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Director's Report to the National Advisory Council on Drug Abuse - May, 2010

Research Findings - Epidemiology and Etiology Research

Racial and Sex Disparities in Life Expectancy Losses among HIV-infected Persons in the U.S.: Impact of Risk Behavior, Late Initiation, and Early Discontinuation of Antiretroviral Therapy

Researchers sought to evaluate sex and racial/ethnic disparities in life-years lost as a result of HIV risk behavior, late presentation for HIV care, and early discontinuation of HIV care. Using a state-transition model of HIV disease (i.e., the Cost Effectiveness of Preventing AIDS Complications or CEPAC model), they simulated cohorts of HIV-infected persons and compared them with uninfected individuals with similar demographic characteristics in the general population. They estimated non-HIV-related mortality with use of risk-adjusted standardized mortality ratios as well as years of life lost due to late presentation of care and early discontinuation of therapy for HIV infection. Cohort data (N=8091) for these analyses were from the HIV Research Network, an ongoing consortium of primary care sites for HIV-infected patients in 4 regions of the U.S., stratified by sex (75% male) and race/ethnicity (50% African American, 27% White, 21% Hispanic). The analyses indicated that, for HIV-uninfected persons who have risk profiles (i.e., substance abuse and other high risk behaviors) similar to individuals with HIV infection, the projected life expectancy starting at 33 years of age was 34.58 years, compared with 42.91 years for the general US population (i.e., an average of 8.33 years of life lost, even in the absence of HIV infection). Persons with HIV infection lost an additional 11.92 years of life if they received HIV care concordant with current guidelines and an additional 3.30 years due to late presentation for HIV care and early discontinuation of therapy. Survival disparities resulting from late initiation and early discontinuation of therapy were most pronounced for Hispanic HIV-infected men and women (3.90 years). The high-risk behavioral profile of HIV-infected persons, HIV infection itself, late initiation of care, and early discontinuation and inadequate retention in care all lead to substantial decreases in life expectancy. These findings underscore the importance of interventions that address HIV risk behaviors and facilitate earlier linkage and retention in HIV care to improve survival for HIV-infected persons in the U.S. Losina E, Schackman B, Sadownik S, Gebo K, Walensky R, Chiosi J, Weinstein M, Hicks P, Aaronson W, Moore R, Paltiel A, Freedberg K. Racial and sex disparities in life expectancy losses among HIV-infected persons in the United States: Impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy. Clin Infect Dis. 2009; 49 (10): 1570-1578.

Neighborhood Poverty and Injection Cessation in a Sample of Injection Drug Users

Researchers examined the relationship between neighborhood socioeconomic environment and injection drug use cessation using data from the ALIVE (AIDS Linked to the Intravenous Experience), a prospective cohort study of injection drug users in Baltimore, MD. The analysis was based on 1,875 IDU followed from 1990 to 2006, who contributed a total of 19,054 study assessment visits. Respondent address information at each visit was geocoded to the 174 the census tracts that serve as proxies for the City's neighborhoods, and data from the 1990 U.S. Census were used to estimate the percentage of residents living in poverty per census tract. After adjustment for potential time-fixed and time-varying confounders, exposure, and outcome, the analysis found a strong inverse association between neighborhood poverty and injection drug use cessation: Living in a neighborhood with fewer than 10%, compared with more than 30%, of residents in poverty was associated with a 44% increased odds of not injecting in the 6 months prior to the current visit (odds ratio = 1.44, 95% confidence interval: 1.14, 1.82). Socioeconomic deprivation and environmental disorder in a neighborhood have been linked to the presence of drug use networks and drug trafficking. This study suggests that such conditions also have important determinative effects on drug injection behaviors, independent of individual-level characteristics. Nandi A, Glass TA, Cole SR, Chu H, Galea S, Celentano DD, Kirk GD, Vlahov D, Latimer WW, Mehta SH. Neighborhood poverty and injection cessation in a sample of injection drug users. Am J Epidemiol. 2010; 171(4): 391-398.

