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National Institute on Drug Abuse

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

September, 1997

Research Findings

AIDS Research

Increased Vertical Transmission of HIV from Hepatitis C Co-infected Mothers

A recent study from the Women & Infant Transmission Study (WITS), an NIH supported HIV cohort study co-funded by NIDA, demonstrated that maternal infection with hepatitis C virus is associated with increased HIV maternal-infant transmission. Among 487 women infected with HIV either heterosexually or through injection drug use, 33% were found to be HCV infected. HIV vertical transmission occurred in 26% of HIV/HCV infected mothers vs. 16% of HCV uninfected mothers (OR, 1.82, p=0.01). Drug use during pregnancy was highly correlated with HCV infection (53% vs. 16% in non-drug users, p=0.001) and with HIV perinatal transmission (24% vs. 16% in non-drug users, OR, 1.66, p=0.03). These data suggest that maternal HCV infection either enhances perinatal HIV transmission directly or is a marker for another co-factor such as maternal drug use. Further study is needed to confirm the findings of this study and to determine whether the association represents a biologic effect of HCV infection or is due to a confounding interaction with drug use or other factors. Hershow R.C., Riester, K.A., Lew, J et al. J of Infectious Diseases, 176, pp. 414-419, 1997.

Association Between Serum Vitamin A and E Levels and HIV-1 Disease Progression

Tang and her colleagues at Johns Hopkins Medical School conducted a non concurrent prospective study to examine the associations between serum vitamin A and E levels and risk of progression to three key outcomes in HIV-1 infection: first AIDS diagnosis, CD4+ cell decline to < 200 cells x 10(6)/l, and mortality. Serum levels of vitamins A and E were measured at the enrollment visit of 311 HIV-seroprevalent homo-/bisexual men participating in the Baltimore/ Washington DC site of the Multicenter AIDS Cohort Study. Cox proportional hazards models were used to estimate the relative hazard of progression to each outcome over the subsequent 9 years, adjusting for several independent covariates. The investigators found that men in the highest quartile of serum vitamin E levels (> or = 23.5 mumol/l) showed a 34% decrease in risk of progression to AIDS compared with those in the lowest quartile [relative hazard (RH), 0.66; 95% confidence interval (CI), 0.41-1.06)]. This effect was statistically significant when comparing the highest quartile of serum vitamin E to the remainder of the cohort (RH, 0.67; 95% CI, 0.45-0.98). Associations between serum vitamin A levels and risk of progression to AIDS were less clear, but vitamin A levels were uniformly in the normal to high range (median = 2.44 mumol/l). Similar trends were observed for each vitamin with mortality as the outcome, but neither vitamin was associated with CD4+ cell decline to < 200 cells x 10(6)/l. Men who reported current use of multivitamin or single vitamin E supplements had significantly higher serum tocopherol levels than those who were not taking supplements (P = 0.0001). Serum retinol levels were unrelated to intake of multivitamin or single vitamin A supplements. These data suggest that high serum levels of vitamin E may be associated with slower HIV-1 disease progression, but no relationship was observed between retinol levels and disease progression in this vitamin A-replete population Tang, A.M., Saah, A.J., Semba, R.D., Graham, N.M. AIDS. 11(5), pp. 613-620, April 1997.

Low Serum Vitamin B-12 Concentrations are Associated with Faster Human Immunodeficiency Virus Type 1 (HIV-1) Disease Progression

