28.  Screening for Human Immunodeficiency Virus Infection

RECOMMENDATION

Clinicians should assess risk factors for human immunodeficiency virus

(HIV) infection by obtaining a careful sexual history and inquiring about

injection drug use in all patients. Periodic screening for infection with

HIV is recommended for all persons at increased risk of infection (see

Clinical Intervention). Screening is recommended for all pregnant women

at risk for HIV infection, including all women who live in states, counties,

or cities with an increased prevalence of HIV infection. There is

insufficient evidence to recommend for or against universal screening

among low-risk pregnant women in low-prevalence areas, but

recommendations to counsel and offer screening to all pregnant women

may be made on other grounds (see Clinical Intervention). Screening

infants born to high-risk mothers is recommended if the mother's antibody

status is not known. All patients should be counseled about effective

means to avoid HIV infection (see Chapter 62).

Burden of Suffering

It is estimated that 0.8-1.2 million persons in the U.S. are infected with

the human immunodeficiency virus (HIV-1) and that 40,000-80,000 new

infections occur each year.1,2 Most people infected with HIV eventually

develop the acquired immunodeficiency syndrome (AIDS), defined by

opportunistic infections or severe immune dysfunction.3 Within 10 years

of infection with HIV, about 50% of persons develop clinical AIDS, and

another 40% or more develop other illnesses associated with HIV

infection.4 A small proportion (5-10%) of persons remain well 10-15

years after HIV infection,5 but there is currently no available curative

treatment for AIDS. Of the 476,899 cases of AIDS reported to the Centers

for Disease Control and Prevention (CDC) through June 1995, 62% had died,

including over 90% of those diagnosed before 1988.6 HIV infection is now

the leading cause of death among men ages 25-44, and the fifth leading

cause of years of potential life lost before age 65.7,8 By the end of 1995,

it is projected that there will be 130,000-205,000 persons living with

AIDS in the U.S., at an annual cost of treatment in excess of $15 billion.9

High-Risk Groups.  Men who have sex with men and injection drug users

(IDUs) together accounted for over 80% of AIDS cases reported in 1994.6

HIV infection is widely prevalent in these groups.10 In seroprevalence

surveys conducted in 1991-1992 at STD clinics and drug treatment

facilities, the median prevalence of HIV infection among men having sex

with men was 26% (range 4-47%)a and ranged from 2-7% among IDUs in

Western cities to 12-40% among IDUs on the East Coast.10 HIV infection

is also prevalent among heterosexual persons with other STDs (median

0.6%), prisoners (range 1-15%), and residents of homeless shelters (range

1-21%).10 Very high rates of HIV infection (up to 30%) have been detected

among inner-city young adults who smoke crack, especially among women

who exchange sex for drugs.11 More than 10,000 cases of AIDS have been

attributed to transfusion of infected blood or blood components (i.e.,

clotting factor) between 1977 and 1985, but the current risk of becoming

infected from blood or tissue products is extremely low.12 

Pregnant Women.  By July 1995, over 5,900 cases of AIDS had been

attributed to perinatal infection.6 An estimated 0.17% of all childbearing

women in the U.S. were infected with HIV in 1991-1992, but prevalence

varied from 0-0.05% in 16 states to 0.6% in New York State. Of 144 urban

family planning clinics conducting blinded surveillance, 13 reported a

prevalence of HIV infection over 1%.10 Of the estimated 7,000 infants

born to infected mothers each year, 80% are born in 20 states where

prevalence of antibody-positive newborns was 0.1% or greater.13 The

probability of vertical transmission from mother to infant is between 13%

and 35%,14-16 increasing with severity of disease in the mother.17

General Population.  The distribution of new AIDS cases may not reflect

the changing pattern of the HIV epidemic due to the long delay between

infection and clinical AIDS. Heterosexual transmission is the most rapidly

growing source of new AIDS cases, accounting for 10% of new AIDS cases

in 1994 (up from 2% in 1985).6 It is the leading cause of new HIV

infections in American women.6,18 Young black and Hispanic women in

large East Coast cities are at greatest risk (due to the higher prevalence

of HIV in their male partners and the more efficient transmission of virus

from men to women during intercourse),19 but women of all races

experienced comparable increases in heterosexually acquired AIDS cases

between 1992 and 1994.18 Large surveys in 1991-1992 of Job Corps

applicants ages 16-21 (seroprevalence 0.27%), military recruits

(seroprevalence 0.06%), and patients at urban hospitals (range 0.1-5.8%)

