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Director's Report to the National Advisory Council on Drug Abuse
May, 2001

Research Findings

Research on AIDS and Other Medical Consequences of Drug Abuse

Regional Cerebral Blood Flow Abnormalities in Early Stages of HIV-Cognitive Motor Complex

Nineteen patients (aged 34-63 yrs) with early HIV-cognitive motor complex and 15 normal controls (aged 19-63 yrs) were evaluated for possible regional cerebral blood flow (rCBF) abnormalities on perfusion magnetic resonance imaging (MRI). Compared with controls, those with HIV had significantly decreased rCBF bilaterally in the inferior lateral frontal cortices and in the interior medial parietal brain region. In contrast, rCBF was increased bilaterally in the posterior inferior parietal white matter. Furthermore, rCBF abnormalities correlated significantly with clinical disease severity as measured by CD4 count, plasma viral load, Karnofsky score, and HIV dementia scale. Chang, L., Ernst, T., Leonido-Yee, M., and Speck, O. Perfusion MRI Detects rCBF Abnormalities in Early Stages of HIV-Cognitive Motor Complex. Neurology, 54(2), pp. 389-396, 2000.

Gender Differences in Behavioral and Psychosocial Predictors of HIV Testing and Return for Test Results in a High-Risk Population

Investigators at UCLA assessed gender differences in psychosocial and behavioral predictors of HIV testing and returning for results in a high-risk sample of 1,049 predominantly minority, impoverished, homeless and/or drug-abusing women (n=621) and men (n=428). Predictors included latent variables representing injection drug use, self-esteem, social support, AIDS knowledge, poor access to health services, perceived risk for AIDS, sexual risk behavior, and the mediators of positive and negative coping styles. Significant predictors of test and return for women included injection drug use, greater social support, more AIDS knowledge, a higher perceived risk for AIDS, and a positive coping style. Significant predictors for the men included injection drug use, greater AIDS knowledge, a higher perceived risk for AIDS, and a positive coping style. The significant predictors of HIV testing and return were generally similar for men and women, except that greater social support was not significant for the men. However, the men evaluated their risk of AIDS significantly lower than the women, although they reported more sexual risk behaviors and equally risky injection drug use behaviors. Results suggest that interventions designed to increase AIDS knowledge, raise the perceptions of risk and promote a positive coping style would be effective in encouraging more HIV testing for both men and women, but raising perceptions of what constitutes personal risk behaviors may need special emphasis when delivering prevention programs to men. Stein, J.A. and Nyamathi, A. Gender Differences in Behavioral and Psychosocial Predictors of HIV Testing and Return for Test Results in a High-Risk Population, AIDS Care, 12(3), pp. 343-366, 2000.

Correlates of HIV Risk-Taking Behaviors Among African American College Students: The Effect of HIV Knowledge, Motivation, and Behavioral Skills

Investigators from UCLA collaborated in a study identifying theoretically based predictors of condom use in a sample of 253 sexually active African-American college students recruited from two historically African-American colleges. The Information-Motivation-Behavioral (IMB) skills model of AIDS-preventive behavior was used to delineate the roles of HIV/AIDS knowledge, experiences with and attitudes toward condom use, peer influence, perceived vulnerability, monogamy, and behavioral skills. A predictive structural equation model revealed significant predictors of more condom use including: male gender, more sexual HIV knowledge, positive experiences and attitudes about condom use, nonmonogamy, and greater behavioral skills. Results imply that attention to behavioral skills for negotiating safer sex and training in the proper use of condoms are key elements in reducing high risk behaviors. Increasing the specific knowledge level of college students regarding the subtleties of sexual transmission of HIV is important and should be addressed. Heightening students' awareness of the limited protection of serial monogamy, and the need to address gender-specific training regarding required behavioral change to reduce transmission of HIV should be an additional goal of college health professionals. Bazargan, M., Kelly, E.M., Stein, J.A., Hasaini, B.A., and Bazargan, S.H. Correlates of HIV Risk-Taking Behaviors Among African American College Students: The Effect of HIV Knowledge, Motivation, and Behavioral Skills, Journal of the National Medical Association, 92, pp. 391-404, 2000.

Efficacy of a Preventive Intervention for Youths Living with HIV

HIV transmission behaviors and health practices were examined among youth living with HIV (YLH) over 15 months after youth received a preventive intervention. YLH aged 13-24 years were assigned by small cohort to (1) a two-module intervention totaling 23 sessions ("Stay Healthy" and "Act Safe"), or (2) a Control condition. 73% in the Intervention Condition attended at least one session. Following the Stay Healthy module, females who attended the Intervention Condition increased their number of positive lifestyle changes and increased active coping styles more often than those in the Control Condition. Following the Act Safe Module, YLH who attended the Intervention Condition reported 82% fewer unprotected sexual acts, 45% fewer sexual partners, 50% fewer HIV-negative sexual partners, and 31% less substance use on a weighted index than those in the Control Condition. It was concluded that prevention programs can effectively reduce risk acts among YLH. Alternative formats need to be identified for delivering the intervention. Efficacy of a Preventive Intervention for Youths Living with HIV. Rotheram-Borus, M.J., Lee, M.B., Murphy, D.A., Futterman, D., Duan, N., Birnbaum, J.M., Lightfoot, M., and the Teens Linked to Care Consortium. American Public Health Association, 91(3), pp. 400-405, 2001.

