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Director's Report to the National Advisory Council on Drug Abuse
May, 2002

Research Findings

Research on AIDS and Other Medical Consequences of Drug Abuse

AIDS-Associated Mild Neurocognitive Impairment is Delayed in the Era of Highly Active Antiretroviral Therapy

Highly active antiretroviral therapy (HAART), the clinical strategy of combining antiretroviral medications from different classes, has restored immune function for many immunosuppressed individuals infected with HIV. Because some antiretroviral agents penetrate poorly into the central nervous system (CNS), patients may remain susceptible to HIV-associated neurocognitive disorders despite viral suppression in other tissues. Recent results suggest that HAART helps to maintain intact cognitive functioning in high-risk patients with relatively unrestricted access to HAART. This protection is predominantly mediated by a HAART-induced improvement in immune function reflected by the CD4 cell count. To examine whether specific classes of antiretroviral drugs afford protection, Dr. Igor Grant and colleagues at the University of California San Diego plan to investigate the role of HIV-RNA viral load, and to extend the observations to individuals in the medically asymptomatic stages of disease. Deutscha, R., Ellisa, R.J., McCutchana, J.A., Marcotte, T.M; Letendrea, S., Grant, I. and the HNRC Group. AIDS-Associated Mild Neurocognitive Impairment is Delayed in the Era of Highly Active Antiretroviral Therapy. AIDS, 15, pp. 1898-1899, 2001.

HIV/AIDS Risk Behaviors among Female Jail Detainees: Implications for Public Health Policy

Women are currently a primary focus in the battle against HIV/AIDS. This study examines the sex- and IDU-HIV/AIDS risk behaviors of female jail detainees and assesses the potential impact of interventions targeting this population. A sample of 948 participants stratified by charge type (i.e., felony vs. misdemeanor) and by race/ethnicity formed be basis of this study. Results indicate that non-hispanic white women, women arrested for less serious charges, women who have prior arrests, women arrested on drug charges, and women with severe mental disorders are at especially high risk for sexual and IDU transmission of HIV/AIDS. Investigators conclude that many women at particular risk of HIV/AIDS - women who use drugs, women who trade sex for money or drugs, homeless women, and women with mental disorder - will eventually cycle through the jail. Because most jail detainees return to their communities within days, providing HIV/AIDS education in the jail must become a public health priority. McClelland, G.M., Teplin, L.A., Abram, K.M., and Jacobs, N. American Journal of Public Health, 92(5), pp. 818-825, 2002.

HIV-1 RNA Viral Load Monitoring in HIV-infected Drug Users on Antiretroviral Therapy - Relationship with Outpatient Care Patterns

HIV-1 viral load (VL) testing is a standard component of HIV care. Investigators examined the use and predictors of VL testing in drug users, a group at risk for problematic care. Using 1996 to 1998 New York State (NYS) Medicaid files, the authors studied drug users who had been enrolled >10 months, had been prescribed antiretroviral agents in 1997 and 1998, and who had undergone any VL testing in 1997. The authors found that nearly half this cohort of drug users did not have regular VL testing. Drug users with HIV-focused care or with regular drug treatment are more likely to have regular VL testing. Laine, C., Zhang, D.Z., Hauck, W.W., and Turner, B.J. Journal of Acquired Immune Deficiency Syndromes, 29(3), pp. 270-274, March 1, 2002

Psychiatric Symptoms, Health Services, and HIV Risk Factors among Homeless Women

The authors determined whether psychiatric symptoms and lack of health and/or social services contacts were associated with HIV risk behaviors among a probability sample of homeless women. Women were interviewed regarding socioeconomic indicators, psychiatric symptoms, health and/or social services contacts, and past-year HIV risk behaviors. Overall, 8 percent of the women injected drugs, 64 percent engaged in unprotected sex, and 22 percent traded sex. Substance abuse was positively associated with injection drug use and trading sex. Homeless women with case managers were less likely to inject drugs. Although barriers to obtaining drug treatment were associated with trading sex, women attending self-help meetings for substance abuse were also more likely to trade sex. Homeless women who are substance abusers are vulnerable to HIV risk behaviors. Risk reduction interventions for homeless women should be implemented through substance abuse and intensive case management programs. Kilbourne, A.M., Herndon, B., Andersen, R.M., Wenzel, S.L., and Gelberg, L. Journal of Health Care for the Poor and Underserved, 13(1), pp. 49-65, February 2002.

Differential Predictors of Emotional Distress in HIV-infected Men and Women

Changes in the AIDS epidemic in many areas of the United States require information about the experience of the growing segment of women afflicted. The authors compared patterns of emotional distress between men and women with symptomatic HIV and examined potential predictors of different levels of vulnerability. A sample of 126 low socioeconomic men and women seeking care from HIV treatment centers was surveyed using measures of physical and psychological well-being. Women had more HIV symptoms, poorer functioning, and greater disruptions in physical and psychosocial well-being. Physical health status and optimism were primary predictors of emotional distress in both men and women. More than 50% of men and women had scores indicative of clinical anxiety. Approximately 1 out of 10 had clinically relevant scores for depression. Gender differences may provide potentially useful information for tailoring assessment interventions for emotional distress in people infected with HIV. van Servellen, G., Aguirre, M., Sarna, L., and Brecht, M.L. Western Journal of Nursing Research, 24(1), pp. 49-72, February 2002.

