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

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

Proteins Made by HIV-1 Block an Enzyme That Normally Destroys Viral Genomes: A Potential for Therapeutic Intervention

HIV/AIDS treatments in part rely on a cocktail of protease inhibitors to stop the enzymes needed for viral replication in infected individuals. One of the major issues in HIV/AIDS therapy is that people discontinue or inconsistently take the medication when the viral load becomes below detectable levels, leading them to believe that they are cured. HIV-1 is notorious for mutating its genome to circumvent the line of defense the medications offer when the medication is not used properly, sometimes rendering the medication useless when the virus resurges. It is imperative, therefore, for researchers to identify new targets for HIV/AIDS therapy. One other barrier in studying HIV/AIDS is the use of animal models because HIV-1 is human specific and using other viruses in other animals makes it difficult to extrapolate any findings to the human condition. Thus understanding the mechanisms behind the species specificity may contribute to the generation of better animal models and better therapeutic options. To this end, researchers have identified an mRNA editing enzyme, called APOBEC3G, which incorporates into the virus upon infection and mutates the viral genome so that the virus is unable to propagate and infect additional cells. HIV-1 encodes a protein called the virion infectivity factor (Vif) and it is required for the production of infectious virions. These researchers discovered that Vif specifically binds to human APOBEC3G and prevents its incorporation into the virus, allowing the virus to propagate at will. These important experiments suggest that therapeutic interventions that either induced APOBEC3G or that blocked the binding of Vif to APOBEC3G so that APOBEC3G incorporation into the virus is restored could be clinically beneficial. Mariani, R., Chen, D., Schrofelbauer, B., Navarro, F., Konig, R., Bollman, B., Munk, C., Nymark-McMahon, H., and Landau, N. Species-Specific Exclusion of APOBEC3G from HIV-1 Virions by Vif. Cell, 114, pp. 21-31, 2003.

A Cross-Border HIV Prevention Intervention for IDUs in China and Vietnam

In this paper, researchers describe the background and early implementation of a peer-based HIV prevention intervention involving social marketing of sterile needles and syringes for injection drug users (IDUs) in a border region of northern Vietnam and southern China. Peer educators collect and safely dispose of used needles and syringes and provide IDUs with a choice of new needles/ syringes or vouchers redeemable in pharmacies and clinics for new needles/syringes. The project arose from a pattern of changing drug use and increasing HIV infection in the region but its development took 4 years and faced many challenges. Implementation of the intervention posed a new set of challenges for the participating health departments, police, peer educators, pharmacists, injection drug users, and the communities at large. Early implementation of the project has revealed successful multi-sectoral collaboration, and broad acceptance by IDUs of pharmacy vouchers and distribution of new needles/syringes. However, IDUs' persistent fear of the police, particularly in Vietnam, has required reliance on separate collection by peer educators of used needles/syringes and distribution of pharmacy vouchers and new needles. In China, new needles/syringes and vouchers are largely being provided through exchange. Understanding the development and implementation challenges and the strategies that were successful in overcoming them (including the importance of being flexible and adaptable to contextual factors) may be useful to those interested in launching similar, much-needed interventions in other parts of the world. Hammett, T., Des Jarlais, D., Liu, W., Ngu, D., Tung, N., Hoang, T., et al. Development and Implementation of a Cross-Border HIV Prevention Intervention for Injection Drug Users in Ning Ming County (Guangxi Province), China and Lang Son Province, Vietnam. Internat J Drug Policy, 14 (5-6), pp. 389-398, 2003.

Boundary-Crossing and Drug Use Among Young Adults in a Low-Income, Minority, Urban Neighborhood

In this paper, researchers examined the relationship between boundary-crossing sexual partnerships (i.e., those between partners who are 5 or more years older, of a different race or ethnicity, or live in a different neighborhood or borough) and use of crack or injected drugs among young adults in Bushwick, Brooklyn. Women who smoked crack or injected drugs were more likely to have a sexual partner who was older, of a different race/ethnicity, or from a different borough than were women who did not use these drugs; men who used these drugs were more likely to have older sex partners than men who did not. Young people who use these drugs are known to be at higher risk of having HIV and a number of other sexually-transmittable infections such as hepatitis B, genital herpes, and syphilis. These results imply that this risk may be even higher for people who cross these boundaries. In addition, if these young people become infected, they may be particularly likely to serve as a gateway for spreading infection to other social groups. Flom, P., Friedman, S., Neaigus, A. and Sandoval, M. Boundary-Crossing and Drug Use Among Young Adults in a Low-Income, Minority, Urban Neighborhood. Connections, 25 (2), pp. 77-87, 2003.

Cognitive-Behavioral Intervention to Reduce HIV Risks in Crack Users and IDUs

This paper presents the results of a study evaluating the efficacy of a theory-based cognitive-behavioral intervention to reduce HIV risk among street-based crack and injection drug users not currently in drug treatment in Long Beach, California. A nine-session, 4-month enhanced intervention (including HIV counseling and testing) was compared to a two-session standard counseling and testing intervention developed by NIDA in terms of their efficacy for reducing drug- and sex-related risk behaviors. The theory-based enhanced intervention rarely was found to be different from NIDA's standard counseling and testing intervention in reducing both drug- and sex-related risks, as indicated by cessation and/or reduction of drug use (measured by urine test and self-report), entry into drug treatment, and increased frequency of condom use. One of the few significant effects was that the enhanced intervention significantly increased injecting drug users' use of their own injection equipment. On the other hand, for both interventions, most risk behaviors were significantly reduced. It is concluded that the theory-based cognitive-behavioral intervention has limited advantage over the standard intervention in terms of both magnitude and frequency of HIV risk reduction achieved by high-risk, active drug users. Hershberger, S.L., Wood, M.M. and Fisher, D. A Cognitive-Behavioral Intervention to Reduce HIV Risks in Crack Users and IDUs. AIDS Behav., 7(3), pp. 229-243, 2003.

Drug Use, Incarceration Rates, and Prison-Associated HIV Risks in Thailand

Incarceration is a known risk for HIV infection in Thai drug users. Through the 1990s, incarceration rates for drug-related offenses rose sharply, whereas HIV prevention and drug treatment in prisons remained limited. In this study, researchers assessed HIV and incarceration risks for injection drug users (IDU) and non-IDU in a large treatment center cohort in northern Thailand to investigate HIV and prison risks in this period. Thai Bureau of Corrections data were used to assess incarceration and prevention funds in prisons, 1992-2000. They found that, among 1,865 drug users in the treatment cohort, 503 (27.0%) had ever been jailed. Men (OR 3.3, 95% CI 2.1, 5.2), IDU (OR 6.3, 95% CI 5.1, 7.9), and MSM (OR 3.4, 95% CI 1.8, 6.3) were more likely to have been jailed. Among male IDUs who had ever been jailed (N = 272), 15.8% had used drugs in prison. In a multivariate model, incarceration and ever IDU remained independently associated with HIV infection; IDU, MSM behaviors, and harmful traditional practices remained independently associated with having been jailed. From 1992 to 2000, overall alleged narcotics offenses increased from 117,000 to 276,000/year. The number of persons incarcerated for narcotics offenses increased fivefold from 1992 to 1999, from 12,860 to 67,440. For FY 2000, narcotics treatment accounted for 0.06% of the Thai corrections budget, whereas HIV programs in prisons were 0.017%. These findings suggest that incarceration rates for narcotics offenses have increased sharply in Thailand, whereas prevention has lagged. Having been jailed is an important independent risk for HIV infection among Thai male drug users, especially IDU and MSM, demonstrating the urgent need for HIV prevention and drug treatment in Thai prisons. Beyrer, C., Jittiwutikarn, J., Teokul, W., Razak, M., Suriyanon, V., Srirak, N., et al. Drug Use, Increasing Incarceration Rates, and Prison-Associated HIV Risks in Thailand. AIDS and Behavior, 7(2), pp. 153-161, June 2003.

