# Presentation: 276679

## How Drug Use Exacerbates 

**Director**
**National Institute on Drug Abuse**
**July 18, 2003**

**How Drug Use Exacerbates **
**the Risk for HIV/AIDS **

## Drug Use Has Played a Prominent 

**Role in the HIV/AIDS Epidemic**
**In Several Ways**

**Disease Transmission**
**    ****IV Drug Use**
**    ****Drug User Disinhibition Leading to **
**    ****High Risk Sexual Behaviors    **
**Progression  of Disease**

## Proportion of Estimated* Adult/Adolescent AIDS Cases 

- 0

- 10

- 20

- 30

- 40

- 50

- 60

- 70

- 1986

- 1988

- 1990

- 1992

- 1994

- 1996

**Year of Diagnosis**

- Percent of Cases

**Proportion of Estimated* Adult/Adolescent AIDS Cases **

**by Exposure Category and Year of Diagnosis, **

**1985 - 2000, United States**

****Data adjusted for reporting delays and proportional redistribution of cases reported without a ris***

***k.***

- 1998

- 2000

**MSM & IDU     **

**Men who have sex with men (MSM)**

**Injection drug use (IDU)     **

**Heterosexual contact**

***Source: Centers for Disease Control and Prevention (CDC)***

**Notes:**
Proportion of Estimated Adult/Adolescent AIDS Cases, by Exposure Category and Year of Diagnosis, 1985-2000, U.S.

The proportional distribution of AIDS cases by exposure category has shifted since the beginning of the epidemic.  Whereas in 1985, men who have sex with men (MSM) accounted for the greatest proportion of diagnosed AIDS cases, the proportion has decreased from nearly 65% of cases diagnosed in 1985 to approximately 40% of cases diagnosed in 2000.

The proportion of estimated AIDS cases attributed to injection drug use increased between 1985 and 1994, then remained stable or declined, accounting for approximately 27% of diagnosed cases in 2000.  

## Estimated* Adult/Adolescent AIDS Cases 

**Exposure Category**

**Men who have sex with men**

**Injection drug use**

**Men who have sex with men**

-          **and inject drugs      **

**Heterosexual Contact**

**Transfusion recipient**

**Hemophilia cases**

**Other/not identified****

**      ****Total**

***** Includes patients whose medical record review is pending; patients who died, were lost to follow***

***-up or  ***

***    ******declined interview; and***

**Number**

**15,917**

**10,988**

**1,752**

**10,672**

**442**

**199**

**145**

**40,106**

**Percent**

**40**

**27**

**4**

**27**

**1**

**<1**

**<1**

**Estimated* Adult/Adolescent AIDS Cases **

**Diagnosed in 2000, by Exposure Category, U.S. **

***Source: Centers for Disease Control and Prevention (CDC)***

***patients with other or undetermined modes of exposure.***

##  AIDS Cases Associated with Injection Drug Use,

**Exposure Category **

**Heterosexual male IDU**

**Female IDU**

**Men who have sex with men IDU**

**Heterosexual sex partners of IDUs**

**Children whose mothers are IDUs**

**or sex partners of IDUs**

**Number**

**5,922**

**2,609**

**1,548**

**1,496**

**60**

**11,635**

**Percent**

**51**

**22**

**13**

**13**

**1**

** ****AIDS Cases Associated with Injection Drug Use,**

** ****by Exposure Category Reported in 2000, U.S. **

**Total**

***Source: Centers for Disease Control and Prevention (CDC)***

## Shifting Routes of Infection

- <date/time>

-  **137,000             61,000****	****          29,000              18,000          # of  new infections**

**Shifting Routes of Infection**

## There is Accumulating Evidence 

**That Use of Some Psychoactive Drugs**
**Can *****Accelerate HIV Progression    ***

**In Addition to *****Increasing the***
***Risk of HIV Transmission*****...**

## Effect of Methadone or Morphine 

**Effect of Methadone or Morphine **
**on HIV Infection**

**effect on**
**microglia**

**effect on **
**monocyte-**
**derived**
**macrophages**

***Source: Li, Y. et al., The Journal of Infectious Diseases, 185, pp. 118-122, 2002.***

## Effects of Cocaine Combined with 

**Effects of Cocaine Combined with **
**HIV Infection In Vivo**

***Source: Roth, M.D. et al., The Journal of Infectious Diseases, 185, pp. 701-705, 2002.***

## Methamphetamine Enhances Cell-Associated 

***Uninfected control***
*** ******astrocytes***

***Astrocyte infection***
***by PBMC-associated***
***virus***

***Inability of cell-free***
***FIV-MD virus to ***
***infect astrocytes***

***Productive cell-free***
***Infection of astrocytes***
*** ******with FIV-MD-A***

***CXCR4 immunoreactive***
***feline G355-5 astrocytes***

***CCR5 immunoreactive***
***feline G355-5 astrocytes***

***Source: Gavrilin, M.A., Mathes, L.E. and Podell, M. Journal of NeuroVirology, 8, pp. 240-249, 2002.***

**Methamphetamine Enhances Cell-Associated **
**Feline Immunodeficiency Virus Replication in Astrocytes**

## Methamphetamine Enhances Viral Replication

**Methamphetamine Enhances Viral Replication**
**in Feline Astrocytes**

***Source: Gavrilin, M.A., Mathes, L.E. and Podell, M. Journal of NeuroVirology, 8, pp. 240-249, 2002.***

## Acceleration of HIV Dementia With 

***Nath, A. et al., Journal of NeuroVirology, 7, pp. 66-71, 2001.***

**Acceleration of HIV Dementia With **
**Methamphetamine and Cocaine**

**Notes:**
  Generalized cerebral atrophy most prominent in the frontal and temporal regions as well as basal ganglia atrophy with its shrinkage of the head of the caudate is noted.
  Diffuse periventricular white matter high signal intensity lesions are seen on a T2 weighted image.

