intraepithelial lesion; LSIL = lowgrade squamous intraepithelial lesion; NAAT = nucleic acid amplifi cation test

Cervical Dysplasia and Management of Abnormal Pap Smear Results

Epidemiology and Diagnosis Management and Treatment

• HPV prevalence is higher among HIVinfected women than among HIV-uninfected women.

• In the WIHS cohort, prevalence of genital HPV among HIV-infected women is 

approximately 64%, compared with 30% 

among HIV-uninfected women.

• HIV-infected women have increased persistence of HPV and greater likelihood 

of high-risk oncogenic types of HPV.

• Women with low CD4 counts tend to 

harbor high-risk HPV types. 

• HIV-infected women are at greater risk 

of cervical dysplasia and cervical cancer.

• The time between diagnosis of carcinoma in situ and development of 

invasive disease is shorter among HIVinfected women who are not on ART 

than among HIV-uninfected women (3.2 

vs 15.7 years).

• However, ART has not been shown 

consistently to prevent or alter the 

course of cervical dysplasia in HIVinfected women.

See Screening: Cancer, Osteoporosis, 

and STDs, above, for screening recommendations.

• Most experts recommend more 

aggressive management of HIV-infected 

women than HIV-uninfected women. 

The American Society for Colposcopy 

and Cervical Pathology (ASCCP) 

recommends managing HIV-infected 

women no differently than HIV-uninfected women. 

• There is controversy about ASCUS: 

management of ASCUS in HIV-infected 

women: 

• Most authorities recommend that 

HIV-infected women with ASCUS 

be referred for colposcopy. 

• In HIV-infected women, there are 

insuffi cient data to recommend 

HPV DNA testing for oncogenic 

HPV types as part of management 

of ASCUS.

• ASC-H (atypical squamous cells, 

cannot exclude HSIL), LSIL, HSIL, 

and atypical glandular cells: Refer 

all patients with these fi ndings for colposcopy. Note that some laboratories 

use the cervical intraepithelial neoplasia 

(CIN) 1, 2, 3 classifi cation; these patients 

should also be referred for colposcopy.

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WOMEN’S HEALTH

264 PRIMARY CARE OF VETERANS WITH HIV

Epidemiology and Diagnosis Management and Treatment

Background

• In small cohort studies, HIV-infected 

women had twice the rate of osteopenia (by DEXA) as HIV-uninfected 

women matched for age, race, and BMI. 

• HIV infection itself appears to be independently associated with reduced 

bone mineral density.

• Exposure to ARVs, specifi cally PIs, has 

not been found to be associated with 

osteoporosis.

Risk factors

• History of fracture as an adult

• Age 

• Female sex 

• Race (Asians and Caucasians at higher risk)

• Family history

• Low body weight (<58 kg, 127 lb) or 

weight loss

• Estrogen defi ciency at early age (amenorrhea >1 year, early menopause)

• Lifestyle: current cigarette smoking, alcohol misuse, inadequate physical activity

• Poor health/nutrition (eg, low calcium 

intake)

• Medications (eg, corticosteroids, anticonvulsants, gonadotropin-releasing 

hormone [GnRH] agonists, lithium)

• Medical conditions (eg, hyperthyroidism, 

gastrectomy, COPD, hyperparathyroidism, multiple myeloma, celiac disease, 

eating disorder)

• Recurrent falls, dementia

Evaluation

• DEXA screening for women with risk 

factors or age >65 (see above):

• Normal = T-score above –1 

• Osteopenia = T-score between –1 

and –2.5 

• Osteoporosis = T-score less than 

–2.5 (a fracture-threshold)

Prevention (for all women)

• Calcium* 1,000 mg per day for premenopausal women; 1,500 mg per day for 

postmenopausal women, in divided doses 

• Vitamin D 400-800 IU QD (800-1,000 

IU in women age >50 years)

• Exercise: 30 minutes of weight-bearing 

exercise ≥4 times per week

• Smoking cessation, limited alcohol intake, 

adequate diet, careful sun exposure

• Women taking calcium and vitamin D 

supplements in the Women’s Health Initiative had a 1% gain in hip bone mineral 

density and a slight but statistically nonsignifi cant reduction in hip fracture (hazard 

ratio: 0.71; 95% confi dence interval: 0.52-

0.97 [for women with ≥80% adherence]).

Treatment

 Treat women with:

• T-score below –2.0 in the absence of 

risk factors 

• T-score below –1.5 + risk factors

• Age >70 + multiple risk factors

Treatment options

• Bisphosphonates offer the most clinically signifi cant benefi t. Randomized 

controlled studies show a 56% reduction in hip fractures in patients treated 

with alendronate. Options include:

• Alendronate 70 mg PO once weekly

• Ibandronate 150 mg PO once 

monthly

• Zoledronic acid 5 mg IV once yearly

Plus:

• Calcium* 1,500 mg per day in divided 

doses 

• Vitamin D 800-2,000 IU QD

• Smoking cessation 

• Limited alcohol intake

• Exercise: 30 minutes of weight-bearing 

exercise ≥4 times per week

* Calcium and other divalent cations may lower serum levels of integrase inhibitors; calcium should 

be taken ≥2 hours apart from integrase inhibitors.

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PRIMARY CARE OF VETERANS WITH HIV 26

Infection Epidemiology and Diagnosis Management 

HSV • Risk factor for HIV acquisition and 

transmission

• Of HIV-infected women, 50-90% have 

concurrent HSV infection

• In the HERS study, there was no difference in rates between HIV-infected and 

high-risk HIV-uninfected women

• Chronic suppressive therapy with acyclovir may increase survival for HIV/

HSV-coinfected women who do not 

take ARVs; this benefi t is not demonstrated in patients on ART

• Infection can be primary, nonprimary 

fi rst episode, or recurrent

• Most genital HSV infections occurring 

in HIV coinfection refl ect reactivation 

syndromes; symptomatic episodes may 

be more severe, more frequent, and 

longer in duration than in HIV-negative 

women

• Genital HSV in HIV-infected women 

ranges in appearance from small 

confi ned ulcers to painful extensive 

necrotic lesions accompanied by constitutional symptoms

• Complications seen more commonly in 

advanced HIV infection include aseptic 

meningitis, sacral radiculopathy, transverse myelitis, scarring, rectovaginal 

fi stulae

Diagnosis: swab base of lesion for testing via viral culture, direct fl uorescentantibody assay, HSV PCR, or Tzanck prep 

(less sensitive)

Differential diagnosis includes: syphilis, 

chancroid, drug eruptions, Behçet syndrome

• Initial episode or severe 

mucocutaneous outbreak: 

hospitalize and treat with 

IV acyclovir (5 mg/kg IV 

Q8H) for 7-14 days, changing to PO therapy when 

lesions improve

• Episodic therapy for outbreaks: valacyclovir 1,000 

mg BID, acyclovir 400 mg 

TID, or famciclovir 500 mg 

BID for 5-14 days

• Suppressive therapy: consider for patients with 

frequent recurrences, 

especially those with CD4 

counts of <100 cells/μL 

and severe protracted 

outbreaks: 

acyclovir 400 mg BID, 

valacyclovir 500 mg BID, 

or famciclovir 500 mg BID 

• During pregnancy, refer 

to OB/GYN specialist for 

management

• Counsel use of latex barriers to prevent HSV 

transmission to uninfected 

partners

Genital 

ulcers

• Risk factor for HIV acquisition and 

transmission

• Research indicates prevalence as high 

as 14% in an urban population, with 

recurrence rate of 19%

Initial episode: 

• Attempt to establish a 

diagnosis: laboratory testing (viral, bacterial culture, 

serology) or biopsy

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WOMEN’S HEALTH

266 PRIMARY CARE OF VETERANS WITH HIV

pathogen

• Differential diagnosis includes syphilis, 

chancroid, HSV (see above); may be 

caused by atypical pathogens identifi ed 

(CMV, Chlamydia trachomatis, Gardnerella vaginalis)

• In women, genital ulcers often are not 

noticed

• Lesions may be large, requiring multiple 

admissions and surgical procedures

lesions, prompt evaluation 

and management, possibly 

including hospitalization 

and surgery, may be needed 

to prevent scarring, vaginal 

or urethral stricture, or 

fi stulae

• Follow up carefully to 

evaluate for recurrence

Bacterial 

vaginosis 

(BV)

• Risk factor for HIV acquisition and 

transmission

• HIV-infected women have increased 

persistence of BV, especially with CD4 

counts of <200 cells/μL

Diagnosis (3 of 4 Amsel criteria):

• Homogeneous, thin, grayish-white 

discharge that smoothly coats the 

vaginal walls

• Vaginal pH >4.5

• Positive whiff-amine test, defi ned as 

the presence of a fi shy odor when 

10% KOH is added to a sample of 

vaginal discharge

• Clue cells on saline wet mount

• Metronidazole 500 mg BID 

for 7 days

Alternatives:

• Topical vaginal therapy 

• e gel Metronidazol

0.75%, 5 g QD for 5 

days

• Clindamycin cream 2%, 

5 g QD for 7 days

• n 300 mg PO Clindamyci

BID for 7 days (less evidence for effi cacy; higher 

risk of Clostridium diffi cile)

Vaginal 

candidiasis

• HIV-infected women may have higher 

rates of persistence and recurrence (≥4 

episodes per year) 

Diagnosis: budding yeast and hyphae on 

10% KOH wet mount of vaginal discharge

• Single episode: 

• Topical azoles for 3-7 days

• e 150 mg PO Fluconazol

for 1 dose

• Itraconazole 200 mg 

PO BID for 1 day or 

QD for 3 days

• Recurrent episodes (≥4 

episodes per year):

• luconazole 150 mg PO F

for 3 doses 72 hours 

apart, followed by fl uconazole 150 mg PO once a 

week for 6 months

Pelvic 

infl ammatory 

disease 

(PID)

• Among women with HIV infection, risk 

for severe morbidity and mortality is 

increased and PID may be more severe 

at time of presentation

• Consider hospitalization 

in event of severe illness, 

pregnancy, or inability to 

take oral therapy

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PRIMARY CARE OF VETERANS WITH HIV 26

incidence of tuboovarian abscesses in 

HIV-infected women

• HIV-infected women with PID respond 

to the same antibiotics as HIV-uninfected women but may need surgical 

interventions more frequently

• Causative organisms include Chlamydia 

trachomatis, Neisseria gonorrhea, Streptococcus spp, Escherichia coli, Klebsiella spp, 

Proteus spp, and BV fl ora

• Risk factors: multiple partners, partner 

with an STD or STD symptoms, prior 

STD, IUD in situ

• Clinical presentation: bilateral lower 

abdo minal pain, often <2 weeks’ duration, 

worse with coitus or jarring movements

Clinical diagnosis:

• Lower abdominal pain, plus one of the 

following:

• Cervical motion tenderness or 

uterine/adnexal tenderness

• Temperature >101oF (>38.3oC)

• Leukocytosis

• Abnormal cervical or vaginal 

mucopurulent discharge

• Presence of WBCs on saline 

microscopy of vaginal secretions

• Elevated erythrocyte sedimentation rate

• Elevated C-reactive protein

• An adnexal mass suggests tuboovarian 

abscess

• Laparoscopic evaluation is recommended for:

• Strongly suspected competing diagnosis (eg, appendicitis)

• Acutely ill patients for whom outpatient treatment of PID has failed

• Patients not clearly improving after 72 

hours of inpatient treatment for PID

• e 250 mg IM for Ceftriaxon

1 dose, plus doxycycline 

100 mg PO BID for 14 

days, with or without 

metronidazole 500 mg 

PO BID for 14 days 

• n 2 g IM for 1 dose Cefoxiti

with probenecid 1 g PO for 

1 dose, plus doxycycline 

100 mg PO BID for 14 

days, with or without 

metronidazole 500 mg 

PO BID for 14 days

• Consultation with OB/

GYN is recommended as 

treatment failures, delayed 

diagnosis, and loss to 

follow-up are common

* STD treatments refl ect current CDC guidelines.

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WOMEN’S HEALTH

268 PRIMARY CARE OF VETERANS WITH HIV

REFERENCES

Centers for Disease Control and Prevention. Sexually transmitted diseases treatment 

guidelines 2006. MMWR 2006. Available at http://www.cdc.gov/std/Treatment/. Accessed 

November 20, 2008.

Kojic EM, Cu-Uvin S. Special care issues of women living with HIV-AIDS. Infect Dis Clin 

North Am. 2007 Mar;21(1):133-48, ix. 

Kojic EM, Wang CC, Cu-Uvin S. HIV and menopause: a review. J Womens Health 

(Larchmt). 2007 Dec;16(10):1402-11. 

McNicholl I. Database of Antiretroviral Drug Interactions. In: Coffey S, Volberding PA, eds. 

HIV InSite Knowledge Base [textbook online]. San Francisco: UCSF Center for HIV 

Information; 2008. Available at http://hivinsite.ucsf.edu/insite?page=ar-00-02. Accessed 

November 20, 2008.

National Institutes of Health, Centers for Disease Control and Prevention (CDC), HIV 

Medicine Association of the Infectious Diseases Society of America. Guidelines for 

Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents – June 18, 2008. Available at http://www.aidsinfo.nih.gov/Guidelines. Accessed 

November 20, 2008.

Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal 

Health and Interventions to Reduce Perinatal HIV Transmission in the United States. 

July 8, 2008. Available at http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf. Accessed 

November 20, 2008.

Screening for Cervical Cancer, Topic Page. January 2003. U.S. Preventive Services Task Force. 

Agency for Healthcare Research and Quality, Rockville, MD. Available at http://www.ahrq.

gov/clinic/uspstf/uspscerv.htm. Accessed November 20, 2008.

Sherin KM, Sinacore JM, Li XQ, et al. HITS: a short domestic violence screening tool for 

use in a family practice setting. Fam Med. 1998 Jul-Aug;30(7):508-12.

Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 American Society for Colposcopy and 

Cervical Pathology-sponsored Consensus Conference. 2006 consensus guidelines for 

the management of women with abnormal cervical cancer screening tests. Am J Obstet 

Gynecol. 2007 Oct;197(4):346-55.

Zinzow HM, Grubaugh AL, Monnier J, et al. Trauma among female veterans: a critical 

review. Trauma Violence Abuse. 2007 Oct;8(4):384-400.

UCS-PCM-08-0701-womens health.indd 268 CS-PCM-08-0701-womens health.indd 268 3/16/09 /16/09 
Neurology, Psychiatry, and Pain

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/19/09 
PRIMARY CARE OF VETERANS WITH HIV 27

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Depression

KEY POINTS

■ Depression can be a life-threatening disorder.

■ Depression among HIV-infected persons is common and is 

associated with increased high-risk behavior, nonadherence to ART, 

and progression of immunodefi ciency.

■ Depression can be diagnosed and treatment can be initiated in the 

primary care setting.

■ Potentially treatable causes of secondary depressive symptoms in 

HIV-infected persons should be investigated and treated.

■ Antidepressant medication and psychotherapy both are effective for 

treating depression in HIV-infected persons.

Linking Primary Care and Mental Health Care Services in the 

Treatment of Depression

VA medical centers and community-based outpatient clinics are now integrating mental health services into primary care settings. The model on which these 

clinics are structured and their services are delivered varies from one facility to 

another, but primary care providers should be knowledgeable about when they 

should refer for mental health consultation and when they can successfully treat 

depressive symptoms themselves.

WHEN TO REFER

Indications for referring depressed patients to a mental health 

care provider: 

• Disabling symptoms

• Suicidal thought with plan or intent

• Severe hopelessness or negativism

• Persistent agitation

• Psychotic symptoms

• Pronounced affective instability

• Suspected bipolar disorder

• 3 or more ineffective therapeutic trials of antidepressant medication

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DEPRESSION

272 PRIMARY CARE OF VETERANS WITH HIV

 Complicated psychopharmacologic regimens requiring medications that the 

care provider is not experienced in prescribing

• Need for tricyclic antidepressants (TCAs)

• Maladaptive social functioning

BACKGROUND

■ Lifetime prevalence of depression among 

HIV-infected persons in the United 

States is 20-40%, up to 2-fold higher 

than it is among HIV-uninfected persons. 

Among veterans, this percentage may 

even be higher (see box at right).

■ Depression increases the risk of 

acquiring HIV infection and the likelihood 

of high-risk sexual behavior among persons already infected with HIV.

■ Depression is associated with nonadherence to ART, progression of HIV 

disease, and decline in CD4 cell count.

■ Treatment of depression improves adherence to ART.

EVALUATION

SCREENING

Recommended Screening for Depression in Primary Care 

Settings

The VA recommends using the PHQ-2 and PHQ-9 instruments to screen 

for depression in the primary care setting, a use for which they are validated, 

and recommends that the result of screens be entered in the chart on the 

day they are administered. Telephone screening is acceptable, provided that 

positive screening results are addressed by appropriate risk assessments and 

interventions.

PHQ-2 and PHQ-9

The PHQ-2 is a 2-question screen. The maximum score is 6, and a positive 

score is 3. If the PHQ-2 result is negative, further screening is unnecessary. If the 

PHQ-2 result is positive, the patient must be screened on the same day with the 

PHQ-9, with responses to all questions and the summary score to be recorded 

Veterans with HIV*

Depression: 49%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-9 

code corresponding to this condition 

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PRIMARY CARE OF VETERANS WITH HIV 27

alone, with responses to all questions and the summary score to be recorded in 

the patient’s chart.

Patients who screen positive for depression should be evaluated for risk factors that indicate a need for urgent intervention. Foremost in this process is 

an explicit assessment for the presence of suicidal ideation. After an evaluation 

of screening results and a discussion with the patient, the provider can decide 

whether the patient may benefi t from urgent intervention or further specialized 

mental health evaluations.

■ Note: The CPRS Clinical Reminder supporting the standard PHQ-2 and 

PHQ-9 tools will display the questions comprising these instruments when 

the “Perform PHQ-2” and “Perform PHQ-9” buttons are clicked, and it allow

for documentation of depression screen results, as shown: 

Acceptable screening is summarized as follows: 

Screening Tool Used PHQ-2 Result PHQ-9 Result

If PHQ-2 initially used: And result Negative, then: Not required 

If PHQ-2 initially used: And result Positive, then: Required on same day

If PHQ-9 initially used: Not required NA 

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DEPRESSION

274 PRIMARY CARE OF VETERANS WITH HIV

Scoring the PHQ-2

PHQ-2 

Score

Probability 

of Major 

Depressive 

Disorder (%)

Probability of 

Any Depressive 

Disorder (%)

1 15.4 36.9

2 21.1 48.3

3 38.4 75.0

4 45.5 81.2

5 56.4 84.6

6 78.6 92.9

Copyright © 1999 Pfi zer, Inc. All rights reserved. 

Reproduced with permission.

Patient Health Questionnaire – 9 (PHQ-9)

Over the last 2 weeks, how often have

you been bothered by any of the 

following problems?

Not 

at all

Several 

days

More 

than half 

the days

Nearly 

every 

day

1. Little interest or pleasure in doing things 0 1 2 3

2. Feeling down, depressed, or hopeless 0 1 2 3

3. Trouble falling or staying asleep, or sleeping too much01 2 3

4. Feeling tired or having little energy 0 1 2 3

5. Poor appetite or overeating 0 1 2 3

6. Feeling bad about yourself – or that you 

are a failure or have let yourself or your 

family down

01 2 3

()

Patient Name: ______________________________ Date of Visit: __________

Over the past two weeks, how often 

have you been bothered by any of 

the following problems?