Real and Perceived HIV Risk by Population Density: An Exploratory Examination

Little is known about HIV and its primary routes of transmission in less populated areas. The purpose of this exploratory study was to contrast the real and perceived HIV risk among out-of-treatment drug users in a multi-site sample of low-, medium-, and high-population density counties in six states and Washington, D.C. Drug users in medium density areas "perceived" their risk of acquiring HIV/AIDS as lower than those in the high-density areas. The perceived risk could be predicted primarily as a function of lifetime HIV, lifetime STDs, needle use, having multiple sexual partners, and community population density. Because of different risk patterns and a "false" sense of risk, it is important to expand HIV risk reduction activities to include less populated areas. Leukefeld, C.G., Farabee, D., McDermeit, M., Dennis, M.L., Wechsberg, W.M., Inciardi, J.A., Surratt, H.L., Compton, W.M., Cottler, L.B., Klein, H., Hoffman, J.A., Desmond, D., and Logan, T.K. Journal of Drug Issues, 31(4), pp. 889-903, Fall 2001.

Analysis of a Population-based Pneumocystis Carinii Pneumonia Index as an Outcome Measure of Access and Quality of Care for the Treatment of HIV Disease

A population-based Pneumocystis carinii pneumonia (PCP) Index was developed in New York City to identify geographic areas and subpopulations at increased risk for PCP. A zip code-level PCP Index was created from AIDS surveillance and hospital discharge records and defined as (number of PCP-related hospitalizations)/(number of persons living with AIDS). Results indicated that in 1997, there were 2262 hospitalizations for PCP among 39,740 persons living with AIDS in New York City (PCP Index=.05691). PCP Index values varied widely across neighborhoods with high AIDS prevalence (West Village=.02532 vs Central Harlem=.08696). Some neighborhoods with moderate AIDS prevalence had strikingly high rates (Staten Island=.14035; northern Manhattan=.08756). The PCP Index highlights communities in particular need of public health interventions to improve HIV-related service delivery. Arno, P.S., Gourevitch, M.N., Drucker, E., Fang, J., Goldberg, C., Memmott, M., Bonuck, K., Deb, N., and Schoenbaum, E. American Journal of Public Health, 92(3), pp. 395-398, March 2002.

Drug Use During Pregnancy and Short-Term Maternal Outcomes

Findings from the largest study of illicit drug use during pregnancy have replicated many of the associations found in studies involving smaller samples. Over a 2-year period, 19,079 mother-infant pairs were screened after delivery for cocaine and opiate exposure at four clinical centers, located in Detroit, Memphis, Miami, and Providence. Of those screened, 16,988 met eligibility criteria, and 11,811 agreed to participate. Analyses involved 8,627 mother-infant pairs, based on ability to confidently classify participants as exposed or not exposed. Exposure was defined as admission of use of cocaine or opiates or both, or the presence of cocaine or opiate metabolites in meconium (using gas chromatography-mass spectroscopy methodology). Nonexposure was defined as a negative drug use history by interview and a negative immunoassay screen. Exposed mothers had a significantly higher risk of infections, including syphilis, gonorrhea, hepatitis, and HIV; psychiatric, nervous, and emotional disorders; and abruptio placenta. However, it should be noted that in this large, sociodemographically diverse cohort study, the prevalence of these risk outcomes was lower than typically reported in previous reports. The authors point out that although the prevalence of serious and life-threatening medical outcomes is low in drug-abusing pregnant women, disadvantaged social and environmental conditions that are often characteristic of the lifestyle of these women may compound these problems. Bauer, C.R., Shankaran, S., Bada, H.S., et al. The Maternal Lifestyle Study: Drug Exposure During Pregnancy and Short-Term Maternal Outcomes. American Journal of Obstetrics and Gynecology, 186, pp. 487-495, 2002.

Current and Former Marijuana Use: Effects on IQ in Young Adults

Studying a cohort of young individuals who have been followed since birth, Peter Fried and colleagues have been able to assess IQ before and after onset of marijuana use. Seventy individuals aged 17-20 years old were involved in the analyses, using self-report of drug use and urinalysis. IQ in the 17-20 year-old period was compared with IQ in the 9-12 year-old period (pre-marijuana use). In addition, IQ differences across the two time periods were compared for current heavy users (at least 5 joints per week), current light users (less than 5 joints per week), former users (had not smoked regularly for at least 3 months), and non-users (never smoked more that once per week and no smoking in the past 2 weeks). Among the factors controlled for in the analyses are socioeconomic status variables (e.g., family income and parental education), education level of participant, age, sex, maternal use of cigarettes, marijuana and alcohol during pregnancy, participant's exposure to secondhand marijuana smoke, and participant's use of alcohol and tobacco. Current marijuana use was negatively associated with global IQ score only in the current heavy users (average decrease of 4.1 points over the time periods, current average IQ of 105.1). A negative effect was not found among subjects who had been heavy users but were no longer using marijuana. The authors caution that the negative effects of current heavy use and the lack of long-term effects found in this study should be interpreted carefully. The relatively small number of subjects for whom data were available, the length of time that the drug was used, the estimated total number of joints smoked, and the young age of the subjects all may serve to moderate effects. The authors also emphasize that broad intellectual functioning was examined in this report (i.e., only overall IQ), and it remains to be ascertained whether the absence of a residual marijuana effect of past use would also be evident in more specific cognitive domains such as memory and attention. Fried, P., Watkinson, B., James, D., and Gray, R. Current and Former Marijuana Use: Preliminary Findings from a Longitudinal Study of Effects on IQ in Young Adults. Canadian Medical Association Journal, 166, pp. 887-891, 2002.