## Research Has Also Shown that 

**Drug Use Can *****Interfere With Judgment***
**Or *****Reduce Inhibitions***** About A **
**Variety of Risk-Taking Behaviors,**
**Including Some That Increase the**
**Chances of Contracting HIV **

## Current and Ex-Users of MDMA

**Have Shown Dramatically Higher**
**Measures of Psychopathology Such As **
**Impulsivity Than Nonusers**

***For Example...***

## Source: Morgan, M.J.  Data presented at the NIDA-sponsored Conference on 

***Source: Morgan, M.J.  Data presented at the NIDA-sponsored Conference on ***
***“******MDMA/Ecstasy Research: Advances, Challenges, Future Directions”, July 2001.  ***

## Among Those Who Are Addicted

**We Know That Some Sell Sex**
** ****to Obtain Drugs**

***AND...***

## In one Study, 25% of Crack Users

**13-19 Years Old Traded**
**Sex for Drugs or Money **

***(******Fullilove, R.E. et al., JAMA, 263(6), pp. 851-855, 1990.)***

**In A More Recent Longitudinal Study **
**Conducted in Atlanta,  35% of Men and **
**57% of Women Reported the**
**Exchange of Sex for Drugs**

***(Rothenberg, R.B. et al., AIDS, 14(14), pp. 2191-2200, 2000.)***

***For Example...***

## Although There’s Not Much Direct

**Evidence To Support The Claim**
**That Some Illicit Drugs **
**Enhance Sexual Experience... **

**Data Show that Both Drugs and Sex**
**Do *****Elevate Dopamine Levels***** in the**
**Same Brain Regions **

## Brain Circuitry Involved in  Reward

**Brain Circuitry Involved in  Reward**

## Effects of Drugs on Dopamine Levels

***Source: Di Chiara and Imperato***

**Effects of Drugs on Dopamine Levels**

## Natural Rewards Elevate Dopamine Levels

**Natural Rewards Elevate Dopamine Levels**

## Recent Data Show That 

- <date/time>

**Recent Data Show That **
**Psychostimulant-Induced Behavioral **
**Sensitization Can “Cross-Sensitize”**
**to a Natural Motivated Behavior,**
**Such As Sex **

***Source: Fiorino , D.F. and Phillips, A.G., Psychopharmacology, 142, pp. 200-208, 1999.***

## Slide 23

## NIDA

***What Are We Doing***
***About All of This?***

## We’ve Identified Some of the 

**We’ve Identified Some of the **
**Fundamental Principles that are**
**Important for HIV Prevention**
**in Drug-Using Populations**

## The Most Effective 

**HIV/AIDS  Prevention Strategy**
**is *****Drug Abuse Treatment***

## HIV Seroconversion at 18 MonthsBy Receipt of Treatment

**0**

**5**

**10**

**15**

**20**

**25**

**Rate of Seroconversion (%)**

**Treatment Status**

**No treatment**

**Partial treatment**

**Continous treatment**

**Source: Metzger, D. S., Woody, G. E., McLellan, A. T., O’Brien, C. P., Druley, P., Navaline, H., De Philipps, D., Stolley, P., & Abrutyn, E. (1993). Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: An 18-month prospective follow-up. Journal of Acquired Immune Deficiency Syndromes, 6, 1049-1056.**

## We’ve Identified Some of the

- <date/time>

**We’ve Identified Some of the**
**Fundamental Principles that are**
**Important for Drug Abuse Treatment**

## We Are Using Science

***We Are Using Science***
***To Improve ******TREATMENT***

**AND...**

## Molecular Targets and Strategies for

**D1 dopamine receptor agonists**
**D3 dopamine receptor agonists**
**DA autoreceptor antagonists**
**Mu/kappa opioid agonists/partial agonists**
**Glucocorticoid receptor antagonists**
**Multi-system effector compounds**
**Drug combinations/cocktails**
**Cannabinoid receptor antagonists**
**Corticotropin-releasing-factor (CRF) antagonists**

**Molecular Targets and Strategies for**
**Addiction Treatment Medications**

## Science-Based Behavioral Therapies 

- <date/time>

**Science-Based Behavioral Therapies **
**Ready for Field Testing/Transfer:**

**Cognitive Behavioral Therapy**
**Contingency Management**
**Supportive-Expressive Psychotherapy**
**Individual Counseling**
**Group Counseling**
**Family Therapies**
**Manualized Drug Counseling**
**Motivational Enhancement Therapy**

## National Drug Abuse Treatment

** ****Clinical Trials Network (CTN)**

**A research infrastructure of**** ****17 Research Centers**** and**** ****115 Community Treatment Programs**** ****across**** ****27 States**

## NIDA Plans to Implement A Number

**NIDA Plans to Implement A Number**
**of New Protocols Focused on:**

**Pregnant drug-abusing women**
**Adolescent drug abusers**
**Drug abusing women with PTSD**
**Spanish speaking drug abusers (conducted**
**  ****in Spanish)**
**HIV risk reduction interventions**
**Cigarette smoking cessation intervention for**
**  ****in-treatment drug  addicts**