indicate that the prevalence of HIV infection varies markedly among

different demographic groups and geographic areas.10 The rate of AIDS

and the prevalence of HIV are substantially higher in Atlantic Coast states

than in Midwest and Mountain states, in large metropolitan areas

(population 500,000 or greater) than in smaller cities or rural areas, and

in black and Hispanic young persons than in whites, Native Americans, or

Asians/Pacific Islanders.6,10,20 Blinded screening of over 20,000

primary care patients in smaller cities and rural areas detected HIV in

0.15% of all patients without known disease, however.10 The regional

variations in HIV prevalence generally mirror the local prevalence of

infection among drug users. IDUs account for a large proportion of new HIV

infections21 and are a leading source of heterosexual and perinatal

transmission of HIV.6

Accuracy of Screening Tests

The initial screening test to detect antibodies to HIV is the enzyme

immunoassay (EIA). Commercially available EIAs use antigens from whole

disrupted virus (first generation), recombinant viral proteins (second

generation), or chemically synthesized peptides (third generation).22 EIA

results are considered "reactive" only when a positive result has been

confirmed in a second test of the original sample. In subjects with

clinical AIDS, the sensitivity of EIA is close to 100%, but newly infected

individuals may not develop detectable antibodies for periods of weeks to

months after infection.23 The median interval between infection and

seropositivity has been estimated at 3 months with earlier EIAs, with

95% seroconverting within 6 months.24 Estimates based on more sensitive

third-generation EIAs, which may be positive within 1 week of peak

antigen levels, suggest that the "window" period with current tests is

substantially shorter (3-4 weeks).25,25a Specificity of EIA is above

99.5% with most tests. Third-generation EIAs had specificities of 99.7-

99.9% when tested against uninfected controls.25-27 False-positive

results can be caused by nonspecific reactions in persons with

immunologic disturbances (e.g., systemic lupus erythematosus or

rheumatoid arthritis), multiple transfusions, or recent influenza or rabies

vaccination.28,29 Food and Drug Administration (FDA) approval has been

granted to rapid tests (<15 minutes) using colorimetric assays,30 and to

an EIA-based test using oral fluid samples collected with a cotton

pad.31,32 Although these tests are sensitive and specific (>99%), neither

method is recommended for the definitive diagnosis of HIV infection.33

To prevent the serious consequences of a false-positive diagnosis of HIV

infection, confirmation of positive EIA results is necessary, using an

independent test with high specificity. The Western blot (WB) is the most

commonly used confirmatory test in the U.S. Indirect immunofluorescence

assay (IFA), which is less expensive and less time-consuming, is also

approved for confirmatory testing.34 The specificity of WB is close to

100% under controlled settings,35 but it is dependent on the skill and

experience of the laboratory and on criteria used to determine positive WB

results.33,35 The sensitivity of WB was 98.5% and specificity 92.5% in a

1989 CDC quality control survey of 140 laboratories;26 most errors

involved misclassification of positive or negative samples as

"indeterminate." Criteria for interpreting WB have been developed to

improve accuracy in clinical testing.35 Many laboratories doing a large

volume of HIV testing achieved sensitivities and specificities of 100%.36

The precise false-positive rate of current HIV testing is not known. A

false-positive rate of less than 1 in 100,000 was reported in experienced,

centralized laboratories using careful quality control procedures.37,38 In

practice, false-positive diagnoses can result from contaminated or

mislabeled specimens,39 cross-reacting antibodies,33 failure to perform

confirmatory tests,40 misinterpretation of WB patterns, or

misunderstanding of reported results by clinicians or patients.41 In one

study, 8 of 900 women referred for treatment of HIV were not infected on

repeat testing.40 To prevent errors due to mistakes in specimen handling

or WB interpretation, a consensus laboratory panel recommended

confirming all new diagnoses of HIV with tests on a freshly obtained

specimen.42

Indeterminate Western Blot Results.  Indeterminate WB results, due to

antibody patterns that do not meet full criteria for positive test, occur in

3-8% of EIA-positive specimens.33,43 In a survey of over 1 million

newborn specimens for maternal HIV antibody, <1 in 4,000 screened

samples produced an indeterminate WB result.43a An indeterminate WB

result may indicate evolving antibody response in recently infected

subjects, but in low-risk persons it usually represents the presence of

nonspecific antibodies. Follow-up of nearly 700 EIA positive/WB

indeterminate blood donors documented seroconversion in only eight

subjects, all but one of whom reported a high-risk behavior.43-45 An

indeterminate WB is more significant in high-risk subjects, but the risk

of seroconversion is variable (13-28%).44,46 Antibodies to p24 antigen