Variation in Health and Risk Behavior Among Youth Living with HIV

Lifetime and current health practices and risk behaviors were examined among 350 youth living with HIV (YLH) aged 14-23 years from four AIDS epicenters (72.6% male; 26.2% African American, 36.9% Latino). YLH were relatively healthy (M CD4 cells = 499), had used substantial health care and were satisfied with the care. YLH's sexual and substance-use histories indicated substantial HIV related risk acts: the median number of lifetime partners was 25 with only 8% using condoms consistently; 14.9% had injected drugs, and 61.2% had used hard drugs. Compared with females, males had more lifetime and recent sexual partners and had used more drugs. Youth who were recently sexually active (81.3%) had multiple partners. Most of the sexually active YLH used condoms consistently (81.6%). YLH who were symptomatic or had an AIDS diagnosis were likely to have recently had more seropositive sexual partners than the asymptomatic youth. Youth disclosed their serostatus to about half of their sexual partners (53.9%). YLH with AIDS used fewer hard drugs than those without an AIDS diagnosis. Health and risk behaviors of the YLH varied significantly based on their disease stage, gender, and ethnicity, suggesting the need for tailoring interventions for subgroups of YLH. Rotheram-Borus, M.J., Lee, M., Zhou, S., O'Hara, P., Birnbaum, J.M., Swendeman, D., Wright, W., Pennbridge, J., and Wight, R.G. Variation in Health and Risk Behavior Among Youth Living with HIV. AIDS Education and Prevention, 13(1), pp. 42-54, 2001.

Drug-Using Women's Communication with Social Supporters About HIV/AIDS Issues

Communication about health issues such as HIV/AIDS is essential for people, especially women, to obtain the social support they need either to prevent illness or manage it. This article compares the kinds of HIV-related issues that HIV positive and HIV negative substance-abusing women (N=211) in New York City talk about with various types of supporters. Despite the stigma associated with AIDS and their unconventional lifestyles, both groups of women talked to a broad spectrum of supporters about a variety of HIV-related issues, though this was more the case for HIV positive women. Although the main topic that both groups discussed with their supporters was their HIV status, the women also talked about risk reduction, their supporters' HIV status, HIV testing, how to live with AIDS, information about HIV/AIDS, and the emotional impact of AIDS (e.g., fear of infection, reactions to learning test results, and the impact of knowing others who have died from the disease). Falkin, G.P., and Strauss, S.M. Journal of Drug Issues, 30(4), pp. 801-822, 2000.

An Alternative Program for Methadone Maintenance Dropouts: Description and Preliminary Data

Time in drug treatment has been shown to be one of the best predictors of post-treatment success. Since as many as half of the enrollees leave methadone treatment during the first year, the project described in this article was designed to test the effectiveness of an alternative program for individuals who have recently dropped out of methadone maintenance treatment. The goals of this "Alternative Program" are to help participants re-connect with formal drug treatment and other community or medical programs, reduce their HIV risk behavior, decrease or eliminate drug use, join self-help groups, and obtain entitlements. Program components include: contacts by local outreach workers, cognitive-behavioral relapse-prevention group counseling, and individual counseling for needs assessment and referral. The authors describe the basis for development of the intervention, summarize the methodology being used, and provide preliminary data on participation in the Alternative Program. Goldstein, M.F., Deren, S., Beardsley, M., and Richman, B.L . Mt. Sinai J Med., 68 (1), pp. 33-40, 2001.

Hepatitis C Disease Among Injection Drug Users: Knowledge, Perceived Risk and Willingness to Receive Treatment

The authors surveyed 306 former injection drug users receiving methadone maintenance treatment in 1997-1998 in Providence, RI regarding, (1) knowledge of hepatitis C transmission: (2) the concordance of self-knowledge of hepatitis C virus (HCV) status versus actual status; (3) perceived risk of cirrhosis: and (4) willingness to receive therapy for hepatitis C. The seroprevalence of HCV was 87%. While 77%, of participants knew that HCV could be sexually transmitted, 30%, did not know that condoms are protective against transmission. Thirty of 45 persons who reported they were HCV seronegative were actually seropositive; 51 of 62 persons (82%) who reported they had never been HCV tested or did not know their HCV status were serologically HCV-positive. Over half of respondents (53%) would 'definitely' or 'probably' use interferon therapy for viral hepatitis when informed of the risks and benefits of treatment. The authors cite significant gaps in knowledge about HCV among IDUs. Serologic confirmation of HCV status is important among drug users, as self-report of HCV infection is often unreliable. This population, with its high prevalence of HCV, may be interested in treatments that include interferon. Stein, M.D., Maksad, J., and Clarke, J. Drug and Alcohol Dependence, 61(3), pp. 211-215, Feb 1, 2001.

Prevalence and Duration of Hepatitis C Among Injection Drug Users in San Francisco, California

Drs. Lorvick, Kral, Seal, Gee, and Edlin conducted a study to determine the prevalence of anti-HCV among IDUs in San Francisco in 1987, and to estimate how long prevalent cases have been infected. The subjects were originally recruited for an HIV prevalence study among street-recruited IDUs (the Urban Health Study). They found that injection drug users (IDUs) are the single population most affected by the hepatitis C virus (HCV). Progression to cirrhosis and/or hepatocellular carcinoma occurs in 20-30% of chronically HCV infected persons 20-30 years after infection. Stored serum samples collected from 372 IDUs in 1987 were tested for HCV antibody. They found that 353/372 (95%) samples were positive for HCV antibody. Prevalence was strongly associated with the duration of injection drug use. Of those injecting ≤ 2 years, 75.9% were infected (95% CI .56, .90). Of those injecting >10 years, 98.8% were infected (95% CI .96, .99). There were no significant differences in prevalence by race, gender or frequency of injection. The median year of commencing injection drug use was 1972 (interquartile range 1967, 1979). Because most HCV infections occur within two years of initiating injection drug use, the majority were likely infected by the mid-1970's. The vast majority of IDUs in this sample were infected with HCV in 1987. Many are entering their third decade of infection and may be progressing to liver disease at this time. Lorvick, J., Kral, A.H., Seal, K., Gee, L., and Edlin, B.R. Prevalence and Duration of Hepatitis C among Injection Drug Users in San Francisco, California. American Journal of Public Health, 91, pp. 46-47, 2000.

