Replication of ZNF804A gene variant associations with risk of heroin addiction.

Heroin addiction is heritable, but few specific genetic variants have been reproducibly associated with this disease. The zinc finger protein 804A (ZNF804A) gene is a biologically plausible susceptibility gene for heroin addiction, given its function as a transcription factor in human brain. Novel associations of two common ZNF804A single nucleotide polymorphisms (SNPs), rs7597593 and rs1344706, with heroin addiction have been reported in Han Chinese. Both SNPs have also been implicated for regulating ZNF804A expression in human brain, including the addiction-relevant dorsolateral prefrontal cortex. In this independent replication study, we tested the rs7597593 and rs1344706 SNP genotypes and their corresponding haplotypes for association with heroin addiction using cases drawn from the Urban Health Study and population controls: total N = 10 757 [7095 European Americans (EAs) and 3662 African Americans (AAs)]. We independently replicated both ZNF804A SNP associations in EAs: the rs7597593-T (P = 0.016) and rs1344706-A (P = 0.029) alleles both being associated with increased risk of heroin addiction, consistent with the prior report. Neither SNP was associated in AAs alone, but meta-analysis across both ancestry groups resulted in significant associations for rs1344706-A [P = 0.016, odds ratio (95% confidence interval) = 1.13 (1.02-1.25)] and its haplotype with rs7597593-T [P = 0.0067, odds ratio (95% confidence interval) = 1.16 (1.04-1.29)]. By showing consistent associations across independent studies and diverse ancestry groups, our study provides evidence that these two ZNF804A SNPs and their risk haplotype are among the few replicable genetic associations with heroin addiction.

Unmet need for recommended preventive health services among clients of California syringe exchange programs: implications for quality improvement.

BACKGROUND: Comprehensive preventive services are recommended for injection drug users (IDU), including screening tests, vaccinations, risk reduction counseling, and sterile syringes. Syringe exchange programs (SEP) may facilitate receipt of preventive services by IDUs, but whether SEP clients receive recommended preventive care is not known. We examined use of recommended preventive services by clients of 23 SEPs throughout California. METHODS: Five hundred and sixty SEP clients were recruited from 23 SEPs throughout California between March and September 2003. Receipt of 10 recommended preventive services and source of care (SEP versus non-SEP providers) was ascertained from client interviews. RESULTS: On average, SEP clients received only 13% of recommended preventive services and 49% of clients received none of the recommended services. Of services that were received, 76% were received from SEPs. In multivariate analysis, use of drug treatment and more frequent SEP visits were associated with receipt of recommended preventive services by clients. CONCLUSIONS: SEPs are often the only source of preventive care for their IDU clients. Still, SEP clients fail to receive most recommended preventive services. Interventions to increase use of preventive services and improve the quality of preventive care received by IDUs, such as increased access to drug treatment and SEPs, are needed.

Trends in HIV seroprevalence and risk among gay and bisexual men who inject drugs in San Francisco, 1988 to 2000.

OBJECTIVES: To determine trends in HIV infection and risk behaviors among street-recruited self-identified gay and bisexual male injection drug users (IDUs) in San Francisco. METHODS: Trends in HIV infection and risk behaviors were calculated for gay/bisexual ( n = 1594 interviews) IDUs in 26 semiannual cross sections from 1988 to 2000. RESULTS: HIV seroprevalence among gay/bisexual IDUs decreased from the range of 35% to 45% in 1988/1989 to 25% in 1996 and then began to increase, reaching 42% in 2000. In contrast, HIV prevalence among heterosexual male IDUs remained stable during the study period. For gay/bisexual IDUs, injection and sex-related HIV risk behaviors declined modestly throughout the study period. As of the last cross section (July 2000), however, over a third of respondents reported recent syringe sharing or unprotected anal sex. CONCLUSIONS: Gay/bisexual men who inject drugs continue to be at elevated risk for HIV, suggesting that interventions such as amphetamine drug treatment and sexual risk reduction programs targeted at this population are needed.

Predictors and prevention of nonfatal overdose among street-recruited injection heroin users in the San Francisco Bay Area, 1998-1999.

