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Director's Report to the National Advisory Council on Drug Abuse
February, 1995

Research Findings

AIDS Research

Efficacy of Vaccines and Behavior Change in Eradicating HIV.

Dr. Sally M. Blower of the University of California at San Francisco, presented results from her research at NIH on December 6, 1994. Dr. Blower and her colleague, Dr. A.R. McLean from Oxford University, employed mathematical modeling to assess the probability of eradicating HIV in San Francisco through the use of prophylactic vaccines (Science, September 2, 1994; 265: 1451-1454). Drs. Blower and McLean quantified necessary vaccine efficacy levels and population coverage levels for HIV eradication and assessed the likely impact of risk behavior changes on HIV vaccination campaigns. They determined that it is unlikely that vaccines will be able to eradicate HIV in San Francisco unless they are combined with considerable reductions in risk behaviors.

New Haven Needle Exchange Program: Decline in HIV-infected Needles Returned.

NIDA grantee Dr. Edward Kaplan and colleagues at the Yale University School of Medicine, published an article in December's American Journal of Public Health (1994;84: 1991-1994) entitled "A Decline in HIV-Infected Needles Returned to New Haven's Needle Exchange Program: Client Shift or Needle Exchange?" He and colleagues analyzed client demographic and behavioral data to determine possible reasons for a decline in the fraction of syringes returned to the New Haven needle exchange program that are contaminated with HIV-1. Only one variable, the race of participating clients, was found to have changed significantly over time, although there was a nonsignificant difference between HIV-1 prevalences in needles given to whites and to non-whites. The authors conclude that client shift does not appear responsible for the decline in the observed HIV prevalence in needles. Rather, they identified needle circulation time as a significant predictor of HIV prevalence.

Single-Use, Non-Retractable Syringe.

In an ongoing project, investigators have developed and have begun production of a single-use, non-reusable retractable syringe. This group also has begun the development of plans for clinical studies of this plastic syringe and has applied for approval from the Food and Drug Administration. The development of this invention could lead to the marketing of a product that -- depending on the extent of its deployment resulting from health care market forces and/or legislation -- could eliminate or significantly lessen the frequency of needle sharing among injection drug users (IDUs). Such would serve to significantly reduce the presently high rates of transmission of the human immunodeficiency virus (HIV) among members of this risk group and, consequently, to the general population. (NIDA-funded study "Single-use Non-reusable Retractable Syringe PI: Shaw).

Risk Factors for Bacterial Pneumonia Among HIV-Infected IDUs.

A study to identify factors that contribute to the excess risk of bacterial pneumonia observed among HIV-infected IDUs was recently completed. This study investigated risk factors for the first episode of bacterial pneumonia among HIV seropositives, using matched HIV seropositives without a first episode. Overall, the incidence of bacterial pneumonia among seropositives was 1.93 per 100 person years (PYS) and 0.45 per 100 PYS among HIV seronegatives. On multivariate analysis, absolute CD4 <200 cells per mm3 and smoking of illicit drugs were significantly associated with bacterial pneumonia (OR=6.75 and OR=2.24, respectively). Cigarette smoking was associated with increased odds (OR=2.08) of bacterial pneumonia, but was not statistically significant because of nearly universal use in the cohort. Smoking illicit drugs had the strongest effect on risk of bacterial pneumonia among HIV positives with a prior history of Pneumocystis carinii pneumonia (OR=22.9). (Caiffa WT, Vlahov D, Graham NMH et al. Am J Respir Crit Care Med 1994; 150:1493-8).

Markers of Disease Progression Among HIV Seroconverters

A study of markers of disease progression among HIV seroconverters has compared longitudinal trends in CD4% and CD8% between cohorts of active IDUs and homosexual men. Prior to seroconversion, the two cohorts were similar in CD4% and CD8% levels. Greater changes in both markers overall were observed in the homosexual cohort compared with the IDUs (p<0.001) in the first two years following seroconversion. Homosexual men had a higher median CD4% as compared to IDUs in the first 6 months post seroconversion, but subsequent trajectories of CD4% over two more years of follow-up coverged and then declined at similar rates in both cohorts. By four years post seroconversion, CD4% levels were 27% among homosexual men and 28% among IDUs. CD8% trajectories showed larger but not statistically significant increases among homosexual men as compared with IDUs in the third and fourth years post seroconversion. While these data suggest that the effect of injection drug use on rate of progression is limited, further follow-up is necessary to determine whether these trends persist. (Galai N, Vlahov D, Margolick JB et al. AIDS 1994; 8:66-74).

Alteration of Immune Function By Opioids.

Dr. Linda Dykstra and her colleagues have been examining conditioned immune suppression caused by prior exposure to morphine. These investigators have found that nadolol (a beta-blocker) may attenuate conditioned morphine-induced changes in immune status. Other studies administering naloxone showed that opioid receptor activity is necessary for the establishment and expression of this conditioned immunosuppression. These important studies describe mechanisms by which opioids can alter immune function, and possibly relate to disease progression in HIV-infected opioid users.

Drug Abuse Treatment for AIDS-Risk Reduction (DATAR).

In a research demonstration study of opioid addicts admitted to 3 methadone treatment programs, Dr. Dwayne Simpson of Texas Christian University found that illicit drug use decreased significantly during and after treatment. In a 12-month follow-up, self-reported weekly use of heroin decreased from 92 percent to 41 percent. Treatment process variables such as cognitive-based (vs. standard) counseling, client engagement in treatment, and therapeutic alliance with counselors were found to be more important than many pre-treatment client attributes in determining outcomes.