Early Mortality and Cause of Deaths in Patients Using HAART in Brazil and the United States

Researchers from the U.S. and Brazil collaborated in the analysis of patterns of mortality and causes of death among patients in their HIV clinical cohorts who initiated HAART. The collaboration was made possible because both cohort studies used similar data collection methods over approximately the same time periods. Cohort data were combined from the Johns Hopkins HIV/AIDS Clinical Cohort in Baltimore and by the Evandro Chagas Clinical Research Institute AIDS Clinic in Rio de Janeiro, Brazil for all participants who entered either cohort between 1999 and 2007 as antiretroviral naïve and, at their first one-year follow-up assessment, had initiated HAART. Cox proportional hazards regression analysis was used to assess the role of the city on the risk of death. A total of 859 and 915 participants from Baltimore and Rio de Janeiro, respectively, were included in the analysis. There were significant differences between Rio de Janeiro and Baltimore in terms of patient age [median 41 years in Rio; 39 years in Baltimore] and HIV risk group [51.2% heterosexual and 29.1% MSM in Rio; 36.2% IDU and 38.5% heterosexual in Baltimore]. There were 34 (3.7%) deaths in Rio and 45 (5.2%) deaths in Baltimore within the first year after initiation of HAART. In Rio de Janeiro, 64.7% of deaths occurred within 90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365 days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%) predominated as causes of death in Rio de Janeiro and Baltimore, respectively. Risk of death was similar in both cities after adjusting for CD4 T cell count, age, sex, HIV risk group, prior AIDS-defining illness, and opportunistic infections; patients with a CD4 T cell count less than or equal to 50 cells/microl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P = 0.03) were more likely to die. These results indicate that late HIV diagnosis is a problem in both developed and developing countries, although differences in timing and in causes of deaths suggest that, besides interventions for early HIV diagnosis, different strategies to curb early mortality need to be tailored in each country. Grinsztejn B, Veloso V, Friedman R, Moreira R, Luz P, Campos D, Pilotto J, Cardoso S, Keruly J, Moore R. Early mortality and cause of deaths in patients using HAART in Brazil and the United States. AIDS. 2009; 23 (16): 2107-2114.

Social and Behavioral Correlates of Sexually Transmitted Infection- and HIV-discordant Sexual Partnerships in Bushwick, Brooklyn, New York

Researchers analyzed data collected during a social network study conducted from 2002 to 2005 in Bushwick, a Brooklyn, NY, neighborhood, that sought to examine linkages between high risk and low risk individuals that may influence patterns of drug use and HIV. The analysis focused on identifying social and behavioral characteristics of respondents (N = 343) involved in HIV-discordant, herpes simplex virus-2- discordant, and chlamydia-discordant partnerships. Just over half the 343 participants were male (53%), the mean age was 33 for men and 27 for women, and the sample was 70% Latino and 21% African American. Nearly 75% reported they had used crack, cocaine, or heroin by non-injection; 38% had ever injected, and all had used non-injection drugs. Almost half (48%) were HSV-2-infected, 10% HIV-infected, and 6% were infected with chlamydia. HIV partnership discordance was associated with injection drug use, but was generally not associated with sexual behaviors including multiple partnerships and sex trade. Herpes simplex virus-2 and chlamydia partnership discordance were associated with multiple partnerships, sex trade, and same-sex partnership history. Additional correlates of sexually transmitted infection (STI)/HIV-discordant partnerships included older age (>or=25 years), noninjection drug use, and incarceration history. The analyses also examined the sensitivity and specificity of CDC's screening tools composed of recommended sexual risk and injection drug indicators for identifying priority risk groups and found that, by adding the social and behavioral indicators correlated with STI/HIV discordance, there was a significant improvement in STI/HIV case-finding effectiveness. Khan MR, Bolyard M, Sandoval M, Mateu-Gelabert P, Krauss B, Aral SO, Friedman SR J AIDS. 2009; 51(4): 470-485.

Emergency Department Utilization among HIV-infected Patients in a Multisite Multistate Study