Changes in HIV and Risk Behaviors Among Male IDUs in New York City, 1990-1999

Male IDUs who have sex with men (MSM) continue to be at particularly high risk for HIV infection. In 1999, over 23% of AIDS patients in the U.S. with a history of injecting drugs were MSM. MSM IDUs may be more likely than other IDUs to engage in some injection and sexual risk behaviors, and these behaviors may serve as a bridge for HIV transmission to various other groups. In New York City, HIV prevalence, HIV incidence, and injection risk behaviors have declined among IDUs, but relatively little is known about differences between MSM IDUs and other male IDUs regarding trends in risk behaviors and HIV prevalence. In this study, data were collected as part of an ongoing series of studies of entrants to a drug detoxification program at Beth Israel Medical Center in New York City. Male subjects entering the program between January 1990 and July 1999, who were 18 or older and had injected illicit drugs within the previous 6 months were eligible for inclusion. Participants were classified as MSM if they reported sexual intercourse with a man in the 5 years prior to the interview. The period of observation was dichotomized into 1990-1994 and 1995-1999, and analyses compared male IDUs who were and were not MSM within and between periods. In general, MSM IDUs tended to be at least as likely as other male IDUs to engage in high-risk injection and sexual behaviors. Both groups of men reduced high-risk injection behaviors and increased protective injection behaviors over time. However, neither group reduced its participation in commercial sex exchange, and only the non-MSM IDU group increased condom use between the first and second periods. MSM IDUs were significantly more likely to be HIV+ than were other male IDUs during the first period, and they tended to be so during the second period as well, even after adjusting for changes in the demographic and behavioral composition of the two groups. Overall, HIV prevalence declined by approximately 15% between periods in each group. The use of needle exchange increased from 21% to 57% for MSM IDUs and from 25% to 47% for non-MSM IDUs. Declining prevalence among MSM IDUs may be partially attributable to the effects of intervention efforts targeting MSM, as well as IDU populations, although it appears that such interventions have primarily affected injection risk. Injection risk behaviors declined among the IDUs in this study, whereas sexual risk behaviors did not. This study highlights the need for multidimensional interventions with heightened sensitivity to and awareness of sexual orientation. Given the high-risk profile of MSM IDUs, such approaches should be prioritized for implementation and assessment in the near future. Maslow, C.B., Friedman, S.R., Perlis, T.E., Rockwell, R., and Des Jarlais, D.C. Changes in HIV Seroprevalence and Related Behaviors Among Male Injection Drug Users Who Do and Do Not Have Sex with Men: New York City, 1990-1999. Am J Public Health, 92, pp. 382-384, 2002.

Differential Effects of Face-to-Face and Computer Interview Modes

Researchers assessed the differential effects of face-to-face interviewing and audio-computer assisted self-interviewing (audio-CASI) on categories of questions. Syringe exchange participants (n=1417) completed face-to-face interviews or audio-CASI. The questionnaire was categorized into the groups "stigmatized behaviors," "neutral behaviors," and "psychological distress." Interview modes were compared for questions from each category. Audio-CASI was found to elicit more frequent reporting of stigmatized behaviors than face-to-face interviews. The researchers found that the interview mode differences between the "stigmatized" HIV risk behaviors and "psychological distress" were notable. There was also significantly more reporting of stigmatized behaviors with audio-CASI and significantly more reporting of "psychological distress" in the face-to-face interviewing. It appears that the process of collecting information regarding depression is facilitated by the face-to-face interview process; respondents may underreport to the computer because the impersonal nature of a computer interview is incongruent with the personal nature of questions regarding one's emotional or mental health. Responding to potentially sensitive questions should not be seen as merely "providing data" but rather as an activity with complex motivations. These motivations can include maintaining social respect, obtaining social support, and altruism. Ideally, procedures for collecting self-report data would maximize altruistic motivation while accommodating the other motives. Clark Newman J., Des Jarlais, D.C., Turner, C.F., Gribble, J., Cooley, P., and Paone, D. The Differential Effects of Face-to-Face and Computer Interview Modes. Am J Public Health, 92, pp. 294-297, 2002.

Validity of Self-Reported NEP Attendance Has Implications for Program Evaluation

Some studies have indicated that needle exchange programs (NEPs) can be effective in reducing drug-related risks for HIV seroconversion; however, others have reported higher HIV incidence rates among NEP attendees. Since many studies rely on self-reports of NEP attendance, the authors investigated the extent to which differential misreporting of NEP attendance could bias risk estimates. Over a 3-year period from 1994 to 1997, self-reports of NEP attendance from participants in a prospective study in Baltimore, Maryland, were compared with NEP records. Of 1,315 participants, 459 (35%) had registered with the Baltimore NEP. There was 86.7% concordance between self-reported and actual NEP use; 11.0% reported NEP attendance but did not attend (overreported), and 2.2% reported not attending NEP but did attend (underreported). In multivariate analyses using generalized estimating equations, persons who overreported NEP attendance were more likely to have injected frequently (adjusted odds ratio (AOR) = 1.29, 95% confidence interval (CI): 1.04, 1.61), denied needle sharing (AOR = 0.69; 95% CI: 0.52, 0.89), and been an HIV seroconverter (AOR = 1.83, 95% CI: 1.11, 3.01). With Poisson regression to model predictors of HIV seroconversion, models that included measures of NEP attendance based on self-reports compared with actual program data underestimated a protective association by 18%. These findings have important implications for evaluations of NEPs. Safaeian, M., Brookmeyer, R., Vlahov, D., Latkin, C., Marx ,M., and Strathdee, S.A.. Validity of Self- Reported Needle Exchange Attendance Among Injection Drug Users: Implications for Program Evaluation. Am J Epidemiol, 155(2), pp. 169-175, 2002.