Effector Cell Mediated Cytotoxicity in HIV Infected Subjects

CD8+ cytotoxic T lymphocyte (CTL) activity is currently believed to be one of the key immunologic mechanisms responsible for the prevention or attenuation of HIV-1 infection. The induction of CD8+ T cell activation may also result in the production of soluble or non-classical lytic factors that are associated with protection from infection or slower disease progression. Traditionally, CD8+ CTL responses have been measured by the classic chromium release assay, monitoring the ability of T cells (Effector cells) to lyse radiolabelled HLA - matched "target cells" that express the appropriate antigen-MHC complex. This method is not only labor intensive, semi quantitative assay at best, but also needs fresh, non-cryopreserved cells. Recently, cytokine specific ELISPOT assays or tetrameric MHC-I/ peptide complexes have been utilized to directly quantitate circulating CD8+ effector cells, and these assays are more sensitive, quantitative and reproducible than the traditional CTL lysis assay and can also be performed on cryopreserved cells. Although these are reproducible assays for the assessment of soluble antiviral activity secreted by activated T cell populations they can be extremely expensive to perform. Authors have used FACS Analysis to measure Granzyme B release as a function of cell mediated cytotoxicity. This method helped quantitate the CTL activity and also identified the phenotype of the cells elucidating this immune response. The method described not only monitors immunological response but is also simple to perform, precise and extremely time efficient and is ideal for screening a large number of samples. Mahajan, S.D., Aalinkeel, R., Schwartz, S.A., Chawda, R.P. and Nair, M.P. Effector Cell Mediated Cytotoxicity Measured by Intracellular Granzyme B release in HIV Infected Subjects. Biol Proced Onlin., 5, pp. 182-188, 2003.

Elevated C-Reactive Protein Levels are Associated with Endothelial Dysfunction in Chronic Cocaine Users

To examine the relationship of the serum C-reactive protein (CRP, a marker for inflammation) and endothelial function and their associations with coronary artery calcification, lipid profile and cardiac changes, researchers performed analyses of serum lipids and CRP, echocardiography, spiral computed tomography scans and endothelial function assays in 53 participants with a history of chronic cocaine use. They found no statistically significant differences in demographic characteristics and drug use between CRP normal (<1.9 mg/l) and abnormal groups. The brachial artery diameter percentage changes in the third scan (immediately after deflation of cuff) and the fourth scan (90 s after deflation of cuff) were significantly associated with the CRP levels (the third: beta=-0.054, S.E.=0.027; P=0.028; the fourth: beta=-0.065, S.E.=0.026; P=0.016). The multiple regression models showed that CRP was the only significant predictor of artery diameter changes (%) in these two scans. The CRP abnormal group had more coronary artery calcification (calcium scores >5, 16.7 vs. 0%; P=0.036) and more cardiac diastolic dysfunction expressed as deceleration time >240 ms (16.7 vs. 0%; P=0.036). They concluded that elevated serum CRP levels are associated with endothelial dysfunction, coronary artery calcification and cardiac diastolic dysfunction in chronic cocaine users. Meng, Q., Lima, J.A., Lai, H., Vlahov, D., Celentano, D.D., Margolick, J.B. and Lai, S. Elevated C-Reactive Protein Levels are Associated with Endothelial Dysfunction in Chronic Cocaine Users. Int J Cardiol., 88(2-3), pp. 191-198, 2003.

Factors Associated with Accelerated Atherosclerosis in HIV-1-Infected Persons Treated with Protease Inhibitors

Recent evidence suggests that as a group protease inhibitors (PIs) may accelerate certain factors associated with atherosclerosis. The objective of this study was to evaluate the effect of individual PIs (indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) on certain factors associated with atherosclerosis. Persons who took saquinavir and/or ritonavir were compared with those on other PIs. Between May 2000 and July 2001, the lipid profiles, C-reactive protein (CRP) levels, coronary artery calcium (CAC) scores, and blood cell morphologic parameters were measured in 98 black adult participants aged 25 to 45 years with HIV-1 infection in Baltimore, MD. Among these 98, there were 55 (56.1%) taking PIs. Students' t-test and chi2 test were used to detect the between-group differences. Study participants in both the PI and non-PI groups were similar in age, sex, body mass index, blood pressure, red and white blood cell counts, time since HIV diagnosis, and duration on anti-retroviral therapy. Compared with those who took non-PI regimens, those who took indinavir, nelfinavir, or saquinavir had significantly higher levels of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Those taking any PI had significantly higher total cholesterol and low-density lipoprotein. Those taking nelfinavir, ritonavir, or saquinavir were more likely to have a higher CAC score (>5) than those on non-PI regimens. There were no differences in the lipid profiles, MCV, MCH, CRP, and CAC between those taking saquinavir and/or ritonavir and those taking other PIs. Overall, the changes noted might lead to anticipation of clinical changes linked to accelerated atherosclerosis in patients on PIs. Lai, S., Lai, H., Celentano, D.D., Vlahov, D., Ren, S., et al. Factors Associated with Accelerated Atherosclerosis in HIV-1-Infected Persons Treated with Protease Inhibitors. AIDS Patient Care STDs,17(5), pp. 211-219, 2003.

Gene Cluster Influences HIV-1 Transmission

MCP-1 (CCL2), MCP-3 (CCL7), and eotaxin (CCL11) are genes for CC chemokines clustered on the long arm of chromosome 17. Previous studies have implicated these chemokines in monocyte recruitment, viral replication, and anti-HIV cytotoxic T cell responses. An epidemiological analysis identified genetic variants influencing HIV-1 transmission and disease progression. In this study, genomic DNA from over 3000 participants enrolled in 5 natural history cohorts in the U.S. were analyzed. Nine single nucleotide polymorphisms (SNP) covering 33 kb containing these 3 genes were genotyped using the polymerase chain reaction. Distortions in allele, genotype, and haplotype frequencies were assessed with respect to HIV-1 transmission and rates of disease progression using categorical and survival analyses. Results indicate that extensive linkage disequilibrium was present. Three SNP (-2136T located in the MCP-1 promoter region, 767G in intron 1 of MCP-1, and -1385A in the Eotaxin promoter) were nearly always found together on a 31 kb haplotype (H7) containing the 3 genes. Frequencies of the 3 variants and the H7 haplotype were significantly elevated (OR, 0.6; P = 0.005-0.01) in uninfected European-Americans repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products. The findings suggest that although the extensive linkage disequilibrium precludes positive identification of the causal variant, genetic variation in the H7 region influences susceptibility to HIV-1 infection. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 or CXCR4, the observed influence on transmission may result from activation of the immune system in response to infection rather than receptor blockage. Modi, W., Goedert, J., Strathdee, S., Buchbinder, S., Detels, R., Donfield, S., O'Brien, S. and Winkler, C. MCP-1-MCP-3-Eotaxin Gene Cluster Influences HIV-1 Transmission. AIDS, 17(16), pp. 2357-2365, 2003.

