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Director's Report to the National Advisory Council on Drug Abuse - May, 2004



Research Findings - Research on AIDS and Other Medical Consequences of Drug Abuse - AIDS Research

Methamphetamine Dependence Increases Risk of Neuropsychological Impairment in HIV Infected Persons

HIV infection and methamphetamine (METH) dependence can each be associated with brain dysfunction. Little is known, however, about the cognitive effects of co-occurring HIV infection and METH dependence. NIDA researchers studied four groups of 200 participants: HIV+/METH, HIV-/METH, HIV+/No METH, and HIV-/ No METH. The groups were similar in age, education, and ethnicity, although there were significantly more females in the HIV-/No METH group. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neuro-behavioral domains. Rates of global impairment were higher in the HIV+/METH (58%), HIV-/METH (40%) and HIV+/No METH (38%) groups compared to the HIV-/No METH (18%) group. A significant monotonic trend for global cognitive status was seen across groups, with the least impairment in the HIV-/No METH group and highest in the HIV+/METH+ group. The results indicate that HIV infection and METH dependence are each associated with neuropsychological deficits, which suggests that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms. Rippeth, J.D., Heaton, R.K., Carey, C.L., Marcotte, T.D., Moore, J.D., Gonzalez, R. and Wolfson, I.G., The HNRC Group. Methamphetamine Dependence Increases Risk of Neuropsychological Impairment in HIV Infected Persons. Journal of the International Neuropsychological Society. 10(1), pp.1-14, January 2004.

Effects of Hepatitis C virus on Neurological Injury HIV+ Methamphetamine Abusers

Given the increased risk for brain injury among methamphetamine abusers (MA), researchers at UCSD questioned whether the addition of Hepatitis C virus (HCV) infection would have a further detrimental effect. In a preliminary study, concentrations of the metabolites NAA, Cho, Ins, and Cr were compared in three groups: HCV+/METH, HCV+/No METH, HCV-/ METH and HCV-/No METH controls. It was expected that NAA would be lowest in HCV+/METH, followed by HCV-/METH and would be highest in HCV-/No METH with a selective increase in the inflammatory markers Ins and Cho in HCV+/METH only, reflecting putative inflammation due to HCV. The preliminary results indicate that HCV infection may worsen METH-associated neuronal injury in white matter. NAA was lower in the white matter region of the right anterior centrum semiovale in the HCV+/METH compared to controls and HCV-/Meth groups. In addition, reduction in this marker of neuronal integrity was correlated with worsening global neuropsychological deficit in the combined METH groups. However, Cho and Ins were not elevated in the HCV+/METH group. Larger studies should determine if this disagreement is due to inadequate power, or whether the combination of methamphetamine and HCV alters the neuropathogenesis of the latter. Taylor, M.J., Letendre, S.L., Schweinsburg, B.C., Alhasson, O.M., Brown, G.G., Gongvatana, A., Grant, I. and The HNRC. Hepatitis C Virus Infection is Associated with Reduced White Matter N-acetylaspartate in Abstinent Methamphetamine Users. Journal of the International Neuropsychological Society. 10(1) pp.110-113, January 2004.

Affects of HIV Infection Coupled with Hepatitis C Virus in Drug Abusers

Hepatitus C virus (HCV) can be detected in the brain and several investigators speculate that HCV has neuroinvasive properties with direct effects on cerebral function. 1MRS studies show that the basal ganglia and white matter of individuals with HCV have abnormal choline/creatine ratios, indicating CNS inflammation or infection and deficits in working memory and IPS have been documented similar to those seen in HIV seropositive individuals. Investigators at the University of Illinois, Chicago, conducted a preliminary study to examine whether HCV co-occurring with HIV exerts additive effects on brain dysfunction. One hundred fifty nine HIV +/- and/or HCV +/- male drug users participated in a reaction time (RT) version of the Stroop task which has been found to be sensitive to HIV-associated cognitive dysfunction. Results revealed a significant monotonic trend for poorer performance among subject groups ordered hierarchically according to infection status, (seronegative, monoinfected, dually infected) and this trend was significant for Congruent and Incongruent conditions. This finding is consistent with the hypothesized additive effects of HIV and HCV on neurocognition. Multiple Comorbid Conditions Appear to Confound Effects on Cognition. Martin, E.M., Novak, R.M., Fendrich, M., Vassileva, J., Gonzalez, R., Grbesic, S., Nunnally, G., and Sworowski, L. Stroop Performance in Drug Users Classified by HIV and Hepatitis C Virus Serostatus. Journal of the International Neuropsychological Society. 10(2), 298-300, March 2004.