Neurobehavioral Outcomes of Cocaine-Exposed Infants

Singer et al. investigated the neurobehavioral outcomes associated with prenatal cocaine exposure. The sample included 319 infants (158 cocaine-exposed and 161 non-exposed) with a mean-corrected age of 43 weeks post-conception. Cocaine exposure was determined by a positive response to one of the following: infant meconium, urine or maternal urine positive for cocaine; maternal report to hospital staff, or; maternal self-report during clinical interview. Cocaine positive infants were further divided into heavy and light categories. When only cocaine-exposed and non-exposed infants were compared, the exposed infants exhibited significantly more abnormalities in movement and tone than the non-exposed, with a trend for greater jitteriness in the exposed infants. When the exposed group of infants was divided into those with heavy and light exposure, heavily exposed infants had significantly more attentional abnormalities and jitteriness than the lightly exposed and non-exposed groups. Heavily exposed infants were also more likely to be identified with any abnormality than non-exposed infants, had more movement and tone abnormalities and sensory asymmetries than non-exposed infants and were four times as likely to be jittery and nearly twice as likely to demonstrate any abnormality than lightly- and non-exposed infants. Singer, L.T., Arendt, R., Minnes, S., Farkas, K., and Salvator, A. Neurobehavioral Outcomes of Cocaine-Exposed Infants. Neurotoxicology and Teratology, 22(5), pp. 653-666, 2000.

Effects of Prenatal Cocaine/Crack and Other Drug Exposure on Electroencephalographic Sleep Studies at Birth and One Year

Electroencephalographic (EEG) sleep patterns can be used to assess cerebral maturation and neurophysiologic organization of the developing central nervous system. Scher and colleagues conducted sleep studies of infants born to 37 women who used crack or one or more lines per day of powder cocaine during the first trimester of pregnancy. A control group of 34 infants had mothers who used neither cocaine nor crack during pregnancy. Maternal substance use was determined by self-report during interviews. Infants were eligible if they had gestations from 38-42 weeks, no general anesthesia, and 5 minute Apgar scores of >5. A total of 71 infants received 2 hour EEG sleep recordings at 24-36 hours after birth, with 57 infants returning for EEG sleep recordings at 1 year postpartum. The results indicated that after controlling for the significant covariates, prenatal cocaine exposure was associated with less well-developed spectral correlations between homologous brain regions at birth, and with lower spectral EEG power values at 1 year of age. Implications of these findings are that the neurotoxic effects of prenatal cocaine/crack use can be detected with quantitative EEG measures. Further research is needed to determine whether the abnormal brain patterns detected are associated with developmental abnormalities. Scher, M.S., Richardson, G.A., and Day, N.L. Effects of Prenatal Cocaine/Crack and Other Drug Exposure on Electroencephalographic Sleep Studies at Birth and One Year, Pediatrics, 105(1 Pt 1), pp. 39-48, 2000.

Drug Abuse Among Athletes

Pope and his colleagues from McLean Hospital/Harvard School of Medicine have observed a substantial drug abuse problem among athletes in the U.S. In a survey of 511 clients entering five gymnasiums (Kanayama et al. 2000), they found that among men, 18% report use of androstenedione and/or other adrenal hormones, 25% report ephedrine use, and 5% report anabolic steroid use within the past three years; while among women, these rates were 3%, 13%, and 0%, respectively. Extrapolating from these figures to the U.S. as a whole, the authors estimate that possibly 1.5 million American gymnasium clients have used adrenal hormones and 2.8 million have used ephedrine within the last three years. They further report that nalbuphine may represent a new drug of abuse among athletes, especially those using anabolic steroids. (Nalbuphine, a nonscheduled opioid agonist/antagonist analgesic, is used for the treatment of pain.). Authors (Wines et al., 1999) conducted interviews on 11 subjects who reported nalbuphine use. Eight subjects were clinically dependent on nalbuphine, and seven of these experienced tolerance and withdrawal symptoms. Further, eight subjects who had never injected drugs intravenously before, reported using nalbuphine by this route. Nalbuphine-related morbidity was extensive and included medical complications and psychiatric symptoms (comorbid Axis I disorders). These observations suggest that nalbuphine may represent a new drug of abuse among anabolic steroids abusing athletes. Finally, the investigators (Halpern and Pope, 2001) also report that there is a widespread use of the Internet among well-educated adults and teenagers for obtaining medical information about hallucinogens and how to obtain and use these drugs. Kanayama, G., Gruber, A.J., Pope, H.G., Borowiecki, J.J., and Hudson J.I. Over-the-Counter Drug Use in Gymnasiums: An Underrecognized Abuse Problem? Psychotherapy and Psychosomatics, May/June issue, 2001; Wines, J.D., Gruber, A.J., Pope, H.G., and Lukas, S. Nalbuphine Hydrochloride Dependence in Anabolic Steroid Abusers. Am. J. Addictions, 8, pp. 161-164, 1999; Halpern, J.H. and Pope, H.G. Hallucinogens on the Internet: A Vast New Source of "Underground" Drug Information. American Journal of Psychiatry, 158, pp. 481-483, 2001.