HCV/HIV Co-Infection Associated Hepatocyte Apoptosis Via an "Innocent Bystander Mechanism"

Hepatitis C virus (HCV) infects approximately 40% of HIV patients, and the resulting hepatic dysfunction is the primary cause of death in patients with co-infection. Groopman and his colleagues at Harvard hypothesize that hepatocytes exposed to hepatitis C virus (HCV) and human immunodeficiency virus (HIV) might be injured via an "innocent bystander" mechanism due to cell-surface binding of viral proteins. To assess this, they studied the effects of HCV envelope protein E2 and T-tropic HIV envelope glycoprotein gp120 on hepatocytes and saw potent apoptosis. Either viral protein alone did not induce this effect. HCV E2 and M-tropic HIV gp120 also induced significant apoptosis. Blocking the CXCR4 receptor led to a reduction in apoptosis. HCV E2 and HIV gp120 acted collaboratively to trigger a specific set of downstream signaling events, including up-regulation of the FAS ligand and dephosphorylation of the anti-apoptotic molecule AKT (Munshi et al. 2003a). The investigators (Balasubramanian et al. 2003b) also report that expression of the pro-inflammatory chemokine IL-8, induced by HCV-E2 and HIV-gp120, may be mediated through p38 MAP kinase and SHP2 in an NF-kappa B-independent manner, albeit through AP-1-driven processes. This research suggests that hepatic injury may occur in HCV/HIV co-infection through the induction of novel downstream signaling pathways and provide a rationale for therapeutic interventions that interfere with specific receptors and signaling molecules. Munshi, N., Balasubramanian, A., Koziel, M., Ganju, R.K. and Groopman, J.E. Hepatitis C and Human Immunodeficiency Virus Envelope Proteins Cooperatively Induce Hepatocytic Apoptosis Via an Innocent Bystander Mechanism. J Infect Dis., 188(8), pp. 1192-1204, October 15, 2003; and Balasubramanian, A., Ganju, R.K. and Groopman, J.E. Hepatitis C Virus and HIV Envelope Proteins Collaboratively Mediate Interleukin-8 Secretion through Activation of p38 MAP Kinase and SHP2 in Hepatocytes. J Biol Chem., 278(37), pp. 35755-35766, 2003.

Hepatitis C Virus Infection and Incident Type II Diabetes

Although hepatitis C virus (HCV) infection is more common among adults with type II diabetes, it is uncertain whether HCV precedes the development of diabetes. The investigators performed a prospective (case-cohort) analysis to examine if persons that acquired type II diabetes were more likely to have had antecedent HCV infection when enrolled in a community-based cohort of men and women between the ages of 44 and 65 in the United States (Atherosclerosis Risk in Communities Study [ARIC]). Among 1,084 adults free of diabetes at baseline, 548 had developed diabetes over 9 years of follow-up evaluation. Incident cases of diabetes were identified by using fasting glucose and medical history and HCV antibodies at baseline. A priori persons were categorized as low-risk or high-risk for diabetes based on their age and body mass index, factors that appeared to modify the type II diabetes-HCV infection incidence estimates. The overall prevalence of HCV in this population was 0.8%. Among those at high risk for diabetes, persons with HCV infection were more than 11 times as likely as those without HCV infection to develop diabetes (relative hazard, 11.58; 95% CI 1.39-96.6). Among those at low risk, no increased incidence of diabetes was detected among HCV-infected persons (relative hazard, 0.48; 95% CI 0.05-4.40). In conclusion, pre-existing HCV infection may increase the risk for type II diabetes in persons with recognized diabetes risk factors. Additional larger prospective evaluations are needed to confirm these preliminary findings. Mehta, S.H., Brancati, F.L., Strathdee, S.A., Pankow, J.S., Netski, D., Coresh, J., Szklo, M. and Thomas, D.L. Hepatitis C Virus Infection and Incident Type II Diabetes. Hepatology, 38(1), pp. 50-56, 2003; and Mehta, S.H., Moore, R.D., Thomas, D.L., Chaisson, R.E. and Sulkowski, M.S. The Effect of HAART and HCV Infection on the Development of Hyperglycemia Among HIV-infected Persons. J Acquir Immune Defic Syndr., 33(5), pp. 577-584, 2003.

HIV Infection, HPA Axis, Cytokines and Cognition

Immediately after infection, HIV-1 enters the central nervous system (CNS) and is localized in highest concentration in the hippocampus and basal ganglia. Since these areas are associated with HPA axis and autonomic activities as well as cognition, it has been hypothesized that these functions will be impacted adversely in HIV-1 infection. In the treatment of HIV infection, although the highly potent antiretroviral (HAART) drugs have been effective in reducing peripheral viral load and prolonging life expectancy, these drugs do not cross the blood-brain barrier in therapeutic concentrations. Therefore, it has been proposed that the beneficial effects of HAART on the CNS will be limited. Investigations among seropositive individuals, showing hypo-reactivity of the autonomic system and HPA axis activity, suggest that HIV-1 infection is a model of chronic stress. Furthermore, an elevated baseline TNF-alpha level as well as its increased reactivity to an alpha-adrenergic challenge among HIV-1+ individuals, may lead to additional neurodegeneration. It is proposed that the effects of HIV-1 infection on the brain will have implications for neurocognitive and mental health functioning in seropositive individuals even in patients undergoing HAART therapy. These outcomes may result in the need to develop facilities for long term "care-giving." Kumar, M., Kumar, A.M., Waldrop, D., Antoni, M.H. and Eisdorfer, C. HIV-1 Infection and Its Impact on the HPA Axis, Cytokines, and Cognition. Stress, 6(3), pp. 167-172, 2003.

HIV Prevention Among Drug Users: Outcome of a Network-Oriented Peer Outreach Intervention

A network-oriented HIV prevention intervention based on social identity theory and peer outreach was implemented for HIV positive and negative drug users. A community sample of 250 were randomly assigned to an equal-attention control condition or a multi-session, small-group experimental condition, which encouraged peer outreach; 94% of participants were African American, and 66% used cocaine or opiates. At follow-up, 92% of participants returned, and experimental compared with control group participants were 3 times more likely to report reduction of injection risk behaviors and 4 times more likely to report increased condom use with casual sex partners. Results suggest that psychosocial intervention emphasizing prosocial roles and social identity, and incorporating peer outreach strategies, can reduce HIV risk in low-income, drug-using communities. Latkin, C.A., Sherman, S. and Knowlton, A. HIV Prevention Among Drug Users: Outcome of a Network-Oriented Peer Outreach Intervention. Health Psychol. 22(4), pp. 332-339, 2003.

HIV Treatments Influence Unsafe Sexual and Injection Practices Among IDUs

Researchers sought to determine if HIV treatment-related attitudes are associated with unprotected sex and needle sharing among HIV-seropositive and -seronegative IDUs in Baltimore, Maryland. IDUs participating in a cohort study between December 2000 and July 2001 completed an interviewer-administered questionnaire on attitudes toward HIV treatment and risk behaviors (593 HIV-seronegative, 338 HIV-seropositive), including: perceived HIV transmissibility through unprotected sex and needle sharing, and safer sex and injection fatigue. Logistic regression was used to examine the role of attitudinal factors on needle sharing and unsafe sex. Results indicate that almost two-thirds of sexually active participants engaged in unprotected sex and approximately half of those injecting drugs shared needles. Among HIV-seropositive IDUs, perception of reduced HIV transmissibility through unprotected sex was significantly associated with unprotected sex (AOR, 3.33; 95% confidence interval (CI), 1.05-10.55). Safer injection fatigue was independently associated with needle sharing among HIV-seropositive IDUs (AOR, 6.55; 95% CI, 1.69-25.39). Among HIV-seronegative IDUs, safer sex fatigue and safer injection fatigue were independently associated with unprotected sex (AOR, 3.12; 95% CI, 1.17-8.35) and needle sharing (AOR, 5.15; 95% CI, 2.33-11.37), respectively. These findings suggest that, among HIV-seropositive IDUs, perceiving that HIV treatments reduce HIV transmission was significantly associated with unprotected sex. Risk reduction fatigue was strongly associated with unsafe sexual and injection behaviors among HIV-seronegative individuals. HIV prevention interventions must consider the unintended impact of HIV treatments on attitudes and risk behaviors among IDUs. Tun, W., Celentano, D., Vlahov, D. and Strathdee, S. Attitudes Toward HIV Treatments Influence Unsafe Sexual and Injection Practices Among Injecting Drug Users. AIDS, 17(13), pp. 1953-1962, September 5, 2003.

