"Drug Abuse and AIDS: Intertwined Epidemics" - Meeting Summary
National Institute on Drug Abuse
On July 15, 1999 the National Institute on Drug Abuse (NIDA) in conjunction with AIDS Impact sponsored a satellite symposium entitled "Drug Abuse and AIDS: Intertwined Epidemics" at the Westin Hotel in Ottawa Canada. The meeting was comprised of three scientific sessions highlighting NIDA sponsored AIDS research. Session presenters addressed issues important to these intertwined epidemics, which included descriptions and analysis of risky behaviors associated with injection drug use, the effect of drugs of abuse and the AIDS virus on the brain (Neuro-AIDS), and adherence to combination therapy in drug abusing populations. In addition, NIDA Staff provided information on funding opportunities, career pathways, and a description of the AIDS program at NIDA. There were over 100 attendees for this daylong symposium. Below is a summary of each speaker's presentation and their conclusions.
For further information about research grant funding opportunities and learn more about NIDA's AIDS research interests, please contact NIDA staff.
Sessions 1: Risky Behavior and AIDS: Injection Drug Use and Needle Sharing
Needle-Sharing in Heroin Addicts: An Underlying Psychological Process
Warren K. Bickel, Ph.D.
Department of Psychiatry and Psychology
University of Vermont
Needle-sharing contributes to the spread of the human immunodeficiency virus (HIV) and remains a persistent problem among injection drug users. One study determined that needle-sharing may be related to the discounting of the value of delayed outcomes. Outpatients in treatment for heroin dependence indicated a preference for immediate versus delayed hypothetical monetary and heroin outcomes in a titration procedure that determined indifference points at various delays. The rate at which the delayed outcomes lost value was estimated with a nonlinear decay model. Participants who agreed to share a needle in a scenario discounted delayed money more steeply than did the nonsharing group. Both groups discounted delayed heroin more steeply than delayed money. Persistent needle-sharing may be related to the relative inability of delayed outcomes to affect current behavior. Training to mitigate the effect of delay on outcome value may offer reductions in needle-sharing and drug abuse.
- Discounting may be a useful model of impulsivity.
- Drug-dependent individuals discount monetary outcomes more than matched controlled normals.
- Heroin-dependent individuals discount heroin more than monetary outcomes.
- Heroin addicts who share needles generally discount heroin and monetary outcomes equivalently and radically.
- Discounting of delayed rewards may be a useful behavioral marker of HIV risk behavior.
Risk for Viral Transmission in Injection Paraphernalia: Heating Drug Solutions May Inactivate HIV-1
Michael C. Clatts, Ph.D.
National Development and Research Institutes, Inc.
Ethnographic observation was used to develop a descriptive typology of the paraphernalia and practices used to prepare and inject illicit drugs and to determine the effects of these practices on potential risk for HIV transmission. Observational data and quantitative HIV-1 microculture assay were used to measure the recovery of infectious HIV-1 from the "cookers" in which drug solutions were prepared. HIV-1 survival inside cookers was a function of the temperature achieved during preparation of drug solutions: HIV-1 was inactivated once temperature exceeded, on average, 65°C. Although different types of cookers, volumes, and heat sources affected survival times, heating cookers 15 seconds or longer reduced viable HIV-1 below detectable levels.
- IDUs routinely share multiple articles of injection paraphernalia, including "cottons," "cookers," and "rinse water," and many remain unaware of risk from these paraphernalia.
- Cookers are a major concern because they are exposed to multiple sources of potential contamination in the course of preparing and dividing drug solutions. Moreover, cookers are often retained and reused in subsequent injection events involving multiple and different IDUs, thereby establishing a chain of cross-contamination that serves to circulate viral pathogens between injection events and injection groups.