Identifying Prenatal Exposure to Illicit Drugs Using Meconium Testing and Maternal Self-Report

In the four-site Maternal Lifestyle Study (Detroit, Miami, Memphis, Providence) of in utero cocaine and/or opiate exposure, meconium specimens of 8,527 newborns were analyzed by immunoassay (EMIT) with GC/MS (gas chromatography/mass spectrometry) confirmation. Maternal self-report of drug use during pregnancy was determined during a hospital interview. Recruitment occurred between May 1993 and May 1995. Prevalence and observed metabolites showed considerable variation across the four sites, and exposure status was higher in low birth weight infants. Results indicated that accurate identification of exposure is likely to be improved with GC/MS confirmation and when the meconium testing is used in conjunction with a maternal hospital interview (e.g., 254 mothers denied use but their infants had positive meconium confirmation for cocaine/opiates, thus allowing identification of an additional 38% of the cocaine/opiate exposed infants by means of meconium testing). Importantly, had the study relied on maternal report only, these 254 infants would have been eligible for inclusion in the unexposed group. However, at the current stage of this new and useful technology, many questions still remain about the disposition of drugs in meconium, and the investigators caution against the use of quantitative analysis of drugs in meconium to estimate the degree of exposure. Lester, B.M., ElSohly, M., Wright, L.L., Smeriglio, V.L., Verter, J., Bauer, C.R., Shankaran, S., Bada, H.S., Walls, H.C., Huestis, M.A., Finnegan, L.P., and Maza, P.L. Pediatrics, 107, pp. 309-317, 2001.

Prenatal Marijuana Exposure - Emerging Theme of Executive Function Deficiencies

In a review of the scientific literature dealing with neurobehavioral consequences of prenatal exposure to marijuana, Fried and Smith identify a degree of consistency in the limited longer-term data that exist, both from cross-sectional reports and from the two available long-term cohort studies, one involving a low-risk sample (Fried, Carleton University) and the other a high-risk sample (Day, University of Pittsburgh). Aspects of executive function appear to be negatively associated with in utero cannabis beyond the age of 3 years, especially attentional behavior and visual analysis/hypothesis testing. Published data are available for children as old as 12 years of age. In addition, the authors note that in work by the Day research group, on the basis of path analysis, it appeared that poor attentional skills of the child mediated an association between maternal report of child delinquency at age 10 years and prenatal marijuana use. Fried and Smith discuss their literature review findings in the context of the broader research fields of marijuana and prefrontal brain function, and they emphasize the need for further, well-controlled investigations. Fried, P.A. and Smith, A.M. Neurotoxicology and Teratology, 23, pp. 1-11, 2001; Goldschmidt, L., Day, N.L., and Richardson, G.A. Neurotoxicology and Teratology, 22, pp. 325-336, 2000.

Drug Treatment is Beneficial, Even for Drug Users In Treatment Less Than 90 Days

Many studies have found that the longer a drug user remains in treatment, the more positive the outcome. The majority of studies on the effects of time in treatment have followed participants from the time they enter treatment. Participants in this study were IDUs and crack users who were out of treatment at the time of their recruitment. Between the initial and six-month follow-up interviews, some chose to enroll in drug treatment. The more time a person spent in treatment during the follow-up period, the more likely it was that s/he was not using heroin or cocaine at follow-up (OR=.51; 95% C.I., .39-.67; p<.001). Unlike the results of some prior studies, positive effects of time in treatment were found even when time in treatment was less than 90 days. The findings of the present study strongly suggest that treatment is beneficial even for those who remain for less than 90 days. Those who provide treatment services to drug users should attempt to maintain contact with dropouts, and support their return to treatment. Goldstein, M.F., Deren, S., Magura, S., Kayman, D., et al. Cessation of Drug Use. J Psychoactive Drugs, 32(3), pp. 305-310, 2000.

Initial Plasma HIV-1 RNA and Progression to AIDS in Men and Women

Differences in plasma HIV-1 RNA levels (viral load) have been observed in some studies comparing HIV-infected men and women, but conclusive results have been limited by study design or small sample sizes. In this new larger analysis in a prospective cohort study of 202 IDUs who underwent seroconversion, viral load was measured and the association of initial viral load with disease progression was assessed. Of these seroconverters, 156 (77%) were men and 46 (23%) were women. The median viral load after seroconversion was significantly lower in women vs. men (15,103 vs. 50,766 copies per millimeter; P<.001), but CD4+ lymphocyte counts (CD4) did not differ according to sex. The median initial viral load remained approximately 0.5 log lower in women vs. men after adjusting for age, time from estimated seroconversion to first viral load test (P=.001), and CD4 at seroconversion (P=.001). The difference in viral load between men and women persisted for several years after seroconversion. HIV infection progressed to AIDS in 29 men and 15 women; time to AIDS did not significantly differ in men vs. women (P=.18). While viral load had a similar qualitative predictive value for progression to AIDS in men vs. women, the same absolute viral load conferred different risks of AIDS in men vs. women, e.g., an initial viral load of 17,149 copies per milliliter was associated with progression to AIDS in women but not in men, while the median viral load among men who did not progress to AIDS was 40,634 copies. Given that viral load has been the basis for the current guidelines regarding initiation of antiretroviral therapy in HIV-infected patients, these findings have implications that require further study. Analyses to determine if there is a threshold viral load value that predicts progression, and research on the underlying biologic mechanism of the observed viral load differences are needed. Sterling, T.R., Vlahov, D., Astemborski, J., Hoover, D.R., Margolick, J.B., and Quinn, T.C. New England Journal of Medicine, 344, pp. 720-725, 2001.