HIV 1 Pharmacogenomics in Clinical Practice: Relevance of HIV-1 Drug Resistance Testing

Throughout most of the past century, physicians could offer patients no treatments for infections caused by viruses. The experience with treatment of infection by human immunodeficiency virus (HIV) has changed the way healthcare workers deal with viral infections and has triggered a growing rate of discovery and use of antiviral agents, the first fruits of the expanding genomics revolution. HIV treatment also provides an informative paradigm for pharmacogenomics because control of infection and its consequences is limited by the development of viral drug resistance and by host factors. This report summarizes studies published to date on the significance of testing of HIV-1 resistance to antiretroviral drugs. The only Food and Drug Administration-approved kit is commercially available through Visible Genetics, Inc., for HIV drug resistance testing by genotypic sequencing. Genotypic sequencing alone is most likely an adequate test to assist in the therapeutic decision-making process in cases of previous regimen failure, treatment-naive patients in areas of high prevalence of transmitted resistant virus, and pregnant women. However, in exceptional cases of highly complex mutation patterns and extensive cross-resistance, it may be useful to obtain a phenotype test, because that result may more easily identify drugs to which the virus is least resistant. There are no published clinical trial results on the usefulness of the so-called virtual phenotype over genotypic sequencing alone. The paradigm of viral pharmacogenomics in the form of HIV genotypic sequencing has been not only useful to the treatment of other viral diseases but also important to the real-life implementation of the growing discipline of genomics or molecular medicine. The application of this paradigm to the thousands of potential therapeutic targets that have become available through the various human genome projects will likely change the landscape of diagnosis and management of many diseases, including cancer. Patarca, R., Isava, A., Campo, R., Rodriguez, N.J., Nunez, E., Alter, M., Marchette, M., et al. HIV Pharmacogenomics in Clinical Practice: Relevance of HIV-1 Drug Resistance Testing (Part 2). J Environ Pathology Toxic Oncolo. 22(4), pp. 235-279, 2003.

Impact of Expanding Syringe Access on Sources of Syringes for IDUs in New York City

Beginning in January 2001, it became legal for pharmacies, health care facilities and certain health care providers in New York State (NYS) to sell or provide syringes (10 maximum) without prescription. Cross-sectional survey data from three research projects recruiting active injection drug users (IDUs) in Harlem and the South Bronx (N=682) were analyzed by calendar quarter, from January 2001 through September 2002, to assist in an evaluation of the impact of the program, the Expanded Syringe Access Demonstration Program (ESAP). The outcome variable examined was having used a pharmacy as the source of the last injection syringe. The percent of IDUs who knew that it was legal to buy a syringe from a pharmacy increased over time (25-54%, P<0.001). Pharmacy as the source of the last injection syringe increased to approximately 20%, and syringe exchange programs (SEPs) remained the most common source (approximately 50%). In a multiple logistic regression analysis, IDUs who knew it was legal were more likely to have purchased their last syringe from a pharmacy (AOR =4.65, CI =2.58-8.36). Pharmacies were more likely to be used by those who were younger (AOR =0.96, CI =0.93-0.99) and those who were White (AOR =2.55, CI =1.30-5.00), and calendar quarter was a significant independent predictor of pharmacy use (AOR =1.22, CI =1.06-1.40). Overall, these data indicate that: (a) knowledge about the option of purchasing syringes from a pharmacy has increased, but enhanced dissemination efforts to IDUs, especially particular sub-groups, are needed; and (b) pharmacies were becoming a supplemental source of syringes for active IDUs (in communities served by SEPs). Deren, S., Fuller, C., Pouget, E., Blaney, S., Tortu, S., Kang, S-Y., McMahon, J., et al. Impact of Expanding Syringe Access in New York on Sources of Syringes for Injection Drug Users in Harlem and the Bronx, NYC, USA. Internat J Drug Policy, 14(5-6), pp. 373-379, 2003.

Iron-deficiency Anemia and the Cycle of Poverty Among HIV-Infected Women in the Inner City

The prevalence of iron-deficiency anemia appears to be extremely high among female injection drug users in the inner city who have HIV and/or HCV infections. Iron deficiency and its associated anemia may contribute to reduced energetic efficiency, lower aerobic capacity, decreased endurance, and fatigue. In practical terms, the functional limitations of iron deficiency and iron-deficiency anemia may affect the ability of women to participate in work, school, social, and family activities. Iron deficiency may contribute to the cycle of poverty in the inner city by limiting the ability of women to work, earn money, and afford iron-rich sources of food. Although iron supplementation may prevent or treat iron deficiency, the use of iron supplements needs to be approached with caution in women with HIV and HCV infections. Semba, R. Iron-Deficiency Anemia and the Cycle of Poverty Among Human Immunodeficiency Virus-Infected Women in the Inner City. Clin Infect Dis.,37 Suppl 2: S105-111, 2003.

Longitudinal Patterns of Drug Injection Behavior in the ALIVE Study Cohort, 1988-2000

The objective of this study was to characterize longitudinal patterns of drug injection behavior for individuals and to identify their early determinants. Participants were 1,339 IDUs recruited into the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, through community outreach efforts. The study was initiated in 1988, and follow-up continued through 2000, with semiannual visits. Patterns of self-reported drug injection (yes/no) were defined for each participant, based on the number of drug-use transitions. The effect of baseline factors was assessed using multinomial logistic regression models. Over the 12-year study period, four patterns were noted: 29% of participants remained persistent drug injectors, 20% ceased injection, 14% relapsed once, and 37% had multiple transitions. Persistent injectors had the shortest follow-up and the highest mortality. For persons who changed their behavior, 3.4 years elapsed before their first cessation attempt, on average. Factors differentiating the groups included history of incarceration, young age, participation in drug treatment programs, recent overdose, and commercial sex. The observed long-term injection patterns are consistent with the view of drug addiction as a chronic disease. This view emphasizes the need for prolonged efforts to sustain cessation and to prevent adverse health and social outcomes among injection drug users. Galai, N., Safaeian, M., Vlahov, D., Bolotin, A. and Celentano, D., ALIVE Study. Longitudinal Patterns of Drug Injection Behavior in the ALIVE Study Cohort, 1988-2000: Description and Determinants. Am J Epidemiol., 158(7), pp. 695-704, 2003.