OBJECTIVES: This study sought to determine prevalence of and risk factors for nonfatal recent overdose among street-recruited injection heroin users. METHODS: From August 1998 through July 1999, 1427 heroin injectors were recruited from 6 inner-city neighborhoods in the San Francisco Bay Area, Calif, and interviewed. Factors hypothesized to be associated with recent overdose were analyzed with logistic regression. RESULTS: Of the 1427 participants, 684 (48%) had had an overdose, 466 (33%) had experienced 2 or more overdose events, and 182 (13%) had had a recent overdose. In multiple logistic regression, being younger (adjusted odds ratio [OR] for each year of increasing age = 0.95; 95% confidence interval [CI] = 0.94, 0.97), having been arrested 3 or more times in the past year (adjusted OR = 2.50; 95% CI = 1.61, 3.87), drinking 4 or more alcoholic drinks per day (adjusted OR = 2.05; 95% CI = 1.37, 3.05), and having participated in methadone detoxification during the past year (adjusted OR = 1.47; 95% CI = 1.03, 2.09) were independently associated with recent overdose. Being homeless; identifying as gay, lesbian, bisexual, or transgender; having spent 5 or more years in prison or jail; and having engaged in sex work also were associated with recent overdose. CONCLUSIONS: Targeted interventions that decrease risk for overdose are urgently needed.

Sexual transmission of HIV-1 among injection drug users in San Francisco, USA: risk-factor analysis.

BACKGROUND: Many new HIV-1 infections in the USA occur in injection drug users (IDUs). HIV-1seroconversion of IDUs is mainly associated with injection-related risk factors. Harm- reduction programmes concentrate on injection-risk behaviour. We aimed to establish whether injection or sexual risk factors, or both, were associated with HIV-1antibody seroconversion of street-recruited IDUs in San Francisco, from 1986 to 1998. METHODS: IDUs were enrolled every 6 months from four community sites. We did a nested case-control study comparing 58 respondents who seroconverted between visits with 1134 controls who remained seronegative. Controls were matched with cases by sex and date. Adjusted odds ratios and 95% CI were calculated for men and women by use of conditional logistic regression. FINDINGS: Men who had sex with men were 8.8 times as likely to seroconvert (95% CI 3.7-20.5) as heterosexual men. Women who reported having traded sex for money in the past year were 5.1 times as likely as others to seroconvert (95% CI 1.9-13.7). Women younger than 40 years were more likely to seroconvert than those 40 years or older (2.8 [1.05-7.6]), and women who reported having a steady sex-partner who injected drugs were less likely to seroconvert than other women (0.32 [0.11-0.92]). INTERPRETATION: HIV-1 seroconversion of street-recruited IDUs in San Francisco is strongly associated with sexual behaviour. HIV-1risk might be reduced by incorporation of innovative sexual-risk-reduction strategies into harm-reduction programmes.

Sex- and drug-related risk among populations of younger and older injection drug users in adjacent neighborhoods in San Francisco.

The objective of this study was to compare drug injection- and sex-related risk behaviors of younger and older injection drug users (IDUs) in two adjacent neighborhoods. IDUs were recruited from street settings in two adjacent neighborhoods in San Francisco in April, 1997. All participants were interviewed using a standardized questionnaire and were tested for HIV antibodies. Drug injection- and sex-related risk behaviors were compared between younger IDUs (< 30 years; n = 56) and older IDUs (> or = 30 years; n = 116). Younger IDUs were more likely to be white, be homeless, have injected amphetamines, and have been arrested in the past year. Older IDUs were more likely to be African American and smoke crack cocaine; they had injected a mean of 18 years longer. Younger IDUs were more likely to have shared syringes in the past month (52% versus 10%; p < .05), report drug overdose in the past 15 months (39% versus 7%; p < .05), and to have had unprotected vaginal intercourse in the past 6 months (77% versus 53%; p < .05). After controlling for confounding factors using logistic regression analysis, all these associations remained significant. There is an urgent need for innovative prevention programs that target younger, homeless IDUs.