Not at 

all

Several 

days

More 

than 

half the 

days

Nearly 

every 

day

1. Little interest or pleasure in doing things 0 1 2 3

2. Feeling down, depressed, or hopeless 0 1 2 3

Total point score: _____

UCS-PCM-08-0701-Depression.indd 274 CS-PCM-08-0701-Depression.indd 274 3/26/09 /26/09 
PRIMARY CARE OF VETERANS WITH HIV 27

g g

reading the newspaper or watching television

8. Moving or speaking so slowly that other 

people could have noticed, or the opposite 

– being so fi dgety or restless that you have 

been moving around a lot more than usual

01 2 3

9. Thoughts that you would be better off 

dead, or of hurting yourself in some way

01 2 3

Add columns:

0 + ____ + _____ + ____

= Total Score:

_______

If you checked off any problems, how diffi cult have these problems made it 

for you to do your work, take care of things at home, or get along 

with other people?

Not diffi cult 

at all



Somewhat 

diffi cult



Very 

diffi cult



Extremely

diffi cult



Copyright © Pfi zer Inc. All rights reserved. Reproduced with permission of Pfi zer, Inc.

Scoring the PHQ-9

1-4 Minimal depression

5-9 Mild depression

10-14 Moderate depression

15-19 Moderately severe depression

20-27 Severe depression

Clinicians should be particularly alert to patients’ responses to question 9, “Thoughts 

that you would be better off dead, or of hurting yourself in some way.” Any affi rmative 

response to question 9, or a PHQ-9 score of >9, requires that a suicide risk assessment be completed within 24 hours (see below).

The PHQ-9 is validated for use only with English-speaking persons of European 

origin; some experts feel it is less sensitive for depression in many patients with 

Asian or Latino backgrounds. As with all symptom questionnaires, assessment 

results should be interpreted and guided by clinical experience.

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DEPRESSION

276 PRIMARY CARE OF VETERANS WITH HIV

major depression

Given the overlap between symptoms of depression and symptoms of other 

illnesses and medication side effects common among HIV-infected persons, all 

potentially treatable or reversible causes of depression (see list below) should be 

considered when HIV-infected persons present with depressive symptoms. 

Screening • PHQ-2 (see above)

• PHQ-9 (see above)

History • Relationship between onset of depression symptoms and major 

life stressors

• Concurrent chronic disease

• Medication history, including recent changes

• Use of alcohol or other psychoactive drugs, whether legal or illegal

• Past history of depression

• Suicidal thoughts

• Family history of mental illness

Physical 

examination

• Mini mental status

• Neurologic screening

• Signs of hypogonadism

• Signs of hypothyroidism

Laboratory 

studies

• Serum electrolytes

• BUN/creatinine

• Calcium (for hypercalcemia)

• CBC (for anemia)

• TSH

• Serum testosterone

• Hepatitis serologies

• RPR

Differential 

diagnosis

• Mood disorders

• Major depression

• Bipolar affective disorder

• Dysthymia (minor depression)

• Demoralization

• Drug use

• Alcohol use/abuse

• Anemia

• HIV-associated dementia, other dementia

• Hypercalcemia

• Renal failure

• Hepatitis

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PRIMARY CARE OF VETERANS WITH HIV 27

ypy

• Hypogonadism

• Drug effects or side effects (eg, EFV, anabolic steroids, corticosteroids, sedative-hypnotics, beta-blockers, reserpine, interferon, 

alcohol, methamphetamine withdrawal)

• CNS infections

• CNS neoplasms

Assessment of suicide risk

Veteran suicide is emerging as a serious public health issue, and primary care 

providers are on the front line in identifying veterans with risk factors for suicide 

and ensuring they receive appropriate interventions. An affi rmative response to 

questions about suicidality on screening instruments, such as the PHQ-9, should 

prompt further investigation. When the PHQ-9 is used, a score >9 or any 

affi rmative response to question 9 requires that a suicide risk assessment be performed within 24 hours; ideally, this risk assessment should 

immediately follow a positive screening result for depression. 

Such assessments may be performed by telephone, provided that the assessment is made by an acceptable provider, and that the results are appropriately 

documented. An acceptable provider is an MD, NP, DO, PsyD or PhD Psychologist, LCSW, APN, PA (or a trainee with appropriate cosignature), or other allied 

health care professional who, by virtue of educational background and approved 

credentialing, privileging, or scope of practice, has been determined by the facility 

to be capable of diagnosing and treating mental illness.

All VA medical centers now have a designated suicide prevention coordinator, 

whose role includes providing general consultation to clinicians concerning risk 

assessment, providing resources for suicidal individuals, and ensuring that highrisk patients receive education and support about approaches to reduce risks.

The CPRS contains a detailed suicide risk assessment template. To assess patient

for suicide risk:

■ Look for warning signs

■ Assess for risk and protective factors

■ Ask the questions

1. Look for warning signs

• Threatening to hurt or kill self

• Looking for ways to kill self; seeking access to pills, weapons, or other means

• Talking or writing about death, dying, or suicide

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DEPRESSION

278 PRIMARY CARE OF VETERANS WITH HIV

y g gq

referral. Consider hospitalization for safety until complete assessment

may be made.

Additional warning signs include:

• Hopelessness

• Rage, anger, seeking revenge

• Acting reckless or engaging in risky activities, seemingly without thinking

• Feeling trapped – like there’s no way out

• Increasing alcohol or drug abuse

• Withdrawing from friends, family, or society

• Anxiety, agitation, unable to sleep or sleeping all the time

• Dramatic changes in mood

• No reason for living, no sense of purpose in life

2. Assess for risk and protective factors

Factors that may increase risk for suicide

Current ideation, intent, plan, access to means

Previous suicide attempt or attempts

Alcohol or substance abuse

Previous history of psychiatric diagnosis

Impulsivity and poor self-control

Hopelessness – presence, duration, severity

Recent losses – physical, fi nancial, personal

Recent discharge from an inpatient unit

Family history of suicide

History of abuse (physical, sexual, or emotional)

Comorbid health problems, especially a newly diagnosed problem or worsening symptoms

Age, gender, race (elderly or young adult, unmarried, white, male, living alone)

Same-sex sexual orientation

Transgender identity

Factors that may decrease risk for suicide

Positive social support

Spirituality

Sense of responsibility to family

Children in the home, pregnancy

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PRIMARY CARE OF VETERANS WITH HIV 27

Reality-testing ability

Positive coping skills

Positive problem-solving skills

Positive therapeutic relationship

3. Ask the questions

(Note: Asking about suicide does not induce patients to contemplate 

killing themselves.)

• Are you feeling hopeless about the present/future? If yes, ask ...

• Have you had thoughts about taking your life? If yes, ask ...

• When did you have these thoughts and do you have a plan to take your life?

• Have you ever had a suicide attempt?

Response to suicide risk

■ Assure the patient’s immediate safety and determine the most 

appropriate treatment setting

■ Refer for mental health treatment or assure that follow-up appointment is 

made

■ Consult with the facility suicide prevention coordinator

■ Inform and involve someone close to the patient

■ Limit access to means of suicide

■ Increase contact and make a commitment to help the patient through the 

crisis

■ Provide number of emergency department or urgent care center to the 

patient and signifi cant others

■ National Suicide Prevention Lifeline: 800-273-TALK (800-273-8255)

 MANAGEMENT

Patients with depressive symptoms who do not require referral to a mental 

health provider (see When to Refer, p. 271) may be managed safely in the 

primary care setting. There is evidence that treatment with SSRIs, SNRIs, TCAs, 

or stimulants is superior to placebo in relieving symptoms of depression in HIVinfected patients. However, a surprisingly high proportion of placebo recipients in 

clinical studies also experience symptom relief.

Psychotherapy of many kinds, including cognitive behavioral therapy, social support counseling, and individual psychodynamic therapy, is also effective in treating 

depression in HIV-infected patients. Comparison of methods is complicated by 

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DEPRESSION

280 PRIMARY CARE OF VETERANS WITH HIV

erogeneity of various scoring instruments. 

Interestingly, a study of the effect of treatment of depression on adherence to 

ART found that participants treated with psychotherapy or psychotherapy plus 

medication were more adherent to ART than those treated with medication 

alone, or with placebo. 

An SSRI or an SNRI usually is recommended as initial pharmacotherapy for 

depression, because of their effi cacy and safety profi le. A patient requiring 

pharmacologic therapy with an agent (particularly a TCA or an MAOI) probably 

should be managed in collaboration with a psychiatrist.

Response to Pharmacotherapy

■ Patients typically start responding to SSRIs in 2-4 weeks. 

■ Patients who show no improvement on maximal-dose therapy after 8 weeks 

should be switched to another medication or be referred to a psychiatrist.

■ Suicidality may remain or emerge during the fi rst several weeks of pharmacologic therapy, even as depression seems to decrease; close follow-up is 

recommended, with screening for suicidality (see above) as needed. 

SSRI Discontinuation Syndrome

SSRIs and SNRIs should be tapered slowly rather than discontinued abruptly. 

Side effects associated with abrupt discontinuation include dizziness, irritability, 

anxiety, chills, myalgias, and nausea. Symptoms typically occur 1 day after discontinuing and can last up to 2 weeks. They remit when the drug is restarted. 

The discontinuation syndrome is more likely with venlafaxine and shorter-acting 

SSRIs, such as paroxetine, than with longer-acting agents, such as fl uoxetine. 

Commonly Used Antidepressant Medications

Generic Drug 

Name

Usual Starting Dosage/

Dosage Titration

Comments/

Drug Interactions

SSRIs

• Favored by some experts because of low potential for fatal overdose Pros:

• Risk of Cons: discontinuation symptoms (see above) with certain agents if 

discontinued abruptly

• Increased risk of suicidality among children and young adults with depression during fi rst month of taking SSRIs

• Most common side effects: sexual dysfunction, nausea, sweating, sleep disturbance

• Contraindicated for use with monoamine oxidase inhibitors (MAOIs) or triptans 

because of risk of serotonin syndrome

• Interactions with ARVs incompletely studied

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PRIMARY CARE OF VETERANS WITH HIV 28

pg y 

increase daily dosage after 

7 days, if no adverse effects; 

maximum dosage: 60 mg QD

y 

however, no signifi cant 

change in citalopram levels 

when coadministered with 

RTV

Escitalopram Start at 5-10 mg QD; may 

increase daily dosage after 

7 days, but no evidence of 

increased effi cacy; maximum 

dosage: 20 mg QD

Metabolized by mixture 

of enzymes, including CYP 

3A4; however, no signifi cant 

change in citalopram levels 

when coadministered with 

RTV

Fluoxetine Start at 10-20 mg QD; not to 

exceed 80 mg QD

Also available in weekly dose 

formulation: 90 mg once weekly

Metabolized by CYP 2D6, 

but no adjustment required 

when coadministered with 

RTV

Paroxetine Start at 10-20 mg QD; may incre -

ase daily dosage by 10 mg every 

7 days to maximum of 50 mg QD

DRV and FPV decrease 

paroxetine levels; titrate 

paroxetine to effect

Must be tapered slowly 

when discontinuing to avoid 

rebound depression symptoms and discontinuation 

symptoms

Slightly more sedating than 

other SSRIs

Sertraline Start at 50 mg QD; may 

increase daily dosage by 25-50 

mg every 7 days to maximum of 

200 mg QD

DRV decreases sertraline 

levels; titrate sertraline to 

effect

SNRIs

• Increased presynaptic levels of serotonin and norepinephrine

• GI events (nausea, diarrhea, constipation), dry Most common side effects:

mouth

• somnolence, insomnia, dizziness, nervousness, headache; Other side effects:

sexual dysfunction can occur

Duloxetine Start at 20 mg QD; may 

increase to BID, then to 60 mg 

QD or divided as 30 mg BID

Hepatically metabolized; not 

recommended for use in 

patients with hepatic 

impairment

To discontinue, taper 

gradually

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DEPRESSION

282 PRIMARY CARE OF VETERANS WITH HIV

Venlafaxine 

immediate 

release

Start at daily dosage of 75 mg 

divided BID (ie, 37.5 mg BID) 

or TID (ie, 25 mg TID) with 

food; may increase total daily 

dosage by up to 25 mg per 

dose every 4 days; maximum 

daily dosage: 375 mg divided 

TID (ie, 125 mg TID) 

Metabolized by CYP 2D6

When stopping venlafaxine, 

it is essential to taper slowly 

to avoid discontinuation 

symptoms

Postmarketing studies 

suggest that venlafaxine 

overdoses are more associated with fatal outcomes 

than are SSRI overdoses, but 

less than TCA overdoses; 

use lowest effective dosage 

of venlafaxine

Venlafaxine 

extended 

release (XR)

Start at 75 mg venlafaxine XR 

QD with food; may increase 

daily dosage by up to 75 mg 

every 4 days; maximum daily 

dosage: 225 mg

Other

Bupropion Formulations

Bupropion Inhibits CYP 2D6 

EFV and TPV decrease 

bupropion levels; titrate 

bupropion to effect

Side effects: restlessness, 

agitation, insomnia

Bupropion increases seizure 

incidence (0.4% at 300 mg/

day or higher); contraindicated in patients with 

elevated risk of seizures

Sexual dysfunction unlikely

Bupropion 

immediate 

release

Start at 75-100 mg BID for 

3 days, increase to 100 mg TID 

on day 4; maximum daily dosage: 

450 mg divided TID

No single dose should 

exceed 150 mg, and doses 

should be taken at least 

6 hours apart

Dosage escalation should be 

delayed for agitation, motor 

restlessness, or insomnia

Bupropion SR Start at 100-150 mg QAM; 

increase to usual dosage of 

150 mg BID no earlier than day 

4; maximum daily dosage: 400 

mg divided BID (ie, 200 mg BID)

Doses of bupropion SR 

should be taken at least 

8 hours apart

Dosage escalation should be 

delayed for agitation, motor 

restlessness, or insomnia

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PRIMARY CARE OF VETERANS WITH HIV 28

ppg 

to usual dose of 300 mg QAM 

no earlier than day 4; maximum 

dosage: 450 mg QD

least 24 hours apart

Dosage escalation should 

be delayed in the event of 

agitation, motor restlessness, 

or insomnia

REFERENCES

Colibazzi T, Hsu TT, Gilmer WS. Human immunodefi ciency virus and depression in primary care: a clinical review. Prim Care Companion J Clin Psychiatry. 2006;8(4):201-11.

Cook JA, Grey D, Burke-Miller J, et al. Effects of treated and untreated depressive symptoms on highly active antiretroviral therapy use in a US multi-site cohort of HIV-positive 

women. AIDS Care. 2006 Feb;18(2):93-100.

Olatunji BO, Mimiaga MJ, O’Cleirigh C, et al. Review of treatment studies of depression 

in HIV. Top HIV Med. 2006 Aug-Sep;14(3):112-24.

VA/DoD Evidence Based Clinical Practice Guideline Working Group. Management of 

Major Depressive Disorder in Adults in the Primary Care Setting. Washington, D.C.: 

Department of Veterans Affairs, Offi ce of Quality and Performance; May 2000. Available 

at http://vaww.oqp.med.va.gov/CPGintra/cpg/cpg.htm. Accessed December 18, 2008.

Yun LW, Maravi M, Kobayashi JS, et al. Antidepressant treatment improves adherence to 

antiretroviral therapy among depressed HIV-infected patients. J Acquir Immune Defi c 

Syndr. 2005 Apr 1;38(4):432-8. 

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/26/09 
PRIMARY CARE OF VETERANS WITH HIV 28

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

Low Back Pain 

KEY POINTS

■ Low back pain (LBP) is a common complaint.

■ When evaluating LBP, assess whether the patient has evidence of 

systemic disease or neurologic compromise. Assess for social or 

psychological distress that may contribute to chronic, disabling pain. 

■ Check for red fl ags: major trauma, age >50, unexplained 

fever, unexplained weight loss, injection drug use (IDU), 

immunosuppression, history of cancer, major muscle weakness, 

bladder or bowel dysfunction, unrelenting night pain, saddle 

anesthesia, decreased sphincter tone, focal neurologic defi cit, 

duration >6 weeks, abdominal pulsating mass.

■ Up to 90% of patients experiencing acute LBP without sciatica or 

systemic symptoms improve within 4 weeks. 

■ All patients with LBP should receive nonpharmacologic 

interventions, nonsteroidal antiinfl ammatory drugs (NSAIDs), 

or acetaminophen as indicated, and other interventions and 

medications as necessary.

■ Follow up in 1-3 weeks and as needed. Reevaluate sooner in 

the event of worsening neurologic symptoms, bowel or bladder 

dysfunction, systemic symptoms, or failure to improve with initial 

management.

BACKGROUND

Epidemiology

■ Back pain is common: In a 2002 U.S. 

National Health Interview Survey of 

30,000 respondents, 26% of adults had 

back pain lasting at least a whole day 

during a 3-month period. 

■ Back pain is the second most common 

reason patients in the United States visit their physicians.

■ Back pain can lead to chronic disability. Among patients who have had treatment for back pain, 72% have discontinued exercise and sports because of the 

Veterans with HIV*

Lumbago, sciatica, or 

backache: 25%

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an ICD-9 

code corresponding to these conditions

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LOW BACK PAIN

286 PRIMARY CARE OF VETERANS WITH HIV

46% have reported refraining from sexual activity. 

■ The physiologic cause of LBP cannot be defi nitively established in 85% of 

patients. Among such patients, LBP has been attributed to disc degeneration 

or muscular and ligamentous sources. 

■ Of patients who have LBP:

• 70% have lumbar strains or sprains

• 10% have age-related degenerative processes of discs and facets

• 4% have herniated discs

• 3% have spinal stenosis

• 4% have osteoporotic compression fractures

• <1% have urgent situations (red fl ags)

Defi nitions

Acute: duration <6 weeks

Chronic: duration >6 weeks 

LBP: pain does not radiate past the knee

Sciatica: pain radiates past the knee along the sciatic nerve (posterior/lateral 

lower extremity)

Radiculopathy: impairment of a nerve root, usually causing radiating pain, 

numbness, or muscle weakness that corresponds to a specifi c nerve root

Cauda equina syndrome: urinary retention with overfl ow incontinence, 

saddle anesthesia, bilateral sciatica, and leg weakness; usually caused by a tumor 

or massive midline disc herniation; represents a medical emergency

Spondylolisthesis: slipping forward of one vertebral body over another; patients 

may have back or leg pain; rarely, bladder or bowel symptoms or radiculopathic pain

Spondylosis: arthritis of the spine, with radiographically apparent disc space 

narrowing and arthritic changes at the facet joint; localized pain or spasms with 

spinal fl exion

Spinal stenosis: local, segmental, or generalized narrowing of the central spinal 

canal by bone or soft tissue; transient tingling in the legs, pain with walking, 

improvement with rest and with leaning forward; pseudoclaudication with 

normal distal arterial pulses 

EVALUATION

Check for red fl ags:

• Major trauma

• Age >50

• Duration >6 weeks

• Diabetes

• History of cancer

• Major muscle weakness

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PRIMARY CARE OF VETERANS WITH HIV 28

ppy

• Unexplained fever

• Unexplained weight loss

• IDU

• CD4 count <200 cells/μL

• Transplant recipient

• Steroid use

y

• Unrelenting night pain

• Saddle anesthesia

• Decreased sphincter tone

• Focal neurologic defi cit

• Abdominal pulsating mass

In general, evaluate whether the patient has evidence of systemic disease, neurologic compromise, or social or psychological distress that may contribute to pain

Identify modifi able risk factors that may affect the risk of LBP recurrence.