Opiate Drug Use: A Potential Contributor to the Endocrine and Metabolic Complications in Human Immunodeficiency Viral Disease

Dobs and her colleagues (Cooper et al., Johns Hopkins) report that endocrine and metabolic abnormalities are common in HIV disease and have been attributed to both the disease and its treatment. Other risk factors and behaviors are also important, however. Approximately 28% of new HIV infections occur in users of injection drugs, such as opiates. This paper focuses on the effects of opiates on metabolic and endocrine systems and their potential to contribute to the metabolic and endocrine problems in HIV. Opiate use has been associated with hypogonadism, adrenal dysfunction, reduced bone mineral density and growth-hormone abnormalities. In addition, some studies have suggested abnormalities in glucose and lipid metabolism among opiate users. Although evidence should be viewed as preliminary, these potential abnormalities should be kept in mind when treating opiate-dependent patients infected with HIV. Cooper, O.B., Brown, T.T. and Dobs A. Opiate Drug Use: A Potential Contributor to the Endocrine and Metabolic Complications in HIV Disease. Clin Infect Dis., 37, S132-136, 2003.

Pilot Study to Enhance HIV Care Using Needle Exchange-Based Health Services for Out of Treatment Injecting Drug Users

Out-of-drug treatment active heroin injectors infected with human immunodeficiency virus (HIV) were recruited to receive HIV therapy by accessing a Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N = 11); 77% (N = 10) had nondetectable levels by 9 months. By 12 months, 54% (N = 7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention. The research results have important implications for the development of strategic community-based programs that address the complex medical needs of out-of-treatment IDUs with HIV disease. They also suggest that when services are organized in a way that is acceptable to drug users, they will utilize them and derive clinical benefit. Altice, F.L., Springer, S., Buitrago, M., Hunt, D.P., and Friedland, G.H. Pilot Study to Enhance HIV Care Using Needle Exchange-Based Health Services for Out-of-Treatment Injecting Drug Users. J Urban Health, 80(3), pp. 416-427, Sept 2003.

Potential Hidden Source Of Hepatitis C Infection Among Non-Injecting Drug Users

Despite a growing awareness of the routes of HCV transmission, a substantial proportion of HCV cases have no identifiable source of infection, especially among non-injection drug users. One explanation is that past and present HCV risk exposures may go unreported in epidemiological surveys. Underreporting of injection drug use, often a stigmatized behavior, may occur due to respondent misrepresentation, inaccurate recall of injection-related behavior, or inadequate questionnaire methodology. Whereas most of the epidemiological studies that have examined non-injection drug use risk factors have focused on potential intranasal routes of HCV transmission (with far less attention paid to possible oral transmission), the opposite is true of biological studies. Virological evidence related to potential oral transmission of HCV is extensive, whereas similar research into potential intranasal transmission is virtually nonexistent. Current evidence neither confirms nor invalidates the existence of oral or intranasal drug-related HCV transmission. Resolution of this question has significant implications for HCV prevention, drug treatment and harm reduction programs, and blood donor screening policies. Although inconclusive, current epidemiological and virological evidence warrants the support of further research in this area. McMahon, J. M. and Tortu, S. A Potential Hidden Source of Hepatitis C Infection Among Non-Injecting Drug Users. Journal of Psychoactive Drugs, 35(4), pp. 455-460, 2003.

Predictors of Sharing Drugs Among IDUs in the South Bronx: Implications for HIV Transmission

HIV may be transmitted in the process of sharing injected drugs, even if all participants have their own syringes. In an effort to gain understanding of the extent and predictors of drug sharing, data were obtained via personal interviews with 1,024 injection drug users from four neighborhoods in the South Bronx. The relationship between drug-sharing and demographic, sexual, and drug-related variables was first examined in a bivariate analysis, and then via multiple logistic regression. Individuals who split drugs were more likely to be female, have had sex with a casual partner, exchanged sex for drugs or other needs, recently smoked crack cocaine, and shared needles. They were less likely to live or inject at their own home or have used a new needle the last time they injected. In a final logistic model, correlates of drug sharing included trading sex, injecting outside one's home, and using borrowed, rented or shared needles. Despite the lack of significance for gender in the final logistic model, females were at high risk of drug sharing because they constituted the great majority of those who exchanged sex. Continuing research is needed to understand how drug-sharing contributes to the spread of HIV and other infections, as are studies of approaches to reducing drug sharing. Prevention strategists and outreach organizations should be aware of the HIV risks inherent in the widespread practice of drug sharing. Fernando, D., Schilling, R.F., Fontdevila, J., El-Bassel, N. Predictors of Sharing Drugs Among Injection Drug Users in the South Bronx: Implications for HIV Transmission. J Psychoactive Drugs, 35(2), pp. 227-236, April-June 2003.

Prevalence and Risk Factors for HIV Among Sniffers, Short-Term Injectors, and Long-Term Injectors of Heroin

The prevalence of HIV and associated risk behaviors were assessed among three groups of heroin users: long term injection drug users (LTIDUs), new injection drug users (NIDUs), and heroin sniffers (HSs) with no history of injection. HIV seroprevalance was similar among NIDUs (13.3%) and HSs (12.7%). LTIDUs had almost twice as high a level of HIV infection (24.7%). After including drug use and sex behavior variables in logistic regression models, both drug and sexual risk factors remained in the models. Attributable risk percent (APR) from injection for HIV infection among injection drug users was estimated to be 55.7% for LTIDUs and 5.8% for NIDUs. High-risk sex behavior plays an important role in the prevalence of HIV among drug users and accounts for nearly all the infection among NIDUs. Both injection and sexual risk behaviors need to be stressed in HIV prevention and intervention programs aimed at drug users. Chitwood, D.D., Comerford, M. and Sanchez, J. Prevalence and Risk Factors for HIV Among Sniffers, Short-Term Injectors, and Long-Term Injectors of Heroin. J Psychoactive Drugs, 35(4), pp. 445-454, 2003.

Prevalence of Mental Disorders, Psychological Distress, and Mental Health Services Use Among Lesbian, Gay and Bisexual Adults in the United States

Recent estimates of mental health morbidity among adults reporting same-gender sexual partners suggest that lesbians, gay men, and bisexual individuals may experience excess risk for some mental disorders as compared with heterosexual individuals. However, sexual orientation has not been measured directly. Using data from a nationally representative survey of 2,917 midlife adults, the authors examined possible sexual orientation-related differences in morbidity, distress, and mental health services use. Results indicate that gay-bisexual men evidenced higher prevalence of depression, panic attacks, and psychological distress than heterosexual men. Lesbian-bisexual women showed greater prevalence of generalized anxiety disorder than heterosexual women. Services use was more frequent among those of minority sexual orientation. Findings support the existence of sexual orientation differences in patterns of morbidity and treatment use. Cochran, S.D., Sullivan, J.G. and Mays, V.M. Prevalence of Mental Disorders, Psychological Distress, and Mental Health Services Use among Lesbian, Gay, and Bisexual Adults in the United States. J Consulting Clinical Psych., 71(1), pp. 53-61, 2003.

Psychological Distress and Progression to AIDS in a Cohort of IDUs

Researchers investigated whether distress was independently associated with more rapid progression to AIDS among HIV-infected injection drug users (IDUs). A cohort study of IDUs in Baltimore was followed from 1988 through 1999. A total of 451 IDUs met the eligibility criteria of being HIV-seropositive but were AIDS-free at baseline. Cox proportional hazards models were used to investigate progression to AIDS within 2 years of baseline, controlling for CD4 lymphocyte count, HIV-1 viral load, and oral thrush. Of the 451 participants, 76.3% were male and 95.8% were African-American; the median age at enrollment was 34 years. The cumulative incidence of AIDS within 2 years of baseline was 7.1%. In multiple regression analysis, distress was associated with more rapid time to AIDS (adjusted relative hazard [RH] = 2.39; 95% CI: 1.16-4.90). The strongest association was observed among IDUs with the lowest (<200 x 10 /L) CD4 counts (adjusted RH = 4.94; 95% CI: 1.30-18.77). Psychological distress was independently associated with shorter time to AIDS among HIV-infected IDUs, especially among those with the lowest CD4 cell counts, but was not predictive of mortality in this cohort. Further study of the effects of psychological distress on AIDS progression within this population is warranted. Golub, E.T., Astemborski, J.A., Hoover, D.R., Anthony, J.C., Vlahov, D. and Strathdee, S.A. Psychological Distress and Progression to AIDS in a Cohort of IDUs. J Acquir Immune Defic Syndr., 32(4), pp. 429-434, 2003.