The effect of syringe exchange use on high-risk injection drug users: a cohort study.

OBJECTIVE: To determine whether syringe exchange program use is associated with cessation of syringe sharing among high-risk injection drug users. DESIGN AND METHODS: Between 1992 and 1996, street-recruited injection drug users were interviewed and received HIV testing and counseling semi-annually, as part of a dynamic cohort study. We examined a cohort of 340 high-risk injection drug users for whom two observations, 6-months apart, were available and who reported syringe sharing at the first interview. Multivariate logistic regression analysis was performed to determine the relationship between syringe exchange program use and cessation of syringe sharing, while controlling for confounding factors. RESULTS: At follow-up interview, 60% (204 of 340) reported quitting syringe sharing. High-risk injection drug users who began using the syringe exchange program were more likely to quit sharing syringes [adjusted odds ratio (AOR), 2.68; 95% confidence interval (CI), 1.35-5.33], as were those who continued using the syringe exchange program (AOR,1.98; 95% CI, 1.05-3.75) in comparison with non-syringe exchange program users, while controlling for confounding factors. CONCLUSIONS: The initiation and continuation of syringe exchange program use among high-risk injection drug users is independently associated with cessation of syringe sharing. Syringe exchange program use can be an important component in reducing the spread of blood-borne infectious diseases among high-risk injection drug users.

High prevalence of abscesses and cellulitis among community-recruited injection drug users in San Francisco.

The prevalence of and risk factors for abscesses and cellulitis were investigated among a community sample of injection drug users (IDUs). Participants were interviewed, and those with symptoms were examined. Of 169 IDUs, 54 (32%) had abscesses (n=35), cellulitis (n=5), or both (n=14); 27% had lanced their own abscesses; and 16% had self-treated with antibiotics they purchased on the street. IDUs who skin-popped (injected subcutaneously or intramuscularly) were more likely to have an abscess or cellulitis than those who had injected only intravenously (odds ratio, 4.9; 95% confidence interval, 2.2-11). The likelihood of abscesses and cellulitis increased with frequency of skin-popping and decreased with increasing duration of injection drug use. Abscesses are extremely prevalent among IDUs in San Francisco. Skin-popping is a major risk factor, and self-treatment is common.

Incentives and accessibility: a pilot study to promote adherence to TB prophylaxis in a high-risk community.

SETTING: A community-based directly observed preventive therapy (DOPT) program for treatment of latent tuberculosis infection among injection drug users (IDUs) in an inner-city neighborhood. OBJECTIVE: To test adherence to a 6-month course of DOPT using cash incentives and an easily accessible neighborhood location. DESIGN: Street-recruited IDUs (N = 205) were screened for Mycobacterium tuberculosis (TB) infection using the Mantoux test and two controls. Subjects who had a purified protein derivative (PPD) reaction of > or =5 mm, were anergic, or had a history of a positive PPD received clinical evaluation at a community field site, provided in collaboration with the San Francisco Department of Public Health Tuberculosis Clinic. Twenty-eight subjects were considered appropriate candidates for prophylaxis with isoniazid, and 27 enrolled in the pilot study. Participants received twice-weekly DOPT at a community satellite office, with a $10 cash incentive at each visit. RESULTS: The 6-month (26-week) regimen was completed by 24/27 (89%) participants. The median time to treatment completion was 27 weeks (range 26 to 34 weeks). The median proportion of dosing days attended in 6 months was 96%. CONCLUSION: Community-based DOPT using cash incentives resulted in high levels of adherence and treatment completion among drug users.

Risk factors among IDUs who give injections to or receive injections from other drug users.