Trends in HIV in Puerto Rican IDUs in Puerto Rico and New York: 1992-1999

Researchers investigated trends in HIV seroprevalence and needle-sharing behaviors among Puerto Rican injection drug users (IDUs) in Puerto Rico and New York City between 1992 and 1999. Data from two studies of IDUs conducted from 1992-1995 and 1998-1999 in Bayamon, Puerto Rico, and East Harlem, New York, were examined to assess trends over this period. Separate analyses were conducted for IDUs who were current crack smokers. Significant decreasing trends in seroprevalence were found among IDUs in the New York and Puerto Rico samples (p <.001). Significant decreasing trends in receptive and distributive needle sharing were found in the New York sample, and a significant decline in receptive sharing was found in the Puerto Rico sample. Overall, higher levels of needle-sharing behaviors were reported in Puerto Rico compared with New York. Decreasing trends in needle sharing and seroprevalence in both communities are an encouraging finding. Ongoing epidemiologic studies to monitor the epidemic and continued prevention efforts to help maintain or further these declines are needed, particularly to address the higher rates of needle sharing in Puerto Rico. Deren, S., Robles, R., Andia, J., Colon, H., et al. Trends in HIV Seroprevalence and Needle Sharing Among Puerto Rican Drug Injectors in Puerto Rico and New York: 1992-1999. J AIDS, 26(2), pp. 164-169, 2001.

Study Examines the Social Network Context of HIV Risk Behavior Among IDUs

Researchers characterized social network context of HIV risk behaviors among injection drug users who participated in the Baltimore Needle Exchange Program (NEP) from 1995-1997. They conducted interviews with 1,184 IDUs in which they asked each respondent to give the initials of up to five of their closest friends and whether, with each friend, they had injected drugs, shared syringes, had sex, or drank alcohol. Of the 203 (17.1%) IDUs who reported using a syringe after someone else, 78.3% reported sharing with close friends, and the adjusted odds ratio of any sharing and sharing with close friends was 30.9. IDUs were more likely to report sharing with strong-tie close friends and less likely to report sharing with other close friends if those friends were weak ties and new to their network. Friendship ties were not stable, with fewer than 30% of the friends being repeat nominations. The findings from this study show that many IDUs engage in selective risk taking that may minimize their disease risk exposure in the short term. In other words, risk taking is not random but rather, is more likely to occur with strong-tie close friends than with weak-tie ones. However, the turnover in relationships among IDUs represents a risk potential for infection transmission that could be ongoing within this population. As a result, as part of a comprehensive HIV prevention program, NEPs need to do more than provide access to sterile syringes and drug treatment referral. Valente, T.W. and Vlahov, D. Selective Risk Taking Among Needle Exchange Participants: Implications for Supplemental Interventions. Am J Public Health, 91, pp. 406-411, 2001.

Research Enumerates a Variety of Sexual Risk Reduction Strategies by Active Drug Users

Recent studies have shown that active drug users continue to report inconsistent use of condoms to reduce their HIV risks from unprotected sexual activity. Interventions with IDUs have also been more effective in changing drug injection behaviors than in changing risky sexual practices; even after the intervention, drug users have shown little evidence of sustained condom use. In this study, researchers sought to understand whether drug users employ alternative strategies (i.e., other than condom use) that they believe will reduce or eliminate their personal risk of acquiring HIV through sexual contact. An ethnographer conducted unstructured, face-to-face interviews with 92 not-in-treatment IDUs and/or crack users (including 68% male; 52% in their 40s and 33% in their 30s; 75% African American, 20%Hispanic, 2% White; 33% homeless; and 15.4% HIV positive). Researchers identified three categories of alternative sexual risk reduction strategies from the drug users participating in the qualitative interviews: before sex, partner screening was used (visual inspection, observation, and reliance on an outside authority, including being shown an HIV negative certificate); during sex, personal hygiene was considered very important, as were selecting or refusing to participate in specific sex acts; and after sex, respondents reported douching (often with vinegar and water or bleach and water) or washing with alcohol, peroxide, or lemon juice to reduce their risks for HIV. This study found that active drug users are aware of their personal risks for HIV from sexual activity, but instead of using condoms consistently, they often report using ineffective strategies to reduce their risks. The finding of a pervasive folk model equating cleanliness and health underscores the challenge to public health researchers and HIV prevention programs to develop more effective, science-based risk reduction and health promotion messages to counteract prevailing myths and misconceptions about HIV/AIDS within specific risk groups. Metsch, L.R., McCoy, C.B., Wingerd, J., and Miles, C.C. Alternative Strategies for Sexual Risk Reduction Used by Active Drug Users. AIDS and Behavior, 5(1), pp. 75-84, 2001.

Relationships of Laws Prohibiting OTC Syringe Sales With Prevalence of IDUs and HIV

A secondary ecologic analysis was conducted of data presented by Holmberg (1996) to assess relationships of laws prohibiting over-the-counter syringe sales with population prevalence of IDUs and HIV prevalence or incidence among 96 U.S. metropolitan areas. In 1992, Holmberg had estimated the population sizes and HIV prevalence and incidence rates of metropolitan subpopulations at particular risk for HIV, including IDUs, and MSMs within each of the 96 largest metropolitan areas of the U.S. Researchers compared metropolitan areas with and without laws that prohibit OTC syringe sales in terms of their population densities of IDUs, HIV prevalence and incidence rates among IDUs, HIV prevalence among MSM, and distance from New York City (because New York has been the epicenter for the epidemic of HIV among IDUs in the U.S.). They found that IDUs accounted for more (0.94%) of the population in the 36 metropolitan areas in states with laws against OTC syringe sales than in the 60 metropolitan areas without these laws (0.82%). Mean HIV prevalence was 13.8% in metropolitan areas with laws against OTC syringe sales and 6.7% in other metropolitan areas. Median HIV prevalence was also greater in cities with OTC laws than in cities without them. In discussing the implications of their findings to public health, the authors conclude that laws prohibiting OTC syringe sales are not associated with lower population proportions of IDUs, but are significantly associated with HIV prevalence and incidence. Friedman, S.R., Perlis, T., and Des Jarlais, D. Laws Prohibiting Over-the-Counter Syringe Sales to IDUs: Relations to Population Density, HIV Prevalence, and HIV Incidence. Am J Public Health, 91(5), 2001.