Risk factors • Obesity

• Older age

• Female sex

• Physically or psychologically strenuous work

• Sedentary work

• Job dissatisfaction

• Smoking

• Low educational attainment 

• Psychological factors: somatization, anxiety, depression, substance 

abuse

History • Mechanism of onset, trauma

• Location of symptoms, involvement of legs

• Duration (acute <6 weeks, chronic >6 weeks)

• Character of pain: mechanical, radicular, claudicatory

• Limitations on activity

• Neurologic symptoms: distribution, bowel or bladder symptoms, 

weakness, saddle anesthesia

• Constitutional symptoms: fever, weight loss

• Night pain

• Previous spinal surgeries

• IDU

• Smoking history

• Cancer

• Corticosteroid use 

• Work-related injuries or repetitive stress

• Psychological stressors, symptoms of anxiety, depression, 

substance abuse

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LOW BACK PAIN

288 PRIMARY CARE OF VETERANS WITH HIV

p

historytaking 

questions

yyp(g yp)

• How do these symptoms limit you? How long can you sit, 

stand, etc?

• When did the current limitations begin?

• What do you hope we can accomplish during this visit? 

Physical 

examination

• Observation of gait, position changes, and stance

• Inspection of back and posture 

(scoliosis = lateral asymmetry; kyphosis = posterior convexity; 

lordosis = lumbar concavity)

• Range of motion, including lumbar fl exion (limited in ankylosing 

spondylosis)

• Palpation of the spine (vertebral tenderness suggests fracture or 

infection)

• Straight leg raising (SLR): sensitive but not specifi c for radiculopathy; pain with lifting leg of affected side (from lying position) 

from 10o to 60o

• Cross-SLR: specifi c but not sensitive for radiculopathy; pain with 

lifting leg opposite affected side (from lying position) from 

10o to 60o

• Neurologic assessment of L5-S1 nerve roots: L5 injury corresponds to numbness in the medial foot and web space between 

fi rst and second toes; S1 injury corresponds to reduced ipsilateral 

ankle refl ex, reduced sensation along the posterior calf and lateral 

foot; reduced ability to walk on tiptoes for 3 steps

• Evaluation for malignancy and infection if history and examination 

suggest a systemic disease (sites of interest include lymph nodes, 

prostate, breasts)

• Inconsistent, incongruous, or contradictory physical signs in 

patients with chronic pain may point to psychological distress

Imaging Imaging is not necessary in the fi rst 4-6 weeks of symptoms unless 

the patient has red fl ag symptoms or has any of the following:

• Progressive neurological fi ndings

• Constitutional symptoms

• History of traumatic onset

• History of malignancy

• Age ≤18 or ≥50 years

• Infection risk: IDU, severe immunosuppression, prolonged 

corticosteroid use, skin or urinary tract infection, indwelling 

urinary catheter

• Osteoporosis

If there is no clinical improvement after 6 weeks, obtain plain anteroposterior and lateral X rays of the lumbosacral spine to evaluate for 

tumor, infection, instability, spondyloarthropathy, or spondylolisthesis.

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PRIMARY CARE OF VETERANS WITH HIV 28

pgpy () ggg () 

is indicated if there are progressive neurologic defi cits or a high 

suspicion of cancer or infection, and should be considered for 

patients with >12 weeks of persistent LBP.

Differential 

diagnosis: 

Red fl ags 

for specifi c 

conditions 

and suggested initial 

workup

• history of cancer, unexplained weight loss, age >50, pain Cancer:

>6 weeks, night pain

Evaluation: check CT or MRI of spine, check complete blood 

count (CBC) and erythrocyte sedimentation rate (ESR), and 

perform directed evaluation for suspected malignancy 

(eg, prostate-specifi c antigen and prostate examination, 

mammogram, serum protein electrophoresis, urine protein 

electrophoresis)

• fever, IDU (consider Infection/osteomyelitis or Pott disease:

sacroiliac or verterbral osteomyelitis), tuberculosis exposure risk, 

recent urinary tract infection, skin infection, pneumonia, corticosteroid use, transplant, diabetes, rest pain

Evaluation: MRI of the spine, CBC, ESR, urinalysis, blood and 

urine cultures

• urinary retention or incontinence, Cauda equina syndrome:

saddle anesthesia, decreased anal sphincter tone, bilateral lower 

extremity weakness/numbness

Evaluation: immediate surgical consultation

• corticosteroid use, age >70, Fracture: osteoporosis, recent trauma 

Evaluation: plain X rays or CT, orthopedic consultation

• pulsating abdominal mass, Acute abdominal aneurysm:

vascular disease, resting or night pain, age >60 

Evaluation: ultrasound or CT to evaluate aorta, surgical 

consultation

• major muscle weakness Signifi cant herniated nucleus pulposus:

Evaluation: MRI of the spine and surgical consultation

 MANAGEMENT

■ Up to 90% of patients with LBP without sciatica or systemic symptoms 

improve within 4 weeks of starting treatment.

■ Recurrences are common, occurring in up to 40% of patients within 6 

months after initial resolution.

■ Goals of management are to reduce pain and disability using conservative measures and to identify patients with more serious conditions that need further care

■ All patients with LBP should get nonpharmacologic interventions and move 

up the analgesic and intervention “ladder”: 

• acetaminophen or NSAIDs +/– adjuvants →

• weak opioids +/– adjuvants →

• strong opioids +/– adjuvants

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LOW BACK PAIN

290 PRIMARY CARE OF VETERANS WITH HIV

■ For chronic and subacute back pain, studies suggest that antiepileptic drugs, 

muscle relaxants, benzodiazepines, and opiates show insuffi cient evidence of 

effectiveness to be recommended as treatment.

Intervention Comments

Nonpharmacologic

• Patient education

• Activity modifi cation

• Exercise

• Physical therapy

• Self-application of heat or 

cold to back

• Manipulation

• Patient education topics include expectations 

for rapid recovery, avoiding worry, coping with 

having a sore back, methods of symptom control, 

activity modifi cations, recognition of certain redfl ag symptoms, and follow-up.

• Limited bed rest: <48 hours. Patients who go on 

longer bed rest have less improvement in pain 

and function than those who remain ambulatory.

• Activity modifi cation should be minimal for acute 

back pain: Modifi cations might include limiting 

prolonged unsupported sitting, avoiding heavy 

lifting, and avoiding bending or twisting the back 

when lifting.

• Maintain or start aerobic conditioning exercises, 

including swimming, walking, and stationary biking.

• Avoid physical therapy for 2 weeks after onset of 

acute back pain.

• Conduct workplace ergonomics evaluation if the 

back pain is related to work activities.

• Manipulation may be helpful in the fi rst month of 

symptoms for selected patients who do not have 

radiculopathy or severe or progressive neurologic 

defi cits. Refer to practitioners with specifi c training in manipulation (eg, osteopathic physicians).

Pharmacologic

(for dosages and additional information, see Pain Medications, p. 321)

Acetaminophen First-line analgesic because of its safety profi le. • 

• Use for patients who cannot tolerate NSAIDs.

• Possible adverse effects include hepatotoxicity 

(especially if taken with alcohol) and nephrotoxicity (with chronic overdose).

NSAIDs 

(eg, ibuprofen, naproxen)

• First-line analgesic; may be combined with 

acetaminophen.

• Avoid use for patients with peptic ulcer disease 

or cirrhosis.

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PRIMARY CARE OF VETERANS WITH HIV 29

yp

(TCAs)

(eg, amitriptyline, nortriptyline)

pp

an adjunct for any type of LBP unresponsive to 

acetaminophen and NSAIDs.

• Anticholinergic and other adverse effects, 

especially at higher doses.

Muscle relaxants 

(nonbenzodiazepines) 

• Cyclobenzaprine

• Baclofen 

• May be useful as adjunctive therapy for acute 

back pain but not recommended for chronic or 

subacute back pain.

Epidural steroid injections 

Medications may include corticosteroids, lidocaine, and opioids

• For short-term relief of radicular pain; consider 

after failure of conservative treatment, as means 

of avoiding surgery. 

• Refer to back pain specialist or orthopedist. 

Opiate analgesics

Options include:

• Tramadol

(not a typical opiate; exact 

mechanism of action is 

unknown; acts in part as a 

central opioid agonist)

• Consider opioids for patients who have severe 

pain refractory to the interventions listed above 

(nonpharmacologic and pharmacologic) or 

cannot receive those therapies.

• For very short-term use in severe acute exacerbations, and for severely disabling chronic 

back pain; start with weak opioids; assess safety, 

effi cacy, and usage; titrate up and move to strong 

opioids as needed.

• Use the lowest effective dosage.

Weak opioids

• Codeine

• Hydrocodone + 

acetaminophen

• Oxycodone + 

acetaminophen

• If needed for acute fl ares, limit use to a designated short period of time.

• If needed for chronic pain, try to use a sustainedrelease opioid with scheduled dosing around 

the clock, with shorter-acting opioids for breakthrough pain as needed.

• Risk of dependence, overdose: monitor closely.

Strong opioids

• Morphine 

• Oxycodone

• Hydromorphone

• Fentanyl transdermal

• Adverse effects include oversedation, hypotension, respiratory depression, central nervous 

system stimulation or somnolence, dizziness, 

constipation, nausea, and pruritus.

• Note that tramadol 37.5 mg + acetaminophen 

325 mg has shown pain relief equivalent to 

codeine 30 mg + acetaminophen 325 mg but with 

fewer side effects (major side effect: headache).

• Chronic opioid therapy should incorporate an opioid use agreement that includes functional goals for 

outcome, not reduced pain intensity alone.

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LOW BACK PAIN

292 PRIMARY CARE OF VETERANS WITH HIV

WHEN TO REFER

Refer immediately to Orthopedic Surgery or Neurosurgery for:

• Cauda equina syndrome

• Spinal cord compression

• Progressive or severe neurologic defi cit 

Consider referral to Orthopedic Surgery or Neurosurgery for patients with persistent 

LBP or sciatica caused by:

• Disc herniation

• Spinal stenosis

• Spondylolisthesis

Consider referral to Physiatry for patients who are not improving:

• Chronic back pain <6 weeks

• Chronic sciatica <6 weeks

• Chronic pain syndrome

• Recurrent back pain

Consider referral to Neurology for:

• Chronic sciatica >6 weeks

• Atypical chronic leg pain (negative SLR)

• New or progressive neuromotor defi cit

Consider referral to Rheumatology for patients with persistent symptoms to:

• Rule out infl ammatory arthropathy

• Rule out fi brositis/fi bromyalgia

• Rule out metabolic bone disease (eg, osteoporosis)

Prevention

• Conduct ergonomic evaluation of work areas and implement ergonomic design of 

job tasks.

• Exercise has shown benefi t in reducing the perception of back pain.

Follow-Up

■ Follow up in 1-3 weeks with a phone call or visit and as needed. Follow-up is 

necessary when there is worsening of neurologic symptoms, bowel or bladder dysfunction, presence of systemic symptoms, or failure to improve with 

initial management.

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PRIMARY CARE OF VETERANS WITH HIV 29

REFERENCES

Bigos S, Bowyer O, Braen G, et al. Acute Low Back Problems in Adults. Clinical Practice 

Guideline, Quick Reference Guide Number 14. Rockville, MD: U.S. Department of Health 

and Human Services; December 1994.

Roelofs PD, Deyo RA, Koes BW, et al. Non-steroidal anti-infl ammatory drugs for low back 

pain. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000396. 

VA/DoD Clinical Practice Guideline Working Group. Diagnosis and Treatment of Low 

Back Pain. Washington, D.C.: Department of Veterans Affairs, Offi ce of Quality and 

Performance; July 2008. Available at http://www.oqp.med.va.gov/cpg/LBP/LBP_Base.htm. 

Accessed December 18, 2008.

World Health Organization. Treatment and Care of Injecting Drug Users; Module 10: 

Managing Pain in HIV-Infected Injecting Drug Users, 2007. Jakarta: ASEAN Secretariat; 

2007. Available at http://www.searo.who.int/LinkFiles/Publications_Module_10_Treatment_&_Care_for_HIV_positive_IDUs.pdf. Accessed August 14, 2008. [Page 13 has useful 

charts on the WHO analgesic ladder and equivalent opiate doses.]

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/11/09 
PRIMARY CARE OF VETERANS WITH HIV 29

Peripheral Neuropathy

KEY POINTS

■ HIV-associated peripheral sensory neuropathy (HIV-SN) includes 

distal sensory polyneuropathy (DSP) and ARV toxic neuropathy.

■ Patients typically present with bilateral tingling, numbness, or 

neuropathic pain starting in their toes and spreading proximally; the 

pain frequently is described as burning or aching and is worse on 

the soles. 

■ For a very simple and brief evaluation: Ask about distal 

numbness and check ankle refl exes. Screening for numbness and 

delayed or absent ankle refl exes has the highest sensitivity and 

specifi city among the clinical evaluation tools.

■ Treat suspected ARV toxic neuropathy by withdrawing the offending 

drug, if possible. 

■ Treat the pain of HIV-SN with analgesics, anticonvulsants, and 

topical medication; if severe, treat with long-acting narcotics.

BACKGROUND

■ HIV-SN is a “dying-back” neuropathy, 

affecting the most distal fi bers fi rst, 

involving myelinated and unmyelinated axons of all sizes. On pathologic 

examination, this pattern of loss is 

indistinguishable from other toxic 

neuropathies.

■ Patients typically present with bilateral 

tingling, numbness, or neuropathic pain that starts in the toes and spreads 

proximally; the pain frequently is described as burning or aching and is worse 

on the soles. It also may be described as shocklike or knifelike. 

■ HIV-SN includes:

• DSP caused by HIV infection itself

• ARV toxic neuropathy resulting from exposure to ARVs, particularly d4T, 

ddI, and ddC (the “dNRTIs” or “d-drugs”). The onset can occur as early 

as 9 weeks after starting the offending agent.

Veterans with HIV*

Peripheral neuropathy: 19% 

* Veterans in the VA HIV Clinical Case 

Registry in care in 2007 who had an 

ICD-9 code corresponding to this 

condition

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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PERIPHERAL NEUROPATHY

296 PRIMARY CARE OF VETERANS WITH HIV

phage overproduction of proinfl ammatory cytokines and chemokines in the 

peripheral nervous system.

■ ARV toxic neuropathy is thought to be associated with mitochondrial 

toxicities of the dNRTIs.

■ Many other drugs and conditions may cause peripheral neuropathy (PN) or 

compound the condition.

Epidemiology

■ A recent study showed the prevalence of HIV-SN was 42% among patients 

at an outpatient clinic in Australia; 92% of patients with sensory neuropathy 

were on ARVs. 

■ The risk of PN is higher for patients with advanced HIV infection.

• The annual incidence of DSP among patients with CD4 counts of <200 

cells/μL is 7%. In two studies from the 1980s, 30% of patients hospitalized 

with advanced AIDS had DSP in the absence of ART.

• The prevalence is lower among patients with less-advanced HIV disease.

Prevention

Prevention and early intervention are vitally important in avoiding or reversing symptoms of neuropathy.

• Initiate ART according to usual guidelines to avoid increased risk of HIV-SN resulting from advanced HIV disease. 

• Avoid ARVs (particularly d4T and ddI) associated with neurotoxicity.

• If possible, avoid non-ARV medications that may cause PN.

• Avoid treatment regimens that have additive neurotoxicity (eg, ddI for a patient 

who is receiving isoniazid).

• With patients who develop ARV toxic neuropathy, discontinue the causative ARV if 

a reasonable substitution can be made.

EVALUATION

DSP and ARV toxic neuropathy are clinically indistinguishable, although the timing 

of symptom onset may help to differentiate the etiology.

Risk factors • Increasing age

• Exposure to d4T, ddI, or ddC

• Advanced untreated HIV (low CD4 count nadir, high HIV RNA)

• Alcohol use

• Nutritional defi ciencies (eg, vitamin B12)

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PRIMARY CARE OF VETERANS WITH HIV 29

g

Dapsone

Hydroxyurea

Metronidazole

Vincristine

Thalidomide

Isoniazid

Linezolid

Ribavirin

• Diabetes, impaired glucose tolerance

SCREENING

Quick Screen

Ask about distal numbness and check ankle refl exes.

• Use the ACTG Brief Peripheral Neuropathy Screen (BPNS) (see p. 301). This 

is a validated screening tool for scaling the degree of PN. It includes subjective and 

objective information, and takes <10 minutes to administer.

• HIV-SN can be diagnosed when a patient exhibits ≥1 symptom specifi ed in the 

BPNS and 1 of the following: diminished ankle refl exes, reduced vibration 

sense at the fi rst toe.

• Serial assessment of BPNS scores allows tracking of symptom severity and response 

to treatment.

History • Ask about numbness, pain, location/distribution of symptoms, 

character or quality of pain, other neurologic symptoms, duration, 

exposure to dNRTIs and other neurotoxic drugs.

• has a sensitivity of 86% and a specifi Numbness city of 81% for the 

clinical diagnosis of HIV-SN. Asking about numbness has greater sensitivity for the diagnosis of HIV-SN than asking about pain. 

Physical 

examination

Perform a thorough neurologic examination. 

Characteristics of HIV-SN:

• Reduced or absent ankle Achilles tendon refl exes; this has a 

sensitivity of 84% and a specifi city of 98% for HIV-SN.

• (temporal progression: loss of vibratory Distal sensory loss

sense occurs fi rst, followed by loss of temperature sensation, followed by pain).

• Findings usually are bilateral and symmetric.

Differential 

diagnosis

• Alcohol toxicity

• Non-ARV medication toxicity

• Nutritional defi ciency (eg, vitamin B12) 

• Diabetes, impaired glucose tolerance

• Hypothyroidism

• Other HIV-associated neuropathies, including:

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PERIPHERAL NEUROPATHY

298 PRIMARY CARE OF VETERANS WITH HIV

y yg pypy

Cauda equina syndrome

Neuromuscular weakness syndrome

Diffuse infi ltrative lymphocytosis syndrome (DILS)

Autonomic neuropathy

Mononeuritis

Polyradiculitis

• Cryoglobulinemia (especially in hepatitis C virus-infected patients)

• Syphilis

• Herpes zoster radiculitis

• Plantar fasciitis, musculoskeletal conditions, tarsal or carpal tunnel 

compression 

Note: Patients with foot pain or numbness may have ≥1 source of 

symptoms.

Findings that 

suggest a 

different 

diagnosis

• Prominent weakness (consider infl ammatory demyelinating polyneuropathies, HIV-associated neuromuscular weakness syndrome, 

especially with d4T use – check lactic acid levels)

• Neuropathy in the hands more so than in the feet (consider carpal 

tunnel syndrome)

• Proximal features (consider infl ammatory demyelinating 

polyneuropathies)

• Marked asymmetry (consider mononeuritis multiplex, especially 

with foot drop)

• Sphincter dysfunction (consider progressive polyradiculoneuropathy, especially caused by cytomegalovirus)

• Cranial nerve involvement (consider progressive polyradiculoneuropathy)

• Tenderness or deformity in plantar foot or joints (consider plantar 

fasciitis, gout)

Laboratory 

evaluation 

Screen for:

• Diabetes (fasting glucose; consider HbA1c) 

• Vitamin B12 defi ciency (check B12 level; if low, check methylmalonic acid levels and intrinsic factor antibody titers)

• Hypothyroidism (TSH, T4)

• Syphilis (RPR or VDRL)

• Renal failure (serum creatinine, blood urea nitrogen; consider 

serum protein electrophoresis) 

• Hepatitis C (HCV IgG/PCR)

Further 

evaluation

• Electromyography and nerve conduction velocity studies are not 

needed unless the symptoms are complex or there are atypical 

fi ndings.