- Heating drug solutions in cookers is a common feature of the way in which some IDUs prepare drug solutions. Laboratory studies of HIV-1 indicate that some heating practices may be protective. Fifteen seconds was the shortest heating interval in which HIV-1 could no longer be recovered. The thin type of bottle-cap cookers—commonly distributed by outreach and syringe exchange programs—reached an inactivating temperature the fastest for any given combination of volume and heat source examined.
- Behavioral practices used to prepare and inject drugs are complex and variable, with implications for understanding the differences in the epidemiology of viral pathogens among IDUs as well as for the development of prevention messages and strategies.
Do Needle Exchange Programs Increase the Spread of HIV Among Injection Drug Users? An Investigation of the Vancouver Outbreak
Martin T. Schechter, M.D., Ph.D.
Division of Epidemiology and Biostatistics
University of British Columbia
Focus of Presentation
A 1996 report showed that IDUs who had ever attended Vancouver's needle exchange program (NEP) had higher HIV prevalence rates than those who had never attended. A number of observers interpreted these findings as evidence that NEPs may promote the spread of HIV. The same researchers then investigated the observed association between the NEP and HIV and found little evidence to support the hypothesis that the NEP was causally associated with the risk of HIV infection. The number of infections was similar to what would be expected from the higher risk profiles of frequent NEP participants. The NEP did not appear to play a role in the formation of new needle-sharing partnerships, nor did it shift users to higher risk behavior. This association should not be cited as evidence that NEPs may promote the spread of HIV.
- Prevalence and incidence rates of HIV were elevated among frequent needle exchange participants in Vancouver due to confounding. Frequent participants had a much higher risk profile than infrequent participants.
- There was no evidence that this NEP contributed to the formation of new needle-sharing partnerships or networks.
- The association of the NEP with elevated HIV incidence in Vancouver should not be cited as evidence that the NEP promotes the spread of HIV.
- The occurrence of an explosive outbreak of HIV among IDUs in Vancouver, despite a high-volume NEP, underscores the fact that the NEP is only one component of what should be a comprehensive strategy. The latter should include an NEP, addiction prevention, adequate addiction treatment availability, and attention to the underlying social determinants of drug use.
Sessions 2: Neuro-AIDS
Animal Models of AIDS-Related Behavioral and Neurological Impairment
Paul D. Cheney, Ph.D.
Mental Retardation and Human Development Research Center
Molecular and Integrative Physiology
University of Kansas Medical Center
Focus of Presentation
The presentation reviewed recent advances in efforts to establish a viable nonhuman primate model of neuro-AIDS. Such a model could be used to investigate mechanisms of neuronal damage from viral infection as well as issues related to the interaction of AIDS and drugs of abuse. It is well established that HIV-1 infects the central nervous system shortly after exposure, and in many cases this leads to demonstrable neurological injury, including motor and cognitive impairment. Neurovirulent forms of simian immunodeficiency virus (SIV) also enter the brain shortly after inoculation and produce classic AIDS-related neuropathology. Data from behavioral, neurophysiological, and pathological studies were presented as evidence that the rhesus macaque infected with neurovirulent strains of SIV is a useful model of human neuro-AIDS.
- Rhesus macaques infected with neurovirulent SIV represent a valid and useful model of human neuro-AIDS.
- Infection with neurovirulent SIV in rhesus macaques follows two distinct patterns of progression: rapid and slow. SIV-infected monkeys with rapidly progressing disease develop both systemic and neurologic disease, whereas those with slowly progressing disease develop systemic AIDS but not neuro-AIDS.
- Monkeys with rapidly progressing disease show behavioral performance deficits, neurophysiological (evoked potential) abnormalities, and neuropathological changes that are similar to those others have described for HIV-1-infected humans. We conclude that neurophysiological and behavioral abnormalities in the fast progressors reflect underlying viral-mediated neuronal injury.
- This model of neuro-AIDS presents the opportunity to begin in vivo experiments aimed at testing various hypotheses about the effects of opiates and other drugs of abuse on the nature and progression of AIDS-related disease.