In another study, Tang et al. examined associations between serum concentrations of vitamin B-6, vitamin B-12 and folate and the risk of progression to first acquired immunodeficiency syndrome (AIDS) diagnosis and CD4+ cell decline to < 2 x 10(8) cells/L. The study population was drawn from a cohort of homosexual and bisexual men in the Baltimore-Washington, D.C., area. Eligible subjects were human immunodeficiency virus type 1 (HIV-1)-seropositive at study entry and had serum available in the serum repository from their 1984 baseline study visit. Serum micronutrient levels were assessed in 310 subjects. The follow-up period (April 1984 through December 1993) was approximately 9 years. In Kaplan-Meier analyses, participants with low serum vitamin B-12 concentrations (< 120 pmol/L) had significantly shorter AIDS-free time than those with adequate vitamin B-12 concentrations (median AIDS-free time = 4 vs. 8 years, respectively, P = 0.004). This effect persisted in Cox proportional hazards models after adjusting for HIV-1-related symptoms, CD4+ cell count, age, serum albumin, use of antiretroviral therapy before AIDS, frequency of alcohol consumption and serum folate concentration [relative hazard (RH)= 1.89, 95% confidence interval (CI) = 1.15-3.10). To further explore the temporal relation between low serum vitamin B-12 concentrations and disease progression, additional analyses were performed excluding subjects with more advanced disease at baseline. In these analyses, the increase in risk of progression to AIDS for those with low serum vitamin B-12 concentrations remained significant (RH = 2.21, 95% CI = 1.13-4.34), providing further evidence that low vitamin B-12 concentrations preceded disease progression. In contrast, low serum concentrations of vitamin B-6 and folate were not associated with either progression to AIDS or decline in CD4+ lymphocyte count. Intervention studies are needed to determine whether correction of low serum vitamin B-12 concentrations in early HIV-1 infection will influence the natural history of disease progression Tang, A.M., Saah, A.J., Chandra, R.K., and Graham, N.M. J Nutr, 127(2), pp. 345-351, February 1997.

Injection Drug Use as an Ecologic Niche for Emerging and Re-emerging Infectious Diseases

Researchers from Seattle, New York City, London, Bangkok, and Rio de Janeiro collaborated in a review of current information on the possible roles of injection drug use in the emergence and re-emergence of infectious diseases. The rapid growth in the use of illicit drugs is discussed in the context of four important factors: (1) there has been a substantial international growth in the use of illicit psychoactive drugs, (2) injecting produces a strong drug effect due to the rapid increase of drug concentration in the brain, (3) the profit margins in the sale of illicit drugs have become so large that even persons who are relatively impoverished are seen as potential customers by drug dealers, and (4) many drug injectors travel internationally (e.g., the phenomenon of "international drug tourism"), and are increasingly being incarcerated together, representing a potential contribution to the spread of blood-borne viruses among IDUs. Illicit drug injection has now been reported in 118 different countries, and is becoming an increasingly more important ecologic niche for the transmission other diseases, such as tuberculosis, that have significant interactions with HIV-related immunosuppression. Public health officials need to plan for the continued international diffusion of injecting drug use and the potential transmission of infectious agents among IDUs, their sexual partners, and their community contacts. For many emerging and re-emerging infectious diseases, protecting the health of the community as a whole will depend on protecting the health of IDUs. Des Jarlais, D.C., Stimson, G.V., Hagan, H., Perlman, D., Choopanya, K., Bastos, F. I., and Friedman, S.R. Emerging Infectious Diseases and the Injection of Illicit Psychoactive Drugs. Current Issues in Public Health, 2, pp. 130-137, 1996.

Risk Behaviors of Young Adults Residing in High Risk Neighborhoods

Researchers in New York City investigated the extent to which young adults who reside in neighborhoods with large numbers of drug injectors are infected with agents transmitted primarily by drug injection or by sexual contact, and to estimate the extent to which such young adults engage in high risk behaviors. A multistage probability household sample survey was conducted with 111 young adults ages 18 to 21 years old, in Brooklyn, from 1994 to 1995. Sexual risk behaviors are prevalent among this population (89% said they had sex in the past year, 45% with 2 or more partners; only 19% said they always used condoms). One respondent indicated a history of crack use and injection drug use, 3% reported ever using heroin, 9% reported ever using cocaine, and 48% reported use of marijuana in the past year. None of 103 subjects tested positive for HIV, HTLV-II, or syphilis, but 2% were positive for HTLV-I, 3% for HCV, 3% for HBV, 12% for chlamydia, and 50% for HSV-2. These findings indicate that heroin and cocaine use, injection drug use, and parenterally-transmitted infections are less prevalent in this population compared to sexual risk behaviors and sexually transmitted infections. STD screening and outreach strategies are needed to prevent STD sequelae, including potential increased susceptibility to HIV infection, and to prevent transmission of infections to sexual partners. Friedman, S.R., Curtis, R., Jose, B., Neaigus, A., et al. Parenterally-and Sexually-Transmitted Diseases in a High Risk Neighborhood. Sexually Transmitted Diseases, 24, pp. 322-326, July 1997.