were present in 29 of 30 subjects who subsequently converted.43,44 A

new indeterminate WB in subjects who were previously seronegative is

more likely to represent recent infection.47 Seroconversion usually

occurs within 2-3 months (range 2-16 weeks in one study).44 A stable

indeterminate WB after 6 months can be assumed to be due to nonspecific

antibody reaction rather than HIV infection.33,48

Viral Culture and Polymerase Chain Reaction Assays.  Viral culture is the

most specific test for HIV infection, but it is time-consuming, expensive,

technically difficult, and insufficiently sensitive for use as a screening

test.22 Polymerase chain reaction (PCR) can detect viral genetic material

in subjects who have not yet developed antibodies, but trace levels of

contamination can produce false-positive results.22 In proficiency testing

of five experienced laboratories, sensitivity of PCR was 98-100% and

specificity was 96-100%.49 With newer, more sensitive EIAs, the

additional value of screening with PCR is small in adults. In over 250

high-risk persons with nonreactive EIAs, PCR detected only two confirmed

cases of HIV.50-53 Since PCR is not 100% specific, a large proportion of

positive PCR results in seronegative patients may be false positives.

Despite their limitations as screening tests, viral culture, PCR, and viral

antigen assays are useful for evaluating patients with symptoms of acute

HIV infection.

Diagnosis of HIV in Infants.  Diagnosing infection in infants born to HIV-

infected mothers is difficult, since maternal antibodies to HIV are

present in both infected and uninfected infants. Uninfected infants

serorevert an average of 10 months after birth, but maternal antibody may

persist up to 18 months.54 Viral culture and PCR are highly specific for

infection in infants, although PCR is occasionally positive in infants who

eventually serorevert and are presumed not to be infected.55 Reported

sensitivity for culture is 60-90%22,56 and 84-98% for PCR, increasing

after 3 months.57,58 Using culture and/or PCR, an estimated 50% of

infected infants can be identified at birth, and up to 90% by 3 months.59

Other tests for perinatal infection include assays for viral antigen

(sensitivity 30-60%)56,59 and IgA (sensitivity 50-80%).59,60

Screening by Risk Factor Assessment.  Patient history is an important but

imperfect way to assess risk for HIV infection. Patients may conceal

high-risk behaviors, and others (especially women in high-risk areas) may

be unknowingly at risk from an infected sex partner. In high-prevalence

family planning clinics, testing women who reported drug use or an IDU

partner detected only 41-57% of all cases.61,62 Offering testing routinely

to all women resulted in greater acceptance (up to 96%),61 and detected

87% of all HIV infections.62 Even in low-prevalence areas such as Sweden,

37% of infected pregnant women did not report clear risk factors for

HIV.63 There are few data comparing the sensitivity of targeted versus

routine screening in male patients. In a seroprevalence study in primary

care practices, physicians were not aware of HIV risk factors in roughly

one third of infected patients.10

Consent, Confidential Versus Anonymous Testing, and Partner Notification. 

There is general consensus that informed consent should be obtained prior

to HIV testing.14,64 The diagnosis of HIV has serious consequences, and

compulsory testing may discourage persons from seeking care. Alternate

forms of consent-right of refusal (i.e., passive consent) versus explicit

consent, active recommendation versus nondirective counseling-have been

considered to facilitate screening during pregnancy.13,65 Universal

newborn screening without consent of the mother was considered but

rejected by the New York State legislature.66

Half of all states require confidential reporting of HIV-infected persons

by name to state or local health departments, and all require reporting of

AIDS patients.6,67 Partner notification (contact tracing) can alert

exposed persons to the need to be tested. Between 50% and 90% of sex

partners can be identified through organized partner notification

programs,68 and costs per case identified compare favorably to screening

high-risk groups.69

In one trial, offering the option of anonymous testing resulted in higher

rates of testing.70 Two thirds of all patients at a public clinic (and a

majority of seropositive patients) chose anonymous testing over

confidential testing.71 Test kits that would allow individuals to submit

specimens (blood or saliva) collected at home for anonymous testing,

using coded identifiers, are being considered by the FDA.71a

Frequency of Testing.  The appropriate frequency of HIV screening is not

known, but it depends in part on the incidence of new infections. Rates are

highest among IDUs in Northeastern cities (3-6 infections/100 patient-

years [py]),21 compared to less than 1/100 py in homosexual men in most

cities,72 and 0.04/100 py among military personnel aged 25-29.73 Due to

the low incidence of new infection and increased sensitivity of new tests,

repeat testing simply to confirm an initial negative EIA is rarely

indicated.