Effects of Sponsorship in 12-Step Treatment of Injection Drug Users

What contributes to sustained abstinence from injection drug use by those who participate in community-based Narcotics Anonymous (NA) and Alcoholics Anonymous (AA) is not well understood. We know that sponsorship is a central element in these programs. To investigate the relationship between sponsorship and abstinence, researchers evaluated NA/AA sponsorship over a1-year period in a longitudinal study of 500 former and current injection drug users in inner-city Baltimore recruited from the community-at-large, independent of treatment center affiliation. The findings indicated that having a sponsor in NA/AA for this population was not associated with any improvement in 1-year sustained abstinence rates than a non-sponsored group. However, being a sponsor over the same time period was strongly associated with substantial improvements in sustained abstinence rates for the sponsors, controlling for involvement with community organizations, NA/AA meeting attendance, marital status, employment, participation in drug and alcohol treatment centers and HIV status. Involvement in community organizations was also strongly associated with successful abstinence, controlling for the same variables. Of those participants involved with community organizations, more than half reported involvement in church activities. This investigation suggests that, for NA/AA sponsors in this study population, providing direction and support to other addicts is associated with improved success in sustained abstinence for the sponsors but does little to improve the short-term success of the persons being sponsored. Crape, B.L., Latkin, C.A., Laris, A.S., and Knowlton, A.R. The Effects of Sponsorship in 12-Step Treatment of Injection Drug Users. Drug Alcohol Depend, 65, pp. 291-301, 2002.

Selection Effect of Needle Exchange in Anchorage, Alaska

Participation bias (selection bias) may be a problem in studies that attempt to evaluate the effects of needle-exchange programs (NEPs). The present study looked at only those injection drug users (IDUs) who were randomly placed in the needle-exchange condition in a two-arm randomized clinical trial of needle exchange. Time to follow-up between the experimental NEP condition (n = 296; median = 261 days) and pharmacy sales condition (n = 304; median = 256 days) was not statistically different [chi (2) (1, N = 600) = 0.42, P =.52]. Within the NEP condition, a similar analysis comparing time to follow-up between IDUs who used the NEP (n = 65; median = 199 days) and those who refrained from using the NEP (n = 231; median = 286 days) was highly significant, chi (2) (1, n = 296) = 17.3, P=.0001. The final logistic regression model predicting use of the NEP was the log 10 transformation of the number of times injected heroin in the last 30 days (odds ratio [OR]=4.9, confidence interval [CI] 2.8, 8.9), ever injected amphetamine in the last 30 days (OR =4.9, CI 1.09, 22.5), and ever shared injection equipment in the last 30 days (OR =2.9, CI 1.5, 5.5). Within the NEP condition, follow-up rates differed between those who used the NEP and those who did not use it. Of drug users randomly assigned to an NEP, the ones who actually used the NEP had higher levels of drug use. Predictors of who used the NEP were consistent with those reported by other researchers. This study demonstrates that selection bias occurs among IDUs who use NEPs. Fisher, D.G., Reynolds, G.L., and Harbke, C.R. Selection Effect of Needle Exchange in Anchorage, Alaska. J Urban Health, 79(1), pp. 128-135, 2002.

Cultural Factors Influencing HIV Risk Behavior Among Dominicans in N.Y.City

Hispanics in the U.S. have disproportionately high rates of HIV. The existence of ethnically and culturally diverse Hispanic communities in the U.S. suggests that qualitative research on HIV-related attitudes and behaviors within Hispanic subgroups can help to inform the development of successful interventions. In this paper, the authors present findings from interviews with 20 Dominicans involved in drug- or sex work-related activities in New York City in terms of predominant cultural influences and specific issues regarding sex work, drug use, and HIV/AIDS. Several directions for interventions in the Dominican community are also discussed, including outreach efforts sensitive to the stigmatization of behaviors such as needle use and homosexuality, and messages to sex workers to use condoms with their partners as well as their clients. The authors discuss how improved knowledge of cultural norms can serve as a foundation for interventions within this community, especially given the need for additional information on contraception, family planning, and drug treatment services. Shedlin, M.G. and Deren, S. Cultural Factors Influencing HIV Risk Behavior Among Dominicans in New York City. J Ethnicity in Subst Abuse,1(1), pp. 71-95, 2002.