Multisite Study Identifies Predictors of HIV Serostatus in Out-of-Treatment Male Drug Users

The risk groups of men who have sex with men (MSMs) and injection drug users (IDUs) together account for 90% of all male AIDS cases. The extent to which each risk behavior contributes to seroprevalence among IDUs has not been determined and is critical for intervention development. Analysis of data on sexual orientation, injection drug use, and HIV serostatus was undertaken in a multisite study of 3002 male drug injectors and crack smokers recruited for HIV prevention projects. Overall HIV seroprevalence was 8.4%; 57.1% for gay men, 25.4% for bisexual men, and 7.4% for heterosexuals (p<.001). Logistic regression analyses indicated being gay and coming from an area where seroprevalence is high among IDUs were the best predictors of serostatus. Ever having injected was significant only in interaction with moderate or high IDU seroprevalence areas. Among this multisite sample of drug users, being a gay drug user is the strongest predictor of serostatus. Drug injection is significant only in areas of moderate or high seroprevalence among injectors. This indicates the importance of targeted outreach and intervention efforts. Deren, S., Estrada, A., Stark, M., et al. A Multisite Study of Sexual Orientation and Injection Drug Use as Predictors of HIV Serostatus in Out-of-Treatment Male Drug Users. Journal of AIDS and Human Retrovirology, 15(4), pp. 289-295, 1997.

The Number and Activities of Syringe Exchange Programs Continue to Expand in the U.S.

In 1996, researchers surveyed Syringe Exchange Programs (SEPs) in the U.S. regarding their activities during 1995 and 1996. They compared the survey findings with findings from earlier surveys in 1994 and early 1995. Eighty-seven (86%) of the 101 SEPs in the North American Syringe Exchange Network (NASEN) in 1996 participated in the survey. Findings indicate that there has been an expansion in the number of SEPs and in the scope of activities since 1994. From 1994 to 1996, there were increases in the number of SEPs participating in the surveys and in the numbers of cities and states with SEPs. The number of syringes exchanged increased by 75% (from 8 million to 14 million) from 1994 to 1996 overall. The 10 most active SEPs exchanged >500,000 syringes each and approximately 9.4 million (69%) of all syringes exchanged. The SEP in San Francisco reported exchanging the largest number of syringes in 1996 (1,461,096). Fifty SEPs reported exchanging 55,000 syringes each, and of these, 23 exchanged a mean of 2815 syringes. All SEPs provided IDUs with information about safer injection techniques and/or use of bleach to disinfect injection equipment. Other services included referral of clients to substance abuse treatment programs (97% of the programs), instruction in the use of condoms and dental dams to prevent sexual transmission of HIV and other sexually transmitted diseases (97%), and STD-prevention education (81%). Health services offered on-site included HIV counseling and testing (40%), primary health care (17%), TB skin testing (26%), and STD screening (20%). Paone, D., Des Jarlais, D. Clark, J., et al. Update: Syringe-Exchange Programs --United States, 1996. Morbidity and Mortality Weekly Report, 46(24), pp. 565-568, 1997.