Effectiveness of Early Detection

Detection of asymptomatic HIV infection permits early treatment to slow

disease progression, interventions to reduce perinatal transmission, and

counseling to prevent transmission of virus to uninfected sex partners or

persons sharing injection needles.

Effectiveness of Early Therapy in Asymptomatic Adults.  Antiretroviral

medications (e.g., zidovudine [ZDV or AZT], didanosine, zalcitabine) reduce

mortality in AIDS patients and delay progression to AIDS in symptomatic

HIV infection.74,75 Due to eventual resistance developed by the HIV

virus,76 however, there is no clear benefit of initiating antiretroviral

therapy (with current drugs as monotherapies) before patients become

symptomatic.74,77,78 In an overview of six randomized, controlled trials

(RCTs) of ZDV for asymptomatic HIV infection, there was no long-term

benefit of early treatment versus deferred treatment (begun at onset of

symptoms) on survival or progression to AIDS.79 For asymptomatic

patients with more advanced immunodeficiency (CD4 200-500/mL), early

ZDV delayed progression to AIDS or AIDS-related complex over the short-

term but did not improve outcomes beyond the first 1-2 years.74,79,80 In

Concorde, the largest and longest trial-over 1,700 men and women with

asymptomatic HIV infection followed over 3 years-there was no

significant difference between patients receiving early versus deferred

treatment in the combined incidence of AIDS or death (18% in each group),

or in total mortality (8% and 6%, respectively).81 The early benefits from

delaying disease progression are offset by the adverse effects of ZDV

(e.g., nausea, headache, and fatigue).82 Early combination antiretroviral

therapy, by reducing drug resistance, may be more effective than

monotherapy in reducing viral burden and delaying immunodeficiency, but

long-term clinical trials of these approaches have not yet been

completed.83,84

Chemoprophylaxis can reduce the risk of Pneumocystis carinii pneumonia

(PCP) in patients with more advanced immunodeficiency. The annual

incidence of PCP rises to 18-25% in persons with CD4 < 200/mL,85,86 and

half of all HIV-infected persons are still asymptomatic at this stage of

disease.85,87,88 In retrospective analyses, prophylaxis with

trimethoprim-sulfamethoxazole (TMP-SMX) or inhaled pentamidine

reduced the incidence of primary PCP by 67-83%,86,89-91 delayed onset

of AIDS by 6-12 months, and prolonged survival in those with low CD4

count by almost 1 year.92-94 In a recent 3-year trial, TMP-SMX, dapsone,

and inhaled pentamidine were equally effective as initial therapy for

primary prophylaxis against PCP.95 TMP-SMX was more effective in

shorter studies89,90,96 and for patients with CD4 < 100,95 and it is

recommended as the preferred prophylactic agent;97 long-term therapy is

limited by the high incidence of side effects (e.g., leukopenia, fever, rash,

or gastrointestinal side effects). TMP-SMX and dapsone also provide

protection against toxoplasmosis,98,99 an uncommon complication of

asymptomatic HIV infection in the U.S.95 Long-term benefits of

chemoprophylaxis are limited by the continuing decline in immune

function.92

HIV-infected persons infected with Mycobacterium tuberculosis are at

increased risk of developing active tuberculosis, primarily at CD4 counts

below 500/mL. In a randomized trial among asymptomatic HIV-infected

persons in Haiti, an endemic tuberculosis area, chemoprophylaxis with

isoniazid reduced the incidence of tuberculosis nearly 75% and delayed

progression to AIDS.100 In a U.S. cohort study, isoniazid prophylaxis

reduced tuberculosis among HIV-positive, PPD-positive drug

users.101,102 Decision analyses suggest that the benefits of prophylaxis

may outweigh risks in both PPD-positive and anergic patients with HIV

when exposure to tuberculosis is prevalent (e.g., in IDUs, homeless

persons, and immigrants from endemic areas; see Chapter 25).103

Chemoprophylaxis with rifabutin is also effective against Mycobacterium

avium complex (MAC), but few asymptomatic patients have sufficiently

advanced disease (CD4 < 75/mL) to warrant MAC prophylaxis.97

Effectiveness of Early Therapy in Asymptomatic Children.  There are few

randomized trials of interventions in asymptomatic HIV-infected children,

but TMP-SMX is safe and effective for PCP prophylaxis in other

immunocompromised children.104 PCP may be the first indication that

infants are infected with HIV: 44% of the children who developed PCP in

one study had never been evaluated for HIV.105 Between 7% and 20% of

children with HIV develop PCP within the first year of life (peak incidence

between 3 and 9 months),105,106 and mortality is high (up to 30%).107