Gender-Related Social Factors Associated with Syringe Sharing Among Injecting Partners

The study of social networks has become an increasingly utilized method of examining the relationship between injection drug users' social environment and risk of HIV. This study examined relational aspects of two injection drug users (IDUs) within a single social network as they relate to sharing syringes. Data presented in this study were derived from baseline interviews of 508 IDUs from Baltimore, MD. Analyses were performed separately for male and female participants in an effort to understand gender differences in social aspects of syringe sharing. Among this sample, women shared syringes with a significantly higher percentage of injecting partners compared to men. In separate multilevel logistic regression models, significant variables associated with males' and females' syringe sharing were: sharing drugs daily with female injecting partners, injecting partners' provision of drugs when indexes' were withdrawing, being sexual partners, and injecting partners' injecting speedballs. Factors associated with male injecting dyads sharing of syringes were: being kin, injecting partners' injection of heroin and daily drug use, and drinking alcohol together. Results from this study demonstrate the usefulness of examining relationship characteristics of injecting dyads related to syringe sharing as they differ between men and women. Sherman, S.G., Latkin, C.A., and Gielan, A.C. Social Factors Related to Syringe Sharing Among Injecting Partners: A Focus on Gender. Subst Use Misuse, 36(14), pp. 2113-2136, 2001.

Gender Differences in HIV Risk Behaviors of PR IDUs and Awareness of Serostatus

Researchers examined HIV injection and sex-related risk behaviors among Puerto Rican injecting drug users by gender, separately for those who were aware of being HIV positive and those who believed they were seronegative or were unaware of their serostatus. The participants (N= 873; 561 in New York and 312 in Puerto Rico) were recruited from January 1998 to July 1999 in the two sites by street outreach workers. Of the participants, 81% were males and 19% self-reported that they were previously told that they had been infected with HIV. More significant gender differences in risk behaviors were found in bivariate analyses among those who were not told they were infected than among those who were aware of their HIV+ status. The factors related to HIV risk behaviors between males and females differed after controlling for the impacts of other variables in multivariate analysis. Among those who were never told they were infected, men were more involved in risky injection behaviors than women. Even among those who knew they were HIV+, men were more likely than women to engage in distributive sharing of injection equipment. Men also used paraphernalia and shared their needles/syringes or paraphernalia with others. Regardless of awareness of infection, women were more likely than men to engage in sex, to exchange sex for drugs or money, and to have multiple sexual partners. The levels of unsafe injection and sexual practices found in this study indicate a critical need for continuing intervention programs to reduce the risk of becoming HIV infected in these communities. Kang, S.Y., Deren, S., Andia, J., Colon, H.M., and Robles, R. Gender Differences in HIV Risk Behaviors Among Puerto Rican Drug Injectors by Awareness of HIV Seropositive Status. AIDS and Behavior, 5(3), pp. 241-249, 2001.

Public Health and Criminal Justice Policy Issues Related to High-Risk Women

Researchers have documented the linkages between sex-for-crack exchanges, prostitution, and rising rates of HIV and other sexually transmitted diseases among cocaine-dependent women. As crack began to fade from the headlines in the 1990s, however, it was assumed by many that crack had declined in popularity in the street drug culture. In this study, researchers describe crack use, street crime, and sex-for-drug exchanges collected during the mid-1990s in Miami, Florida from interviews with a sample of 851 multi-ethnic/racial women. Of the women, 708 or 83.2% were cocaine dependent and reported trading sex (defined as periodic exchange of sex for money or drugs, as opposed to regular or commercial sex work) in the past 30 days. All the women also had criminal histories, used illicit drugs 2-3 years before the initiation of reported criminal activity, and traded sex before the initiation of crack cocaine. The women are at high risk for HIV/AIDS, given their histories of injecting drug use, sex with an IDU who is HIV+, unprotected sex, and number of sex partners. Recent studies of HIV infection among crack-using women in Miami have reported HIV prevalence as high as 24% in non-sex traders and 35% in sex traders. The authors conclude that crack use continues to occupy a prominent place in the culture of drug-dependent women in Miami. They argue that their data contradict the argument that legalizing drugs would reduce crime associated with drug use, and suggest instead that drug addiction is a disorder of the whole person, including cognitive problems, psychological dysfunctions, and educational and employment deficits. Moreover, they found significant gaps in conventional HIV prevention outreach activities: of 53 women participating in focus groups, almost none had ever come into contact with an HIV prevention outreach worker, largely because outreach occurs during the day and early evening and sex trading occurs late at night. The HIV prevention messages must also be made more relevant to the lives, culture, and concerns of the drug-involved women they are intended to reach. Inciardi, J.A. and Surratt, H.L. Drug Use, Street Crime, and Sex-Trading Among Cocaine- Dependent Women: Implications for Public Health and Criminal Justice Policy. J Psychoactive Drugs, 33(4), pp. 379-389, 2001.

Ethnographic Accessing, Sampling, and Screening of Heroin Sniffers in N.Y. City

In this article, researchers describe various ways in which ethnographic methods were used in a cohort study of HIV risk and transitions to injecting among non-injecting heroin users (NIUs) or "sniffers" in New York City. In preparation for and in conjunction with an epidemiological questionnaire survey and biological specimen collection, ethnographic methods were used to explore the meaning of non-injecting and injecting rates of heroin administration for NIUs, how non-injecting heroin use was imbedded in the everyday life of the user, and the relationship of users to the retail markets for heroin. The study utilized different ethnographic techniques to access, sample, and screen heroin "sniffers" for the epidemiological survey. These techniques included ethnographic accessing, targeted canvassing, and interactive screening. The article concludes that ethnographic methods can be fruitfully integrated with epidemiological survey research and are necessary for conducting research among non-institutionalized, hard-to-reach or hidden populations of drug users. Sifaneck, S.J. and Neaigus, A. The Ethnographic Accessing, Sampling, and Screening of Hidden Populations: Heroin Sniffers in New York City. Addiction Research and Theory, 9(6), pp. 519-543, 2001.