The aim of this study was to examine Emergency Department (ED) utilization and clinical and sociodemographic correlates of ED use among HIV-infected patients. During 2003, 951 patients participated in face-to-face interviews at 14 HIV clinics in the U.S. multisite, multistate HIV Research Network. Gender, age, race/ethnicity, the reported means of becoming HIV-infected, CD4 cell count in 2003, and the proportion with an undetectable viral load were similar between respondents and in the larger population of patients at these clinics. Using logistic regression, researchers identified factors associated with visiting the ED in the last 6 months and admission to the hospital from the ED. Thirty-two per cent of respondents reported at least one ED visit in the last 6 months. In multivariate analysis, any ED use was associated with Medicaid insurance, high levels of pain (the third or fourth quartile), more than seven primary care visits in the last 6 months, current or former illicit drug use, social alcohol use and female gender. Of those who used ED services, 39% reported at least one admission to the hospital. Patients with pain in the highest quartile reported increased admission rates from the ED as did those who made six or seven primary care visits, or more than seven primary care visits vs. three or fewer. These findings indicate that the likelihood of visiting the ED has not diminished since the advent of highly active antiretroviral therapy (HAART). More ED visits were for treatment of illnesses not related to HIV or injuries than to treat direct sequelae of HIV infection. The findings suggest that, with the growing prevalence of people living with HIV infection in the U.S., the numbers of HIV-infected patients visiting the ED may increase. ED providers will also need to identify and understand the potential complications associated with HIV disease. Josephs J, Fleishman J, Korthuis P, Moore R, Gebo K, Gebo K. Emergency department utilization among HIV-infected patients in a multisite multistate study. HIV Med. 2010; 11(1): 74-84.

Smoking of Crack Cocaine as a Risk Factor for HIV Infection among People who Use Injection Drugs

Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, researchers sought to examine whether use of this illicit drug has become a risk factor for HIV infection. They analyzed data from 1048 participants in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrollment, lived in the greater Vancouver area, were HIV-negative at enrollment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, they used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996-Nov. 30, 1999 (period 1), Dec. 1, 1999-Nov. 30, 2002 (period 2), and Dec. 1, 2002-Dec. 30, 2005 (period 3). Of the 1048 participants, 137 acquired HIV infection during follow-up. The mean proportion who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, researchers found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57-1.85; period 2: HR 1.68, 95% CI 1.01-2.80; and period 3: HR 2.74, 95% CI 1.06-7.11). These results indicate that smoking of crack cocaine is an independent risk factor for HIV seroconversion among people who inject drugs, underscoring the need for evidence-based public health initiatives targeted at people who smoke crack cocaine. DeBeck K, Kerr T, Li K, Fischer B, Buxton J, Montaner J, Wood E. Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs. CMAJ. 2009; 181(9): 585-589.

Unstable Housing and Hepatitis C Incidence among Injection Drug Users in a Canadian Setting

There has been a growing recognition of the link between housing and health, and in Vancouver, Canada, there have been increasing concerns about homelessness brought about by urban renewal in the lead-up to the 2010 Winter Olympic Games. Researchers sought to evaluate hepatitis C virus (HCV) incidence among injection drug users (IDU) with and without stable housing in Vancouver. Data were derived from two prospective cohort studies of IDU in Vancouver, Canada. Cox Proportional Hazards regression was used to compare HCV incidence among participants with and without stable housing, and to determine independent predictors of HCV incidence. Overall, 3074 individuals were recruited between May 1996 and July 2007, among whom 2541 (82.7%) were baseline HCV-infected. Among the 533 (17.3%) individuals who were not HCV-infected at baseline, 147 tested HCV antibody-positive during follow-up, for an incidence density of 16.89 (95% confidence interval: 14.76 - 19.32) per 100 person-years. In a multivariate Cox regression model, unstable housing remained independently associated with HCV infection (relative hazard = 1.47 (1.02 - 2.13). These findings indicate that HCV prevalence and incidence are high in this setting and are associated with unstable housing. Efforts to protect existing low-income housing and improve access to housing may help to reduce HCV incidence. Kim C, Kerr T, Li K, Zhang R, Tyndall M, Montaner J, Wood E. Unstable housing and hepatitis C incidence among injection drug users in a Canadian setting. BMC Public Health. 2009; 9: 270-276.