Adverse reactions (rash, cytopenia) from TMP-SMX occur in up to 15% of

HIV-infected children. New CDC guidelines for PCP prophylaxis in infants

recommend  prophylaxis for all HIV- infected or possibly infected infants

during the first year of life.107 Studies are currently under way to

evaluate the benefit of different antiretroviral therapies in asymptomatic

children.

A variety of precautions are routinely recommended for HIV-infected

children and adults, due to the increased susceptibility to viral and

bacterial infections:108-110 vaccination against influenza,

pneumococcus, hepatitis B, and Haemophilus influenzae;111 avoidance of

oral (live virus) polio vaccine in children;112 attention to nutrition;113

avoiding uncooked foods and high-risk sexual practices; and more frequent

Papanicolaou (Pap) screening for women (due to an increased risk of

invasive cervical cancer).67,114 The benefit of these interventions in

persons with asymptomatic HIV infection has not been determined.

Effectiveness of Early Intervention in Asymptomatic Pregnant Women.  A

randomized placebo-controlled trial (ACTG 076) demonstrated that a

regimen of ZDV begun between weeks 14 and 34 of pregnancy and

continued through delivery and for 6 weeks in newborn infants

significantly reduced perinatal HIV infection (8.3% vs. 25.5%) among

infants born to seropositive mothers with mildly symptomatic HIV

infection (CD4 > 200/mL).16 ZDV is associated with a low incidence of

severe side effects in mothers or infants, but the long-term effects on

the health of infants, and on the course of HIV disease in mothers, are not

known. Cesarean delivery is also associated with lower rates of vertical

transmission; a trial of operative versus vaginal delivery in HIV-infected

pregnancies is under way in Italy.115

Identifying seropositive women during pregnancy may have other

important benefits: some women may be candidates for PCP prophylaxis;

male partners can be advised to be tested and to use condoms; infants can

be monitored for evidence of HIV infection and started on appropriate

therapy; and early involvement of social services may facilitate care for

infected mothers and infants. Infected mothers are advised to avoid

breastfeeding: a meta-analysis of cohort studies estimated that

breastfeeding increases vertical transmission by 14%.116 The extent to

which early detection actually leads to these benefits is difficult to

estimate. There is no clear effect of testing and counseling on fertility

decisions: in two U.S. studies, pregnancy rates were similar for HIV-

positive and HIV-negative women.117 Infected women were more likely to

choose abortion than uninfected women in one study,118 but the large

majority of women with HIV chose to continue the pregnancy.63

Effectiveness of Testing and Counseling to Prevent Transmission of HIV. 

Determining whether HIV testing and counseling reduces HIV transmission

is complicated by many factors:119 a paucity of well-controlled trials;

variable quality of counseling interventions; reliance on intermediate

endpoints, such as self-reported changes in behavior; differences between

screened and unscreened patients in observational studies; population-

wide changes in high-risk behavior; and the uncertain importance of

testing versus counseling. The effect of testing and counseling varies

with the specific behavior and population being targeted.117 Programs

that targeted couples in which one member was infected provide the

strongest evidence of the benefits of testing and counseling: compared

with historical controls, counseled couples increased regular condom use

and significantly reduced the rate of seroconversion in partners.120-123

Among homosexual men, high-risk sexual practices and new HIV infections

have declined substantially since the development of HIV tests.

Community-wide changes may have been more important than

identification of seropositive persons, however, and there are worrisome

signs of persisting unsafe practices among younger gay men.124 Condom

use is generally higher among seropositive men than seronegative or

untested men, but longitudinal studies suggest increasing use of condoms

across all groups.125-127 Unprotected anal intercourse and number of sex

partners have declined over time in both tested and untested men. The

absolute change in risk may be greater in seropositive men, who engage in

higher-risk behavior at baseline.128 A substantial proportion of

seropositive men continue to have sex with multiple partners and engage

in oral intercourse; 5-15% continue unprotected anal intercourse.128

The effects of screening in injection drug users are less consistent.