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PRIMARY CARE OF VETERANS WITH HIV 29

y g py g

• Punch biopsy for pathologic evaluation of epidermal nerve density 

may be useful in differentiating HIV-SN and other causes. 

• Consider referral of patients to neurologist or podiatrist if the 

diagnosis is unclear.

 MANAGEMENT

■ Goals: relieve pain, halt progression of symptoms.

■ Patients taking neurotoxic medications: discontinue these if possible.

■ Patients not on ART: consider initiation, if low CD4 cell count or high HIV 

viral load.

■ Pharmacologic treatment often is multimodal, involving several types of 

medications.

• Consider starting with an anticonvulsant such as gabapentin or pregabalin 

and titrating to effect.

• Add or use antidepressants, especially for patients with comorbid depression

• Add or use topical agents for patients who cannot tolerate systemic pain 

medications.

• For breakthrough pain, add topical agents or NSAIDs.

• For severe or recalcitrant symptoms, consider adding a long-acting opioid

WHEN TO REFER

Refer to a pain specialist or neurologist if symptoms are not controlled with 

initial trials of medication.

Intervention Comments

Pharmacologic 

Discontinuation 

of offending 

drug (eg, switching from dNRTIs, 

avoiding combinations with additive 

neurotoxicity)

• Differentiate DSP and ARV toxic neuropathy by timing of symptom onset.

• Prompt discontinuation of a neurotoxic medication may 

prevent progression of symptoms, and may allow reversal of 

symptoms.

• Before discontinuing an offending drug, carefully weigh risks and 

potential benefi ts.

• Consider dosage reduction of d4T, if discontinuation is not 

possible.

• With ARV toxic neuropathy caused by a dNRTI, symptoms often 

improve within 3 months (though they may be permanent).

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PERIPHERAL NEUROPATHY

300 PRIMARY CARE OF VETERANS WITH HIV

ART

• Avoid dNRTIs

p

patients with advanced HIV who have uncontrolled viremia and 

low CD4 counts.

Medications

(for dosages and additional information, see Pain Medications, p. 321)

Mild analgesics

• Acetaminophen

• NSAIDs

• Use as fi rst-line therapy for mild symptoms.

• Can use in combination with tricyclic antidepressants (TCAs), 

anticonvulsants, and topical adjuncts. 

• Avoid use or limit dosages for patients with underlying liver or 

renal disease.

Anticonvulsants

• Gabapentin

• Pregabalin

• Lamotrigine

• Gabapentin: considered fi rst-line for its tolerability. 

• Pregabalin: sometimes better tolerated than gabapentin. Little 

evidence of effi cacy for HIV-SN.

• Lamotrigine: has shown the greatest effi cacy in clinical trials for 

HIV-SN. 

• To discontinue these agents, taper slowly over course of ≥7 

days. 

Antidepressants: TCAs 

and others

• Amitriptyline

• Nortriptyline

• Other potential 

agents include 

venlafaxine 

and duloxetine; 

these have 

shown limited 

effi cacy or are 

inadequately 

studied in people with HIV 

infection

• Consider for patients with comorbid depression.

• Small studies have shown limited or negative results with antidepressants.

• Monitor serum TCA levels to avoid cardiotoxicity at higher 

dosage levels.

POTENTIAL ARV INTERACTIONS !

• Drug interactions: RTV and other PIs may increase the level of 

TCAs; start at low dosage, increase slowly.

Topical 

anesthetics

• Capsaicin patch 

or cream

• Lidocaine patch

• A single capsaicin patch application can provide some degree of 

pain relief for up to 12 weeks.

• Topical lidocaine has not shown signifi cant benefi t over placebo, 

and is expensive. Consider brief trial for patients with incomplete pain relief on other therapies.

!

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PRIMARY CARE OF VETERANS WITH HIV 30

p

analgesics

Long-acting narcotics preferred:

• Transdermal 

fentanyl

• Long-acting 

morphine

• Methadone 

• Long-acting 

oxycodone

qp

to the therapies listed above.

• Titrate carefully. (For more information, see Pain Medications, p. 321.)

• Methadone: acts on NMDA receptors; may give adjunctive benefi t. Caution: start at low dosage and titrate slowly because of 

its long half-life; consult with pharmacist.

• Transdermal fentanyl is appropriate only for patients already on 

stable dosage of other opiates: start at equianalgesic (or lower) 

dosage.

Brief Peripheral Neuropathy Screening Tool

NIAID Adult AIDS Clinical Trials Group

1. Elicit Subjective Symptoms

Ask the subject to rate the severity of each symptom listed in Question 1 on a scale 

of 01 (mild) to 10 (most severe) for right and left feet and legs. Enter the score for 

each symptom in the columns marked R (right lower limb) and L (left lower limb). 

If a symptom has been present in the past, but not since the last visit, enter “00 – 

Currently Absent.” If the symptom has never been present, enter “11 – Always Been 

Normal.”

Always 

Been 

Normal

Currently 

Absent Mild Severe

11 00 01 02 03 04 05 06 07 08 09 10

Symptoms R L

a. Pain, aching, or burning in feet, legs

b. “Pins and needles” in feet, legs

c. Numbness (lack of feeling) in feet, legs

2. Grade Subjective Symptoms

Use the single highest severity score from Question 1 above to obtain a subjective sensory neuropathy score. If all severity scores are “00” or “11,” the subjective 

sensory neuropathy score will equal “0.” 

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PERIPHERAL NEUROPATHY

302 PRIMARY CARE OF VETERANS WITH HIV

Subjective Sensory Neuropathy Score

(based on highest severity rating)

01 – 03 = grade of 1 

04 – 06 = grade of 2 

07 – 10 = grade of 3 

11 or 00 = grade of 0

3. Evaluate Perception of Vibration

Compress the ends of a 128-Hz tuning fork just hard enough that the sides touch. 

Place the vibrating tuning fork on a bony prominence on the subject’s wrist or hand 

to be sure that he/she can recognize the vibration or “buzzing” quality of the tuning 

fork. Again, compress the ends of the tuning fork just hard enough that the sides 

touch. Immediately place the vibrating tuning fork gently but fi rmly on the top of the 

distal interphalangeal (DIP) joint of one great toe and begin counting the seconds. 

Instruct the subject to tell you when the “buzzing” stops. Repeat for the other 

great toe. 

Vibration perception

a. Great toe DIP joint perception of vibration in seconds 

b. Vibration perception score (see below)

0 = felt >10 seconds (normal)

1 = felt 6-10 seconds (mild loss)

2 = felt <5 seconds (moderate loss)

3 = not felt (severe loss)

8 = unable to or did not assess 

4. Evaluate Deep Tendon Refl exes 

With the subject seated, the examiner uses one hand to press upward on the ball of 

the foot, dorsifl exing the subject’s ankle to 90 degrees. Using a refl ex hammer, the 

examiner then strikes the Achilles tendon. The tendon refl ex is felt by the examiner’s 

hand as a plantar fl exion of the foot, appearing after a slight delay from the time the 

Achilles tendon is struck. Use reinforcement by having the subject clench his/her fi st 

before classifying the refl ex as absent. 

Ankle Refl exes Score

0 = absent 

1 = hypoactive 

2 = normal deep tendon refl exes 

3 = hyperactive 

4 = clonus 

8 = unable to or did not assess 

R L

R L

R L

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PRIMARY CARE OF VETERANS WITH HIV 30

REFERENCES

Cherry CL, Wesselingh SL, Lal L, et al. Evaluation of a clinical screening tool for HIVassociated sensory neuropathies. Neurology. 2005 Dec 13;65(11):1778-81.

Gonzalez-Duarte A, Robinson-Papp J, Simpson DM. Diagnosis and management of HIVassociated neuropathy. Neurol Clin. 2008 Aug;26(3):821-32.

McArthur JC, Brew BJ, Nath A. Neurological complications of HIV infection. Lancet Neurol. 2005 Sep;4(9):543-55.

Smyth K, Affandi JS, McArthur JC, et al. Prevalence of and risk factors for HIV-associated 

neuropathy in Melbourne, Australia 1993-2006. HIV Med. 2007 Sep;8(6):367-73.

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/17/09 
DrugTables

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PRIMARY CARE OF VETERANS WITH HIV 30

Common Medications: ARV Interactions

For information on potential ARV interactions with the following medications, 

see the specifi ed chapters: 

Acid-lowering medications (see GERD, p. 155)

Fluticasone (see Asthma, p. 97; COPD, p. 107)

Hormonal contraceptives (see Women’s Health, p. 249)

Lipid-lowering medications (see Lipid-Lowering Medications, p. 315)

PDE5 (see Urology, p. 227)

Psychoactive medications: antidepressants, sedatives, antipsychotics 

(see Psychoactive Medications, p. 327)

St. John’s wort (see Food and Supplements, p. 313)

Medication ARV Interactions Comments

Antiepileptic Medications: Carbamazepine, phenytoin, and phenobarbital may ↓ PI 

and NNRTI levels substantially. 

Carbamazepine

CYP450 inducer

PIs: may ↓ PI levels 

• ATV: ↑ carbamazepine levels

• DRV: ↑ carbamazepine levels; 

↓ DRV levels

• RTV: ↑ carbamazepine levels

• TPV: ↑ carbamazepine levels; 

↓ TPV levels

Other PIs: may also ↑

carbamazepine levels

Avoid concomitant use if 

possible; use alternative 

antiepileptics.

Two-way interactions 

also affect PI and NNRTI 

levels. 

NNRTIs: may ↓ NNRTI levels 

• EFV: ↓ carbamazepine AUC 27%; 

↓ EFV levels

• ETR: expect ↓ ETR levels

Avoid use with EFV, if 

possible; use alternative 

antiepileptics.

Do not use concurrently 

with ETR.

MVC: ↓ MVC levels If used concurrently, give 

MVC 600 mg BID.

Phenobarbital

CYP450 inducer

PIs: may ↓ PI levels 

• DRV: ↓ phenobarbital levels

• RTV: ↓ phenobarbital levels

• TPV: ↓ phenobarbital levels and ↓

TPV levels

Avoid concomitant use if 

possible; use alternative 

antiepileptics.

Two-way interactions 

also affect PI and NNRTI 

levels.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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COMMON MEDICATIONS: ARV INTERACTIONS

308 PRIMARY CARE OF VETERANS WITH HIV

y 

• EFV and NVP: ↓ phenobarbital 

levels

• ETR: ↓ ETR levels

if possible; use alternative 

antiepileptics.

Do not use concurrently 

with ETR.

MVC: ↓ MVC levels If used concurrently, give 

MVC 600 mg BID.

Phenytoin

CYP450 inducer

PIs: may ↓ PI levels 

• DRV: ↓ phenytoin levels

• FPV: ↓ phenytoin levels

• LPV/r: ↓ LPV Cmin 46%, 

↓ RTV Cmin 47%; 

↓ phenytoin Cmin 34%

• NFV: ↓ M8 levels 20-30%, 

↓ phenytoin Cmin 39%

• RTV: anticipate ↓ phenytoin levels

• TPV: ↓ TPV levels 

Avoid if possible; use 

alternative antiepileptics.

Two-way interactions 

also affect PI and NNRTI 

levels. 

NNRTIs: may ↓ NNRTI levels

• EFV: ↓ phenytoin levels, 

↓ EFV levels

• ETR: ↓ ETR levels 

Avoid use with EFV if 

possible.

Do not use concurrently 

with ETR.

MVC: ↓ MVC levels If used concurrently, give 

MVC 600 mg BID.

Valproate PIs

• /r: LPV ↑ LPV Cmax 33%, 

↑ AUC 75%, may ↓ valproate 

levels 

• RTV and TPV: ↓ valproate levels

Titrate to effect.

NNRTIs: no signifi cant changes in 

NNRTI or valproate levels

Lamotrigine • LPV/r: ↓ lamotrigine levels 50%

• RTV: ↓ lamotrigine levels

Titrate to effect.

Antifungal Medications

Fluconazole

Inhibitor of 

CYP 2C9

PIs 

• ATV/r: no signifi cant change

• TPV: ↑ TPV levels

TPV: Avoid fl uconazole 

>200 mg daily.

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PRIMARY CARE OF VETERANS WITH HIV 30

• NVP: 100% ↑ in NVP levels 

• EFV: no signifi cant change 

• ETR: potential ↑ in ETR levels 

EFV, ETR: dosage adjustment not required.

Itraconazole

Inhibitor and 

substrate of 

CYP 3A4

PIs: ↑ PI levels and ↑ itraconazole 

levels

• LPV/r: ↑ itraconazole levels

Avoid itraconazole dosages >200 mg daily with 

patients who take PIs. 

NNRTIs

• EFV: ↓ itraconazole levels 

• ETR: ↓ itraconazole levels and ↑

ETR levels

• NVP: ↓ itraconazole levels and ↑

NVP levels

If used concomitantly, 

consider monitoring itraconazole levels and adjust 

itraconazole dosage as 

necessary.

Avoid with ETR.

MVC: ↑ MVC levels MVC 150 mg BID

Ketoconazole: 

Inhibitor and 

substrate of 

CYP 3A4

PIs: may ↑ PI levels and ↑

itraconazole levels

• ATV/r, FPV/r: ↑ ketoconazole 

levels

• DRV/r: ↑ ketoconazole levels, 

↑ DRV levels

• LPV/r: ↑ ketoconazole levels; 

may ↑ or ↓ LPV/r levels

Avoid ketoconazole 

dosages >200 mg daily 

with patients who take 

RTV-boosted PIs.

NNRTIs

• EFV: no data

• NVP: ↓ ketoconazole levels; ↑

NVP levels

• ETR: ↓ ketoconazole levels and ↑

ETR levels

Not recommended for 

use with NVP. 

Dosage adjustment for 

ETR not established.

MVC: ↑ MVC levels MVC 150 mg BID

Posaconazole 

Inhibitor of 

CYP 3A4

PIs

• RTV: ↑ RTV levels

• ATV: ↑ ATV levels 

Monitor laboratory 

values frequently for 

signs of toxicity.

NNRTIs

• EFV: ↓ posaconazole levels 

• ETR: ↑ ETR levels

Consider alternative 

antifungal or monitor 

posaconazole level.

Monitor for ETR-related 

adverse effects.

Terbinafi ne:

Inhibitor of 

CYP 2D6 

PIs: no signifi cant changes No dosage adjustments 

necessary.

NNRTIs: no signifi cant changes No dosage adjustments 

necessary.

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COMMON MEDICATIONS: ARV INTERACTIONS

310 PRIMARY CARE OF VETERANS WITH HIV

CYP 3A4, 

CYP 2C9, and 

CYP 2C19 inhibitor; CYP 2C19 

substrate

• RTV: voriconazole AUC ↓ 39% 

with RTV 100 mg BID

for use with RTV 100 

mg QD or BID unless 

benefi t outweighs risk. If 

used, consider monitoring voriconazole levels.

NNRTIs 

• EFV: substantial ↓ voriconazole 

and ↑ EFV; similar effect expected 

for NVP 

• ETR: ↑ voriconazole and ↑ ETR

Contraindicated at 

standard dosages; use 

voriconazole 400 mg BID 

and EFV 300 mg QD.

Dosage adjustments for 

ETR and voriconazole not 

established; use alternative antifungal or monitor 

voriconazole level and 

ETR adverse effects.

MVC: anticipated ↑ MVC levels MVC 150 mg BID

Calcium Channel Blockers (CCBs)

Amlodipine • FPV, RTV, and SQV: ↑ amlodipine 

levels

• IDV: ↑ amlodipine Cmax and AUC 

89%

Incompletely studied. 

PIs may inhibit metabolism of CCBs, increasing 

risk of adverse effects 

including hypotension, 

conduction block, and 

bradycardia. 

NNRTIs may induce 

metabolism of CCBs, 

reducing their effect. 

Avoid use in patients 

with CHF.

Avoid immediate-release 

forms.

Diltiazem • ATV: ↑ diltiazem Cmax 200%

• IDV: ↑ diltiazem Cmax 25%

• SQV/r: ↑ diltiazem levels

• EFV: ↓ diltiazem AUC 70%

• NVP: ↓ diltiazem levels

Methadone 

PIs

• ATV: ↓ total methadone AUC 6%; 

↑ R-methadone AUC 3%, Cmin 11%

• DRV/r: ↓ methadone AUC 16%

• FPV: ↓ methadone AUC 18%

• LPV/r: ↓ methadone AUC 53%

• NFV: ↓ methadone AUC 47%

• SQV/r: ↓ methadone AUC 

• TPV/r: ↓ methadone AUC 48%

Most PIs ↓ methadone 

levels, particularly LPV/r, 

NFV, and TPV.

Of NNRTIs, EFV and 

NVP ↓ methadone, 

whereas ETR is anticipated to have no effect. 

DLV ↑ methadone levels.

Monitor for methadone 

effi cacy, and signs and

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PRIMARY CARE OF VETERANS WITH HIV 31

ypp

drawal. Titrate dosage 

cautiously as needed. 

NNRTIs 

• DLV: ↑ methadone AUC 

• EFV: ↓ methadone AUC 60%

• ETR: no change in methadone 

level anticipated 

• NVP: ↓ methadone AUC 46%

With DLV, monitor for 

methadone toxicity; may 

need to decrease methadone dosage. 

With EFV, ETR, and NVP, 

monitor for methadone 

effi cacy and signs and 

symptoms of opiate withdrawal. Titrate methadone dosage cautiously 

as needed.

Warfarin

PIs

• FPV, IDV, SQV, ATV: ↑ warfarin 

levels

• LPV/r: may ↑ or ↓ warfarin levels

• RTV: may ↓ warfarin levels

• DRV: ↓ warfarin levels 

• TPV: no change in warfarin levels

Start at low dosage; 

monitor INR closely. 

Adjust warfarin dosage as 

indicated.

Monitor INR closely, may 

need increased warfarin 

dosage.

NNRTIs

• EFV: warfarin levels may ↑ or ↓

• NVP: ↓ warfarin levels 

(anticipated)

• ETR: ↑ warfarin levels 

(anticipated)

Monitor INR closely, 

adjust dosage as 

indicated.

REFERENCES

McNicholl I. HIV InSite Database of Antiretroviral Drug Interactions. San Francisco: UCSF 

Center for HIV Information. Available at http://www.hivinsite.org/insite?page=ar-00-02. 

Accessed December 10, 2008.

Micromedex® Healthcare Series [Internet database]. Greenwood Village, CO: Thomson 

Healthcare. Available at http://www.micromedex.com/index.html. Accessed 

December 10, 2008.

Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the Use of 

Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Rockville, MD: Department of Health and Human Services; November 3, 2008. Available at http://www.aidsinfo.

nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed December 10, 2008. 

Also see product labeling for the individual ARVs.

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PRIMARY CARE OF VETERANS WITH HIV 31

Food and Supplements: 

ARV Interactions

ARVs: Food Requirements

ARV 

Class

No Food 

Restrictions

Take with 

Food Take on Empty Stomach

NRTI

3TC

ABC

d4T

FTC

TDF

ZDV

ddI: gastric acid impairs absorption; take 

30 minutes before or 2 hours after a 

meal (if coadministered with TDF, may 

be taken with food)

NNRTI

DLV

NVP

ETR: take 

after a meal

EFV: fat increases absorption and may 

increase the risk of EFV adverse effects

PI

FPV

LPV/r 

(tablets)

TPV

ATV 

DRV

NFV

RTV

SQV

IDV: heavy meals interfere with absorption; if unboosted, IDV should be taken 

1 hour before or 2 hours after a meal; 

may be taken with a light, nonfatty, snack; 

if boosted with RTV, IDV may be taken 

with or without food

Integrase 

Inhibitor

RAL

Entry 

Inhibitor

ENF

MVC

ARV Interactions with Specifi c Foods, Nutritionals, Herbs

Calcium (other divalent cations): May interfere with activity of integrase.