Drs. Dwayne Simpson and Don Dansereau of Texas Christian University have developed an innovative counseling tool using a visual representation strategy (called "node-link mapping"). Node-link mapping was found to improve client-counselor communication and the client's understanding of how to deal with problem situations. The strategy has been shown to strengthen the therapeutic relationship and decrease relapse to drug use.

Inhibition of Human T Cell Activation.

Researchers at UCLA have demonstrated that cocaine, alcohol, and cocaine/alcohol mixtures inhibit the in vitro activation of and ability to migrate of CD4+ but not CD4-T lymphocytes. Further studies will determine the extent and significance of the specific inhibition of the CD4+lymphocyte, the primary effector cell of cell-mediated immunity and the primary "target" of HIV, by these abused substances (Chiappelli, F., Frost, P., Kung, M., et al. Cocaine blunts human T cell activation. Immunopharmacol, 1995, in press).

Platelet Destruction in HIV Infected Individuals.

Researchers at the New York University School of Medicine found that the proportion of CD5+ to CD5-B lymphocytes is four-fold higher in HIV-1-infected individuals with thrombocytopenia than in controls (HIV-1-infected individuals without thrombocytopenia) and are attempting to establish the role of IgM and IgG and/or the complex of the two antibodies in an autoimmune mechanism of platelet destruction in such patients. The results of this study, when completed, may definitively establish the mechanism involved in platelet destruction in HIV-infected individuals. (Karpatkin, S., Nardi, M.A., and Hymes, KB. Sequestration of antiplatelet GP3a and rheumatoid factor-immune complexes of HIV-1 and ITP patients, 1995, Proc Natl Acad Sci., in press; Kouri, YH., Basch, RS., and Karpatkin, S. B Cell subset and platelet counts in HIV-1 seropositive subjects, Lancet, 339:1445-1446, 1992).

Elucidating the Mechanism and Consequences of HIV Infection of the Brain.

Researchers at the University of Miami School of Medicine have developed methods for the isolation--from human brain tissue--of cells of the macrophage/monocyte series, which serve as primary reservoirs of HIV-l; detected macrophage infection in proximity to markers of inflammation in both brain and spinal cord neurons; and observed the apparent end-stage of HIV-1 infection in the form of the death of neurons and associated monocytes. Additionally, they have detected several specific HIV-1 genetic sequences and those for other biochemical mediators of inflammation in brain tissue from members of various HIV-1 risk groups. These studies, by elucidating the mechanism of HIV infection of the brain and its consequences, hopefully will suggest ways of intervening in this set of events in drug abusing populations. (Singer, EJ., Syndulko, K., Fay-Chandon, BN., Shapshak, P. et al. Cerebrospinal fluid p24 antigen levels and intrathecal immunoglobulin G synthesis are associated with cognitive disease severity in HIV-1, AIDS 8(2):197-204, 1994; Yoshioka M., Shapshak P., Srivastava AK., et al. Expression of HIV-1 and intraleukin-6 in lumbosacral dorsal root ganglia of patients with AIDS, Neurology, 44(6):1120-1130, 1994).

Mother-to-Child Transmission of HIV infection.

In a longitudinal project, risk of HIV infection was examined relative to a child's birth order following a mother's known HIV infection. Analyses to date suggest that in this sample a significantly higher HIV infection risk was found for children born subsequent to the birth of an older HIV-infected sibling than for those children born subsequent to the birth of an older, uninfected seroreverter. While additional information (e.g., stage of maternal disease progression) is critical for a conclusive interpretation of these results, the findings stimulate hypotheses with implications for research on mother-to-child transmission of HIV infection (Simpson, BJ; Andiman, WA; Shapiro, ED. The risk of HIV-1 infection in children born to HIV-infected women with serial pregnancies, Ped AIDS and HIV Inf 4:304, 1993).

HIV, Prenatal Care, and Disease Progression in the Children of HIV-Infected Mothers.

In a study attempting to identify health care delivery and clinical factors related to risk of infection and rate of disease progression in the child of an HIV-infected mother (e.g., methadone treatment, level of prenatal care for pregnant HIV-infected women, history of untreated maternal drug abuse, and mother's and child's anti-retroviral and prophylactic drug treatment), analyses of over 2,000 pregnancies have shown that very few HIV-infected women received adequate prenatal care (20% reported no prenatal care and an additional 45% reported too few visits). These findings have important implications for the translation of clinical findings into actual practice, e.g., clinical trial findings of a two-thirds reduction in the rate of mother-to-infant HIV transmission by women treated with zidovudine during pregnancy (with short-term treatment of the infant after delivery). The project has also shown that prenatal care was associated with reduced adverse birth outcomes (e.g., low birth weight and preterm birth). Further analyses are examining associations of health care patterns and clinical factors with the child's clinical course. This study is the largest population of pregnant, HIV-infected women to be analyzed to date, and constitutes the first detailed analysis of prenatal care to be conducted for this population (Turner, BJ; Markson, LE; Hauck, W; et al. Prenatal care of HIV-infected women: Analysis of a large New York State cohort. J Acquir Immune Defic Syndr, 1995, in press.)

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