Among drug users in treatment, drug use and needle sharing decline after

HIV counseling and testing but also declined among unscreened

patients.117,129 In a community survey, IDUs who had received testing

and counseling were half as likely to share needles as untested

subjects.130 Testing has inconsistent effects on high-risk sexual

behavior among drug users. Seropositive IDUs are more likely to report

condom use in some cross-sectional studies, but 30-70% use condoms only

occasionally or not at all.117,131

Counseling and testing patients at STD clinics has had variable results.

Rate of recurrent STDs was unchanged 1 year after testing in one

study,132 was lower among HIV-positive than HIV-negative subjects in

another (15% vs. 23%),133 and declined among seropositive patients while

rising among seronegative patients in a third.134 In one randomized trial,

testing and counseling reduced unprotected intercourse more than

counseling alone.135 Other longitudinal studies suggest little change in

sexual behavior in seronegative subjects after testing and counseling.

Routine testing and counseling among students at a college health clinic

did not improve low rates of condom use.136 Among women tested in

community health clinics, seronegative women did not reduce sexual risk

factors after testing and counseling, compared with untested controls.137

Efforts to modify high-risk behaviors in infected and high-risk persons

are often hindered by substance abuse, poverty, limited education, denial,

or economic necessity (i.e., prostitutes). A minority of seropositive

persons abstain completely from sex or drug use after diagnosis. Those

who do not may have trouble obtaining condoms or clean needles but may

not inform sex partners that they are infected.138 Female partners of

infected men may minimize risk or be unable to get their male partner to

consistently use a condom.139

Adverse Effects of Testing and Counseling.  The diagnosis of HIV infection

can have significant adverse effects, among them intense anxiety,

depression, somatization, or anger.140,141 Among 1,718 newly diagnosed

patients with HIV, 21% met criteria for depression at first visit, but

psychological distress was related more to symptoms than diagnosis and

diminished with time.142 Testing reduces anxiety in high-risk persons

who are seronegative. Despite recent efforts to improve public

perceptions and attitudes, the stigma associated with the diagnosis of

HIV/AIDS is still significant.143 Disclosure of test results can result in

disrupted personal relationships, domestic violence, social ostracism, and

discriminatory action, such as loss of employment, housing, health

insurance, and educational opportunities.144 Recent legislation and the

expanded case definitions for AIDS may help prevent some forms of

discrimination and help ensure medical care for those with more advanced

infection. Information on the frequency or consequences of false-positive

diagnoses are largely anecdotal. Although retesting and follow-up can

resolve most errors, misdiagnosis may cause irreparable harm  (divorce,

abortion, etc.). Finally, negative test results may provide false

reassurance unless patients are counseled about their continuing risk of

infection from drug use and high-risk sexual activity.

Recommendations of Other Groups

Counseling and HIV testing of high-risk individuals are recommended by

the CDC14 and numerous medical organizations: the Canadian Task Force

on the Periodic Health Examination (CTF),145 the American Academy of

Family Physicians,146 the American Medical Association (AMA),147 the

American College of Obstetricians and Gynecologists (ACOG),114 the

American College of Physicians, and the Infectious Disease Society of

America.148 High-risk individuals include men who have sex with men;

persons seeking treatment for STDs; injection drug users and their sex

partners; recipients of transfusion between 1978 and 1985; and persons

who have had multiple sex partners or exchanged sex for money or drugs.

Bright Futures149 and the AMA Guidelines for Adolescent Preventive

Services (GAPS)150 recommend offering HIV testing to all at-risk

adolescents, including those with more than one sex partner in the last 6

months.

The CDC recommends that health care facilities where the prevalence of

infection exceeds 1%, or the AIDS diagnosis rate is greater than 1/1,000

hospital discharges, consider routine, voluntary screening among patients

aged 15-54 years.151 The AMA approves of routine HIV testing in the

clinical setting, based on local considerations such as planned medical

procedures and local seroprevalence.147 GAPS150 and AAFP146

recommend offering screening to sexually active adolescents and adults

from high-prevalence communities.

The U.S. Public Health Service (PHS) released new guidelines in 1995,

recommending that all pregnant women be routinely counseled and

encouraged to have HIV testing.152 Similar policies have been approved by

American Academy of Pediatrics (AAP)65 and ACOG.153 Pregnant women

should be screened as soon as the woman is known to be pregnant; repeat

testing may be indicated near delivery for women at high risk of infection.