Multistage Genomewide Association Study Identifies a Locus at 1q41 Associated with Rate of HIV-1 Disease Progression to Clinical AIDS

A mean of 9-10 years of HIV-1 infection elapses before clinical AIDS develops in untreated persons, but this rate of disease progression varies substantially among individuals. To investigate host genetic determinants of the rate of progression to clinical AIDS, researchers performed a multistage genomewide association study. The discovery stage comprised 156 individuals from the Multicenter AIDS Cohort Study, enriched with rapid and long-term nonprogressors to increase statistical power. This was followed by replication tests of putatively associated genotypes in an independent population of 590 HIV-1-infected seroconverters from five natural history cohorts of persons with HIV/AIDS (including the ALIVE and MACS). Significant associations with delayed AIDS progression were observed in a haplotype located at 1q41, 36 kb upstream of PROX1 on chromosome 1 (relative hazard ratio, 0.69; Fisher's combined P = 6.23 X 10(-7)). This association was replicated further in an analysis stratified by transmission mode, with the effect consistent in sexual or mucosal and parenteral transmission (relative hazard ratios, 0.72 and 0.63, respectively; combined P = 1.63 X 10(-6)). This study identified and replicated a locus upstream of PROX1 that is associated with delayed progression to clinical AIDS. PROX1 is a negative regulator of interferon-gamma expression in T cells and also mitigates the advancement of vascular neoplasms, such as Kaposi sarcoma, a common AIDS-defining malignancy. This study adds to information about the cumulative polygenic host component that effectively regulates the progression to clinical AIDS among HIV-1-infected individuals, raising prospects for potential new avenues for therapy and improvements in AIDS prognosis. Herbeck J, Gottlieb G, Winkler C, Nelson G, An P, Maust B, Wong K, Troyer J, Goedert J, Kessing B, Detels R, Wolinsky S, Martinson J, Buchbinder S, Kirk G, Jacobson L, Margolick J, Kaslow R, O 'Brien S, Mullins J. Multistage genomewide association study identifies a locus at 1q41 associated with rate of HIV-1 disease progression to clinical AIDS. J Infect Dis. 2010; 201(4): 618-626.

Characterization of the Emerging HIV Type 1 and HCV Epidemics among Injecting Drug Users in Dushanbe, Tajikistan

This study sought to determine HIV, HCV, and syphilis prevalence and correlates, and to characterize the molecular epidemiology of HIV-1 among IDUs in Dushanbe, Tajikistan. A cross-sectional study was conducted to assess risk factors for HIV and HCV using an interview survey. A total of 491 active adult IDUs were recruited from May to November 2004 in Dushanbe, Tajikistan. HIV-1 antibody status was determined with rapid testing and confirmed with ELISA. HCV antibody testing was conducted using a BIOELISA HCV kit. HIV-1 subtyping was completed on a subset with full-length sequencing. Correlates of HIV and HCV infection were assessed using logistic regression. Overall prevalence of HIV was 12.1%, HCV was 61.3%, and syphilis was 15.7%. In a multivariate logistic regression model controlling for gender and ethnicity, daily injection of narcotics [odds ratio (OR) OR 3.22] and Tajik nationality (OR 7.06) were significantly associated with HIV status. Tajik nationality (OR 1.91), history of arrest (OR 2.37), living/working outside Tajikistan in the past 10 years (OR 2.43), and daily injection of narcotics (OR 3.26) were significantly associated with HCV infection whereas being female (OR 0.53) and always using a sterile needle (OR 0.47) were inversely associated with HCV infection. Among 20 HIV-1-positive IDU with specimens available for typing, 10 were subtype A, 9 were CRF02_AG, and one was an A-CRF02_AG recombinant. Epidemics of HIV-1, HCV, and drug use are underway in Dushanbe. The molecular epidemiology is distinctive, with West African variants accounting for roughly 50% of prevalent infections. These findings underscore the need for targeted prevention programs that offer both needle exchange programs and opiate substitution therapies to prevent further epidemic spread of HIV and HCV in Tajikistan. Beyrer C, Patel Z, Stachowiak J, Tishkova F, Stibich M, Eyzaguirre L, Carr J, Mogilnii V, Peryshkina A, Latypov A, Strathdee S. Characterization of the emerging HIV type 1 and HCV epidemics among injecting drug users in Dushanbe, Tajikistan. AIDS Res Hum Retroviruses. 2009; 25(9): 853-860.