 Separate dosing by 2 hours.

Garlic: Capsules ↓ SQV (unboosted) levels. Avoid.

Grapefruit juice: ↑ SQV levels. Separate dosing by 2 hours.

 ↓ IDV levels. Monitor virologic response.

St. John’s wort: ↓ levels of all NNRTIs and PIs. Avoid with PIs and NNRTIs.

 ↓ levels of MVC; increase MVC dosage to 600 mg BID.

Vitamin E: ↑ risk of bleeding associated with TPV. Avoid. 

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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PRIMARY CARE OF VETERANS WITH HIV 31

LipidLowering Medications: 

ARV Interactions

PIs and NNRTIs can affect hepatic metabolism of HMG-coenzyme A reductase 

inhibitors (statins). ARVs do not generally affect the metabolism of other classes 

of lipid-lowering agents.

PIs NNRTIs

Most PIs inhibit the metabolism 

of most statins and can signifi cantly 

increase serum statin levels, thus 

increasing the risk of toxicity, including 

myopathy and rhabdomyolysis.

NNRTI effects vary according to specifi c 

NNRTI.

The degree to which statin metabolism is affected by PIs varies according 

to the statin as well as the specifi c PI.

EFV generally induces statin metabolism, 

resulting in lower serum statin levels.

In general, the potential for inhibition 

of statin metabolism is as follows: 

simvastatin and lovastatin > atorvastatin >> fl uvastatin, pravastatin, 

rosuvastatin.

NVP has not been studied well in combination with statins, but its interactions 

with statins would be expected to be 

similar to those of EFV.

Fluvastatin and rosuvastatin have few 

recognized interactions with PIs.

ETR has not been studied thoroughly in 

combination with statins. Its interactions 

are expected to depend on the specifi c 

statin.

DLV inhibits hepatic cytochrome P450 

metabolism. Thus, DLV increases statin 

levels and the risk of statin-related adverse 

effects.

Medical providers should consult with a clinical pharmacist or review 

published information on drug interactions before prescribing 

statins for patients taking PIs or NNRTIs, as dosage adjustments are 

frequently required and some combinations are contraindicated.

Other classes of ARVs (NRTIs, fusion inhibitors, chemokine coreceptor antagonists, and integrase inhibitors) do not have recognized interactions with statins. 

Other types of lipid-lowering medications are not metabolized by hepatic cytochrome P450 and are not affected by ARVs.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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316 PRIMARY CARE OF VETERANS WITH HIV

LIPID-LOWERING MEDICATIONS: ARV INTERACTIONS

pg

Medication Considerations

Statins

• Hepatic metabolism including CYP 3A4 metabolism. Atorvastatin • 

• PIs: signifi cant ↑ in atorvastatin levels with most PIs (Cmax ↑

100-300%).

• Start with lowest dosage (10 mg). Monitor antilipid activity and 

titrate the statin dosage cautiously.

• TPV/r: atorvastatin Cmax ↑ 760%. Consider alternative statin. If 

prescribed, use lowest possible dosage, monitor carefully. 

• EFV: ↓ in atorvastatin levels (↓ AUC 58%); may need ↑ dosage.

• ETR: ↓ in atorvastatin levels (↓ AUC 37%); may need ↑ dosage.

• Metabolized by CYP 2C9 (75%), CYP 3A4 (20%). Fluvastatin • 

• Not well studied; no known signifi cant interactions with most 

PIs; theoretic risk of ↓ NFV levels. 

• ETR, DLV may ↑ fl uvastatin.

• Extensively metabolized by CYP 3A4. Lovastatin • 

• PIs: substantial ↑ in statin levels, high risk of adverse effects.

• Do not use in patients taking PIs or DLV.

• Renal excretion and some hepatic metabolism. Pravastatin • 

• PIs: variable effects; moderate ↑ pravastatin AUC and Cmax with 

most. No dosage adjustment of pravastatin is required. 

Exceptions:

• DRV/r: pravastatin AUC ↑ 80-500%. Consider alternative 

statin. If prescribed, use lowest possible dosage, monitor 

carefully.

• SQV + RTV: pravastatin AUC ↓ 35- 50%. May need to ↑

pravastatin dosage to reach lipid goals. 

• NFV: pravastatin AUC ↓ 46%. May need to ↑ pravastatin 

dosage to reach lipid goals. 

• EFV: pravastatin AUC ↓ 40%. May need to ↑ pravastatin dosage 

to reach lipid goals.

• Metabolized by CYP 2C9 and CYP 2C19. Mostly excreted in Rosuvastatin • 

bile. 

• No signifi cant interactions expected with most PIs or NNRTIs; 

studies under way. Exceptions: 

• DRV/r: rosuvastatin expected to ↑. Use lowest possible 

dosage (5 mg/day), monitor carefully.

• LPV/r: rosuvastatin Cmax ↑ 466%. Consider alternative statin. 

If prescribed, use lowest possible dosage (5 mg/day), monitor carefully.

• TPV/r: rosuvastatin Cmax ↑ 123%. Use lowest possible dosage 

(5 mg/day), monitor carefully.

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PRIMARY CARE OF VETERANS WITH HIV 31

y y 

• PIs: substantial ↑ in simvastatin levels, high risk of adverse effects 

(eg, simvastatin Cmax and AUC ↑ 3,000% with SQV + RTV).

• Do not use in patients taking PIs or DLV.

• EFV: ↓ simvastatin AUC >50%. May need to ↑ simvastatin 

dosage to reach lipid goals.

Fibrates • No signifi cant interactions with ARVs expected.

Bile Acid 

Sequestrants

• No drug interactions with ARVs, but may interfere with absorption of ARVs. Avoid in patients who take ARVs.

Ezetimibe • Not metabolized by hepatic P450 system; no signifi cant interactions with ARVs.

Niacin • Not metabolized by hepatic P450 system; no signifi cant interactions with ARVs.

N-3 (Omega-3) 

Fatty Acids

• Not metabolized by hepatic P450 system; no signifi cant interactions with ARVs.

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LIPID-LOWERING MEDICATIONS: ARV INTERACTIONS

318 PRIMARY CARE OF VETERANS WITH HIV ATV DRV/r FPV IDV LVP/r NFV RTV SQV TPV EFV ETR Atorva statin Atorva- statin Cmax

↑ >760%

May need 

↑

atorvastatin dosage 

May need 

↑

atorvastatidosage

Fluva statin Possible 

↓ in NFV levels

May need 

↑

fl uvastatin dosage 

May 

↑

fl uvastatin levels

Lova statin May need 

↑ lovastatin dosage 

May need ↑ lovastatin dosage

Prava statin

↑ pravastatin AUC up to 500%

May need ↑ pravastatin dosage

SQV + RTV: May need 

↑

pravastatin dosage 

May need 

↑

pravastatin dosage 

Rosuva statin

↑ rosuvastatin C

max

466%

May need 

↑

rosuvastatin dosage 

Simva statin May need 

↑

simvastatin dosage 

May need 

↑

simvastatin dosage

Note: NVP in combination with statins has not been well studied; its interactions would be expected to be similar to those of EFV. DLV’s interactions would be expecte

LIPID

-LOWERING MEDICATIONS: ARV INTERACTIONS

Recommendations for Coadministration of PIs and NNRTIs with Statin Medications

Generally safe to begin treatment with usual starting dosageCaution; start with low dosage, monitor effectsCoadministration is contraindicated

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PRIMARY CARE OF VETERANS WITH HIV 31

REFERENCES

Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. Pharmacokinetic interactions between 

protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. 

AIDS. 2002 Mar 8;16(4):569-77. 

Gerber JG, Rosenkranz SL, Fichtenbaum CJ, et al. Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 

5108 Study. J Acquir Immune Defi c Syndr. 2005 Jul 1;39(3):307-12.

Kiser JJ, Gerber JG, Predhomme JA, et al. Drug/drug interaction between lopinavir/

ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defi c Syndr. 2008 Apr 

15;47(5):570-8. 

McNicholl I. Database of Antiretroviral Drug Interactions. In: Coffey S, Volberding PA, eds. 

HIV InSite. San Francisco: UCSF Center for HIV Information; 2008. Available at http://

hivinsite.ucsf.edu/insite?page=ar-00-02. Accessed December 1, 2008.

Pham PA, Lee L, Fuchs E, et al. Pharmacokinetic interaction between tipranavir/ritonavir 

and rosuvastatin. In: Program and abstracts of the 15th Conference on Retroviruses and 

Opportunistic Infections; February 3-6, 2008; Boston. Abstract 767.

Sekar VJ, Spinosa-Guzman S, Marien K, et al. Pharmacokinetic drug-drug interaction 

between the new HIV protease inhibitor darunavir (TMC114) and the lipid-lowering agen

pravastatin. In: Program and abstracts of the 8th International Workshop on Pharmacology 

of HIV Therapy; April 16-18, 2007; Budapest. Abstract 55.

U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral 

Agents in HIV-1-Infected Adults and Adolescents. November 3, 2008. Available at http://

aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7. Accessed December 1, 

2008. 

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PRIMARY CARE OF VETERANS WITH HIV 32

Pain Medications: 

Dosage and Indications

(please refer to Osteoarthritis, Low Back Pain, Peripheral Neuropathy)

Medication Standard Dosage Comments

Acetaminophen1 g Q6H PRN or 650 mg 

Q4H PRN

Maximum dosage: 4 g per 24 

hours or 2 g per 24 hours in 

patients with comorbid liver 

disease

• First-line analgesia in noninfl ammatory mild OA, LBP, mild PN 

because of safety profi le

• Possible adverse effects: hepatotoxicity (especially if taken with 

alcohol), nephrotoxicity (with 

chronic overdose): monitor liver 

and renal function when using 

maximal dosages

• Use caution and consider reducing total dosage for patients with 

comorbid liver disease or excessive alcohol intake

NSAIDs Ibuprofen

• 600-800 mg TID PRN for 

pain

• Take with food

• Schedule around the 

clock for infl ammatory 

condition (eg, infl ammatory OA) or persistent 

symptoms

• Can titrate up as tolerated and based on risks 

to 800 mg TID

• Maximum dosage: 3,200 

mg/day in divided doses 

or 1,800 mg/day for 

patients at increased risk 

of adverse effects

• For persistent noninfl ammatory 

and infl ammatory OA, LBP, mild 

PN

• Possible adverse effects: GI bleeding, abdominal pain, rash and 

hypersensitivity, renal and hepatic 

impairment, platelet aggregation 

abnormalities

• Avoid use in patients with peptic 

ulcer disease or cirrhosis

• Avoid ibuprofen in patients with 

history of aspirin-induced asthma

• Increased bleeding risk with concurrent warfarin; if used, monitor 

closely

• Increased risk of renal impairment in patients on diuretics and 

those with baseline renal dysfunction, congestive heart failure, or 

cirrhosis

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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PAIN MEDICATIONS: DOSAGE AND INDICATIONS

322 PRIMARY CARE OF VETERANS WITH HIV

Naproxen: 250-500 mg BID

Sulindac: 150-200 mg BID

Celecoxib: 200 mg QD

Meloxicam: 7.5 mg QD

For chronic pain, use for 

2 weeks at initial dosage 

and reevaluate effi cacy; 

titrate up as needed and 

if safe; if not effective after 

a 4-week trial, consider 

changing NSAID, or adding 

or changing to another 

intervention

effective dosage and try to use for 

short periods of time

• COX-2 inhibitors, such as celecoxib, have higher risk of cardiovascular events but fewer GI side 

effects than nonselective COX 

inhibitors 

• Indomethacin is associated with 

increased joint destruction; avoid 

using for OA or LBP

Antidepressants: TCAs 

and others

Amitriptyline

Start at 10-25 mg QHS; 

titrate upward every 3 

days by 25 mg to achieve 

symptom relief, if tolerated; 

maximum daily dosage is 

150 mg (use lower dosages 

for older patients)

Nortriptyline

Start at 10-25 mg QHS; 

titrate upward every 3 

days by 25 mg to achieve 

symptom relief, if tolerated; 

maximum daily dosage is 

150 mg (use lower dosages 

for older patients)

• Consider for patients with comorbid depression

• Consider for neuropathic pain; also 

as an adjunct in any type of LBP 

unresponsive to acetaminophen 

and NSAIDs

• Small studies of PN have shown 

limited or negative results with 

antidepressants

• Drug interactions: RTV and other 

PIs may increase the level of TCAs; 

start at low dosage, increase slowly

• Monitor serum TCA levels to 

avoid cardiotoxicity at higher dosage levels

• Possible TCA adverse effects: 

anticholinergic (dry mouth, dizziness, constipation, urinary retention, blurred vision, orthostatic 

hypotension), extrapyramidal 

symptoms, incoordination; risk 

of cardiac conduction abnormalities and overdose at higher 

dosages

• For neuropathic pain, other potential agents include venlafaxine and 

duloxetine; these are inadequately 

studied in people with HIV infection or show limited effi cacy

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PRIMARY CARE OF VETERANS WITH HIV 32

santsmg QHS; may increase 

every few days, as tolerated, to achieve symptom 

relief; fi rst increase to BID, 

then TID, then increase by 

300 mg per dose to maximum of 1,200 mg TID

• start at Pregabalin: 

25-50 mg TID; may 

increase by 25-50 mg 

per dose every few days 

as tolerated to achieve 

symptom relief; maximum 

dosage: 200 mg TID

• start at Lamotrigine: 

25 mg every other day; 

titrate slowly to 200 mg 

BID over the course of 

6-8 weeks

• Gabapentin: considered fi rst-line 

for HIV-SN (See Peripheral Neuropathy, p. 295) 

• Common adverse effects 

include nausea, constipation, 

fatigue, somnolence, dizziness, 

truncal ataxia, weight gain

• To discontinue, taper over 

course of ≥7 days

• Pregabalin: sometimes better tolerated than gabapentin

• Uncertain effi cacy in HIVrelated PN

• Possible adverse effects include 

somnolence, constipation, dizziness, ataxia, and weight gain 

• To discontinue, taper over 

course of ≥7 days 

• Lamotrigine: has shown the greatest 

effi cacy in clinical trials for HIV-SN 

• Possible adverse effects: rash 

(including Stevens-Johnson syndrome), cytopenias, dizziness

• To discontinue, taper slowly

• Drug interactions: LPV/r may 

decrease lamotrigine levels; 

may need to increase lamotrigine dosage for therapeutic 

effect

Muscle 

relaxants 

(nonbenzodiazepines) 

Cyclobenzaprine 

(Flexeril)

5-10 mg TID; start with 5 mg 

doses for elderly patients 

and those with hepatic 

impairment; maximum dosage is 30 mg per 24 hours

Baclofen

5-10 mg TID or QID; start 

with 5 mg doses for elderly 

patients and those with renal 

impairment; maximum dosage 

is 80 mg QD in divided doses

• May be useful as adjunctive therapy 

for acute back pain but not recommended for chronic or subacute 

back pain

• Common adverse effects include 

drowsiness, dry mouth, and dizziness

• Severe adverse effects include 

arrhythmias, altered mental status, 

and seizures

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PAIN MEDICATIONS: DOSAGE AND INDICATIONS

324 PRIMARY CARE OF VETERANS WITH HIV

analgesics

Tramadol (not a typical 

opiate; exact mechanism 

of action is unknown; acts 

in part as a central opioid 

agonist)

Start with 50 mg QAM PRN 

pain, titrate upward by 50 

mg/day every 3 days to 50 

mg Q6H

Maximum dosage: 400 mg/

day, or 300 mg/day if >70 

years of age; to discontinue, 

taper dosage in the same 

way

In renal insuffi ciency with 

CrCl <30, reduce dose frequency to Q12H, and maximum dosage to 200 mg/day 

Weak opioids

• Codeine

15-30 mg every 4-6 hours; 

titrate up by 15 mg every 

2-3 days to achieve pain 

relief, if tolerated

Maximum dose: 60 mg; take 

with food

• Hydrocodone + 

acetaminophen

5 mg/500 mg fi xed-dose 

tablet, 1-2 tablets Q6H PRN 

pain

Maximum dosage: 12 tablets 

per 24 hours; 6 tablets for 

elderly patients and those 

with liver disease 

• Oxycodone + 

acetaminophen

5 mg/325 mg fi xed-dose tablet (other dosages available), 

1-2 tablets Q6H PRN pain

severe pain refractory to other 

interventions (pharmacologic or 

nonpharmacologic) or who cannot 

receive those interventions 

• Start with weak opioids, assess 

safety, effi cacy, and usage; titrate up 

and move to stronger opioids as 

needed

• Use the lowest effective dosage

• Use opioids cautiously in elderly 

patients

• If needed for acute fl ares, try to 

limit use to a designated short 

period of time 

• If needed for chronic pain, try to 

use a sustained-release opioid 

(eg, sustained-release morphine) 

around the clock, plus shorteracting opioids (eg, hydrocodone) 

for breakthrough pain as needed

• Opioid therapy for chronic pain 

should use a fi xed-dose schedule, 

not PRN dosing 

• Methadone may have utility for 

neuropathic pain owing to its 

action on NMDA receptors; start 

at low dosage and titrate slowly 

because of its long half-life; consult 

with pharmacist

• Risk of dependence, overdose; 

monitor closely

• Adverse effects include oversedation, hypotension and respiratory 

depression, central nervous system 

stimulation or somnolence, dizziness, constipation, nausea, pruritus

• Codeine and morphine can cause 

urticarial reactions (hives)

• For patients with renal and hepatic 

impairment, use low dosages and 

monitor carefully

• When prescribing opioids, remember to also give treatment for constipation (docusate and senna)

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PRIMARY CARE OF VETERANS WITH HIV 32

per 24 hours; 6 tablets for 

elderly patients and those 

with liver disease

Strong opioids

• Morphine (immediate 

release)

10-30 mg every 3-4 hours 

PRN pain

• Morphine (sustained 

release)

15-30 mg Q12H as scheduled doses; if pain control is 

inadequate, consider dosing 

Q8H; may titrate up by 

15-30 mg PRN pain

• Oxycodone (immediate release)

5-30 mg Q4H PRN pain

• Oxycodone (sustained 

release)

10 mg Q12H as scheduled 

doses; titrate up by 10-20 

mg PRN; monitor carefully

• Methadone

Consult with pharmacist

• Hydromorphone

2-4 mg Q4H PRN

• Fentanyl transdermal

12-100 mcg patch Q72H; a 

small proportion of patients 

will need dosing Q48H to 

maintain a stable blood level

Appropriate only for 

patients already on stable 

dosage of other opiates; 

start at equianalgesic (or 

lower) dosage; consult with 

pharmacist; use for chronic 

severe pain

acetaminophen 325 mg has shown 

pain relief equivalent to codeine 30 

mg + acetaminophen 325 mg but 

with fewer adverse effects (major 

adverse effect: headache)

• Chronic opioid therapy should 

incorporate an opioid use agreement that includes functional goals 

for outcome, not reduction of pain 

intensity alone

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PAIN MEDICATIONS: DOSAGE AND INDICATIONS

326 PRIMARY CARE OF VETERANS WITH HIV

anesthetics

• 0.025% or 0.075% cream; 

apply to skin over affected 

joint(s) or limb TID-QID 

• High-dose capsaicin topical dermal patch; apply for 

30-90 minutes

Lidocaine dermal patch 

5%

Apply 1-3 patches over 

affected area for 12 hours 

QD; must be removed for 

12 hours 

• For noninfl ammatory and infl ammatory OA, HIV-SN

• For OA or neuropathy, apply to 

skin over affected joint or area

• May take several days to achieve 

pain relief; initial application usually 

accompanied by sensation of heat 

or burning

• For neuropathy, a single capsaicin 

patch application can provide pain 

relief for up to 12 weeks

Lidocaine

• Topical lidocaine may be used for 

neuropathic pain, but for HIV-SN 

it has not shown signifi cant benefi t 

over placebo, and is expensive; 

consider brief trial in patients with 

incomplete pain relief on other 

therapies

Colchicine 0.6 mg BID For infl ammatory OA with refrac- • 

tory symptoms

• Avoid use for patients with renal 

or hepatic disease

• Use in conjunction with NSAIDs

• Consider for patients with refractory infl ammatory OA, as many 

have calcium pyrophosphate crystals in the synovial fl uid

Abbreviations: CrCl = creatinine clearance; GI = gastrointestinal; HIV-SN = HIV sensory neuropathy; 

LBP = low back pain; OA = osteoarthritis; PN = peripheral neuropathy; TCAs = tricyclic 

antidepressants

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PRIMARY CARE OF VETERANS WITH HIV 32

Psychoactive Medications: 

ARV Interactions

Class of 

Medication Interactions Comments

Antidepressants

SSRI Interactions with ARVs are 

incompletely studied.