Association of Drug Abuse with Inhibition of HIV-1 Immune Responses: Studies with Long-term of HIV-1 Non-Progressors

Recreational drug use has been proposed to affect the course of human immunodeficiency virus (HIV) infections. To investigate the effects of substance abuse on HIV infections, we compared virus-specific cytotoxic T lymphocyte (CTL) responses and the expression of IL-16, TGF-beta1, and CXCR4 in three different cohorts of HIV-infected patients: (1) long-term non-progressors (LT-NPs) of HIV infection who do not use recreational drugs; (2) non-drug using normal progressors (NPs), and (3) drugs using NPs. Our results show that LT-NPs manifest increased CTL activity and IL-16 expression and decreased expression of TGF-beta1 and CXCR4 compared to NPs, regardless of recreational drug usage. Furthermore, drug- using NPs showed significantly lower levels of CTL and IL-16 expression and increased TGF-beta1 and CXCR4 expression compared to non-drug using NPs. Our results suggest that recreational drug use may reduce CTL and IL-16 expression and increase the expression of TGF-beta1 and CXCR4, all of which may facilitate progression of HIV infection. Nair, M.P., Mahajan, S., Hewitt, R., Whitney, Z.R. and Schwartz, S.A. J. Neuroimmunol, 147 (1-2), pp. 21-25, 2004.

Fat Distribution in Relation to Drug Use, Human Immunodeficiency Virus (HIV) Status, and the Use of Antiretroviral Therapies in Hispanic Patients with HIV Infection

Human immunodeficiency virus (HIV)-associated fat-redistribution syndrome is still a subject of controversy. There is, as yet, little agreement on the definition, etiology, and prevalence of the syndrome. Many studies have examined medication or disease-related factors. Fewer studies have examined patient-related factors. Illicit drug use is an important risk factor for HIV infection, yet the role of drug use in fat distribution has not been well described. We examined fat distribution, measured by dual energy x-ray absorptiometry, in relation to drug use, smoking, and alcohol use in Hispanic patients with HIV infection and a control group of HIV-negative drug users. Our results suggest that neither drug use nor alcohol consumption is a predictor of fat distribution. However, among men, smoking was independently associated with less total fat, less trunk fat, and more appendicular fat. The role of patient-specific factors in the etiology of HIV-associated fat-redistribution syndrome warrants further investigation. Forrester, J.E. and Gorbach, S.L., CID, 37(suppl 2), s62-s68, 2003.

Determinants of Health Care Use Among Puerto Rican Drug Users

Researchers sought to identify factors accounting for differences in health care and drug treatment utilization between Puerto Rican drug users residing in two separate locations. Survey findings from 334 drug users in Puerto Rico and 617 in New York City showed that those in Puerto Rico were 6 times less likely than their counterparts in New York to have used inpatient medical services and 13 to 14 times less likely to have used outpatient medical services or methadone. They also were less likely to have health insurance or past drug treatment. After controlling for site-related variables, health insurance and previous use of physical or mental health services remained significant predictors of health care and drug treatment utilization. Although Puerto Rican drug users in Puerto Rico are not an ethnic minority, they reported significant disparities in health services use compared with Puerto Rican drug users in New York, and were less likely to use physical health services, mental health services, and drug treatment. By contrast, drug users in East Harlem reported more chronic medical problems and more HIV/AIDS diagnoses, that is, more health care needs, than did Puerto Ricans residing in Puerto Rico. This might explain the differences in utilization of physical health care between the two study groups. Puerto Rican islanders, although significantly younger, were more likely to be drug injectors and to inject drugs more frequently, behaviors related to HIV/AIDS and other infectious disease. Puerto Rican drug users in Puerto Rico were also less likely to have health insurance than were their counterparts in New York. This may account for the significant lack of health care utilization among drug users, and has implications for reducing drug use and HIV/AIDS risk behaviors in Puerto Rico and in many sites on the US mainland. Robles, R., Matos, T., Colón, H., Deren, S., Reyes, J., Andia, J., Marrero, C. and Sahai, H. Determinants of Health Care Use Among Puerto Rican Drug Users in Puerto Rico and New York City. Clin Infect Dis, 37(Suppl 5), S392-S403, 2003.