Health Care Utilization in Female African-American Crack Cocaine Users

Researchers examined utilization of health care services by urban female African-American crack cocaine users recruited for a larger study developing HIV risk reduction interventions. Structured interviews were conducted with 149 women at a community-based field site. Nearly all women regularly sought health care during the past year, although only 40% had any type of health insurance. Two- thirds had no regular primary care provider, with the highest percentage among women who did not have health insurance. Typically, women received care at public hospital outpatient clinics or emergency rooms and the most common care issues were female-related health issues and substance use. Many women reported having had routine exams such as general medical, pelvic, or pap smear in the past 2 years. However, fewer had dental, eye or mammogram exams during that same time period, with many never having had such exams. Twenty-three percent of the women reported a lifetime diagnosis of a mental illness. Analyses by amount of crack use indicated that those who used most were least likely to be insured, and most likely to seek care at hospital emergency rooms. Multivariate analyses revealed that self-rated health and having a minor child predicted amount of health care received in the past year. Many female African American crack cocaine users are not receiving important health care exams and services. Steps must be taken to improve preventive and primary care to female African American crack cocaine users prior to the necessity of care in a more expensive hospital setting. Kidder, D.P., Elifson, K.W., and Sterk, C.E. Health Care Utilization in Female African-American Crack Cocaine Users. Women and Health, 34(1), pp. 79-97, 2001.

Practical Guidelines on Research and Services Projects for Hard-to-Reach Populations

Researchers from the National Development and Research Institutes (NDRI) in New York City have prepared a recent book to serve as a practical guide for conducting research and delivering services to marginalized groups and populations. The knowledge and expertise represented in the book span more that 15 years of accumulated experience in working with people outside the mainstream, including drug users, the homeless, street prostitutes, runaway teenagers, and drug dealers. The book follows a step-by-step format, with guidelines on setting up research projects; the outreach process and qualities that make a good outreach worker; conducting clinical and research interviews; strategies for locating, following up, and maintaining contact with hard-to- reach study participants; managing service delivery projects; the importance of community collaborations; ethical considerations; and the integration of service provision and research in a single setting. Tortu, S., Goldsamt, L.A., and Hamid, R. (eds.). A Practical Guide to Research and Service With Hidden Populations, Boston: Allyn & Bacon, 2002.

The Pharmacokinetics of Methadone Following Co-Administration with a Lamivudine/ Zidovudine Combination Tablet in Opiate-Dependent Subjects

The investigators determined methadone pharmacokinetics in an open-label, within subject study in 16 methadone-maintained, non-HIV-infected subjects prior to and following administration of one lamivudine 150-mg/zidovudine 300-mg combination tablet to determine whether this antiretroviral therapy alters methadone serum concentrations. No significant differences in the mean area under the serum concentration-time curve (AUC0-24h; 8753 ±4280 vs. 8641 ± 4431 g-h/L), oral clearance (CL/F; 9.9 ± 4.9 vs. 10.3 ± 5.5 L/h), oral volume of distribution (Vd/F; 647 ±465 vs. 481 ± 305 L), maximum serum concentration (Cmax; 514 ± 223 vs. 5510 ± 237 µ g/L), or terminal elimination half-life (t1/2; 55.3 ± 61.0 vs. 35.0 ± 17.5 h) were detected. These results suggest that methadone dose change is not likely to be necessary for patients treated with lamivudine/ zidovudine combination pharmacotherapy. Rainey, P.M., Friedland, G.H., Snidow, J.W., McCance-Katz, E.F., Mitchell, S.M., Andrews, L., Lane, B., and Jatlow, P., Am J. Addictions, 11(1), pp. 66-74, 2002.

High Prevalence of Iron Deficiency and Anemia Among Female Injection Drug Users with or Without HIV Infection

Based on the fact that anemia is associated with HIV disease progression and high mortality, Semba et al. measured hemoglobin and plasma ferritin in a cohort of 136 HIV+ and 61 HIV-negative women IDUs in Baltimore, Maryland. The prevalence of anemia was 44.1% and 26.2%; iron deficiency was 37.5% and 42.6%; and the iron deficiency anemia 20.6% and 14.7%, in HIV+ and HIV- women, respectively. The overall prevalence of hepatitis C infection was 90.5%. Iron deficiency accounted for 46.7% and 56.1% of the anemia among HIV+ and HIV- negative female IDUs. The iron deficiency accounted for about half of the anemia among female IDUs. However, they stated that although iron supplementation is indicated for anemia in patients, such treatment should be approached with caution in women co-infected with HIV and hepatitis C virus, because iron supplementation and overload have been associated with increased progression of HIV infection, worsening of hepatitis C infection and higher mortality. Semba, R., Shah, N., Strathdee, S.A., and Vlahov, D. JAIDS, 29, pp. 142-144, 2002.