AIMS: To assess risk factors associated with injection drug users (IDUs) who give injections to or receive injections from other IDUs. DESIGN AND SETTING: IDUs were recruited into a cross-sectional study using targeted sampling methods in Oakland, Richmond, and San Francisco, California from August 1996 to January 1997. "Street docs" are IDUs who reported having given injections to other IDUs in the past month. "Injection recipients" are IDUs who reported having received injections from other people in the past month. PARTICIPANTS: Of 1166 IDUs interviewed, 283 (24%) reported being injection recipients and 427 (37%) reported being street docs. MEASUREMENTS: Socio-demographic characteristics and injection-related risk behaviors. FINDINGS: Injection recipients and street docs were significantly more likely (p < 0.001) than other IDUs to report sharing syringes (33% of injection recipients, 21% of street docs and 7% of others), cookers (71% of injection recipients, 55% of street docs and 24% of others), rinse water (44% of injection recipients, 35% of street docs and 13% of others), and filters (60% of injection recipients, 47% of street docs and 20% of others). In a logistic regression model, injection recipients (adjusted odds ratio (AOR) = 4.29) and street docs (AOR = 1.91) were more likely than other IDUs to report having shared syringes. CONCLUSIONS: Giving and receiving injections is common among IDUs in the San Francisco Bay area. Qualitative and epidemiological studies are needed to understand better the infectious disease risks associated with giving and receiving injections. Interventions need to address these issues and provide practical solutions.

Use of an illegal syringe exchange and injection-related risk behaviors among street-recruited injection drug users in Oakland, California, 1992 to 1995.

OBJECTIVE: To determine factors associated with syringe and injection supply sharing among injection drug users (IDUs) in a community with an illegal underground syringe exchange program (SEP). METHODS: From 1992 to 1995, semiannual cross-sectional samples of IDUs were recruited in Oakland, California. To account for multiple observations from the same individual, we used general estimating equations with logit transformations to determine factors associated with sharing syringes and other injection supplies. RESULTS: 1304 IDUs were interviewed; 684 (53%) returned for more than one interview. 2830 interviews were available for analysis. SEP use increased and syringe and supply sharing declined from 1992 to 1995 among study participants. In multivariate analysis, SEP users were less likely to share syringes than non-SEP users (adjusted odds ratio [AOR] = 0.57; 95% confidence interval [CI] = 0.46-0.72). SEP use was not significantly associated with the sharing of injection supplies (AOR = 0.85; 95% CI = 0.68-1.07). Syringe sharing and injection supply sharing were significantly less likely to occur among African American and HIV-positive IDUs. CONCLUSIONS: These data suggest that illegal SEPs can be effective HIV prevention programs. Lower rates of syringe-based risk behaviors among African American and HIV-positive IDUs are encouraging.

HIV seroprevalence among street-recruited injection drug and crack cocaine users in 16 US municipalities.

OBJECTIVES: This study deter- mined human immunodeficiency virus (HIV) seroprevalence and factors associated with HIV infection among street-recruited injection drug users and crack cocaine smokers. METHODS: An analysis was performed on HIV serologies and risk behaviors of 6402 injection drug users and 3383 crack smokers in 16 US municipalities in 1992 and 1993. RESULTS: HIV seroprevalence was 12.7% among injection drug users and 7.5% among crack smokers. Most high-seroprevalence municipalities (>25%) were located along the eastern seaboard of the United States. In high-seroprevalence municipalities, but not in others, HIV seroprevalence was higher for injection drug users than for crack smokers. Among injection drug users, cocaine injection, use of speedballs (cocaine or amphetamines with heroin), and sexual risk behaviors were independently associated with HIV infection. Among crack smokers, sexual risk behaviors were associated with HIV infection. CONCLUSIONS: Injection drug users and crack smokers are at high risk for HIV infection.

Suicidal behavior and sexual/physical abuse among street youth.