RTV may ↑ SSRI levels; this usually is not signifi cant but there 

are case reports of SSRI toxicity. 

Start at low dosage, monitor for 

adverse effects.

Citalopram, escitalopram: 

• RTV causes no change in levels

No dosage adjustment of citalopram or escitalopram required. 

Fluoxetine: 

• RTV: ↑ RTV AUC 19%, no 

change in Cmax

Start fl uoxetine at low dosage, 

use lowest effective dosage; 

monitor for adverse effects.

Paroxetine: 

• DRV/r: paroxetine AUC and Cmin

↓ 38%

• FPV/r: paroxetine AUC ↓ 58%

Titrate paroxetine to effect.

Sertraline: 

• DRV/r: sertraline AUC and Cmin

↓ 48%

Titrate sertraline to effect.

SNRI Venlafaxine, duloxetine:

• No data; PIs may ↑ SNRI levels

Start at low dosage, use lowest 

effective dosage; monitor for 

adverse effects.

Tricyclic 

(TCA)

Amitriptyline, nortriptyline, 

imipramine, desipramine, and 

others:

• NFV, RTV known to ↑ TCA levels; other PIs may ↑ TCA levels

Start at low dosage, use lowest 

effective dosage; monitor for 

adverse effects.

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary 

(http://www.pbm.va.gov/NationalFormulary.aspx). Consult VA pharmacists for alternatives.

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PSYCHOACTIVE MEDICATIONS: ARV INTERACTIONS

328 PRIMARY CARE OF VETERANS WITH HIV

antidepressants

pp

• EFV: ↓ bupropion AUC 55%

• TPV: ↓ bupropion AUC 46%

yy 

increased dosage.

Mirtazapine:

• No data; RTV may ↑ mirtazapine levels

Start at low dosage, use lowest 

effective dosage; monitor for 

adverse effects.

Nefazodone: 

• RTV may ↑ nefazodone levels

• Nefazodone may ↑ MVC levels

Start at low dosage, use lowest 

effective dosage; monitor for 

adverse effects. 

MVC dosage: 150 mg BID

Trazodone: 

• RTV: ↑ trazodone AUC >200% 

• DRV, IDV, LPV/r: ↑ trazodone AUC 

Start at low dosage, use lowest 

effective dosage; monitor for 

adverse effects.

St. John’s wort:

• Substantial ↓ in levels of most 

PIs, NNRTIs, and MVC 

Do not coadminister.

Sedatives, Hypnotics

BenzodiazepineMidazolam: 

• SQV/r: ↑ oral midazolam 

AUC 1,144%

• Other PIs: large ↑ in serum 

midazolam levels expected

Triazolam: 

• RTV: ↑ triazolam half-life 

1,200%; ↑ AUC 20% 

• Other PIs: large ↑ in serum 

triazolam levels expected

Avoid midazolam and triazolam for patients taking PIs.

For procedures, may consider 

single-dose IV midazolam with 

close monitoring.

Alprazolam: 

• RTV: ↑ alprazolam half-life 200%

Avoid for patients taking PIs.

Diazepam:

• All PIs: ↑ diazepam levels

• ETR: ↑ diazepam levels

Start at low dosage, use lowest 

effective dosage; monitor for 

adverse effects.

Alternatives:

Consider use of the following 

benzodiazepines: lorazepam, 

oxazepam, temazepam (these 

benzodiazepines are metabolized 

via non-CYP450 pathways; lower 

potential for interactions). Start at 

low dosage, use lowest effective 

dosage; monitor for adverse effects.

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PRIMARY CARE OF VETERANS WITH HIV 32

p

• RTV: ↑ zolpidem AUC 27%

g

effective dosage; monitor for 

adverse effects.

Antipsychotics: Few data on interactions between ARVs and antipsychotics

Olanzapine: 

• RTV: ↓ olanzapine AUC 53%, 

half-life ↓ 50%

Start at low dosage, use lowest 

effective dosage; monitor for 

adverse effects. 

Pimozide: 

• PIs and EFV may ↑ pimozide 

levels

Contraindicated with PIs and 

with EFV.

REFERENCES

McNicholl I. HIV InSite Database of Antiretroviral Drug Interactions. San Francisco: UCSF 

Center for HIV Information. Available at http://www.hivinsite.org/insite?page=ar-00-02. 

Accessed December 10, 2008.

Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the Use of 

Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Rockville, MD: Department of Health and Human Services; November 3, 2008. Available at http://www.aidsinfo.

nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed December 10, 2008. 

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PRIMARY CARE OF VETERANS WITH HIV 33

Index

Primary Care of Veterans with HIV

Page numbers followed by t or f indicate tables or fi gures, respectively

PRIMARY CARE OF VETERANS WITH HIV

A

Abacavir, 76, 221t, 251

Abbreviations, xii

Abdominal aneurysm, 289

Abuse. See also Alcohol use and misuse; 

Substance use

alcohol, 3–4

domestic violence, 260–261

military sexual trauma, 260

substance, 70

Acamprosate, 13, 15

ACE inhibitors, 138, 176, 177t, 180t

Acetaminophen

in combination with opioids, 209, 

324–325

dosage and indications for, 321, 324

for low back pain, 289–290, 291

for osteoarthritis, 208, 209

for peripheral neuropathy, 300

Acid-suppressive agents, 161–164, 167

Acne, 119

ACTG Brief Peripheral Neuropathy 

Screen, 297, 301–302

Activity modifi cation, 290

Acute renal failure, 211, 219–220

Acyclovir, 223t, 265

Addiction, 70

Adrenergic agonists, beta

ARV interactions with, 105

for asthma treatment, 100, 101, 102, 

103, 104, 105

for COPD treatment, 112

long-acting, 104, 105

short-acting, 100, 101, 103, 104

Adrenergic blockers

alpha, 182–183t, 232

alpha-/beta, 179–180t

beta, 176, 177t, 179t

Airfl ow obstruction, in asthma, 99

Albumin/creatinine ratio, 139, 212, 214

Albuterol, 103, 112

Alclometasone, 122

Alcohol use and misuse, 3–15

alcohol abuse, 3–4

alcohol dependence, 3–4

and diabetes, 131, 132

epidemiology of, 5

and hypertension, 176t

key points of, 3

and liver disease, 187, 188, 194

management of, 7–8, 11–12

pharmacotherapy for, 13, 14–15

recommended limits for, 3, 4–5

referrals for, 13

resources for, 176t

risk assessment for, 41, 42–43

risky drinking, 3

screening for, 5–7, 9–10

in women, 264

Alcoholic liver disease, 188

Alcoholics Anonymous, 7, 8

Aldosterone antagonists, 177t, 181–182t

Alendronate, 264

Alfuzosin, 232

Alkaline phosphatase, 187, 188

Alpha-/beta-blockers, 179–180t

Alpha1

-antitrypsin defi ciency, 109

Alpha-fetoprotein, 198

5-alpha-reductase inhibitors, 232, 233

Alprazolam, 328

Alprostadil, intraurethral, 239

ALT (alanine transaminase), 187, 188

Amitriptyline, 300, 322, 327

Amlodipine, 181t, 310

Amphotericin B, 224t

Anabolic steroids, 94

Anal dysplasia, 83–88

evaluation of, 84–86

key points of, 83

management of, 86–88

overview of, 83–84

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332 PRIMARY CARE OF VETERANS WITH HIV

screening for, 85–86

and squamous cell cancer of the anus, 

83–84, 88

in women, 262

Analgesics

dosage and indications for, 321–322, 

324

for low back pain, 289–290, 291

opiate, 208–209, 324–325

for osteoarthritis, 208–209

for peripheral neuropathy, 300

Anal intraepithelial neoplasia, 86, 87–88

Anal pap tests, 85–86, 262

Androgen defi ciency, 89–94

causes of, 90

defi nition of, 89

and erectile dysfunction, 237

evaluation of, 91–92

key points of, 89

management of, 92–94

mechanisms of, 89–90

overview of, 89–90

referrals for, 94

symptoms of, 90, 91

Anesthetics, topical, 300, 326

Aneurysm, abdominal, 289

Angiotensin converting enzyme (ACE) 

inhibitors, 138, 176, 177t, 180t

Angiotensin receptor blockers, 138, 176, 

177t, 180–181t

Ankle refl exes, 297, 302

Antabuse (disulfi ram), 14–15

Antacids, 162, 164, 167

Anti-adrenergic agents, 182–183t

Antibiotics, 113, 241

Anticholinergic bronchodilators, 103, 112

Anticonvulsants, 300, 323

Antidepressants, 280–283

ARV interactions with, 327–328

bupropion, 282–283, 328

dosage and indications for, 322

SNRIs, 280, 281–282

SSRIs, 280–281, 327

tricyclic, 291, 300, 322, 327

Antiepileptic medications, 300, 307–308, 

323

Antifungal medications, 121, 308–310

Antihypertensive medications, 176, 177t,

178–183t

Antipsychotic medications, 329

with acid-lowering medications, 167

with alfuzosin, 232

with alpha-/beta blockers, 179t

with alprazolam, 328

with amitriptyline, 327

with amlodipine, 181t, 310

with antacids, 167

with antidepressants, 327–328

with antiepileptic medications, 307–308

with antifungal medications, 121, 

308–310

with antihypertensives, 178–183t

with antipsychotics, 329

with asthma medications, 105

with atenolol, 179t

with benzodiazepines, 328

with beta agonists, 105

with beta-blockers, 179t

with buprenorphine, 74, 76

with bupropion, 62, 328

with calcium channel blockers, 181t,

310

with carbamazepine, 307

with carvedilol, 179t

with corticosteroids, 105, 114

with desipramine, 327

with diazepam, 328

with diltiazem, 181t, 310

with duloxetine, 327

with fl uconazole, 308–309

with fl uoxetine, 327

with fl uticasone, 105, 114

with food, 313

with GHB, 76, 77

with hormonal contraceptives, 

258–259

with H2RAs, 167

with hypnotics, 328–329

with imipramine, 327

with itraconazole, 309

with ketoconazole, 309

with lamotrigine, 308

with leukotriene receptor antagonists, 

105

with lipid-lowering medications, 152, 

315–318

with MDMA, 76

with methadone, 73, 76, 310–311

with methamphetamine, 74–75

with metoprolol, 179t

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PRIMARY CARE OF VETERANS WITH HIV 33

with mirtazapine, 328

with montelukast, 105

with nefazodone, 328

with nifedipine, 181t

with nortriptyline, 327

with olanzapine, 329

with paroxetine, 327

with PDE5 inhibitors, 238

with phenobarbital, 307–308

with phenytoin, 308

with pimozide, 329

with posaconazole, 309

with proton pump inhibitors, 167

with salmeterol, 105

with sedatives, 328–329

with sertraline, 327

with SNRIs, 327

with SSRIs, 327

with St. John’s wort, 313, 328

with statins, 152, 315–318

with supplements, 313

with terbinafi ne, 309

with theophylline, 105, 114

with trazodone, 328

with triazolam, 328

with tricyclic antidepressants, 300, 

327

with valproate, 308

with venlafaxine, 327

with voriconazole, 310

with warfarin, 311

with zafi rlukast, 105

with zolpidem, 329

Antiretroviral therapy. See also Antiretroviral drug interactions

abbreviations for, xii

and comorbid conditions, x

and depression, 272, 280

and diabetes, 131

and dyslipidemia, 144, 152

and gastroesophageal refl ux disease, 

168

and hypertension, 172

and liver disease, 188

during pregnancy, 255–256

and renal disease, 217–218, 220–225

and smoking, 54

and substance abuse, 71

toxicities associated with, ix, 188, 194

for women, 250, 251

262

Anxiety, and erectile dysfunction, 237

Arthritis

osteoarthritis, 203–209

rheumatoid, 205

of the spine, 286

Arthroscopic surgery, 209

ARV toxic neuropathy, 295, 296

ASC-H (atypical squamous cells/cannot 

exclude HSIL), 31t, 86, 87–88, 

263

Ascites, 195

ASCUS (atypical squamous cells of undetermined signifi cance), 30, 86

87, 263

Aspirin, 138

AST (aspartate transaminase), 187, 188

Asthma, 97–105

acute, 102–104

chronic, 100–102

epidemiology of, 98

evaluation of, 98–100

key points of, 97

management of, 100–105

medications for, 103–105

occupational, 99

referrals for, 102

symptoms of, 97, 98

vs. COPD, 97, 110

Atazanavir

food requirements for, 313

interactions with

antacids, 167

antiepileptics, 307

antifungal medications, 308, 309

calcium channel blockers, 310

corticosteroids, 105, 114

H2RAs, 167, 168

methadone, 310

oral contraceptives, 258

protein pump inhibitors, 167, 168

statins, 318

warfarin, 311

and renal disease, 221, 223t

Atenolol, 179t

Atorvastatin, 151, 152, 316, 318

Atrophy, defi ned, 125

AUDIT-C questions, 5, 6–7

Autoimmune hepatitis, 189, 195

Avascular necrosis, 205

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334 PRIMARY CARE OF VETERANS WITH HIV

Back pain, low, 285–292

acute, 286

cauda equina syndrome, 286, 289

chronic, 286

differential diagnosis of, 289

epidemiology of, 285–286

evaluation of, 286–289

key points of, 285

management of, 289–291

prevention of, 292

radiculopathy, 286

referrals for, 292

sciatica, 285, 286

spinal stenosis, 286

spondylolisthesis, 286

spondylosis, 286

treatment follow-up for, 292

Baclofen, 291

Bacterial vaginosis, 266

Barium studies

double-contrast enema, 22t

esophagram, 160

Barrett esophagus, 156, 157–158, 160, 

161

Beclomethasone, 104

Bed rest, for back pain, 290

Behavior modifi cation

for alcohol misuse, 7–8, 11–12

for benign prostatic hypertrophy, 231

for diabetes, 130–131, 132

for dyslipidemia, 149

for gastroesophageal refl ux disease, 

162, 164–165

for hypertension, 175–176t

of sexual practices, 40–41, 46–48, 49

for smoking cessation, 57–59

for substance abuse, 73–76

Benazepril, 180t

Benign prostatic hypertrophy, 228–233

evaluation of, 228–231

key points of, 227

management of, 231–233

referrals for, 233

Benzodiazepines, 328

Beta-adrenergic agonists

ARV interactions with, 105

for asthma treatment, 100, 101, 102, 

103, 104, 105

for COPD treatment, 112

short-acting, 100, 101, 103, 104

Beta-blockers, 176, 177t, 179t

Biguanides, 133

Bile acid sequestrants, 152, 317

Biliary cirrhosis, primary, 189

Bilirubin, 188

Biopsy, liver, 192

Bisphosphonates, 264

Bleeding

menstrual irregularities, 256–257

variceal/GI, 196

Blood pressure. See also Hypertension

and diabetes, 139, 177t

home monitoring, 177

measuring, 173

Bone densitometry, 262, 264

Breast cancer screening, 24–27

effectiveness of, 26

epidemiology, 25–26

methods for, 26

positive results in, 27

recommendations for, 17, 25, 26–27, 262

reminders for, 27

Breast examinations, 25, 26, 262

Breastfeeding, 256

Brief interventions

for alcohol misuse, 7–12

for preventing HIV transmission, 41, 

46–50

for smoking cessation, 55–59, 110

for substance abuse, 72–75

Bronchitis, chronic, 107, 108. See also Chronic 

obstructive pulmonary disease

Bronchodilators, 103, 112

Bronchoprovocation testing, 100

Bronchospasm. See Asthma

Bullae, 124

Buprenorphine, 73–74, 76

Bupropion

ARV interactions with, 62, 328

for depression treatment, 282–283

for methamphetamine abuse, 74

for smoking cessation, 60–66, 67

Bursitis, 205

C

Calcium, 264, 313

Calcium channel blockers, 176, 177t, 181t,

310

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PRIMARY CARE OF VETERANS WITH HIV 33

tion, 205

Cancer

anal, 83–84, 85–86, 88, 262

breast, 24–27, 262

cervical, 27–31, 261, 263

colorectal, 18–24

hepatocellular carcinoma, 197–199

and low back pain, 289

prostate, 31–34

risk of, and HIV, 17, 18, 28, 31

screening for, 17–34

vaginal, 261–262

vulvar, 261–262

Candesartan, 180t

Candidiasis

onychomycosis, 121

vaginal, 266

Cannabis, 76

Capsaicin, 207, 300, 326

Carbamazepine, 307

Carcinoma, hepatocellular, 17, 197–199

Cardiovascular disease

and diabetes, 128, 131

and dyslipidemia, 143–144, 145

and hypertension, 171, 177t

risk factors for, 145

Carvedilol, 179t

Cauda equina syndrome, 286, 289

Ceftriaxone, 241

Celecoxib, 322

Cervical cancer screening, 27–31

effectiveness of, 29

epidemiology and pathogenesis, 28

methods for, 29

positive results of, 29–31, 263

recommendations for, 17, 29, 261

reminders for, 29

Cervical intraepithelial neoplasia, 28, 30

Change

assessing readiness for, 47, 49, 55, 72

stages of, 47, 49

Child-Turcotte-Pugh classifi cation, 193

Chlamydia, 45t

Chlorthalidone, 179t

Cholangitis, primary sclerosing, 189

Cholesterol

HDL, 144, 150

LDL, 143, 144, 146, 147–148, 

149–150

total, 143, 144, 148

and ART, 217–218

evaluation of, 215–217

management of, 217–218

referrals for, 217

risk factors for, 211, 216

stages of, 215t

Chronic obstructive pulmonary disease 

(COPD), 107–114

acute exacerbations of, 112

chronic, stable, 111–112

epidemiology of, 107–108

evaluation of, 108–110

key points of, 107

management of, 110–114

medications and therapies for, 112–114

referrals for, 112

and smoking, 57, 106, 110

types of, 108

vs. asthma, 97, 110

Cialis (tadalafi l), 238

Cidofovir, 224t

Cimetidine, 163, 167

Cirrhosis, 192–194. See also Liver disease

clinical features of, 187–188, 192

compensated, 192

decompensated, 192

defi nitions, 185, 192

diagnostic tests for, 192–193

primary biliary, 189

staging and classifi cation of, 193–194

Citalopram, 281, 327

Clinical breast examination, 25, 26

Clobetasol, 122

Clonidine, 182t

Club drugs, 70, 76–78

Cocaine, 71, 75

Codeine, 209, 291, 324

Colchicine, 208, 326

Colonoscopy, 19, 21–22t

Colorectal cancer screening, 18–24

epidemiology and pathogenesis, 18–19

methods for, 19, 20–22t

positive results of, 24

recommendations for, 17, 18, 19, 22–24

reminders for, 24

Colposcopy, 30, 31

Comorbid conditions

related to alcohol misuse, 5

related to diabetes, 128

related to dyslipidemia, 143–144

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336 PRIMARY CARE OF VETERANS WITH HIV