Evaluation of Needle and Syringe Combinations

HIV transmission among IDUs is commonly attributed to the practice of sharing contaminated needles and syringes. The minimal infectious dose of HIV is unknown, but the volume of inoculum and quantity of virus in an exposure are believed to influence the risk of transmission. Both factors may be affected by the type of syringe used by an IDU. For example, a change was observed in syringes used by IDUs in Texas during the HIV epidemic. Syringes in current use have permanently attached needles and retain visibly less fluid and blood than syringes with detachable needles used previously. Earlier research has quantified the amount of blood in needle and syringe sharing simulations, but the type of needle and detachable or integral cannula (permanently attached) were not specified, and only one simulation incorporated the common practice among IDUs of rinsing with water between uses. Therefore, researchers undertook a series of experiments to measure differences in fluid and blood retained in four needle and syringe combinations. They found that, with the plunger fully depressed, syringes with detachable needles retained over 40 times as much fluid as integral cannula syringes. In simulations using whole blood and two rinses, syringes with detachable needles retained a minimum of 300 times as much blood as integral cannula syringes. The authors conclude that, if the volume of inoculum and the quantity of virus in an exposure affect the probability of infection, then integral cannula syringes are a less efficient means of transmission and thus a safer instrument for drug injection. Needle exchanges should be encouraged to distribute integral cannula syringes only and IDUs using syringes with detachable needles should be warned of the higher risks. Zule, W., Ticknor-Stellato, K., Desmond, D. Et al. Evaluation of Needle and Syringe Combinations. Journal of AIDS and Human Retrovirology, 14, pp. 294-297, 1997 (letter).

Risk for HIV in IDUs Who Use Crack Cocaine and the Role of Nonbehavioral Factors

Researchers analyzed self-reported data and blood tests for HIV antibodies from a study of 4705 out-of-treatment IDUs recruited for interviews in Newark and Jersey City, New Jersey, who did or did not also use crack cocaine. The HIV seroprevalence rate in this sample was 40.5% overall. IDUs who used crack cocaine were found to have a significantly lower HIV infection rate (30.8% HIV+) compared to IDUs who did not use crack (45.0% HIV+). They were significantly more likely to be younger in age, female, Black, and frequent users of alcohol and marijuana. IDUs who used crack were also significantly different from IDUs who did not use crack in terms of: having had more multiple sex partners, having traded sex for drugs, lacking permanent housing, having a shorter history of drug injection, being less likely to inject on a daily basis, having a history of syphilis and gonorrhea, and having a sex partner who injects drugs. Possible geographic asymmetries in the distribution of HIV were examined to determine whether local neighborhood levels of HIV seroprevalence could have mediated the relationship, but the results were nonsignificant. Although the crack-using IDUs engaged in sexual and needle use risk behaviors at higher rates than IDUs who did not use crack, they were much younger, had shorter histories of drug injection, and injected drugs less frequently. In addition, the structure of social networks among the IDUs who did or did not use crack may have influenced the distribution of contagion in subgroups of IDUs who use crack. The authors cite four factors (initial rates of infection in the subgroup, rates of risk behaviors among subgroup members, likelihood of transmission from a given contact, and rate of mixing between subgroups) in describing how, if subgroups have insularity from one another --that is, if inter-group mixing patterns are relatively infrequent--there will be fewer opportunities for HIV to be introduced into the network. They caution, however, that the IDUs who used crack in this study also engaged in very high risk behaviors. Therefore, the chances are poor that the disparities in HIV infection rates between risk networks will be maintained over time. Iguchi, M. and Bux, D. Reduced Probability of HIV Infection among Crack Cocaine-Using Injection Drug Users. American Journal of Public Health, 87(6), pp. 1008-1012, 1997.

HIV Risk Behaviors Vary In Large Part by How IDUs Group into Social Networks

Researchers examined data from a study of the social networks of IDUs in Chicago and Washington, D.C. to determine how individual behavior and social network characteristics change over time. The results indicated few changes in standard network measures, such as density of ties or network size, over time. However, specific network change measures, that is, indicators of movement of network members into and out of networks (turnover-in, turnover-out) were significantly associated with more risky injection behaviors over a 3-month period. Ethnographic work showed that members of networks with few resources had to move around much more in order to secure drug supplies, syringes, and places to inject. Thus, it is not surprising that they were also forced to take substantial risks, such as sharing needles and other paraphernalia. The researchers conclude that the significant relationship between movement of members into a network and a higher likelihood of risky injection drug use over time is indicative of a lack of a stable resource base among IDU networks. Hoffman, J.P., Su, S.S., and Pach, A. Changes in Network Characteristics and HIV Risk Behavior Among Injection Drug Users. Alcohol and Drug Dependence, 46, pp. 41-51, 1997.