Designing an HIV Counseling and Testing Program for Bathhouses

Researchers describe the process through which HIV testing was initiated at bathhouses for high risk men who have sex with men in Seattle and make recommendations for the optimal design of an HIV counseling and testing program in the bathhouse environment. They examined logistical considerations that had previously been identified as influencing the initiation, effectiveness, and maintenance of HIV testing programs in bathhouses for men who have sex with men, including building alliances with community agencies, hiring and training staff, developing techniques for offering testing, and providing options for counseling, testing, and disclosure of results. The design included ways to provide client support and follow-up for partner notification and treatment. Bathhouse clients were found to engage in multiple high-risk behaviors: of 437 clients tested, 159 (36%) reported past month drug use and 118 (27%) reported past month binge drinking; 36% reported engaging in more sexual risks while drinking alcohol or taking drugs; 77% reported 4 or more sex partners since their past HIV test; and 25% reported engaging in unprotected sex during the past 2 months. The researchers found that early detection of HIV infection and HIV prevention can be achieved for some high-risk MSM through an acceptable and accessible HIV counseling and testing program in bathhouses. Spielberg, F., Branson, B., Goldbaum, G., Kurth, A. and Wood, R. Designing an HIV Counseling and Testing Program for Bathhouses: The Seattle Experience with Strategies to Improve Acceptability. Homosexuality, 44(3/4), pp. 203-220, 2003.

HIV Prevention Among Drug Users: An International Perspective from Thailand

All too often in reviews of HIV prevention needs, the role of drugs is summarily dismissed, especially in contexts where the heterosexual epidemic is the primary mode of transmission. Substance use and abuse, particularly injection drug use, play a paramount role in maintaining the heterosexual spread of HIV, as well as in maintaining epidemics where heterosexual spread of the infection has come under control due to prolonged and concerted HIV prevention activities. This paper presents several themes to place in the developing country context what we have learned about substance use-related HIV prevention and the special problems of HIV interventions. First, the paper briefly examines the international production and trade routes of opium and heroin, and their role in the HIV epidemic, as well as the importance of substance abuse in heterosexual epidemics. Second, it presents a case study of HIV control that has been internationally acclaimed as one of the few successes in achieving a meaningful reduction in heterosexually transmitted HIV--Thailand. The Thai response to the injection drug use HIV epidemic, however, has been muted, and its impact on future epidemic dynamics is evaluated. It concludes with a discussion of existing research gaps concerning the role of drug use in HIV epidemics in the developing world, with Thailand as an example. Celentano, D. HIV Prevention Among Drug Users: An International Perspective from Thailand. J Urban Health, 80(4), suppl 3, pp. 97-105, 2003.

HIV Prevention Among IDUs: The Need for Integrated Models

Opportunistic infections (OIs) were first recognized among injection drug users (IDUs) in New York City in 1981. By the mid-1980s, OIs had become associated with HIV infection and attention began to focus on efforts to prevent HIV transmission among IDUs. Since then, a range of prevention strategies have been implemented and evaluated in an attempt to reduce the spread of HIV infection among drug users. Evaluations of these strategies have provided substantial evidence of effectiveness, and have helped to inform network-based and structural interventions. Despite the cumulative empirical evidence, however, research findings have yet to be widely disseminated, adopted, and implemented in a sustained and integrated fashion. The reasons for this are unclear, but point to a need for improved communications with program developers and community planners to facilitate the implementation and evaluation of integrated intervention strategies, and for collaborative research to help understand policy, legal, economic, and local barriers to implementation. This paper reviews the research findings on core strategies of HIV prevention that have targeted IDUs and concludes with a discussion of the potential association between substance abuse treatment completion and reductions in risky sexual behaviors among drug users. Metzger, D. and Navaline, H. HIV Prevention Among IDUs: The Need for Integrated Models. J Urban Health, 80(4), suppl 3, pp. 59-66, 2003.