related to hypertension, 171, 174–175t

related to liver disease, 186–187

related to smoking, 54

related to substance abuse, 71

Condoms, 50, 252

Condylomata, 87

Confi dentiality, patient, 43

Contraception, 50, 252–253, 258–259

Coronary heart disease

and diabetes, 128, 131

and dyslipidemia, 143–144, 145

and hypertension, 171, 177t

risk factors for, 145

Corticosteroids

ARV interactions with, 105, 114

for asthma treatment, 103–104

for COPD treatment, 112

epidural injections of, 291

intraarticular injection of, 208

for psoriasis treatment, 122

Cough, with COPD, 109, 112

Counseling

for alcohol misuse, 7–8

for HIV transmission prevention, 

46–50

preconception, 253–255

for smoking cessation, 58–59, 110

CPRS reminders

for breast cancer screening, 27

for cervical cancer screening, 29

for colorectal cancer screening, 24

for depression screening, 273

for prostate cancer screening, 33–34

Creatinine, serum, 212

Creatinine clearance, 212, 221–222t

Cromolyn, 104

Crust, skin, 125

Crystal Meth Anonymous, 75

Cyclobenzaprine, 291, 323

Cytology

anal, 86–88

cervical, 30–31, 263

D

Darunavir

food requirements for, 313

interactions with

antidepressants, 327, 328

antiepileptics, 307, 308

corticosteroids, 105, 114

methadone, 310

oral contraceptives, 258

statins, 316, 318

warfarin, 311

DASH diet, 175t

Date-rape drug (Rohypnol), 70, 77

Degenerative joint disease. See Osteoarthritis

Delavirdine, 311, 315, 316, 317

Dementia, 128, 259

Dependence

alcohol, 3–4

physical, 70

substance, 70

Depo-Provera (medroxyprogesterone), 

253, 258

Depression, 271–283

and ART adherence, 272, 280

associated with other illnesses, 

276–277

and erectile dysfunction, 237

and HIV infection, 272

key points of, 271

management of, 279–283

medications for, 280–283, 322, 

327–328

mental health services for, 271

prevalence of, 272

referrals for, 271–272

screening for, 272–277

and smoking cessation, 67

and suicide, 277–279

in women, 250, 259

Dermatitis, seborrheic, 115, 116, 117

Dermatologic conditions, 115–125

according to clinical status, 116

epidemiology of, 115–116

evaluation and management of, 

117–123

folliculitis, 115, 117–119

HPV-associated warts, 115, 123

key points of, 115

onychomycosis, 115, 119–121

psoriasis, 115, 122

seborrheic dermatitis, 115, 116, 117

terminology for, 124–125

Dermatophytes, 119

Desipramine, 327

Desonide, 122

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PRIMARY CARE OF VETERANS WITH HIV 33

Dextroamphetamine, 74

Diabetes, 127–140

complications of, 128

defi nitions of, 128–129

evaluation of, 129–130

and hypertension, 139, 177t

key points of, 127

management of, 130–139

and alcohol intake, 131, 132

ART regimens in, 131

behavior modifi cation in, 130–131, 132

diet in, 131, 132, 133, 140

exercise in, 131, 132, 140

insulin in, 135–136, 137f

monitoring and prevention strategies in, 138–140

oral medications in, 131, 133–135

other therapies in, 138

patient education in, 131, 133

self-monitoring of blood glucose in, 

131, 138–139

treatment goals, 131

weight loss in, 130, 132, 140

medications that increase risk of, 129

overview of, 128

referrals for, 139

risk factors for, 128, 129

screening for, 129–130

Type 2, 131, 132f, 137f

Diazepam, 328

Didanosine, 221t, 295, 313

Diet

in diabetes management, 131, 132, 133, 

140

in GERD management, 162, 164

in hypertension management, 175t

resources for, 176t

Digital rectal exam, 19, 32, 33, 262

Diltiazem, 181t, 310

Diphtheria immunization, 38

Distal sensory polyneuropathy, 295, 296

Distal subungual onychomycosis, 119

Disulfi ram, 14–15

Diuretics

potassium-sparing, 181–182t

thiazide, 176, 177t, 178–179t

Domestic violence, 260–261

Dosing

for antihypertensives, 178–183t

for atazanavir, 168

for NRTIs, 221–222t

for pain medications, 321–326

for PDE5 inhibitors, 238

terminology for, xii

Doxazosin, 182t, 231–232

Doxycycline, 241

Drugs. See Medications; Substance use

Duloxetine, 281, 300, 327

Dutasteride, 233

Dyslipidemia, 143–152

and ART, 144, 152

and coronary heart disease, 143–144, 

145

evaluation of, 145–148

and HIV infection, 144

hypertriglyceridemia, 146, 148, 150

key points of, 143

LDL cholesterol goals and treatment, 

147

management of, 148–152

medications for, 149–152, 315–318

overview of, 143–144

screening for, 144

Dyspnea, with COPD, 108, 112

E

Ecstasy (MDMA), 70, 77

Education, patient

in diabetes management, 131, 133

for HIV transmission prevention, 46

for low back pain, 290

Efavirenz

food requirements for, 313

interactions with

antidepressants, 328

antiepileptics, 307, 308

antifungals, 309, 310

antipsychotics, 329

calcium channel blockers, 310

methadone, 311

oral contraceptives, 259

statins, 315, 316, 317, 318

warfarin, 311

Emphysema, 107, 108. See also Chronic 

obstructive pulmonary disease

Emtricitabine, 221t

Encephalopathy, hepatic, 196–197

Endoscopic therapies, 166

Enema, barium, 22t

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338 PRIMARY CARE OF VETERANS WITH HIV

Epididymitis, 239–241

acute, 239, 241

chronic, 239

evaluation of, 240

key points of, 227

management of, 241

overview of, 239–240

Epidural steroid injections, 291

Erectile dysfunction, 233–239

causes of, 234

evaluation of, 235–237

key points of, 227

management of, 237–239

medications associated with, 234

overview of, 233–234

refractory, 238

Erosion, skin, 125

Escitalopram, 281, 327

Esomeprazole, 163

Esophagitis, 156, 162

Esophagogastroduodenoscopy, 156, 160

Esophagram, barium, 160

Esophagus. See also Gastroesophageal 

refl ux disease

Barrett, 156, 157–158, 160, 161

lower sphincter dysfunction, 156

Etravirine

food requirements for, 313

interactions with

antiepileptics, 307, 308

antifungals, 309, 310

benzodiazepines, 328

methadone, 311

oral contraceptives, 259

statins, 315, 316, 318

warfarin, 311

Excoriation, 125

Exenatide, 135

Exercise

asthma induced by, 104

for back pain, 290

and diabetes, 131, 132, 140

and erectile dysfunction, 237

and hypertension, 176t

and osteoarthritis, 207

resources for, 176t

tolerance for, 109

for women, 264

Eye examinations, 139

Ezetimibe, 152, 317

Famotidine, 163

Fecal occult blood testing, 19, 20t, 21t

Feet

examination of, 139

osteoarthritis in, 206

Fenofi brate, 151

Fentanyl transdermal, 209, 291, 301, 325

Fibrates, 151, 316

Finasteride, 233

Fingernails, fungal infections of, 115, 119–121

Fissures, 125

Fixed-dose combinations, 176

Flexeril (cyclobenzaprine), 323

Fluconazole, 308–309

Flunisolide, 104

Flunitrazepam, 70, 77

Fluocinonide, 122

Fluoroquinolones, 241

Fluoxetine, 280, 281, 327

Fluticasone, 104, 105, 114

Fluvastatin, 151, 316, 318

Folate, 255

Follicle-stimulating hormone, 89–90, 92

Folliculitis, 115, 117–119

Food interactions with ARVs, 313

Forced expiratory volume (FEV1

)

in asthma, 99, 101–102

in COPD, 107, 111, 113

Forced vital capacity (FVC)

in asthma, 99, 101–102

in COPD, 107, 111

Formoterol, 104

Fosamprenavir, interactions with

antidepressants, 327

antiepileptics, 308

antifungals, 309

calcium channel blockers, 310

methadone, 310

oral contraceptives, 258

statins, 318

warfarin, 311

Foscarnet, 224t

Fosinopril, 180t

Fractures, 289

G

Gabapentin, 300, 322

Gamma-hydroxybutyrate (GHB), 70, 76, 

77

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PRIMARY CARE OF VETERANS WITH HIV 33

Gastroesophageal refl ux disease, 155–168

acute, 161–165

Barrett esophagus, 156, 157–158, 160, 

161

chronic, 165–166

complicated, 156, 157

diagnostic tests for, 159–160

dietary and lifestyle modifi cations for, 

162, 164–165

evaluation of, 156–161

extraesophageal, 158–159

key points of, 155

management of, 161–166

medications for

acid-suppressive agents, 161–164, 

167

antacids, 162, 164, 167

ARV interactions with, 167

dosage recommendations, 168

prokinetic agents, 162, 164

nonerosive refl ux disease, 156, 162

overview of, 155–156

referrals for, 166

surgery and endoscopic treatments 

for, 166

symptoms of, 155–156, 157, 158–159

Gastrointestinal bleeding, 196

Gemfi brozil, 151

Genital tract infections

bacterial vaginosis, 266

chlamydia, 45

genital ulcers, 265–266

gonorrhea, 45

herpes simplex virus, 45, 265

pelvic infl ammatory disease, 266–267

sexually transmitted, 42, 44–45, 

262–263

syphilis, 45

trichomoniasis, 45

vaginal candidiasis, 266

warts, 115, 123

GHB (gamma-hydroxybutyrate), 70, 76, 

77

Gleason score, 32

Glipizide, 133–134

Glomerular fi ltration rate, 212–213, 

215–216t, 219

Glucocorticoids, 112

Glucose, blood

impaired fasting, 129

testing, 129

tolerance test, 128, 129

Glyburide, 133–134

Glycopyrrolate, 112

Gonorrhea, 45t

Gout, 205

Grapefruit juice, interactions with, 313

Gum, nicotine polacrilex, 60–66, 67

Gynecological issues

contraception, 252–253, 258–259

genital tract infections, 265–267

menopause, 256–257

menstrual irregularities, 256–257

preconception counseling, 253–255

pregnancy, 45, 255–256

sexual function, 257

H

H2 receptor antagonists (H2RAs), 161–162

ARV interactions with, 167

atazanavir dosages with, 168

for chronic GERD, 166

dosages for, 163–164

and relapse of GERD symptoms, 165

Hands, osteoarthritis in, 204, 206

HbA1c, 131, 132, 138

HDL cholesterol, 144, 150

Heart disease

and diabetes, 128, 131

and dyslipidemia, 143–144

and hypertension, 171, 177t

risk factors for, 145

Heart failure, 171, 177t

Heartburn, 155, 156, 158

Hemodialysis, 218

Hemorrhage, variceal, 196

Hepatic encephalopathy, 196–197

Hepatitis, autoimmune, 189, 195

Hepatitis A immunization, 38

Hepatitis B

and hepatocellular carcinoma, 17

immunization for, 37, 38

laboratory fi ndings in, 189, 190

and liver disease, 186, 189, 190, 195

prevalence of, 186

treatment of, 195

Hepatitis C

and hepatocellular carcinoma, 17

laboratory fi ndings in, 189, 191

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340 PRIMARY CARE OF VETERANS WITH HIV

and liver transplantation, 200

prevalence of, 186

treatment of, 195

Hepatocellular carcinoma, 17, 197–199

Hepatotoxicity, and ARVs, 188, 194

Herniated nucleus pulposus, 289

Heroin, 73–74

Herpes simplex virus, 45t, 265

High-resolution anoscopy, 87

Hips, osteoarthritis in, 204, 206

HITS scale, 260

HIV-associated nephropathy, 212, 217, 

218–219

HIV-associated sensory neuropathy, 

295–296, 297

HIV infection

and alcohol misuse, 3, 5

and anal dysplasia, 83–84

and androgen defi ciency, 89, 90

and cancer risk, 17, 18, 28, 31

comorbid conditions related to, ix–x

and COPD, 108

and depression, 272

and dermatologic conditions, 115–116

and dyslipidemia, 143, 144

epidemiology of, 39–40

and epididymitis, 240

and erectile dysfunction, 233–234

and liver disease, 186–187

and peripheral neuropathy, 295, 296

preventing transmission of, 39–50

follow-up for, 50

key points of, 39

patient evaluation in, 41, 42–45

patient management in, 41, 46–50

patient support in, 50

pregnancy screening, 45

risk assessment in, 41, 42–44

with safer sexual behaviors, 40–41, 

46–48, 49

and STDs, 42, 44–45, 262–263

in women, 252

and renal disease, 211–212, 217, 

218–219

and smoking, 54

and substance abuse, 70–71

transmission routes for, 40, 250

in women, 249–251

HMG-CoA reductase inhibitors, 151, 

315–318

lesion), 31t, 86, 87–88

Human papillomavirus

and anal dysplasia, 83–84

and cervical dysplasia, 28, 29, 263

immunization for, 38

warts associated with, 115, 123

Hydralazine, 182t

Hydrochlorothiazide, 138, 179t

Hydrocodone, 209, 291, 324

Hydrocortisone, 122

Hydromorphone, 209, 325

Hypertension, 171–183

and ART, 172

defi nitions of, 173–174t

evaluation of, 172–175

key points of, 171

lifestyle modifi cations for, 175–176t

management of, 175–183

medications for

ACE inhibitors, 177t, 180t

aldosterone antagonists, 177t,

181–182t

angiotensin receptor blockers, 177t,

180–181t

anti-adrenergic agents, 182–183t

ARV interactions with, 178–183t

beta-blockers, 177t, 179t

calcium channel blockers, 177t,

181t, 310

classes of, 177t

direct vasodilators, 182–183t

drug dosing for, 178–183t

mixed alpha-/beta-blockers, 179–180t

potassium-sparing diuretics, 

181–182t

thiazide diuretics, 177t, 178–179t

portal, 192

rationale for detecting and treating, 

171–172

referrals for, 178

screening for, 172–173

treatment for, 172, 173–174t, 177

Hypertriglyceridemia, 146, 148, 150

Hypnotics, 328–329

Hypogonadism, 89, 237

I

Ibandronate, 264

Ibuprofen, 321

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PRIMARY CARE OF VETERANS WITH HIV 34

for asthma, 99

for back pain, 288–289

for COPD, 109

for epididymitis, 240

for liver disease, 192–193

for nephrolithiasis, 243

for osteoarthritis, 206

Imipramine, 327

Immunizations, 37–38, 140

Impaired fasting glucose, 129

Impaired glucose tolerance, 128, 129

Indinavir

interactions with

antidepressants, 328

calcium channel blockers, 310

grapefruit juice, 313

oral contraceptives, 258

statins, 318

theophylline, 105, 114

warfarin, 311

and nephrolithiasis, 242, 243–244

and renal disease, 221, 223t

Infections. See also HIV infection

epididymitis, 239–241

and low back pain, 289

sexually transmitted, 42, 44–45

spontaneous bacterial peritonitis, 

196

Infectious monoarticular disease, 205

Infl uenza immunization, 37, 38, 140

Injections

of medications, 208, 291

in substance use, 70, 71

Insulin, 128, 135–136, 137f

International Index of Erectile Function 

(IIEF-5), 235–236

International Prostate Symptoms Score, 

228, 229–231

Interventions, brief

for alcohol misuse, 7–12

for preventing HIV transmission, 41, 

46–50

for smoking cessation, 55–59, 110

for substance abuse, 72–78

Intrauterine devices, 253

Intravaginal ring, 253, 258

In vitro fertilization, 254

Ipratropium, 103, 112

Irbesartan, 180t

Itraconazole, 309

Joint aspiration, 206–207

Joint pain. See Osteoarthritis

K

Ketamine hydrochloride, 70, 78

Ketoconazole, 309

Kidney disease, chronic, 211, 213, 215–

218. See also Renal disease

Kidney stones. See Nephrolithiasis

Knees, osteoarthritis in, 204, 206

L

Labetalol, 180t

Lamivudine, 221t

Lamotrigine, 300, 308, 323

Lansoprazole, 163

LDL cholesterol

and cardiovascular disease, 143, 144

elevated, drug treatments for, 149–150

thresholds for treatment of, 147–148

treatment goals for, 147–148

Lesions, skin, 124–125. See also Dermato

logic conditions

Leukotriene receptor antagonists, 104, 

105

Levalbuterol, 103, 112

Levitra (vardenafi l), 238

Levofl oxacin, 241

Lichenifi cation, 125

Lidocaine, 300, 326

Lifestyle modifi cation

for dyslipidemia, 149

for GERD management, 162, 164–165

for hypertension, 175–176t

Lipid-lowering medications, 149–152, 

315–318

Lipids, fasting, 139, 144

Lisinopril, 180t

Liver biopsy, 192

Liver disease, 185–201

abdominal imaging in, 192–193

and alcohol misuse, 187, 188, 194

and ARVs, 188

causes of, 186–187

cirrhosis, 185, 187–188, 189, 192–194

clinical features of, 187–188

comorbidities associated with, 

186–187

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342 PRIMARY CARE OF VETERANS WITH HIV

end-stage, 186, 194

epidemiology of, 186

evaluation of, 187–194

and hepatitis, 186–187, 189, 190, 191

hepatocellular carcinoma, 197–199

key points of, 185

laboratory fi ndings in, 187, 188–191, 192

liver transplantation, 200–201

management of, 194–197

nonalcoholic fatty liver disease, 189

staging and classifi cation of, 193–194

Liver function testing, 139, 187, 188

Liver transplantation, 200–201

Long-acting beta-agonists, 104, 105

Lopinavir/ritonavir, interactions with

antidepressants, 328

antiepileptics, 308

antifungals, 309

corticosteroids, 105, 114

methadone, 310

oral contraceptives, 258

statins, 316, 318

warfarin, 311

Losartan, 181t

Lovastatin, 316, 318

Lozenges, nicotine polacrilex, 60–66

LSIL (low-grade squamous intraepithelial 

lesion), 31t, 86, 87

Lumbago, 285

Luteinizing hormone, 89–90, 92

M

Macules, 124

Mammography, 25, 26–27

Manipulation, for back pain, 290

Maraviroc, interactions with

antidepressants, 328

antiepileptics, 307–308

St. John’s wort, 313, 328

Marijuana, 76

Mast cell inhibitors, 104

MDMA (methylenedioxymethamphetamine), 70, 76, 77

Measles immunization, 38

Medications. See also Antiretroviral drug 

interactions; Antiretroviral 

therapy; Substance use

for alcohol misuse relapse prevention, 

13, 14–15

antiepileptic, 300, 307–308, 323

antifungals, 121, 308–310

antihypertensive, 176, 177t, 178–183t

antipsychotics, 329

for asthma treatment, 103–105

for benign prostatic hypertrophy, 

231–233

for COPD, 112–114

for diabetes, 133–138

and diabetes risk, 129

dosing terminology for, xii

for dyslipidemia, 149–152, 315–318

for erectile dysfunction, 237–239

for folliculitis, 117–119

for gastroesophageal refl ux, 161–165, 

167–168

for onychomycosis, 119–121

for osteoarthritis, 207–209

for pain, 290–291, 321–326

for peripheral neuropathy, 300–301

for psoriasis, 122

for seborrheic dermatitis, 117

for smoking cessation, 58, 59, 60–67

for substance abuse, 73–76

testosterone replacement therapy, 

92–94

Medroxyprogesterone, 253, 258

MELD score, 194

Meloxicam, 322

Meningococcus immunization, 38

Menopause, 256–257

Menstrual irregularities, 256–257

Mental health, 42, 271–272. See also

Depression

Metformin, 131, 133

Methadone, 73, 76, 301, 310–311, 325

Methamphetamine, 71, 74–75

Methylenedioxymethamphetamine 

(MDMA), 70, 76, 77

Methylprednisolone, 112

Metoclopramide, 162, 164

Metoprolol, 179t

Microalbuminuria, 213, 214

Midazolam, 328

Military sexual trauma, 260

Mirtazapine, 328

Mixed alpha-/beta-blockers, 179–180t

MMR immunization, 37, 38

Model for end-stage liver disease (MELD) 

score, 194

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PRIMARY CARE OF VETERANS WITH HIV 34