Study Examines Sex-Specific Behaviors and HIV Among IDUs in Montreal

The objective of this study was to examine sex-specific behaviors associated with HIV infection among injection drug users in Montreal. Researchers recruited a total of 2,741 active drug users (2,209 [80.6%] men) between 1988 and 1998 for interviews regarding sociodemographic characteristics, drug use history and current drug use, drug-related behavior, sexual behavior, and other information. Participants were also tested for HIV antibodies. Sex-specific independent predictors of HIV prevalence were assessed by stepwise logistic regression. The overall prevalence of HIV among study participants was 11.1%; the prevalence was 12.0% among men and 7.5% among women. In multivariate models, a history of sharing syringes with a known seropositive partner (odds ratio [OR] for men 2.44, 95% confidence interval [CI] 1.72-3.46; OR for women 3.03, 95% CI 1.29-7.13) and of sharing syringes in the past 6 months (OR for men 0.61, 95% CI 0.44-0.85; OR for women 0.32, 95% CI 0.14-0.73) were independently associated with HIV infection. Other variables associated with HIV infection were homosexual or bisexual orientation, cocaine rather than heroin as drug of choice, frequency of injection drug use, and obtaining needles at a pharmacy or through needle exchange programs (for men only) and obtaining needles at shooting galleries and being out of treatment (for women only). Findings support the hypothesis that risk factors and processes related not only to sexual behaviors, but also to the social contexts of drug use and service utilization, might differ with regard to HIV prevalence between men and women. These sex-related differences should be taken into account in the development of preventive and clinical interventions. Bruneau, J., Lamothe, F., Soto, J., Lachance, N., et al. Sex-Specific Determinants of HIV Infection Among Injection Drug Users in Montreal. Canadian Medical Assoc Journal, 164(6), pp. 767-73, 2001.

An Event Analysis of Drug-Using Women's Sexual Risk

Researchers used event analysis to describe the most recent sexual events of drug-using women and their male partners, and to identify relationship-specific and event-specific determinants of condom use. Women drug users (n=320) were recruited from the streets of East Harlem. After validation of drug use, they participated in structured interviews and were offered HIV testing and counseling. Data were collected on demographic characteristics, relationship factors (including age of partner, race/ethnicity concordance, and HIV serostatus of partners), and event-specific factors, including sexual repertoire, communication about condom use, and perception of HIV risk. Univariate and multivariate analyses identified 5 major variables associated with event-specific condom use: Closeness to partner, perceived dyadic serostatus, sexual repertoire, communication about condoms, and perceived control of condom use. Behavioral interventions to reduce sexual risk should focus on dyads with long-standing sexual relationships and on the dynamics of the relationship, especially the issues of dyadic serostatus, intimacy, communication, and control. Tortu, S., McMahon, J., Hamid, R., and Neaigus, A. Drug-Using Women's Sexual Risk: An Event Analysis. AIDS and Behavior, 4(4), pp. 329-340, 2000.

Women IDUs Who Have Sex With Women Exhibit Increased HIV-Related Risk Behaviors

Researchers reviewed the published literature on HIV seroprevalence and HIV-related risk behaviors among women IDUs who have sex with women. They report that, since the late 1980s, published studies have converged into a consistent pattern concerning this population. Specifically, compared to other IDUs, women IDUs who have sex with women report higher levels of HIV-related risk behaviors (risky injection practices, unprotected sex), and in many cases exhibit higher levels of HIV seroconversion or seroprevalence. For example, a large study of 9,621 out-of-treatment IDU women found that women IDUs who had sex with both men and women during the prior six months were more likely than the other women to inject cocaine at least daily and score higher on a summary index on needle risk. Data from these and additional studies suggest that a relatively large proportion of women IDUs are women who have sex with women. Information regarding women injectors who have sex with women are widely collected but infrequently reported, indicating the need to apply promising research and analysis strategies to explore the meaning behind this pattern of increased vulnerability to HIV. Young, R.M., Friedman, S.R., Case, P., Asencio, M.W., and Clatts, M. Women Injection Drug Users Who Have Sex With Women Exhibit Increased HIV Infection and Risk Behaviors. J Drug Issues, 30(3), pp. 499-524, 2000.