The CTF (prior to ACTG 076) concluded there was insufficient evidence to

recommend for or against routine screening in pregnancy, due to the low

rate of infection in Canada.145 In cases where the HIV serostatus of the

mother is not known, PHS and AAP guidelines suggest that health care

providers educate the mother about benefits to her infant and encourage

her to allow testing for the newborn.65,152 A 1991 Institute of Medicine

task force (before ACTG 076) recommended voluntary screening of all

pregnant women in high-prevalence areas and of high-risk women in other

areas, but it found insufficient evidence to recommend routine newborn

screening.64

Both the AMA and the AAP have endorsed alternate procedures for pretest

counseling and consent, including right of refusal, to facilitate routine

testing in specific situations. Mandatory testing for HIV is currently

required on entrance to the military, and for donors of blood, organs, and

tissue; federal prisoners; and persons seeking to immigrate to the U.S.

Individual state laws vary regarding mandatory testing, confidentiality of

results, informed consent, and reporting of seropositive persons to public

health officials.67 The CDC recommends that seropositive persons be

instructed how to notify their partners, but suggests that physicians or

health department personnel should use confidential procedures to ensure

that partners are notified.14

Discussion

Early detection of asymptomatic HIV infection can reduce morbidity and

mortality in infected persons, but the long-term benefits are currently

limited by the relentless course of disease in most patients. The most

compelling argument for early detection is the potential to prevent

transmission of HIV, which may occur over many years before infected

persons develop symptoms of HIV infection. Although there is only

indirect evidence that screening reduces the incidence of new HIV

infections, even small changes in transmission will have important public

health benefits.

Screening is most important in the high-risk groups that currently

account for the large majority of AIDS cases and new HIV infections.154

The ability of ZDV to reduce perinatal transmission of HIV provides strong

evidence of the benefit of screening during pregnancy. In high-risk

communities, offering HIV testing to all pregnant women is more

acceptable to patients, easier to implement, and more sensitive than

screening on the basis of self-reported risk factors. In areas where HIV

infection is uncommon, however, the choice between targeted screening

and universal screening is a policy decision. Universal screening may

detect occasional cases of HIV infection among women without reported

risk factors, but it will subject many women at negligible risk to the

potential harms from a false-positive or indeterminate test result. If

specificity of testing is 99.98%, routine screening in low-risk populations

(e.g., pregnant women in low-prevalence states) will generate one false-

positive and many additional indeterminate results for every true-

positive. Although indeterminate and false-positive results can generally

be resolved with follow-up testing, some women may decide to terminate

the pregnancy before infection status can be definitively determined.

Counseling and testing many thousands of low-risk women to detect a

single case of HIV may also divert resources from more important issues.

If routine testing can be provided with the combination of accuracy and

low costs achieved by large, centralized screening programs,37,63,155

the justification for universal screening would be stronger.

A growing number of HIV infections occur in persons who are infected

through heterosexual contact. The risk of heterosexual transmission

varies widely among different communities, with the highest risk among

poor minority women in large cities and the rural South. In high-risk

communities or clinics, routine screening of sexually active young women

and men may be appropriate. In populations where prevalence of infection

is low, more selective screening is likely to be more efficient: 5% of

women and 12% of men report multiple sex partners within the last 12

months without consistent condom use.156 Deciding what constitutes a

"high-risk" community is a policy decision,64 depending in part on

available data and resources for testing. A prevalence of 1/1,000 among

newborns,157 or an AIDS diagnosis rate of more than 1/1,000 hospital

discharges,151 has been used to justify routine screening in other

settings. Community prevalence provides only a crude measure of

individual risk, however, and should not replace careful assessment of

high-risk behaviors in each patient.

Screening for HIV in high-risk groups is cost-effective under a wide range

of assumptions. In an analysis of federally funded programs (where HIV

prevalence was 2.6%) testing and counseling activities saved money even

if only one new infection is avoided for every 100 seropositive subjects

identified.158 In Sweden, where prevalence of infection is only 0.01% in

pregnant women, routine prenatal HIV testing costs approximately $10 per

patient and $100,000 per case identified.63 Screening is less cost-

effective in asymptomatic adults if only the benefits from early

treatment are considered.154 Revised cost-effectiveness analyses of

alternate screening strategies for asymptomatic persons are needed,

incorporating new data on antiretroviral therapy in pregnant and

nonpregnant adults, regional variations in prevalence, targeted versus

universal screening, and the costs of testing and counseling in the primary

care setting.