Runaway and Homeless Youth at Risk for HIV from Drug Use and Unsafe Sex

A study was conducted with data from 775 runaway and homeless youth under age 19 who were recruited from street settings and youth agencies in three U.S. cities. Nearly all respondents (98%) reported having engaged in sexual intercourse, and 49% had first intercourse by age 13. Fewer than half reported consistent condom use for vaginal intercourse in the last 3 months. Nearly a quarter of the males (23%) and 14% of the females reported having exchanged sex for money. Most (97%) had used alcohol or drugs, and 21% had injected drugs. Overall, 75% of the youth reported having had sex while under the influence of alcohol or drugs. The findings show that runaway and homeless youth are at very high risk for HIV from both use of drugs and unsafe sexual activity. Kral, A.H., Molnar, B.E., Booth, R.E., and Watters, J.K. Prevalence of Sexual Risk Behavior and Substance Use Among Runaway and Homeless Adolescents in San Francisco, Denver, and New York City. International Journal of STDs and AIDS, 8, pp. 109-117, 1997.

Innovative Risk Prevention Efforts are Needed for Substance Abusers Who Engage in High Risk Sex

In this critical review of the literature, researchers focus on subgroups of gay and bisexual men who, in spite of near-universal knowledge about HIV infection and sexual safety and widespread intentions to be safe, continue to use drugs, engage in unprotected sex, and experience high rates of HIV seroconversion. Explanatory models that link risk taking and prevention to rational processes such as those involved in knowledge processing, social norms, behavioral intentions, or perceived vulnerability to infection cannot fully account for this continued risk behavior. Innovative conceptions of risk prevention are needed that emphasize nonrational, affective processes in risk taking and decision making. The authors examine psychosocial models of HIV risk behavior, outline a cognitive escape model with particular emphasis on substance abuse as a behavioral risk factor, and discuss implications of an escape model for behavioral interventions aimed at gay and bisexual men who combine substance use with risky sexual behaviors. They argue that, for many people, sexual risk does not stem from a lack of community norms or personal standards, but from a desire to escape cognitive awareness of very rigorous norms and standards. They propose that both substance use and the approach of high-stimulation or other sexual settings facilitate this cognitive disengagement, wherein people enact automatic sexual scripts and/or become more responsive to external pressures toward risk. Ostrow D. And McKirnan, D. Prevention of Substance-Related High-Risk Sexual Behavior Among Gay Men: Critical Review of the Literature and Proposed Harm Reduction Approach. Journal of the Gay and Lesbian Medical Association, 1(2), pp. 97-110, 1997.

HIV Seropositivity is Associated with Travel to AIDS Epicenters by IDUs

Injection drug users continue to be at risk for HIV despite having high levels of knowledge about the risk factors for HIV transmission. Yet, the chances of becoming HIV seropositive vary substantially among not-in-treatment IDUs. In this study, researchers examined the factors which may facilitate the introduction of HIV into networks of IDUs in low seroprevalence cities. Specifically, they analyzed data from a large (n=9,492), multisite sample of IDUs recruited in 11 low seroprevalence cities between June 1988 and June 1991 as part of NIDA's National AIDS Demonstration Research (NADR) project. Univariate and multivariate associations between drug injection, sexual behaviors, and travel to an AIDS epicenter suggest that, next to male-to-male sexual contact, having sex at least twice in an AIDS epicenter was the strongest predictor of HIV infection. Racial/ethnic characteristics, daily drug injection, and injecting drugs in an AIDS epicenter were also associated with an increased likelihood of being HIV seropositive. The authors discuss the role of travel to and from AIDS epicenters in facilitating the spread of HIV into areas of low HIV seroprevalence. Specifically, when traveling to a high seroprevalence area, IDUs residing in a low seroprevalence area can become infected with HIV as a result of multi-person use of syringes and other injection equipment as well as high risk sexual behaviors. When returning home, these same persons may introduce the virus into a local network of drug injectors who, in spite of their injection behaviors, have remained free of HIV because of their relative isolation in a low seroprevalence area. The findings suggest that an extremely important consideration in preventing the spread of HIV/AIDS is the continuation of prevention efforts in areas where HIV infection among injectors are low. Williams, M., Zhao, Z., Bowen, A., et al. Introduction of HIV into Drug Injector Networks Outside AIDS Epicenters. International Journal of STDs and AIDS, In press.