Qualitative Evaluation of a Volunteer AIDS Outreach Intervention

Qualitative research can play an important role in explaining outcomes of behavioral interventions and constitutes a largely unrealized potential of ethnographic methods in AIDS research. The Self Help in Eliminating Life Threatening Diseases (SHIELD) intervention trained African American injection drug users to conduct outreach among their drug-using peers and sexual partners. Though the intervention was not targeting adolescents, some participants chose to conduct outreach with youth fortuitously found on the street. Still others spoke to groups of youth in their homes. This paper seeks to understand the dynamics of outreach encounters between older, drug-using outreach workers and adolescents. Contextual features that were important in determining the quality of outreach encounters with youth included the setting (on the street or in the home), characteristics of the outreach worker such as gender, content of the outreach message, and style of interpersonal communication. Dickson-Gomez, J., Knowlton, A. and Latkin, C. Hoppers and Oldheads: Qualitative Evaluation of a Volunteer AIDS Outreach Intervention. AIDS Behav., 7(3), pp. 303-315, 2003.

Referring Drug Users from an NEP to Treatment with a Mobile Van and LAAM

Researchers evaluated program entry, retention, and early treatment response of needle exchange program (NEP) attenders referred to a drug treatment program using levomethadyl acetate hydrochloride (LAAM). Of 163 referrals, 114 (70%) entered the program, and 84% were retained for at least 90 days. Comparing baseline and follow-up visits after 1 month, there were significant reductions in the Addiction Severity Index subscale scores for drug and alcohol use and legal situation. A 31% and 22% reduction in heroin- and cocaine-positive urine tests was observed, respectively (p < .0001). Although LAAM is no longer considered a first line treatment for heroin addiction, these results demonstrate the feasibility of utilizing long-acting agonist therapies such as LAAM to treat opioid dependence among NEP attenders. Kuo, I., Brady, J., Butler, C., Schwartz, R., Brooner, R., Vlahov, D. and Strathdee, S. Feasibility of Referring Drug Users from a Needle Exchange Program into an Addiction Treatment Program: Experience with a Mobile Treatment Van and LAAM Maintenance. J Subst Abuse Treat., 24(1), pp. 67-74, 2003.

Readiness for Cessation of Drug Use Among NEP Attenders and Non-Attenders

Needle exchange programs (NEPs) represent a bridge to drug abuse treatment. NEP attenders tend to have more severe drug problems, however, and may be less ready to reduce their drug use than other drug users. This study investigated the relationship between NEP attendance and readiness for cessation of drug use. Since the period from 1988 through 1989, a community-based sample of IDUs in Baltimore has undergone semiannual interview-administered questionnaires and HIV testing. A total of 288 IDUs completed a questionnaire on readiness for cessation of drug use. Readiness for drug use cessation was assessed from a 28-item validated scale of problem drug use and intention to quit, based on the "stages of change" model. Logistic regression was used to determine factors associated with readiness for cessation of drug use, including socio-demographics, drug use behaviors, and NEP attendance. Thirty percent of respondents attended the NEP in the past month. Stage of change in readiness for cessation of drug use did not differ between NEP attenders and nonattenders (OR= 0.9; 95% CI: 0.5-1.6). Similar proportions of persons recently attending and not attending the NEP were classified as ready to stop drug use (about 30%). In multivariate analysis, readiness for cessation of drug use was associated with speedball injection and previous enrollment in drug treatment but not with NEP attendance. NEP attenders, although exhibiting characteristics consistent with more severe drug dependence, were as motivated for cessation of drug use as were nonattenders. These findings suggest that formal collaboration between NEPs and drug treatment programs could increase the proportion of IDUs in treatment. Henderson, L.A., Vlahov, D., Celentano, D.D. and Strathdee, S. Readiness for Cessation of Drug Use Among Recent Attenders and Non-Attenders of a Needle Exchange Program. J Acquir Immune Defic Syndr., 32(2), pp. 229-237, 2003.

Recruitment of Heterosexual Couples in Public Health Research: A Study Protocol

Public health research involving social or kin groups (such as sexual partners or family members), rather than samples of unrelated individuals, has become more widespread in response to social ecological approaches to disease treatment and prevention. This approach requires the development of innovative sampling, recruitment and screening methodologies tailored to the study of related individuals. In this paper, researchers examine and describe a set of sampling, recruitment and screening protocols developed to enlist urban, drug-using, heterosexual couples into a public health research study. This population is especially hard to reach because they are engaged in illegal and/or stigmatized behaviors. The protocols were designed to integrate adaptive sampling, street-and referral-based recruitment, and screening procedures to verify study eligibility and relationship status. Recruitment of heterosexual couples through one partner, preferably the female, can be an effective enlistment technique. Verification of relationship status is an important component of dyadic research. Comparison of parallel questionnaires administered to each member of a dyad can aid in the assessment of relationship status. However, multiple independent sources of information should be used to verify relationship status when available. Adaptive sampling techniques are effective in reaching drug-using heterosexual couples in an urban setting, and the application of these methods to other groups of related individuals in clinical and public health research may prove to be useful. However, care must be taken to consider potential sources of sampling bias when interpreting and generalizing study results. McMahon, J., Tortu, S., Torres, L., Pouget, E. and Hamid, R. Recruitment of Heterosexual Couples in Public Health Research: A Study Protocol. BMC Med Res Methodol., 3(1), 24, 2003.

Safer Injection Sites in NYC: A Utilization Survey of IDUs

HIV, HBV, HCV, drug overdose, and other drug-related health problems still pose significant health risks to IDUs and their sex partners, indicating the need for further development of innovative public health interventions. A relatively new intervention implemented in many municipalities throughout the world is the "safer injection site" (SIS). An SIS is a legal facility that allows people to prepare and inject pre-obtained drugs in a hygienic, anxiety-free atmosphere under the supervision of health personnel. In this paper, researchers examine the responses of a sample of IDUs in New York City to whether they would use an SIS should one be implemented in mid-town Manhattan. The SIS would be part of a comprehensive effort to offer needle-exchange, street outreach, testing and counseling, support groups, referral services including drug treatment, and on-site primary and dental services. The results of this study indicate that a large majority of the IDUs sampled would utilize an SIS should one be implemented, and that those most likely to use it are IDUs at the highest risk for contracting or spreading blood-borne diseases such as HIV and hepatitis, and for experiencing a drug overdose. Broadhead, R., Borch, C., Van Hulst, Y., Farrell, J., Villemez, W. and Altice, F. Safer Injection Sites in New York City: A Utilization Survey of Injection Drug Users. J Drug Issues, 22(3), pp. 733-750, 2003.