Impact of Selenium Status on Pathogenesis of Mycobacterial Disease in HIV-1-infected Drug Users During the Era of Highly Active Antiretroviral Therapy

The risk of Mycobacterial disease is significantly increased in drug users as well as in immunocompromised HIV-1-infected individuals. Since the essential trace element selenium has an important function in maintaining processes and may, thus, have a critical role in clearance of mycobacteria, the investigators examined the impact of selenium status on the development of mycobacterial disease in HIV-1-seropositive drug users over a 2-year period (1999-2000). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections that were matched on age, sex, and HIV status. Significant risk for mycobacterial disease was associated with a CD4 cell count of <200/mm3, malnutrition, and selenium levels of 135 g/L (patients with these levels were 13 times more likely to develop mycobacterial disease). Multivariate analyses controlling for antiretroviral treatment and CD4 cell count revealed that both body mass index and selenium level remained significant factors in the relative risk for developing mycobacterial disease (RR=3, p=0.015); these findings suggest that selenium status may have a profound impact on the pathogenesis of mycobacterial disease. Shor-Posner, G., Miguez-Burbano, M.J., Pineda, L.M., Rodriguez, A., Ruiz, P., Castillo, G., Burbano, X., Lecusay, R., and Baum, M., JAIDS, 29, pp., 169-173, 2002.

The Effects of Cannabinoids on the Pharmacokinetics of Indinavir and Nelfinavir

Dr. Abrams and colleagues present pharmacokinetic data from a randomized placebo-controlled study showing that the magnitude of pharmacokinetic parameter changes in two protease inhibitor antiretroviral medications, indinavir and nelfinavir, in marijuana users are likely to have no significant short-term clinical consequences, and that the use of marijuana or dronabinol is unlikely to impact antiretroviral efficacy. The investigators conducted a placebo-controlled randomized clinical in-patient study in HIV+ subjects who were on indinavir (n=28; 800 mg tid) or nelfinavir (n=34; 750 mg, tid) randomized to either arm: marijuana smoke (3.9% THC; up to 3 complete marijuana cigarettes daily, 1 hr prior to meals) or dronabinol (2.5 capsules, oral) or placebo capsules. Serial blood sampling was performed at baseline and on day 14 of treatment. Data showed that a statistically significant but clinically insignificant decrease (14%, p=0.074) occurred in median Cmax of indinavir in the marijuana group of patients. Statistically non-significant changes occurred in the nelfinavir concentrations in the marijuana group. Due to large inter-subject variability, there were no significant changes in the PI levels in the dronabinol group either. In summary, the use of marijuana did not impact adversely on the pharmacokinetics of protease inhibitors used in the treatment of HIV infection. Kozel, B.W., Aweeka, F.T., Benowitz, N.L., Shade, S.B., Hilton, J.F., Lizak, P.S., and Abrams, D.I., AIDS, 16, pp. 543-550, 2002.

Use of Highly Active Antiretroviral Therapy in HIV-Infected Women: Impact of HIV Specialist Care

The objectives of this analysis were to evaluate factors associated with use of HIV specialist care by women, and to determine whether medical indications for therapy validate lower rates of antiretroviral use in women not using HIV specialty care. Results indicate that 81% of 273 women included in the analysis used HIV specialists vs. 19% who did not. Predictors of use of specialty care included having health insurance, not being an IDU, and the presence of depression (p< =.05). Medical indications for therapy were comparable between the users of HIV specialty care vs. non-users, but the use of HAART was significantly greater for those women using specialty care (27%) vs. those who did not (7.8%). Lower rates of HAART and other antiretroviral therapies (ART) at all CD4 cell count levels occurred in women not receiving specialty care. In the six months prior to study interview, women who utilized specialty care received significantly more advice to initiate ART vs. those not receiving such care (RR, 2.4). Among women with CD4 cells <500 who were current IDUs, the proportion receiving HAART was very low, irregardless of whether or not they were in specialty care (14% vs. 17%, p=NS). For women with CD4 cells <500 who were not IDUs, 31% in specialty care received HAART vs. 0% not in specialty care (p=.002). The overall low level of HAART use (23%) and use of any ART (47%) in this study of HIV-infected women indicate that substantial gaps remain for HIV-infected women in access to specialty care and therapy. Gardner, L.I., Holmberg, S.D., Moore, J., Arnsten, J.H., Mayer, K.H., Rompolo, A., Schuman, P., Smith, D.K. for the HIV Epidemiology Research Study Group, JAIDS, 29, pp. 69-75, 2002.

Cocaine Modulation of HIV Growth in SCID Mice

Epidemiologic studies have identified cocaine as a co-factor for development of acquired immunodeficiency syndrome (AIDS). In a recent study published in the February 2002 issue of Journal of Infectious Diseases, Dr. Michael Roth and his associates at University of California, Los Angeles, School of Medicine clearly show a link of cocaine exposure to accelerated HIV replication. This study was undertaken to examine whether systemic exposure of severe combined immunodeficient (huPBL-SCID) mice to cocaine would affect HIV burden and alter distribution of T cells subsets in vivo. The researchers observed that systemic cocaine administration resulted in accelerated infection of human peripheral blood leukocytes (PBL), a decrease in CD4 cells, a decrease in the CD4:CD8 ratio, and a dramatic rise in circulating virus load. Since exposure to cocaine alone did not affect the implantation of PBL, it suggested a specific interaction between cocaine and HIV. These findings are important as they suggest a causal relationship between cocaine exposure and enhanced HIV replication in vivo, supporting the role of cocaine as an important cofactor in the pathobiology of AIDS. Roth, M.D., Tashkin, D.P., Choi, R., Jamieson, B.D., Zack, J.A., and Baldwin, G.C. Cocaine Enhances Human Immunodeficiency Virus Replication in a Model of Severe Combined Immunodeficient Mice Implanted with Human Peripheral Blood Leukocytes. J Infect Diseases, 185, pp. 701-705, 2002.