Sociometric Risk Networks Are Pathways for HIV among IDU Peer Groups

A cross-sectional serosurvey was conducted of 767 street-recruited injection drug users to measure larger scale (i.e., "sociometric") risk networks. Linkages were analyzed using graph-theoretical algebraic techniques to detect 92 separate connected components (i.e., drug injectors who are linked to each other directly or through others) and a 105-member 2-core within a large connected component of 230 members. IDUs in the 2-core of the large component were found to be more likely to be infected with HIV. Seronegative 2-core members engage in a wide range of high risk behaviors, including engaging in risk behaviors with infected drug injectors. The findings suggest that sociometric risk networks seem to be pathways through which HIV travels among drug injecting peer groups. The cores of large components can be centers of high risk behaviors and can become a pocket of HIV infection. Preventing HIV from reaching the cores of large components may thus be crucial in preventing widespread HIV epidemics. Network-based prevention programming may help reduce HIV transmission in high prevalence localities and prevent new epidemic breakouts. Friedman, S. R., Neaigus, A., Jose, B., et al. Sociometric Risk Networks and HIV Risk. American Journal of Public Health, August 1997.

Drug Treatment Experiences of Rural and Urban Drug Users

A study was conducted to investigate the treatment seeking behaviors of drug users in urban and rural populations. Data were drawn from the Miami and Immokalee sites of NIDA's Cooperative Agreement for AIDS Outreach/Intervention Research Program. As expected, drug users in Miami were more likely to have been in drug treatment compared to their rural counterparts (2.57 times more likely), likely because of rural/urban differences in the availability, accessibility, and acceptability of drug treatment and health care services. Metsch, L.R. and McCoy, C.B. Drug Treatment Experiences: Rural and Urban Comparisons. Substance Use and Misuse, In press.

Predictors of Behaviors and Beliefs of Female Drug Users in Two Cities

This study was conducted to examine predictors of behaviors and beliefs about the use of condoms among women who use drugs and who report having recent vaginal sex with main and/or paying partners. A total of 338 drug-using women were recruited for the study, all of whom reported vaginal sex during the past 30 days. Forty percent of the women resided in East Harlem, N.Y., a high HIV seroprevalence area, and 60% of the women resided in Long Beach, California, a low HIV seroprevalence area. Recruitment site was identified as a significant predictor for a number of variables for both main and paying partners: Women recruited in East Harlem were more likely than those recruited in Long Beach to believe that use of condoms for sex with a main partner would harm the relationship, for example. They were also more likely to have used condoms with a main partner in the past 30 days, and to believe that condoms provided protection from disease. Race/ethnicity was a significant predictor for main sex partners, with African American women significantly more likely to have positive cognitions about use of condoms and to report greater self-efficacy for, and greater intention of, using condoms with main partners. The researchers discuss the implications of their findings in terms of intervention development to prevent HIV and other diseases. Specifically, because factors which predict condom beliefs, intention to use, and behaviors are different for main and paying partners, interventions which are designed to increase condom use should recognize that cognitive factors associated with condom use may vary by partner type, race/ethnicity, and recruitment site, particularly when contextual variables, such as local seroprevalence levels, vary. Wood, M. Tortu, S., Rhodes, F., and Deren, S. Differences in Condom Behaviors and Beliefs among Female Drug Users Recruited from Two Cities. Women and Health, In press.

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