CLINICAL INTERVENTION

Clinicians should assess risk factors for HIV infection in all patients by

obtaining a careful sexual history and inquiring about drug use. Counseling

and testing for HIV should be offered to all persons at increased risk for

infection: those seeking treatment for sexually transmitted diseases; men

who have had sex with men after 1975; past or present injection drug

users; persons who exchange sex for money or drugs, and their sex

partners; women and men whose past or present sex partners were HIV-

infected, bisexual, or injection drug users; and persons with a history of

transfusion between 1978 and 1985 ("A" recommendation).

Pregnant women in these categories, and those from communities (e.g.,

states, counties, or cities) where the prevalence of seropositive newborns

is increased (e.g., 0.1%) should be counseled about the potential benefit to

their infant of early intervention for HIV, and offered testing as soon as

the woman is known to be pregnant ("A" recommendation). Repeat testing

may be indicated in the third trimester of pregnancy for women at high

risk of recent exposure to HIV. There is insufficient evidence to

recommend for or against universal prenatal screening for HIV in low-

prevalence communities ("C" recommendation). A policy of offering

screening to all pregnant women may be recommended on other grounds,

including patient preference, easier implementation, and increased

sensitivity compared to screening based on community prevalence and

reported risk factors. Careful quality control measures and patient

counseling are essential to limit the potential adverse effects from

indeterminate and false-positive test results during pregnancy. Testing

infants born to high-risk mothers, with permission of mother, is

recommended when antibody status of mother is unknown. ("B"

recommendation).

There is insufficient evidence to recommend for or against routine HIV

screening in persons without identified risk factors ("C" recommendation).

Recommendations to screen sexually active young women and men in high-

risk communities can be made on other grounds, based on the increasing

burden of heterosexual transmission and the insensitivity of screening

based on self-reported risk factors. Similarly, routine HIV screening may

be reasonable in groups such as prisoners, runaway youth, or homeless

persons, where the prevalence of high-risk behaviors and HIV is generally

high. The definition of high-risk community is imprecise. Clinicians should

consult local public health authorities for advice and information on the

epidemiology of HIV infection in their communities. More selective

screening may be appropriate in low-risk areas. Testing should not be

performed in the absence of informed consent and pretest counseling,

which should includes the purpose of the test, the meaning of reactive and

nonreactive results, measures to protect confidentiality, and the need to

notify persons at risk. Patients who wish to be tested anonymously should

be advised of appropriate testing facilities.

A positive test requires at least two reactive EIAs and confirmation with

WB or IFA, performed by experienced laboratories that receive regular

external proficiency testing. A separate sample should be submitted for

persons found to be seropositive for the first time, to rule out possible

error in specimen handling. Patients with indeterminate WB results should

be evaluated individually to determine whether findings are likely to

represent recent seroconversion. Repeat testing should be performed 3-6

months after indeterminate test results, or sooner if recent

seroconversion is suspected. A stable indeterminate WB pattern is not

indicative of HIV infection.

Seropositive patients should receive information regarding the meaning of

the results, the distinctions between casual nonsexual contact and proven

modes of HIV transmission, measures to reduce risk to themselves and

others, symptoms requiring medical attention, and available community

resources for HIV-infected persons. Clinicians should explore potential

barriers to changing high-risk behavior in seropositive and seronegative

individuals. Guidelines for HIV counseling have been published by the

PHS.159 Seropositive persons should be evaluated for severity of immune

dysfunction and screened for other infectious diseases such as

tuberculosis (see Chapter 25). Guidelines for the management of early HIV

infection and prevention of opportunistic infections have been published

by the Agency for Health Care Policy and Research67 and the

CDC.97,107,111 Arrangements for follow-up medical care are especially

important for drug users, who may require assistance in gaining entrance

to a drug treatment program (see Chapter 53). All seropositive individuals

should be encouraged to notify sex partners, persons with whom injection

needles have been shared, and others at risk of exposure. Seropositive

cases should be reported confidentially or anonymously to public health

officials in accordance with local regulations.

Persons with nonreactive test results should be informed that the risk of

acquiring subsequent HIV infection can be prevented by maintaining

monogamous sexual relationships with uninfected partners. Other

measures to reduce the risk of infection (consistent use of condoms, etc.)

should be specifically mentioned (see Chapter 62). The frequency of repeat

testing of seronegative individuals is a matter of clinical discretion.

Periodic testing is most important in patients who continue high-risk

activities. In patients with recent high-risk exposure (e.g., sex with HIV-

infected partner), repeat testing at 3 months may be useful to rule out

initial false-negative tests.

The draft update of this chapter was prepared for the U.S. Preventive

Services Task Force by David Atkins MD, MPH.

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