OBJECTIVE: To examine the relationship between home life risk factors and suicide attempts among homeless and runaway street youth recruited from both shelters and street locations in Denver, CO; New York City; and San Francisco, CA. METHOD: Street youth 12-19 years old (N = 775) were recruited by street outreach staff in Denver, New York City and San Francisco in 1992 and 1993 and interviewed. Cross-sectional, retrospective data were analyzed to examine the relationship between suicide attempts and antecedent home life variables. Logistic regression was used to identify factors predicting suicide attempts. RESULTS: Forty-eight percent of the females and 27% of the males had attempted suicide. The mean number of suicide attempts was 6.2 (SD = 12.9) for females and 5.1 for males (SD = 7.6). Among females, 70% reported sexual abuse and 35% reported physical abuse. Among males, 24% reported sexual abuse and 35% reported physical abuse. Sexual and physical abuse before leaving home were independent predictors of suicide attempts for females and males. Other home life factors hypothesized to be risk factors for suicide attempts were not significant. Interaction terms were not significant. Among street youth who were sexually or physically abused in this sample, the odds of attempting suicide were 1.9 to 4.3 times the odds of attempting suicide among those not sexually or physically abused. CONCLUSIONS: Interventions attempting to reduce risky behaviors in this population must include assessments of suicidal behaviors as well as components for assisting youth in dealing with the behavioral and emotional sequelae of physical and sexual abuse.

HIV risk profile of drug-using women who have sex with women in 19 United States cities.

The objective of this study was to analyze HIV-related risks of women injection drug users (IDU) and crack cocaine users (CCU) who have sex with women (WSW). IDU and CCU women (N = 3856) were recruited from street settings in 19 U.S. cities between 1992 and 1994. For this study, we analyze data on 231 women who reported female sex partners in the 30 days before interview. In the 30 days before interview, 53% of IDUs had shared syringes, and 66% had shared injection supplies. Only 11 women (6%) always used barrier protection while giving oral sex to women and 5 (3%) while receiving oral sex from women in the 30 days before interview. Fifty percent had sex with men as well as women in the previous 30 days. Thirty percent of women who reported sex with men had used condoms for penile-vaginal sex, and 26% for penile-anal sex. In logistic regression analysis modeling sex with men in the previous 30 days, sex work was predictive, "lesbian" self-identification was protective, and the interaction between these two terms was predictive, while controlling for race and age. Differences in risk perception were significant between women who reported varying sexual risks, but not significant between women who reported varying injection-related risks. There is a high prevalence of risky sex and drug behaviors among drug-using WSWs. There is a need for epidemiological studies specifically geared toward studying risk behaviors among WSWs. Risk reduction activities need to focus on injection-related risks, as well as sex-related risks, among WSWs.

Prevalence of sexual risk behaviour and substance use among runaway and homeless adolescents in San Francisco, Denver and New York City.

We aim to assess the prevalence of HIV sexual risk behaviours and substance use among runaway and homeless adolescents in San Francisco, Denver and New York City. Survey data were examined from 775 runaway and homeless adolescents recruited from street settings and youth agencies during 1992/1993. Nearly all (98%) reported having engaged in sexual intercourse, of whom 49% first had intercourse by the age of 13. Condom use during all vaginal intercourse in the previous 3 months was reported by 42%. Among males, 23% indicated that they had exchanged sex for money, as did 14% of the females. Ninety-seven per cent had used alcohol or drugs and 21% had injected drugs. Overall, 75% reported having had sex while under the influence of alcohol or drugs. Systematic epidemiological studies of this population and the development of innovative interventions are essential to reduce the threat of HIV among runaway and homeless youth.

Impact of law enforcement on syringe exchange programs: a look at Oakland and San Francisco.

Drug paraphernalia and prescription laws make syringe exchange programs (SEPs) illegal in most states in the U.S. Nonetheless, SEPs have been started in 25 states and the District of Columbia as of September 1995. In some states like California and New Jersey, SEPs have operated despite police arrest of volunteers and clients. We examine the impact of police action and threat on SEPs by comparing an underground syringe exchange site (SES) in West Oakland to a tolerated SES in the Fillmore neighborhood of San Francisco. The following data sources are utilized: demographic and service utilization data from Alameda County Exchange (ACE) in West Oakland and Prevention Point Needle and Syringe Exchange (PPNSE) in the Fillmore, San Francisco; demographic and syringe exchange utilization information collected from street-recruited samples of injection drug users (IDUs) in West Oakland and the Fillmore; and participant observation of SES in these two communities. We found that police action and the threat of police action in West Oakland decreased utilization of SEP by IDUs, limited the number and diversity of volunteers at SES, and inhibited the operation and expansion of SEP.