Temporal Trends in Spatial Access to Pharmacies that Sell Over-the-Counter Syringes in New York City Health Districts: Relationship to Local Racial/Ethnic Composition and Need

Pharmacies that sell over-the-counter (OTC) syringes are a major source of sterile syringes for injection drug users in cities and states where such sales are legal. In these cities and states, however, black injectors are markedly less likely to acquire syringes from pharmacies than white injectors. This analysis documents spatial and temporal trends in OTC pharmacy access in New York City health districts over time (2001-2006) and investigates whether these trends are related to district racial/ethnic composition and to local need for OTC pharmacies. For each year, researchers estimated spatial access to OTC pharmacies within each health district, with higher values indicating better access to the pharmacies. "Need" was computed using two the indices, the number of newly diagnosed injection-related AIDS cases per 10,000 residents (averaged across 1999-2001) and the number of drug-related hospital discharges per 10,000 residents (averaged across 1999-2001). District sociodemographic characteristics were assessed using 2000 US decennial census data. Hierarchical linear models (HLM) were used for descriptive and inferential analyses of whether the relationship between need and temporal trajectories in accessing the Expanded Syringe Access Demonstration Program varied by district racial/ethnic composition after controlling for district poverty rates. The analyses indicated that mean spatial access to OTC pharmacies across NYC health districts was 12.71 in 2001 and increased linearly by 1.32 units annually thereafter. Temporal trajectories in spatial access to OTC pharmacies depended on both need and racial/ethnic composition. Within high-need districts, OTC pharmacy access was twice as high in 2001 and increased three times faster annually in districts with higher proportions of non-Hispanic white residents versus districts with low proportions of these residents. In low-need districts, "whiter" districts had substantially greater baseline access to OTC pharmacies than districts with low proportions of non-Hispanic white residents. Access remained stable thereafter in low-need districts, regardless of racial/ethnic composition. The results show that in both high- and low-need districts, spatial access to OTC pharmacies was greater in "Whiter" districts in 2001; in high-need districts, access increased more rapidly over the time period in "whiter" districts. These findings highlight the importance of equitable spatial access to OTC pharmacies to help reduce injection-related HIV transmission overall, and to reduce racial/ethnic disparities in HIV incidence among injectors. Cooper H, Bossak B, Tempalski B, Friedman S, Des Jarlais D. Temporal trends in spatial access to pharmacies that sell over-the-counter syringes in New York City health districts: Relationship to local racial/ethnic composition and need. J Urban Health. 2009; 86(6): 929-945.

Factors Associated with Initiation of Ecstasy Use Among US Adolescents: Findings from a National Survey

This study investigated adolescent pathways to ecstasy use by (1) examining how early onsets of smoking, drinking, and marijuana use are related to a child's risk of initiation of ecstasy use and (2) assessing the influence of other individual and parental factors on ecstasy use initiation. Data on 6426 adolescents (12-17 years old at baseline) from the National Survey of Parents and Youth (NSPY), a longitudinal, nationally representative household survey of youth and their parents, were used in the analyses. Information on youth substance use, including ecstasy use, as well as familial and parental characteristics, was available. Findings show that initiation of ecstasy use is predicted by an adolescent's early initiation of smoking, drinking, or marijuana use. In particular, early initiation either of marijuana use, or of both smoking and drinking, increases a child's risk for ecstasy use initiation. Among the familial and parental variables, parent drug use emerged as significantly predictive of child initiation of ecstasy use; living with both parents and close parental monitoring, on the other hand, are negatively associated with ecstasy use initiation, and may be protective against it. At the individual level, sensation seeking tendencies and positive attitudes towards substance use, as well as close associations with deviant peers, are predictive of adolescent initiation of ecstasy use. These findings on the risk and protective factors for initiation of ecstasy use, especially with regard to factors that are modifiable, will be useful for prevention programs targeting youth use not only of ecstasy, but also of other drugs. Wu P, Liu X, Fan B. Factors associated with initiation of ecstasy use among US adolescents: findings from a national survey. Drug Alcohol Depend. 2010; 106(2-3): 193-198.

Syringe Exchange, Injecting and Intranasal Drug Use

Researchers sought to assess trends in injecting and non-injecting drug use after implementation of large-scale syringe exchange in New York City. They were particularly interested in examining the belief that implementation of syringe exchange will lead to increased drug injecting, which has been a persistent argument against syringe exchange. They analyzed administrative records on route of administration for primary drug of abuse among drug users enrolling in the Beth Israel methadone maintenance program from 1995 to 2007. Approximately 2000 participants enter the program each year. The researchers found that during and after the period of large-scale implementation of syringe exchange, the numbers of methadone program entrants reporting injecting drug use decreased while the numbers of entrants reporting intranasal drug use increased (P <0.001). Although it is difficult to assess the possible effects of syringe exchange on trends in injecting drug use, these results may be the strongest to date showing no increase in drug injecting following the implementation of syringe exchange. Des Jarlais D, Arasteh K, McKnight C, Ringer M, Friedman S. Syringe exchange, injecting and intranasal drug use. Addiction. 2010; 105(1): 155-158.