Secondary Syringe Exchange Among Injection Drug Users

Syringe-exchange programs (SEPs) have proven to prevent the spread of blood-borne pathogens, primarily HIV, among IDUs. In the U.S., only about 7% of IDUs have access to and use SEPs. Some IDUs engage in secondary syringe exchange (SSE), meaning that one IDU (a "provider") obtains syringes at an SEP to distribute to other IDUs ("recipients"). This formative qualitative research was conducted to understand why and how IDUs engage in SSE to aid in the development of a large-scale peer HIV prevention intervention. Interviews with 47 IDUs in Oakland and Richmond, California, indicated that SSE was embedded in existing social networks, which provided natural opportunities for peer education. SSE providers reported a desire to help other IDUs as their primary motivation, while recipients reported convenience as their primary reason for using SSE. Building SSE into SEP structures can facilitate an effective provision of risk reduction supplies and information to IDUs who do not access SEPs directly. Snead, J., Downing, M., Lorvick, J., Garcia, B., Thawley, R., Kegeles, S. and Edlin, B. Secondary Syringe Exchange Among Injection Drug Users. J Urban Health, 80(2), pp. 330-348, 2003.

Study Demonstrates the Risk of Sexual Transmission of HCV is Low

In this study, the risk of sexual transmission of HCV within a sexually active population was measured and found to be low. Sexual behaviors and HCV antibody status were measured in persons seeking repeat HIV testing in San Francisco from October 1997 through March 2000. Among 981 repeat testers, the prevalence of HCV antibody was 2.5%. Among men who have sex with men who denied intravenous drug use (n=746), factors associated with HCV antibody positivity included age greater than 50 years (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.6-27.7), HIV infection (OR, 5.7; 95% CI, 1.6-20.6), and being nonwhite (OR, 3.3; 95% CI, 1.1-10.0). HCV antibody positivity was not associated with sexual risk behaviors. In 576.6 person-years of observation, no new HCV seroconversions occurred (incidence=0 per 100 person-year; 95% CI, 0-.6), whereas 6 new herpes simplex virus-2 infections (2.8 per 100 person-years) and 10 new HIV infections (1.8 per 100 person-years) occurred. Hammer, G.P., Kellogg, T.A., McFarland, W.C., Wong, E., Louie, B., Williams, I., et al. Low Incidence and Prevalence of Hepatitis C Virus Infection Among Sexually Active Non-Intravenous Drug-Using Adults, San Francisco, 1997-2000. Sex Trans Dis., 30, pp. 919-924, 2003.

Substance Use and High-Risk Sex among People with HIV: A Comparison Across Exposure Groups

Substance use is associated with increased risk for HIV transmission by HIV-positive people to uninfected partners through sexual contact. The largest risk groups for infection, men who have sex with men (MSM) and injecting drug users (IDUs), have high rates of substance use, but little is known about their substance use post-HIV diagnosis. Researchers compared the prevalence of substance use between these two groups and a third group, heterosexual men and women, and tested for differential associations between substance use and sexual behaviors across exposure groups in a national sample of patients in treatment for HIV. Substance use was most prevalent among MSM. Substance use and current dependence were associated with being sexually active among MSM but not IDUs; marijuana, alcohol, and hard drug use were most strongly associated with being sexually active among MSM. Whereas substance use predicted high-risk sex, there were few differences among exposure groups in these associations. Beckett, M., Burnam, A., Collins, R.L., Kanouse, D.E., Beckman, R. Substance Use and High-Risk Sex Among People with HIV: A Comparison Across Exposure Groups. AIDS Behav. 7(2), pp. 209-219, 2003.

Self-Report Data and the Correlates of HIV Status: Conditional and Marginal Approaches

Researchers examined whether relationships between individual characteristics and HIV status can be identified when self-report data are used as a proxy for HIV serostatus results. The analyses use data obtained from HIV serostatus and face-to-face interviews with 7,256 out-of-treatment drug users in 10 sites from 1992 to 1998. Relationships among 17 individual characteristics were determined by comparing and evaluating the fit of both standard and nonstandard loglinear models and evaluating the fit of marginal homogeneity models. The loglinear analyses showed that HIV was related to individual characteristics in 38% of the relationships. In most cases, the strength of the relationships between HIV status and individual characteristics did not differ when HIV status was measured as self-report data. Rindskopf, D., Strauss, S., Falkin, G. and Deren, S. Assessing the Consequences of Using Self-Report Data to Determine the Correlates of HIV Status: Conditional and Marginal Approaches. Multivariate Behav Research, 38(3), pp. 325-352, 2003.

The Impact of Needle-Exchange Programs on the Spread of HIV Among IDUs: A Simulation Study

Researchers sought to determine the impact of the implementation of a needle-exchange program (NEP) on the spread of HIV in an IDU community. They conducted a Monte Carlo simulation study of a theoretical population of 10,000 IDUs. The population was followed monthly from 1984 to 2000. HIV was assumed to be transmitted only by needle sharing. The NEP was introduced in 1989 and evaluated over a period of 11 years. The impacts of the proportion of the population attending the NEP, the risk level of IDUs attending the NEP, the reduction in needle-sharing frequency, and the number of new needle-sharing partners acquired at the NEP on prevalence and incidence of HIV were determined. Increasing the proportion of the population who always attend the NEP and eliminating needle-sharing incidents among IDUs who always attended the NEP were the most effective ways of reducing the spread of HIV. Attracting high-risk users instead of lower risk users to the NEP also reduced the spread of HIV, but to a lesser extent. NEPs are effective at reducing the spread of HIV; even under the worst case scenario of low risk users more likely to attend the NEP, one additional partner per month as a result of attending the NEP, and poor NEP attendance, the estimated prevalence was still less than that from the scenario without an NEP. Under our model, NEPs were shown to reduce the spread of HIV significantly. Efforts should be focused on getting as many IDUs as possible to become regular NEP attenders and stop sharing needles rather than partially reducing the frequency of sharing by a larger number of IDUs. Raboud, J.M., Boily, M.C., Rajeswaran, J., O'Shaughnessy, M.V., and Schechter, M.T. The Impact of Needle-Exchange Programs on the Spread of HIV Among IDUs: A Simulation Study. J Urban Health, 80(2), pp. 302-320, 2003.

The PRECEDE Model for Predicting HIV Risks in Puerto Rican IDUs

The PRECEDE model for health promotion proposes three types of influences on health behaviors: Predisposing, Enabling, and Reinforcing factors. This model was used to examine a range of influences on HIV risk behaviors (sharing syringes and other injection-related paraphernalia) among Puerto Rican injection drug users (IDUs). A total of 698 IDUs were interviewed (438 in East Harlem, New York, and 260 in Bayam, Puerto Rico). Both types of risk behaviors were more prevalent in Puerto Rico. Similarities in influences on syringe sharing behaviors were found in the two sites and included self-efficacy (for reducing injection-related sharing) and norms. Influences on the sharing of other injection-related paraphernalia were primarily enabling factors in both communities, and purchasing drugs with others was the strongest predictor of paraphernalia sharing. These findings underscore the importance of addressing risks associated with joint drug purchasing in both locations and enhancing efforts to reduce risks among IDUs in Puerto Rico. Deren, S., Kang, S-Y., Rapkin, B., Robles, R.R., Andia, J.F. and Colón, H.. The Utility of the PRECEDE Model in Predicting HIV Risk Behaviors Among Puerto Rican Injection Drug Users. AIDS and Behavior, 7(4), pp. 405-412, 2003.