Studies of Opiate-Systems Regulation of Immune Function

Studies continue to correlate opiate action with HIV growth in human lymphocytes, macrophages and microglia. Herein, methadone was shown to enhance growth of HIV under in vitro conditions. Methadone also activated latent viruses in the lymphocytes, in vitro, of HIV-infected populations. As this action correlates with the up-regulation of the CCR5 receptor, a coreceptor for HIV, this is of great interest and it is important that work continues to clarify the nature of this action. Opiate abuse has been postulated to be a cofactor in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS). This study evaluated whether methadone, a drug widely prescribed for the treatment of drug abusers with opioid dependence, affects human immunodeficiency virus (HIV) infection of human immune cells. When added to human fetal microglia and blood monocyte-derived macrophage cultures, methadone significantly enhanced HIV infection of these cells. This enhancement was associated with the up-regulation of expression of CCR5, a primary coreceptor for macrophage-tropic HIV entry into macrophages. Most importantly, the addition of methadone to the cultures of latently infected peripheral blood mononuclear cells from HIV-infected patients enhanced viral activation and replication. Although the in vivo relevance of these findings remains to be determined, the data underscore the necessity of further studies to define the role of opioids, including methadone, in the immunopathogenesis of HIV infection and AIDS. Li,Y., Wang, X., Tian, S., Guo, C.J. Douglas, S.D. and Ho, W.Z. Methadone Enhances Human Immunodeficiency Virus Infection of Human Immune Cells. J Infect Diseases, 185, pp. 118-122, 2002.

Effects of Fetal and Adolescent Nicotine Exposure on CNS Vulnerability

It is widely believed that nicotine is a neuroteratogen that targets synaptic function during critical developmental stages. Recent studies indicate that central nervous system (CNS) vulnerability extends into adolescence, the time that smoking typically commences. In the past year, NIDA supported researchers, Dr. Theodore Slotkin and his associates at Duke University Medical Center have demonstrated that nicotine administration during development alters the functioning of the serotonergic (5-HT) systems, the neurotransmitter pathway closely associated with depression, throughout the brain. Dr. Slotkin examined indices of the development of 5-HT projections and 5-HT presynaptic activity following prenatal and adolescent nicotine exposure of rats. These studies used the nicotine dose rates that replicate the plasma nicotine levels found in smokers. Fetal nicotine exposure (gestational days 4-21) showed a decrease in the cerebrocortical binding of paroxetine (PXT), a marker for the 5-HT transporter, indicative of a decrease in nerve terminals in that region. This effect lasted into adulthood. There was a corresponding increase in PXT binding in the midbrain and brainstem, the region containing the 5-HT cell bodies that project to the cerebral cortex, a pattern typical of reactive sprouting in response to nerve terminal damage. After adolescent nicotine treatment (postnatal days 30-47), PXT binding was reduced in the hippocampus and striatum instead of the cerebral cortex, again accompanied by increased binding in the midbrain and brainstem. These effects within each region were gender selective, although both males and females displayed abnormalities. Superimposed on this overall effect, there were transient changes of 5-HT transporter expression likely due to the acute stimulant effects of nicotine. Additional studies showed that withdrawal from adolescent nicotine treatment led to suppression of activity in the cerebral cortex and activation in the midbrain. These results indicate that both fetal and adolescent nicotine exposure elicit apparent damage to 5-HT projections with reactive increases in regions containing 5-HT cell bodies. These findings are important as long-term changes in 5-HT innervation and /or synaptic activity may play a role in the subsequent development of depression in the offspring of women who smoke during pregnancy or in adolescent smokers. Xu, Z., Seidler, F.J., Ali, S.F., Slikker Jr., W., and Slotkin, T.A. Fetal and Adolescent Nicotine Administration: Effects on CNS Serotonergic Systems. Brain Research, 914, pp.166-178, 2001.

Offspring of Women who Smoke during Pregnancy Show Behavioral Abnormalities

Behavioral abnormalities, including increased incidence of attention deficits, learning disabilities, and cognitive dysfunction are shown by the offspring of women who smoke. Researchers at Duke University Medical Center, Dr. Theodore Slotkin and his team recently reported alterations in cellular morphology and regional architecture in the juvenile and adolescent brain regions involved in learning and memory (hippocampus) and in pain pathways (somatosensory cortex) in rats previously exposed to nicotine prenatally. These investigations were designed to compare the vulnerabilities of neuronal populations arising from different germinal zones as well as similar types of cells located in different regions. Their data showed that prenatal nicotine exposure, at blood levels comparable to those seen in human smokers or in user of transdermal nicotine patches, elicited structural abnormalities in the hippocampus and somatosensory cortex before the reemergence of functional deficits. Nicotine appeared to target specific sub-regions and cell types, including cells with postnatal birth dates, indicating that exposure alters the program for brain cell development and for architectural assembly of critical regions involved in learning and memory. Roy, T.S., Seidler, F.J. and Slotkin, T.A. Prenatal Nicotine Exposure Evokes Alterations of Cell Structure in Hippocampus and Somatosensory Cortex. J. Pharmacology Experimental Therapeutics, 300, pp. 124-133, 2002.

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