Syphilis in Drug Users in Low and Middle Income Countries

Genital ulcer disease (GUD), including syphilis, is an important cause of morbidity in low and middle income (LMI) countries and syphilis transmission is associated with HIV transmission. Researchers conducted a literature review to evaluate syphilis infection among drug users in LMI countries for the period 1995-2007. Countries were categorized using the World Bank Atlas method according to 2006 gross national income per capita. Thirty-two studies were included (N=13,848 subjects), mostly from Southeast Asia with some from Latin America, Eastern Europe, Central and East Asia, North Africa and the Middle East but none from regions such as Sub-Saharan Africa. The median prevalence of overall lifetime syphilis (N= 32 studies) was 11.1% (interquartile range: 6.3-15.3%) and of HIV (N=31 studies) was 1.1% (interquartile range: 0.22-5.50%). There was a modest relationship (r=0.27) between HIV and syphilis prevalence. Median syphilis prevalence by gender was 4.0% (interquartile range: 3.4-6.6%) among males (N=11 studies) and 19.9% (interquartile range: 11.4-36.0%) among females (N=6 studies). There was a strong relationship (r=0.68) between syphilis prevalence and female gender that may be related to female sex work. Drug users in LMI countries have a high prevalence of syphilis but data are limited and, in some regions, entirely lacking. Further data are needed on the risks among women, for example, to develop effective interventions that promote safer sex, HIV and STD testing, counseling and education and prevent new syphilis infections and reduce HIV transmission among drug users and their partners in LMI countries. Coffin LS, Newberry A, Hagan H, Cleland CM, Des Jarlais DC, Perlman DC. Int J Drug Policy. 2010; 21(1): 20-27.

Survival Sex Work Involvement as a Primary Risk Factor for Hepatitis C Virus Acquisition in Drug-Using Youths in a Canadian Setting

This study examined whether there were differential rates of hepatitis C virus (HCV) incidence in injecting drug-using youths who did and did not report involvement in survival sex work. Data were derived from two prospective cohort studies of injecting drug users (May 1, 1996, to July 31, 2007) in Vancouver, British Columbia, Canada. Analyses were restricted to HCV antibody-negative youths who completed baseline and at least 1 follow-up assessment. Of 3074 injecting drug users, 364 (11.8%) were youths (aged 14-24 years) with a median age of 21.3 years and a duration of injecting drug use of 3 years. The main exposure variable of interest was survival sex work involvement. The Kaplan-Meier method and Cox proportional hazards regression were used to compare HCV incidence among youths who did and did not report survival sex work. Baseline HCV prevalence was 51%, with youths involved in survival sex work significantly more likely to be HCV antibody positive (60% vs 44%; P = .002). In baseline HCV antibody-negative youths, the cumulative HCV incidence at 36 months was significantly higher in those involved in survival sex work (68.4% vs 38.8%; P < .001). The HCV incidence density was 36.8 (95% confidence interval [CI], 24.2-53.5) per 100 person-years in youths reporting survival sex work involvement at baseline compared with 14.1 (9.4-20.3) per 100 person-years in youths not reporting survival sex work. In multivariate Cox proportional hazards analyses, survival sex work was the strongest predictor of elevated HCV incidence (adjusted relative hazard, 2.30; 95% CI, 1.27-4.15). This study calls attention to the role of unsafe sex among youth who also use injecting drugs as a factor in the acquisition of HCV and potentially of other serious infectious diseases including HIV. There is a critical need for evidence-based social and structural HCV prevention efforts that target youths who use injecting drugs and engage in survival sex work. Shannon K, Kerr T, Marshall B, Li K, Zhang R, Strathdee S, Tyndall M, Montaner J, Wood E. Survival sex work involvement as a primary risk factor for hepatitis C virus acquisition in drug-using youths in a Canadian setting. Arch Pediatr Adolesc Med. 2010; 164(1): 61-65.