(MDRD) Study equation, 212–213

Mold infections, in nails, 119, 121

Montelukast, 104, 105

Morbidity and mortality

due to comorbid conditions, ix

due to liver disease, 186

due to renal disease, 211

Morphine, 209, 291, 301, 325

Motivation, to quit smoking, 68

Mumps immunization, 38

Muscle relaxants, 291, 323

Myocardial infarction, 171

N

N-3 (omega-3) polyunsaturated fatty 

acids, 151, 317

Nails, fungal infections of, 115, 119–121

Naloxone, 74

Naltrexone, 13, 14, 74, 75

Nandrolone, 94

Naproxen, 322

Narcotics Anonymous, 73, 75, 76

Necrosis, avascular, 205

Nedocromil, 104

Nefazodone, 328

Nelfi navir

food requirements for, 313

interactions with

antiepileptics, 308

antifungals, 309

methadone, 310

oral contraceptives, 258

statins, 316, 318

tricyclic antidepressants, 327

Nephrolithiasis, 242–244

evaluation of, 242

key points of, 227

management of, 243–244

overview of, 242–243

Nephropathy, HIV-associated, 212, 217, 

218–219

Neuropathy, peripheral, 295–302

ARV toxic, 295, 296, 299–300

distal sensory polyneuropathy, 295, 

296, 299–300

epidemiology of, 296

evaluation of, 296–298

HIV-associated sensory neuropathy, 

295–296, 297

management of, 298–301

prevention of, 296

referrals for, 299

screening for, 297, 301–302

symptoms of, 295

Neuropsychiatric disorders, in 

women, 259. See also

Depression

Nevirapine, interactions with

antiepileptics, 308

antifungals, 309

calcium channel blockers, 310

methadone, 311

oral contraceptives, 258

statins, 315

warfarin, 311

Niacin, 152, 316

Nicotine

replacement therapies for, 59, 60–67

withdrawal from, 59, 67

Nifedipine, 181t

Nizatidine, 164

NNRTIs (nonnucleoside reverse transcriptase inhibitors)

and dyslipidemia, 144

interactions with

antiepileptics, 307–308

antifungals, 121

food and supplements, 313

methadone, 76

oral contraceptives, 258, 259

St. John’s wort, 313, 328

statins, 315–318

Nodules, skin, 124

Nonalcoholic fatty liver disease, 189

Nonbenzodiazepines, 291, 323

Nonerosive refl ux disease, 156, 162

Noninvasive positive pressure ventilation, 

113

Nortriptyline, 67t, 300, 322, 327

NRTIs (nucleoside reverse transcriptase 

inhibitors)

and diabetes, 128, 129

and dyslipidemia, 144

interaction with food and supplements

313

interaction with methadone, 76

and renal disease, 220, 221–222t

NSAIDS (nonsteroidal anti-infl ammatory 

drugs)

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344 PRIMARY CARE OF VETERANS WITH HIV

for low back pain, 289–290

for osteoarthritis, 208

for peripheral neuropathy, 300

Numbness, distal, 295, 297

NuvaRing (intravaginal ring), 253, 258

O

Obesity

and diabetes, 128, 130

and erectile dysfunction, 237

and osteoarthritis, 207

Occult blood testing, 19, 20t, 21t

Ofl oxacin, 241

Olanzapine, 329

Omalizumab, 104

Omeprazole, 163, 167

Onychomycosis, 115, 119–121

Opioids

abuse of, 73–74

dosage and indications for, 324–325

for low back pain, 289, 291

for osteoarthritis, 208–209

for peripheral neuropathy, 301

Opportunistic illnesses, 157, 162

Oral contraceptives, 253, 258–259

Oral glucose tolerance test, 128, 129

Organ injury, ix, 174–175t

Osteoarthritis, 203–209

classifi cation of, 203–204

defi nitions of, 203–204

diagnostic criteria for, 204

differential diagnosis of, 205

evaluation of, 205–207

key points of, 203

medications for, 207–209

nonpharmacologic interventions for, 

207

surgery for, 209

Osteomyelitis, 289

Osteonecrosis, 205

Osteoporosis/osteopenia screening, 262, 

264

Oxandrolone, 94

Oxycodone, 209, 291, 301, 324–325

Oxygen therapy, 113

P

Pain, low back, 285–292

Pain medications

for low back pain, 289–290, 291

for osteoarthritis, 207–209

for peripheral neuropathy, 300–301

and substance abuse disorders, 78–79

Pantoprazole, 163

Pap smear

anal, 85–86, 262

cervical, 28, 29, 261, 263

Papules, 124

Paroxetine, 67t, 280, 281, 327

Patches, skin, 124

Patient education

in diabetes management, 131, 133

for HIV transmission prevention, 46

for low back pain, 290

PDE5 inhibitors, 237–238

Peak expiratory fl ow rate, 99–101, 102, 103

Pelvic infl ammatory disease, 266–267

Penile self-injectable drugs, 239

Pentamidine, 224t

Peripheral vascular disease, 128

Peritonitis, spontaneous bacterial, 196

Personality disorders, 259

Pertussis immunization, 38

pH monitoring, ambulatory, 160

Phenobarbital, 307–308

Phenytoin, 308

PHQ-2 and PHQ-9 questionnaires, 

272–275, 277

Physical dependence, 70

Physical therapy, 290

Pimozide, 329

Pioglitazone, 134–135

Pirbuterol, 112

Pityrosporum folliculitis, 118

Plaques, skin, 124

Pneumococcus immunization, 37, 38, 140

Polycystic ovarian syndrome, 256

Portal hypertension, 192

Posaconazole, 309

Posttraumatic stress disorder, 259

Pott disease, 289

Pravastatin, 151, 152, 316, 318

Prazosin, 183t

Prednisone, 103

Pregabalin, 300, 323

Pregnancy

antiretroviral therapy during, 255–256

preconception counseling, 253–255

screening for, 45

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PRIMARY CARE OF VETERANS WITH HIV 34

Primary biliary cirrhosis, 189

Primary sclerosing cholangitis, 189

Problem-solving skills, for smoking 

cessation, 58

Prokinetic agents, 162, 164

Propranolol, 179t

Prostate, benign hypertrophy of, 228–233

evaluation of, 228–231

key points of, 227

management of, 231–233

referrals for, 233

Prostate cancer screening, 31–34

effectiveness of, 33

epidemiology, 32

methods for, 32

positive results for, 34

recommendations for, 17, 31, 33

reminders for, 33–34

and testosterone replacement 

therapy, 93

treatment for, 32–33

Prostate-specifi c antigen, 32, 93–94

Prostatectomy, 32–33

Protease inhibitors

and diabetes, 128, 129, 131

and dyslipidemia, 144, 152

potential interactions with

antidepressants, 300, 327

antiepileptics, 307–308

antifungals, 121

antipsychotics, 329

benzodiazepines, 328

buprenorphine, 76

food and supplements, 313

inhaled corticosteroids, 105, 114

methadone, 76

oral contraceptives, 258, 259

St. John’s wort, 313, 328

statins, 152, 315–318

Protein/creatinine ratio, 214

Proteinuria, 212, 213–215

Proton pump inhibitor therapy

ARV interactions with, 167

atazanavir dosages with, 168

dosage for, 163

for gastroesophageal refl ux disease, 

159–160, 161–163

Proximal subungual onychomycosis, 120

Pseudomonal folliculitis, 118

Psoriasis, 115, 122

antidepressants, 280–283, 322, 

327–328

antipsychotics, 329

ARV interactions with, 327–329

sedatives and hypnotics, 328–329

Psychotherapy, 237, 279–280

Pulmonary function testing, 99–100, 

109

Pustules, 124

Q

Questionnaires

AUDIT-C, 5, 6–7

IIEF-5, 235–236

PHQ-2 and PHQ-9, 272–275, 277

R

Rabeprazole, 163

Race, and HIV infection, 250

Radiation therapy, 33

Radiculopathy, 286

Ramipril, 180t

Ranitidine, 164, 167

Rectum, examination of, 19, 32, 33, 262

Referrals

for alcohol misuse, 13

for androgen defi ciency, 94

for asthma, 102

for benign prostatic hypertrophy, 233

for COPD, 112

for depression, 271–272

for diabetes, 139

for GERD, 166

for HIV transmission prevention, 50

for hypertension, 178

for liver transplantation, 200–201

for low back pain, 292

for peripheral neuropathy, 299

for renal disease, 217

Refl exes, ankle, 297, 302

Regurgitation, 155, 158

Relapse

of alcohol misuse, 13–15

of tobacco use, 67–68

Renal calculi. See Nephrolithiasis

Renal disease, 211–225

acute renal failure, 211, 219–220

ARVs for patients with, 220–222

caused by ARVs, 222–225

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346 PRIMARY CARE OF VETERANS WITH HIV

and diabetes, 128

HIV-associated nephropathy, 218–219

and HIV infection, 211

and hypertension, 171

key points of, 211

overview of, 211–212

referrals for, 217

risk factors for, 211–212

screening for, 212–215

Renal function

in chronic kidney disease, 215–216

estimating, 212–213

and NRTI dosing, 221–222t

Renal replacement therapy, 218

Reproductive issues

contraception, 252–253, 258–259

preconception counseling, 253–255

pregnancy, 45, 255–256

sexual function, 257

Retinopathy, 128

Rheumatoid arthritis, 205

Risk assessments

for alcohol misuse, 41, 42–43

for HIV transmission, 41, 42–48, 49

for suicide, 277–279

Risk factors

for anal dysplasia, 84

for asthma, 98

for back pain, 287

for breast cancer, 25–26

for cardiovascular disease, 145

for cervical cancer, 28

for colorectal cancer, 19, 22–24t

for COPD, 108

for diabetes, 128, 129

for GERD, 158

for hepatocellular carcinoma, 197

for HIV transmission, 40–41, 47t

for osteoarthritis, 205

for osteoporosis, 264

for peripheral neuropathy, 296–297

for renal disease, 211–212, 216

for suicide, 278

Ritonavir

food requirements for, 313

interactions with

antidepressants, 300, 327, 328

antiepileptics, 307, 308

antifungals, 309, 310

antipsychotics, 329

corticosteroids, 105, 114

oral contraceptives, 258

sedatives/hypnotics, 328–329

statins, 316, 318

theophylline, 105, 114

Rohypnol (fl unitrazepam), 70, 77

Rosiglitazone, 134–135

Rosuvastatin, 151, 316, 317

Rubella immunization, 38

S

Salmeterol, 104, 105

Saquinavir

food requirements for, 313

interactions with

benzodiazepines, 328

calcium channel blockers, 310

food, 313

methadone, 310

oral contraceptives, 259

statins, 316, 318

warfarin, 311

Scales, skin, 125

Scars, 124

Sciatica, 285, 286

Screening

for alcohol misuse, 5–7, 9–10

for anal dysplasia, 85–86

for cancer, 17–34

anal, 85–86, 262

breast, 24–27, 262

cervical, 27–31, 261, 263

colorectal, 18–24

hepatocellular carcinoma, 198–199

prostate, 31–34

vaginal, 261–262

vulvar, 261–262

cost-benefi ts of, x

for depression, 272–277

for diabetes, 129–130

for dyslipidemia, 144

for HIV transmission risk behaviors, 

42–44

for hypertension, 172–173

importance of, ix

for osteoporosis/osteopenia, 262, 264

for peripheral neuropathy, 297, 

301–302

for pregnancy, 45

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PRIMARY CARE OF VETERANS WITH HIV 34

for sexually transmitted diseases, 42, 

44–45, 262–263

for substance abuse, 71

Seborrheic dermatitis, 115, 116, 117

Sedatives, 328–329

Self-monitoring of blood glucose, 131, 

138–139

Sensory loss, 297

Serosorting, 43

Sertraline, 281, 327

Sex partners, 241

Sexual behaviors

and erectile dysfunction, 237

modifying, 40–41, 46–48, 49

risk assessment of, 41, 42–43, 47t, 49

Sexual function

erectile dysfunction, 227, 233–239

in women, 257

Sexual trauma, military, 260

Sexually transmitted diseases, 42, 44–45, 

262–263

Short-acting beta-agonists, 100, 101, 103, 

104

Shoulders, osteoarthritis in, 206

Sigmoidoscopy, fl exible, 19, 20–21t

Sildenafi l, 238

Simvastatin, 317, 318

Sitagliptin, 135

Skin lesions, 124–125. See also Dermatologic conditions

Smoking cessation, 53–68

and asthma, 100

and COPD, 57, 110

and diabetes, 138

effectiveness of programs for, 54

evaluation for, 55–56

and GERD, 164

and hypertension, 175

key points of, 53

management of, 57–68

overview of, 54

patient relapse, 67–68

pharmacologic interventions for, 58, 

59–67

for women, 264

SNRIs (serotonin-norepinephrine 

reuptake inhibitors), 280, 

281–282, 327

Social support, for smoking cessation, 

59, 67

Spermicides, 252

Spinal stenosis, 286

Spine, 206, 286

Spirometry, 99, 109

Spironolactone, 182t

Spondylolisthesis, 286

Spondylosis, 286

Spontaneous bacterial peritonitis, 196

Sputum production, 109, 112

Squamous cell cancer of the anus, 83–84, 

85, 86, 88

SSRIs (selective serotonin reuptake inhibi

tors), 280–281, 327

St. John’s wort, 313, 328

Stages of change theory, 47, 49

Staphylococcal folliculitis, 115, 118

Statins, 151, 315–318

Stavudine, 222t, 295

Steatohepatitis, 189

Steroids, anabolic, 94

Stroke, 128, 171, 177t

Substance use, 69–79. See also Alcohol 

use and misuse; Smoking cessation

and antiretroviral therapy, 71

defi nitions of, 70

epidemiology of, 70–71

and HIV infection, 71

key points of, 69

management of, 71–79

and ARV interactions, 76

brief interventions, 72

cannabis, 76

club drugs, 76–78

cocaine, 75

heroin and other opioids, 73–74

methamphetamine, 74–75

and pain management, 78–79

screening for, 71

substance abuse, 70

substance dependence, 70

types of, 69–70

Suicide, 277–279

Sulfonylureas, 131, 133

Sulindac, 322

Supplements, interactions with ARVs, 313

Support

for alcohol use goals, 11, 12

for HIV transmission prevention, 50

for smoking cessation, 59, 67

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348 PRIMARY CARE OF VETERANS WITH HIV

Syphilis, 45t

T

Tadalafi l, 238

Tamsulosin, 232

Telmisartan, 181t

Tenofovir, 220–221, 222–223t

Terazosin, 183t, 231–232

Terbinafi ne, 309

Testes, 239, 240

Testosterone

defi ciency of, 89–94

measuring, 91–92

replacement therapy, 92–93, 237

Tetanus immunization, 38

Theophylline, 104, 105, 113, 114

Thiazide diuretics, 176, 177t, 178–179t

Thiazolidinediones, 132, 134–135

Tipranavir, interactions with

antidepressants, 328

antiepileptics, 307, 308

antifungals, 308

methadone, 310–311

oral contraceptives, 258

statins, 316, 318

vitamin E, 313

warfarin, 311

TMP-SMX, 224–225t

Tobacco use, 53–54. See also Smoking 

cessation

Toenails, fungal infections of, 115, 119–121

Tolerance

drug, 70

for exercise, 109

glucose, 128, 129

Tramadol, 209, 291, 324

Transdermal administration of drugs

for contraception, 253, 258

fentanyl, 209, 291, 301, 325

nicotine replacement, 60–66, 67

Transplantation, liver, 200–201

Trazodone, 328

Treatment programs, substance abuse, 72

Triamcinolone, 104, 122

Triamterene, 182t

Triazolam, 328

Trichomoniasis, 45t

Tricyclic antidepressants, 291, 300, 322, 

327

Tumors, 124

U

Ulcers

genital, 265–266

skin, 125

Urine, protein in, 212, 213–215

Urology, 227–244

benign prostatic hypertrophy, 227, 

228–233

epididymitis, 227, 239–241

erectile dysfunction, 227, 233–239

nephrolithiasis, 227, 242–244

V

Vacuum devices, for erectile dysfunction, 

239

Vagina

bacterial vaginosis, 266

cancer of, screening for, 261–262

candidiasis of, 266

Valproate, 308

Valsartan, 181t

Vardenafi l, 238

Varenicline, 59, 60–66

Variceal hemorrhage, 196

Varicella immunization, 37, 38

Vascular disease, peripheral, 128

Vasodilators, 182–183t

Vegetating, defi ned, 125

Venlafaxine, 67t, 280, 282, 300, 327

Verapamil, 181t

Vesicles, 124

Viagra (sildenafi l), 238

Violence, domestic, 260–261

Vitamin D, for women, 264

Vitamin E, interactions with, 313

Voriconazole, 310

Vulvar cancer screening, 261–262

W

Warfarin, 311

Warts, HPV-associated, 115, 123

Weight

gain of, and smoking cessation, 68

loss of

and diabetes, 130, 132, 140

and erectile dysfunction, 237

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PRIMARY CARE OF VETERANS WITH HIV 34

and hypertension, 176t

and osteoarthritis, 207

resources for, 176t

Wheals, 124

White superfi cial onychomycosis, 120

Withdrawal

from alcohol, 8, 13

nicotine, 59, 67

Women

alcohol drinking limits for, 4, 5, 9

anal cancer screening in, 262

androgen defi ciency in, 89, 90, 92–93

bacterial vaginosis in, 266

barriers to care for, 250

breast cancer screening in, 24–27, 262

breastfeeding by, 256

cervical cancer screening in, 27–31, 

261, 263

contraception for, 252–253, 258–259

depression in, 250

domestic violence in, 260–261

genital herpes simplex virus in, 265

genital ulcers in, 265–266

health issues for, 249

HIV in, 40, 249–251

HPV immunization for, 38

menopause in, 256–257

menstrual irregularities in, 256–257

military sexual trauma in, 260

neuropsychiatric disorders in, 259

262, 264

pelvic infl ammatory disease in, 

266–267

preconception counseling for, 253–255

pregnancy in, 45, 255–256

sexual function in, 257

STD screening in, 45t, 262–263

vaginal cancer screening in, 261–262

vaginal candidiasis in, 266

vulvar cancer screening in, 261–262

X

X-rays, chest, 99, 109

Y

Yeast infections

of nails, 119

vaginal, 266

Yohimbine hydrochloride, 239

Z

Zafi rlukast, 104, 105

Zalcitabine, 295

Zidovudine, 222t

Zoledronic acid, 264

Zolpidem, 329

Zoster immunization, 37

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