Risk Reduction Among Drug-Using Men Who Have Sex With Men

This paper focuses on sexual risk reduction interventions for HIV-positive men who have sex with men (MSM), the largest group of HIV-positive individuals in the U.S. It reviews factors associated with high-risk behaviors, and discusses some findings from research with HIV-positive methamphetamine users, including: 1) data from a small qualitative study and its implications for the development of new interventions; and 2) baseline data from an ongoing large-scale study of the efficacy of a theory-based sexual risk reduction intervention for HIV-positive methamphetamine-using MSM. Currently, less than one percent of the total U.S. population is infected with HIV. Targeting behavioral interventions to this smaller group of HIV-positive individuals has the potential for making cost-effective reductions in the number of new infections. In this era of highly active antiretroviral therapy (HAART), interventions for HIV-positive individuals are more critical than ever to address the unique challenges and issues they face regarding disclosure and partner notification, use of HAART and sexual risk behavior, and HIV-related stigma. Patterson, T. and Semple, S. Sexual Risk Reduction Among HIV-Positive Drug-Using Men Who Have Sex With Men. J Urban Health, 80(4), suppl 3, pp. 77-87, 2003.

Sex Work and Drug Use in a Subculture of Violence

In this paper, researchers examine the subculture of violence thesis as it relates to female street sex workers in Miami. Interview and focus group methods were used to study the intersection of childhood trauma, drug use, and violent victimization among 325 women. Using targeted sampling, crack- and heroin-using sex workers were recruited through street outreach into an HIV-prevention research program. Interviews used standard instrumentation and focused on drug-related and sexual risk for HIV, sex work, violence, childhood trauma, and health status. Past drug use among the women was found to be substantial, and large percentages reported high levels of substance use in the past month, including use of alcohol. Nearly half of the respondents reported physical (44.9%) and/or sexual (50.5%) abuse as children, and over 40% experienced violence from clients in the prior year: 24.9% were beaten, 12.9% were raped, and 13.8% were threatened with weapons. Consistent relationships between historical and current victimization suggest that female sex workers experience a continuing cycle of violence throughout their lives. Surratt, H., Inciardi, J., Kurtz, S. and Kiley, M. Sex Work and Drug Use in a Subculture of Violence. Crime and Delinquency, 50(1), pp. 43-59, 2004.

Sharing of Non-Injection Drug Use Implements as a Risk Factor for Hepatitis C

Researchers examined sharing of non-injection drug implements as a risk factor for hepatitis C (HCV) infection among women drug users (n=123) with no history of drug injection. Participants were street-recruited from East Harlem, New York City, between October 1997 and June 1999. They were administered a survey measuring risk factors for HCV. Prevalence of HCV and HIV infections was 19.5% and 14.6%, respectively. Multiple logistic regression determined significant associations between sharing non-injection drug use implements and HCV infection. "Ever shared both oral and intranasal non-injection drug implements" was independently associated with HCV infection (OR 2.83, CI 1.04, 7.72; p=0.04); "ever shared non-injected heroin implements with an injector" was a trend (OR 3.06, CI .85, 10.79; p=0.08). The strongest association between sharing non-injection drug use implements and HCV infection was found among HIV positive individuals (chi square=8.8, p<0.01). The strong association between HIV and HCV seropositivity among women reporting no history of injecting drugs indicates that HIV may facilitate the transmission of HCV through non-injecting routes. These findings suggest that sharing non-injection drug implements, either for intranasal or oral drug use, may be a risk factor for HCV and may explain the higher than expected prevalence of HCV infection observed in this sample. Tortu, S., McMahon, J., Pouget, E. and Hamid, R. Sharing of Non-Injection Drug Use Implements as a Risk Factor for Hepatitis C. Subst Use & Misuse, 39(2), pp. 211-224, 2004.