Binge Use and Sex and Drug Use Behaviors among HIV(-), Heterosexual Methamphetamine Users in San Diego

This study identified sociodemographic factors, drug using practices, sexual behaviors, and motivational factors associated with binge (a period of uninterrupted) methamphetamine (MA) use among heterosexual MA users. The FASTLANE study provided cross-sectional data collected by audio computer-assisted self-interview (ACASI) between June 2001 and August 2004 from 451 HIV-negative MA users in San Diego, California, who had engaged in unprotected sex and used MA in the previous two months. The study sample was 67.8% male, 49.4% Caucasian, 26.8% African-American, and 12.8% Hispanic with a mean age of 36.6 years; 183 (40.5%) reported binge use in the past 2 months. Compared with non-binge users, binge users of MA were more likely to report risky drug use and sex behaviors and differed in motivations to initiate and currently use MA. The final logistic regression model for binge use included more days of MA use in the last month, ever treated for MA use, injection drug use, higher Beck Depression Inventory score, "experimentation" as a motivation for initiating MA use, and engaging in sex marathons while high on MA. HIV prevention efforts should differentiate and address these differences in motivations for MA use and the associated HIV-risk sex and drug use behaviors as key targets for effective intervention. Cheng W, Garfein R, Semple S, Strathdee S, Zians J, Patterson T. Binge use and sex and drug use behaviors among HIV(-), heterosexual methamphetamine users in San Diego. Subst Use Misuse. 2010; 45(1-2): 116-133.

Evaluating the Use of Respondent-Driven Sampling in a Major Metropolitan Area

This study sought to empirically evaluate respondent-driven sampling (RDS) recruitment methods, which have been proposed as an advantageous means of surveying hidden populations. The National HIV Behavioral Surveillance system used RDS to recruit 370 injection drug users (IDU) in the Seattle area in 2005 (NHBS-IDU1). Researchers compared the NHBS-IDU estimates of participants' area of residence, age, race, sex, and drug most frequently injected to corresponding data from two previous surveys, the RAVEN and Kiwi Studies, and to persons newly diagnosed with HIV/AIDS and reported from 2001 through 2005. The NHBS-IDU population was estimated to be more likely to reside in downtown Seattle (52%) than participants in the other data sources (22%-25%), to be older than 50 years of age (29% vs. 5%-10%), and to report multiple races (12% vs. 3%-5%). The NHBS-IDU population resembled persons using the downtown needle exchange in age and race distribution. An examination of cross-group recruitment frequencies in NHBS-IDU suggested barriers to recruitment across different areas of residence, races, and drugs most frequently injected. These results indicate that substantial differences in age and area of residence between NHBS-IDU and the other data sources suggest that RDS may not have accessed the full universe of Seattle area injection networks. Further empirical data are needed to guide the evaluation of RDS-generated samples. Burt RD, Hagan H, Sabin K, Thiede H. Evaluating respondent-driven sampling in a major metropolitan area: Comparing injection drug users in the 2005 Seattle area national HIV behavioral surveillance system survey with participants in the RAVEN and Kiwi studies. Ann Epidemiol. 2010; 20(2): 159-167.

Health Outcomes and Costs of Community Mitigation Strategies for an Influenza Pandemic in the United States

The optimal community-level approach to control pandemic influenza is unknown. Researchers estimated the health outcomes and costs of combinations of 4 social distancing strategies and 2 antiviral medication strategies to mitigate an influenza pandemic for a demographically typical US community. They used a social network, agent-based model to estimate strategy effectiveness and an economic model to estimate health resource use and costs and data from the literature to estimate clinical outcomes and health care utilization. They found that, at 1% influenza mortality, moderate infectivity (R(o) of 2.1 or greater), and 60% population compliance, the preferred strategy is adult and child social distancing, school closure, and antiviral treatment and prophylaxis. This strategy reduces the prevalence of cases in the population from 35% to 10%, averts 2480 cases per 10,000 population, costs $2700 per case averted, and costs $31,300 per quality-adjusted life-year gained, compared with the same strategy without school closure. The addition of school closure to adult and child social distancing and antiviral treatment and prophylaxis, if available, is not cost-effective for viral strains with low infectivity (R(o) of 1.6 and below) and low case fatality rates (below 1%). High population compliance lowers costs to society substantially when the pandemic strain is severe (R(o) of 2.1 or greater). The findings show that multilayered mitigation strategies that include adult and child social distancing, use of antivirals, and school closure are cost-effective for a moderate to severe pandemic. Choice of strategy should be driven by the severity of the pandemic, as defined by the case fatality rate and infectivity. Perlroth DJ, Glass RJ, Davey VJ, Cannon D, Garber AM, Owens DK. Health outcomes and costs of community mitigation strategies for an influenza pandemic in the United States. Clin Infect Dis. 2010; 50(2):165-174.