Drug User Characteristics Related to HIV Testing and Returning for Test Results

As part of the 23-site NIDA cooperative agreement for the prevention of HIV/AIDS, researchers examined demographic and behavioral factors related to taking an HIV test and returning for test results. They recruited out-of-treatment IDUs and crack smokers in East Harlem, New York City (N=1,682) and administered the Risk Behavior Assessment (RBA). Almost 56% (n=934) of the participants agreed to test for HIV; persons reporting no prior HIV testing were more likely to test, as were persons reporting having had drug injecting sex partners in the prior 30 days (p<.05). Drug-related risks, including frequency of injection or crack use in the prior 30 days, were not related to testing vs. not testing. Eighty-one percent of those who tested (n=753) returned for their results. Persons who were HIV positive were less likely to return for their results, as were persons who reported exchanging sex for money or drugs, and persons who considered themselves homeless (p<.05). Those more likely to return for their test results included African Americans, older drug users, persons with a high school or GED diploma, persons reporting unprotected vaginal sex in the past 30 days, current crack smokers, and persons who had been previously incarcerated (p<.05). The findings from this study demonstrate that it is possible to get high-risk individuals to get tested for HIV. However, they also show that younger high-risk drug users were less likely to get tested and to return for test results than older persons, and that high-risk subgroups (e.g., those who exchange sex for money or drugs) may be less likely to return for results. The data suggest that targeted strategies, including community-based outreach HIV risk reduction strategies, should be assessed and if necessary, improved, to enhance their effectiveness in encouraging persons at risk to seek HIV testing and return for their test results, particularly younger drug users and others at high risk for HIV. Ziek, K., Goldstein, M., Beardsley, M, Deren, S., and Tortu, S. Factors Associated with HIV Testing and Returning for Test Results in a Sample of Out-of-Treatment Drug Users. J Drug Issues, 30(3), pp. 675-686, 2000.

Neurotoxicity of HIV Proteins and Drugs

Little is known about the neurologic impairment resulting from mixed drug administration and HIV exposure. Some recent papers have brought new insight into this area. This study describes neurotoxicity of HIV proteins in select neural areas and the potentiation by stimulant drugs. Infection with the human immunodefiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia. Nath, A., Anderson, C., Jones, M., Maragos, W., Booze, R., Mactutus, C., Bell, J., Hauser, K.F., and Mattson, M. Neurotoxicity and Dysfunction of Dopaminergic Systems Associated with AIDS Dementia. J Psychopharm., 14, pp. 222-227, 2000.

Neurotoxicity in the Presence of Opioids

Human immunodeficiency virus (HIV) infection selectively targets the striatum, a region rich in opioid receptor-expressing neural cells, resulting in gliosis and neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration. To determine whether opioids modify the response of neurons to human immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural cell cultures from mouse striatum were initially characterized for mu and/or kappa opioid receptor immunoreactivity. These cultures were continuously treated with morphine, the opioid antagonist naloxone, and/or HIV-1 Tat protein, a non-neurotoxic HIV-1 Tat deletion mutant protein, or immunoneutralized HIV-1 'toxic' Tat protein. Morphine significantly increased Tat-induced neuronal losses at 24h following exposure. The synergistic effects of morphine and Tat were prevented by naloxone, indicating the involvement of opioid receptors. Furthermore, morphine was not toxic when combined with mutant Tat or immunoneutralized Tat. Neuronal losses were accompanied by chromatin condensation and pyknosis. Astrocyte viability was unaffected. These findings demonstrate that acute opioid exposure can exacerbate the neurodegenerative effect of HIV-1 Tat protein in striatal neurons, and infer a means by which opioids may hasten the progression of HIV-associated dementia. Nath, A., Sun, Q., Zhang, J., Martin, K.M., Chen, Y., and Hauser, K.F. Synergistic Neurotoxicity of Opioids and Human Immunodeficiency Virus-1 Tat Protein in Striatal Neurons in Vitro. Neuroscience, 102, pp. 555-563, 2001.

Chemokine Receptor Function

Chemokine receptors are necessary for HIV entry into a cell. Therefore, morphine's modulation of chemotaxis, an action of chemokines may be important in HIV neurotoxicity. The beta-chemokine RANTES has recently been implicated in the neuropathogenesis of the human immunodefiency virus. Based upon previous studies of the effects of morphine on microglial cell production of cytokines and chemotaxis towards the activated complement component C5a, authors tested the hypothesis that this opiate would alter the production of and migration towards RANTES by human microglia. Treatment of microglial cells with morphine was found to suppress chemotaxis. The inhibitory effects of morphine on RANTES production and on chemotaxis were blocked by naloxone and beta-funaltrexamine, indicating that morphine mediated its suppressive effects via activation of microglial mu-opioid receptors. Morphine's inhibitory effect on chemotaxis did not appear to be associated with an alteration in RANTES-induced [Ca2+] mobilization. While the clinical significance of these in-vitro findings is unknown, they suggest that mu-opioid receptor agonists could alter certain neurodegenerative and inflammatory processes within the brain. Hu, S.X., Chao, C.C., Hegg, C.C., Thayer, S., and Peterson, P.K. Morphine Inhibits Human Microglial Cell Production of, and Migration Towards, RANTES. J Psychopharm., 14, pp. 238-243, 2000.

Chemokine Receptors and Lymphoid Cells

In non-neural systems scientists presented evidence about the specific mechanisms whereby mu-type (morphine) compounds stimulate the growth of HIV in human blood cells. Strong evidence for the direct modulation of the immune system by opioids is well documented. Mu-opioids have been shown to alter the release of cytokines important for both host defense and the inflammatory response. Proinflammatory chemokines monocyte chemoattractant protein-1 (MCP-1), RANTES, and IFN-gamma-inducible protein-10 (IP-10) play crucial roles in cell-mediated immune responses, proinflammatory reactions, and viral infections. In this report, authors show that DAMGO, a mu-opioid-selective agonist, augments the expression in human PBMCs of MCP-I, RANTES, and IP-10 at both the mRNA and protein levels. Because of the proposed relationship between opioid abuse and HIV-1 infection, we also examined the impact of DAMGO on chemokine expression in HIV-infected cells. Results show that DAMGO administration induces a significant increase in RANTES and IP-10 expression, while MCP-I protein levels remain unaffected in PBMCs infected with the HIV-1 strain. In contrast, results show a dichotomous effect of DAMGO treatment on IP-10 protein levels expressed by T-and M-tropic HIV-infected PBMCs. The differential modulation of chemokine expression in T- and M-tropic HIV-1-infected PBMCs by opioids supports a detrimental role for opioids during HIV-1 infection. Modulation of chemokine expression may enhance trafficking of potential noninfected target cells to the site of active infection, thus directly contributing to HIV-1 replication and disease progression to AIDS. Wetzel, M.A., Steele, A.D., Eisenstein, T.K., Adler, M.W., Henderson, E.E., and Rogers, T.J. Mu-opioid Induction of Monocyte Chemoattractant Protein-1, RANTES, and IFN-gamma-inducible protein-10 Expression in Human Peripheral Blood Mononuclear Cells. J Immunol., 165, pp. 6519-6524, 2000.