The Dynamics of Substance Use and Sex Networks in HIV Transmission

This paper reviews the research literature to identify mechanisms that may underlie HIV heterosexual transmission in developed and developing countries; examines linkages between sex and substance use HIV transmission risks; and describes sex network measurement issues relevant to developing HIV preventive interventions. It describes how the research contributions of developed countries to understanding sexually transmitted HIV have long recognized the influence of substance use and sex networks. By comparison, research in developing countries has contributed significantly to the environmental and biological understanding of HIV sexual transmission dynamics, but few studies have explicitly examined the relationship between HIV sex risk and substance use in these contexts. Given that HIV sexual transmission dynamics are linked to interactions between substance use and sex network factors, it is critical to examine substance use as a framework within which HIV sexual transmission occurs, particularly in developing countries that focus on either substance use or sex-mediated HIV transmission though not on both. The characteristics of network members and structural relationships within and across sex networks have identifiable roles in the spread of HIV. These characteristics and relationships are measurable at the individual level and can contribute substantively to improving network and community surveillance. They are also essential for the development and evaluation of network- and community-based interventions. Miller. M. The Dynamics of Substance Use and and Sex Networks in HIV Transmission. J Urban Health, 80(4), suppl 3, pp. 88-96, 2003.

The Role of Sexual Transmission of HIV Among IDUs and Non-Injecting Drug Users

Many early studies of injecting drug users (IDUs) suggested that most HIV infections in this population were due to needle sharing, and that sexual transmission was negligible or was overshadowed by parenteral routes. A few of the early studies suggested a potentially important role for heterosexual transmission, but these tended to be limited to cross-sectional data or had only a few years of prospective follow-up. Studies of sexual risk factors for HIV infection among non-injecting drug users are similarly sparse. Recently, investigators prospectively examined both drug-related and sexual risk factors for HIV seroconversion among male and female IDUs with an adequate number of person-years to identify statistically significant associations. Other studies among never and former IDUs have identified associations suggesting that sexual transmission accounts for a substantial number of HIV seroconversions in these populations. Herein, highlights are discussed from recent investigations among IDUs in Baltimore, Maryland and corroborating findings from the literature. Results from a ten-year prospective analysis of the ALIVE study and an analysis of the REACH studies spanning a seven year period indicate that sexual risk factors for HIV infection are important in both female and male IDUs. These findings underscore the need for HIV interventions among drug users that incorporate sexual risk reduction. Based on the existing literature, a narrow focus on injection-related risks is an ineffective prevention strategy. Interventions that target specific subgroups of high-risk IDUs, such as men who have sex with men and inject drugs, sex worker-IDUs and HIV-infected IDUs deserve special attention. Strathdee, S. and Sherman, S. The Role of Sexual Transmission of HIV Among IDUs and Non-Injection Drug Users. J Urban Health, 80(4), suppl 3, pp. 7-14, 2003.

The Social Course of Drug Injection and Sexual Activity Among YMSM and Other High-Risk Youth

The cumulative epidemiological literature indicates that many injecting drug users (IDUs) initiate injection as a mode of drug administration during late adolescence or early adulthood. Recent studies have shown that IDUs are often exposed to viral infections relatively early in the course of injection, highlighting the importance of understanding this initiation process for both epidemiology and prevention. Epidemiological evidence similarly suggests that at least some youth populations, most notably young men who have sex with men (YMSM), are at substantial risk for exposure to HIV and other sexually transmitted diseases (STDs) from early sexual activity. Despite the importance of this issue for both epidemiology and prevention, however, there is surprisingly little information available on the social course of injection initiation, including the individual, social, or ecological factors that might mitigate or exacerbate transmission risks within the critical phase of early injection drug use. Similarly, little is known about the ways that YMSM and other high-risk youth understand risk, the kinds of exchanges and relationships in which they participate in the context of initiating sexual activity, or how drug use is operant in these exchanges and early sexual experiences. In this paper, researchers explore key dimensions of the early initiation of injection and sexual risk, and discuss how a social network approach might be instrumental in understanding the social course of drug injection and sexual activities among youth and young adult populations. Clatts, M., Goldsamt, L., Neaigus, A. and Welle, D. The Social Course of Drug Injection and Sexual Activity Among YMSM and Other High-Risk Youth: An Agenda for Future Research. J Urban Health, 80(4), suppl 3, pp. 26-39, 2003.