Neurobehavioral Consequences of HIV
Igor Grant, M.D.
Department of Psychiatry
University of California, San Diego
Focus of Presentation
Neurobehavioral complications are commonplace in HIV disease, and they become more severe and disabling in a small subset of persons with advanced AIDS. The types of impairments range from asymptomatic neuropsychological impairment through mild neurocognitive disorders to frank dementia. The neurobiologic basis of these neurocognitive impairments remains poorly understood, but it appears that viral products, inflammatory signaling molecules, changes in trophic factors, or some combination of these affect neurons to produce neural injury, the chief hallmark of which is loss of dendritic arbor and decrease in synaptic complexity. These disorders are not steadily progressive but rather relapse and remit. Heightened viral load in the cerebrospinal fluid, abuse of drugs such as methamphetamines, and rapid decline in CD4 + cell counts are all associated with increased likelihood of neurocognitive disorder. Although some of these disorders are subtle in nature, they affect everyday life, and persons with impairment are at heightened risk of unemployment, increased difficulties in medication management, increased problems with driving skills as measured by a driving simulator, and increased risk of early death. New combination antiretroviral therapies are promising in reducing the risk of neurocognitive impairment, and research is continuing on more targeted central nervous system-sparing drugs.
- HIV is a disease of the brain as well as of the immune system.
- Although HIV does not directly infect neurons, they are damaged via more indirect effects of viral products, inflammatory responses, or both.
- The neurocognitive disorders are generally subtle in nature and tend to wax and wane.
- Despite their subtle nature, these disorders affect everyday life.
- New antiretroviral treatment combinations are promising, and their ability to reduce CSF viral load specifically may be predictive of improved neurocognitive performance.
Sessions 3: Adherence to Combination Therapy and Drug Abuse
Myths in the Care of HIV-1-Infected Drug Users
Michael Stein, M.D.
Focus of Presentation
There are myths about the behaviors of persons with a history of drug abuse that affect provider attitudes and performance. I hope to present statements (myths) that seem reasonable and are widely disseminated but for which there is no empirical support. I will critically examine these myths—for example, "Patients drop out of substance abuse treatment when they learn they are HIV positive"—in the context of the complex problems that confront this population.
- Drug users are no less willing than other risk groups to be tested for HIV.
- Drug users do not delay in seeking medical care after learning their serostatus.
- Drug users are no more likely than others to leave substance abuse treatment when they become HIV seropositive.
Adherence, Resistance, and Risky Behavior: Challenges for the Long-Term Management of HIV/AIDS
Margaret A. Chesney, Ph.D.
Center for AIDS Prevention Studies
University of California, San Francisco
Focus of Presentation:
Combination therapy has significantly altered the HIV/AIDS landscape. The available evidence suggests that adherence to combination therapy is a problem. Numerous surveys indicate that the level of adherence shown by substantial numbers of patients is insufficient to achieve adequate viral suppression and prevent the development of drug resistance. Surveys have asked patients why they miss doses. The most common reasons, in descending order, are simply forgetting, being away from home, changing routines, being busy with other things, and sleeping through doses. It is important to note that other reasons—such as side effects, depressed mood, and stress—are also commonly reported. A very important predictor of nonadherence is alcohol and other drug intake. For example, alcohol consumption per month is approximately two times higher among those reporting nonadherence compared with those who report taking all their doses. These reasons and predictors are particularly important in that they also predict unsafe behavior. Thus, there is a likelihood that those who are at greatest risk for developing resistance are also those who are engaging in unsafe behavior. These findings have very important implications for treatments to enhance adherence and prevent the development of resistant strains of HIV.
- Nonadherence increases the risk of viral resistance.
- Resistant strains of the virus can be transmitted, limiting the treatment alternatives of the newly infected person.
- Alcohol and other drug use is significantly associated with nonadherence.
- Alcohol and other drug use is significantly associated with unsafe behavior.