Women's Drug Injection Practices in the High-Risk Community of East Harlem

This study examined the most recent injection events of injection-drug-using women, determined the prevalence of HIV, hepatitis B (HBV), and hepatitis C (HCV), and identified significant predictors of injection-related risk behaviors. After validation of drug use, 185 street-recruited women participated in structured interviews and were offered HIV, HBV, and HCV testing and counseling. Interview topics included (1) demographic characteristics, (2) characteristics of injection partners (IPs), and (3) relevant situation-specific factors. Prevalence was 28% for HIV infection, 80% for HBV, and 70% for HCV. Injection events were either solitary (n=110) or social (n=75). Most were safe, and 75% of syringes used were obtained from a syringe exchange. Inferential analyses identified two variables that independently predicted unsafe events: (1) respondent had injected previously with her IP, and (2) her IP was her spouse or primary heterosexual partner. Two trends were identified: Injection events in which women felt "very close" to their IP or reported lack of control over injection practices tended to be unsafe. Although most events were safe, safe practices were not adhered to with spouses or primary partners. These findings suggest that syringe exchanges should be supported and may be an ideal setting for interventions targeted to drug-injecting couples. Tortu, S., McMahon, J., Hamid, R. and Neaigus, A. Women's Drug Injection Practices in East Harlem: An Event Analysis in a High-Risk Community. AIDS and Behavior, 7(3), pp. 317-328, 2003.

Zinc Status in Human Immunodeficiency Virus Type 1 Infection and Illicit Drug Use

Zinc deficiency is the most prevalent micronutrient abnormality seen in HIV infection. Low levels of plasma zinc predict a 3-fold increase in HIV-related mortality, whereas normalization has been associated with significantly slower disease progression and a decrease in the rate of opportunistic infections. Studies in Miami, Florida, indicated that HIV-positive users of illicit drugs are at risk for developing zinc deficiency, at least partially because of their poor dietary intake. Zinc deficiency characterized by low plasma zinc levels over time enhances HIV-associated disease progression, and low dietary zinc intake is an independent predictor of mortality in HIV-infected drug users. The amount of zinc supplementation in HIV infection appears to be critical, because deficiency, as well as excessive dietary intake of zinc, has been linked with declining CD4 cell counts and reduced survival. More research is needed to determine the optimal zinc supplementation level in HIV-infected patients, to prevent further burden on an already compromised immune system. Baum, M.K., Campa, A., Lai, S., Lai, H. and Page, J.B. Zinc Status in HIV Type 1 Infection and Illicit Drug Use. Clin Infect Dis., 37, Suppl 2:S117-123, 2003.

Contextual Factors and Other Correlates of Sexual Risk of HIV Among African-American Crack-Abusing Women

This study examined differences in contextual factors, substance use, sexual risk behaviors, and comorbid histories between African-American, out-of-treatment, crack-abusing women who had either a single sexual partner or multiple partners. Bivariate analysis indicated that women with multiple partners were more likely than women with a single partner to be homeless, financially dependent, and to have histories of sexual, physical, and emotional abuse. Women with multiple partners reported higher levels of depression, anxiety, and more symptoms of posttraumatic stress disorder (PTSD). In multiple logistic regression analysis, being unemployed, difficult childhood, and number of days of crack use in the previous 30 days, longer crack runs, and more frequent unprotected fellatio were associated with increased odds of having multiple sexual partners. Being married or living as married was associated with decreased odds of having multiple sexual partners. The importance of assessing contextual and historical factors and implications for future research is discussed. Roberts, A.C., Wechsberg, W.M., Zule, W. and Burroughs, A.R. Addictive Behaviors, 28, pp. 523-536, 2003.

Spiritual Beliefs, World Assumptions, and HIV Risk Behavior Among Heroin and Cocaine Users

Dr. Arthur Margolin and colleagues examined the relationship between spirituality and HIV risk behavior in a sample of 34 inner-city cocaine-using methadone-maintained patients. Spirituality was operationally defined in terms of "life meaningfulness" and included the Santa Clara Strength of Religious Faith (T. G. Plante & M. T. Boccaccini, 1997b) and the World Assumptions Scale (R. Janoff-Bulman, 1989; assessing benevolence, meaningfulness, and worthiness of the self). Hierarchical multiple regression analyses of self-reported drug- and sex-related risk behavior were conducted with sex and race entered as control variables. The full models accounted for 23% and 42% of the variance in drug- and sex-related risk behavior, respectively. Strength of spiritual/religious faith (B = .37) and belief in a benevolent (beta = .50) and meaningful (beta = .46) world were independent predictors of sex-related, but not drug-related, HIV preventive behavior. Avants, S.K., Marcotte, D., Arnold, R., and Margolin A. Psychology of Addictive Behaviors, 17(2), pp. 159-162, June 2003.

A Randomized Clinical Trial of a Manual-Guided Risk Reduction Intervention for HIV-positive Injection Drug Users

Dr. Arthur Margolin and colleagues randomized 90 HIV-seropositive, methadone-maintained injection drug users (IDUs) to an HIV Harm Reduction Program (HHRP+) or to an active control that included harm reduction components recommended by the National AIDS Demonstration Research Project. The treatment phase lasted 6 months, with follow-ups at 6 and 9 months after treatment entry. Patients in both treatments showed reductions in risk behaviors. However, patients assigned to HHRP+ were less likely to use illicit opiates and were more likely to adhere to antiretroviral medications during treatment; at follow-up, they had lower addiction severity scores and were less likely to have engaged in high risk behavior. Findings suggest that enhancing methadone maintenance with an intervention targeting HIV-seropositive IDUs increases both harm reduction and health promotion behaviors. Margolin, A., Avants, S.K., Warburton, L.A., Hawkins, K.A., and Shi. J. Health Psychology, 22(2), pp. 223-228, March 2003.

Methamphetamine Abuse as a Barrier to HIV Medication Adherence Among Gay and Bisexual Men

This paper is a qualitative analysis of HIV-medication adherence from an interview conducted with 23 HIV-infected participants who entered a 16-week behavioral drug treatment program for gay and bisexual male methamphetamine abusers. Participants discussed the effects of their methamphetamine use on their medication adherence. Methamphetamine use as a barrier to adherence was coded into two main themes: (1) planned non-adherence and (2) unplanned non-adherence. Planned non-adherence was a strategy for coping with demanding HIV medication schedules, or was linked to sexual behaviors while using methamphetamine or to fears of interaction effects from mixing methamphetaime with HIV medications. Participants did not define their medication regimen adjustments as non-adherence but as a way to achieve a sense of control over their lives. Unplanned non-adherence was linked to methamphetamine-related disruptions in food and sleep schedules. Medication adherence among persons with HIV infection is important not only because of the effect of non-adherence on an individual's health but also because non-adherence can lead to medication-resistant viral strains. The findings reported here are helpful in designing culturally specific HIV medication adherence interventions for this population. Reback, C.J., Larkins, S., and Shoptaw, S. AIDS Care, 15, pp. 775-785, 2003.

HIV Risk-Reduction Strategies for Substance Abusers: Effecting Behavior Change

Substance abuse has a strong link to HIV/AIDS in the United States. Use and abuse of alcohol and other drugs often reduce inhibitions and encourage engagement in high-risk sexual behaviors that can ultimately result in HIV and AIDS. The HIV/AIDS epidemic in the United States has disproportionately affected minorities with African Americans being the group hardest hit. This article presents some of the behavioral, social, and psychological factors that influence the risk for drug use. It highlights and assesses the effectiveness of HIV risk-reduction strategies developed for drug-using populations and makes recommendations for a more holistic and integrated approach utilizing multiple interventions at multiple levels. Jones, D.J. Journal of Black Psychology, 30(1), pp. 59-77, February 2004.


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