Transmission of STIs/HIV at the Partnership Level: Beyond Individual-Level Analyses

Mathematical modeling of transmission dynamics of sexually transmitted infections (STIs) and HIV has considerably advanced HIV research by highlighting the importance of certain types of partnerships in epidemic spread. Concurrent partnerships, defined as a sexual partnership in which one or more of the partnership members have other sexual partners while continuing sexual activity with the original partner, have been shown to play a fundamental role in potentiating the spread of STIs and HIV. Risk behaviors such as concurrency and sex without condoms as well as STI/HIV prevalence vary with physical, social, and emotional factors within partnerships. The efficiency of HIV/STI transmission appears to vary across types of concurrent partnerships according to the differing dynamics within them. Previous research on partnership dynamics has improved our understanding of the multidimensional aspects of sexual partnering, but little is understood of how these aspects of sexual partnering interact and increase risks for HIV, nor how types of partnerships, partnership dynamics, and concurrency work together to affect both the behavior of condom use and the biological transmission of disease. In this paper, researchers discuss the need to extend our understanding of concurrency to include partnerships among men who have sex with men (MSM) and to differentiate between types of partnerships and to develop interventions to modify risk within partnerships. They also introduce a conceptual framework that reflects how individual and partner characteristics influence partnership dynamics that, in turn, influence risk behaviors, such as concurrency and not using condoms, and associated risks for STIs and HIV. Gorbach, P. and Holmes, K. Transmission of STIs/HIV at the Partnership Level: Beyond Individual-Level Analyses. J Urban Health, 80(4), suppl 3, pp. 15-25, 2003.

Contextual Determinants of Drug Use Risk Behavior: A Theoretical Framework

Over the past two decades, public health research has emphasized the role of individual risk behaviors, primarily injection and sexual risk behaviors, in the spread of HIV infection. Much less emphasis has been given to understanding the determinants of these risk behaviors. Although individual characteristics are partly responsible for risky injection and sexual behaviors, they do not explain all the inter-personal variability in risk behavior. Contextual factors associated with HIV risk behavior may include structural factors (e.g., availability of services), social norms and attitudes (e.g., social trust), disadvantage (e.g., neighborhood socio-economic status), and features of the physical environment (e.g., housing quality). This paper presents a conceptual framework that incorporates some of the key contextual domains that may affect drug use behavior. It also presents data from a study of street-recruited drug users as an example of the relations between social contextual factors and frequency of injecting drug use, and discusses some methodological challenges in the study of contextual determinants of drug use behavior. Galea, S., Ahern, J. and Vlahov, D. Contextual Determinants of Drug Use Risk Behaviors: A Theoretic Framework. J Urban Health, 80(4), suppl 3, pp. 50-58, 2003.

Social Network Correlates of Self-Reported Non-Fatal Overdose

The leading cause of death among heroin users is drug overdose. This study examined the relationship between history of self-reported drug overdoses and social network characteristics among cocaine and opiate users. Data were from cross-sectional surveys administered from March 2001 through February 2003 as part of follow-up of an experimental network oriented HIV prevention intervention. A total of 838 participants with histories of cocaine and opiate use completed the survey. Several social network variables were found to be significantly associated with drug overdose in the prior 2 years, including larger number of network members who were injection drug users and more conflicts among the network members. Even after controlling for age, gender, frequency of injection drug and alcohol use, and health status, network variables continued to have a strong association with history of recent overdose. Specifically, the number of injectors in the network and the number of networks that the index had conflict with was associated with recent overdose. Social network factors have been found to be associated with other health conditions among drug users, such as HIV and STIs, and behaviors such as sharing needles and using shooting galleries. The data suggest that large drug networks should be targeted for drug overdose prevention interventions. For example, key network members or several network members could be trained in overdose prevention and in treating overdose victims with Naloxone (Narcan). Using peer-based prevention models have been shown to be successful among drug users in reducing needle sharing behavior. Latkin, C., Wei, H. and Tobin, K. Social Network Correlates of Self-Reported Non-Fatal Overdose. Drug and Alcohol Depend., 73(1), pp. 61-67, 2004.


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