A related paper reports the increased expression of CCR5 receptors in human derived cells used to culture SIV. This would indicate that morphine might enhance growth of these retro-viruses in specific cell types. All HIV-1 strains studied to date use CCR5, CXCR4, or both receptors to enter cells, Simian immunodeficiency virus (SIV) infection of non-human primates has served as a useful model for understanding AIDS pathogenesis in humans. Research on several genetically divergent SIV isolates has revealed that SIV uses CCR5, and not CXCR4, for entry. CEMx174, a human lymphoid cell line, has been routinely used to cultivate and maintain various SIV strains. However, questions have arisen about how CEMx174, which reportedly was unable to express detectable amounts of CCR5 transcripts, efficiently supports the growth of SIV. In searching for an answer, authors resorted to a sensitive competitive reverse transcriptase-polymerase chain reaction procedure in an attempt to detect as well as quantify the amount of CCR5 expression. Here findings are presented which indicate that CEMx174 indeed expresses CCR5 and that the amount of CCR5 is increased in cells pretreated with morphine. These results correlate well with previous observations that morphine treatment causes CEMx174 cells to be more susceptible to SIV infection. Similar morphine effect was not observed on CEMx174 cells infected with simian retroviruses, which do not depend on CCR5 for entry. These findings suggest a plausible mechanism whereby opiate drug users render themselves more susceptible to HIV infection, thereby explaining the vast prevalence of HIV infection among endemic drug use populations. Miyagi, T., Chuang, L.F., Doi, R.H., Carlos, M.P., Torres, J.V., and Chuang, R.Y. Morphine Induces Gene Expression of CCR5 in Human CEM x174 Lymphocytes. J Biol. Chem., 275, pp. 31305-31310, 2000.

Morphine Induced Sepsis

Recently, it was observed that sepsis produced by enteric bacteria entering into the peritoneum after opiate administration caused sepsis and death. A follow up study describes the possible action whereby morphine produces this disease enhancement through the activation of a cytokine. In this study authors investigated the capacity of morphine to modulate expression of cytokines in peritoneal macrophages. Mice were implanted subcutaneously with a 75-mg morphine slow-release pellet, and 48 h later resident peritoneal macrophages were harvested. Control groups received placebo pellets, naltrexone pellets, or morphine plus naltrexone pellets. Adherent cells were stimulated with lipopolysaccharide plus interferon-gamma to induce cytokine production. Morphine enhanced mRNA expression of interleukin (IL)-12 and tumor necrosis factor alpha (TNF-alpha) compared with controls, whereas IL-10 levels were unchanged by drug treatment. The enhancement of IL-12 at both the mRNA and protein levels was antagonized by naltrexone, indicating that the modulation of this cytokine by morphine is via a classic opioid receptor. These results are particularly interesting in light of the previous observation that 48 h after morphine pellet implantation, the peritoneal cavity is colonized with gram-negative and other enteric bacteria. The enhancement of IL-12 by morphine might be related to morphine-induced sepsis. Peng, X.H., Mosser, D.M., Adler, M.W., Rogers, T.J., Meissler, J.J. and Eisenstein, T.K. Morphine Enhances Interleukin-12 and the Production of Other Pro-inflammatory Cytokines in Mouse Peritoneal Macrophages. J Leukocyte Biology, 68, pp. 723-728, 2000.

Substance P and Opiates

Substance P is a neurotransmitter in the central nervous system and it appears to play an important role in the immune system. Macrophages and other immune cells produce substance P. Substance P is also associated with higher levels of stress and anxiety and communicates between the central nervous system and the immune system, much the same as opiates do. In this study investigators observed an interaction between substance P and opiates. In vitro and in vivo studies have indicated that there is an important relationship between morphine and neuropeptide substance P (SP). This study investigated the interaction of morphine and cultured human immune cells on the expression of SP, a neuropeptide recently demonstrated to be produced by human monocytes and lymphocytes. Morphine up-regulated SP production in human mononuclear phagocytes and lymphocytes at both the mRNA and the protein level. In addition, morphine induced SP receptor (NK-1R) expression in human lymphocytes. The specific morphine receptor antagonist, (naltrexone) blocked morphine-induced SP expression in human mononuclear phagocytes, supporting the concept of authentic morphine receptor-mediated regulation. Since SP modulates neurogenic inflammation and immunologic events, these data suggest that morphine-induced SP expression in cells of the immune system may be of importance in the pathogenesis of immune-mediated diseases, including neuroimmunologic diseases and AIDS. Li, Y., Tian, S., Douglas, S.D. and Ho, W.Z. Morphine Up-regulates Expression of Substance P and its Receptor in Human Blood Mononuclear Phagocytes and Lymphocytes. Cell Immunol., 205, pp. 120-127, 2000.

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