Effectiveness and Cost-Effectiveness of Expanded Antiviral Prophylaxis and Adjuvanted Vaccination Strategies for an Influenza A (H5N1) Pandemic

The pandemic potential of influenza A (H5N1) virus is a prominent public health concern of the 21st century. This study estimated the effectiveness and cost-effectiveness of alternative pandemic (H5N1) mitigation and response strategies. A compartmental epidemic model was used in conjunction with a Markov model of disease progression, drawing data from the literature and expert opinion. Residents of a U.S. metropolitan city with a population of 8.3 million were the target population, over the lifetime. The interventions involved 3 scenarios: 1) vaccination and antiviral pharmacotherapy in quantities similar to those currently available in the U.S. stockpile (stockpiled strategy), 2) stockpiled strategy but with expanded distribution of antiviral agents (expanded prophylaxis strategy), and 3) stockpiled strategy but with adjuvanted vaccine (expanded vaccination strategy). All scenarios assumed standard non-pharmaceutical interventions. The outcome measures were infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. The base-case analysis showed that expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404 030 QALYs at $10,844 per QALY gained relative to the stockpiled strategy. Expanded vaccination remained incrementally cost-effective over a wide range of assumptions. The model assumed homogenous mixing of cases and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread, and interventions were not modeled for children or older adults; the model is not designed to target interventions to specific groups. Results indicate that expanded adjuvanted vaccination is an effective and cost-effective mitigation strategy for an influenza A (H5N1) pandemic. Expanded antiviral prophylaxis can help delay the pandemic while additional strategies are implemented. Khazeni N, Hutton DW, Garber AM, Owens DK. Effectiveness and cost-effectiveness of expanded antiviral prophylaxis and adjuvanted vaccination strategies for an influenza A (H5N1) pandemic. Ann Intern Med. 2009; 151(12): 840-853.

Parsing Social Network Survey Data from Hidden Populations Using Stochastic Context-Free Grammars

Human populations are structured by social networks in which individuals tend to form relationships based on shared attributes. Certain attributes that are ambiguous, stigmatized or illegal can create a hidden population, so-called because its members are difficult to identify. Many hidden populations are also at an elevated risk of exposure to HIV and other infectious diseases. Consequently, public health agencies are adopting modern survey techniques that traverse social networks in hidden populations by soliciting individuals to recruit their peers, e.g., respondent-driven sampling (RDS). The concomitant accumulation of network-based epidemiological data, however, is rapidly outpacing the development of computational methods for analysis. Moreover, current analytical models rely on unrealistic assumptions, such as that the traversal of social networks can be modeled by a Markov chain rather than a branching process. In this analysis, researchers developed a new methodology based on stochastic context-free grammars (SCFGs) that are well-suited to modeling tree-like structure of the RDS recruitment process. They applied this methodology to an RDS case study of injection drug users (IDUs) in Tijuana, Mˇxico, a hidden population at high risk of blood-borne and sexually-transmitted infections (i.e., HIV, hepatitis C virus, syphilis). Survey data were encoded as text strings that were parsed using a customized implementation of the inside-outside algorithm in a publicly-available software package (HyPhy), which uses either expectation maximization or direct optimization methods and permits constraints on model parameters for hypothesis testing. The researchers identified significant latent variability in the recruitment process that violates assumptions of Markov chain-based methods for RDS analysis: firstly, IDUs tended to emulate the recruitment behavior of their own recruiter; and secondly, the recruitment of like peers (homophily) was dependent on the number of recruits. These findings indicate that SCFGs provide a rich probabilistic language that can articulate complex latent structure in survey data derived from the traversal of social networks. Such structure—that has no representation in Markov chain-based models—can interfere with the estimation of the composition of hidden populations if left unaccounted for, raising critical implications for the prevention and control of infectious disease epidemics. Poon A, Brouwer K, Strathdee S, Firestone-Cruz M, Lozada R, Pond S, Heckathorn D, Frost S. Parsing social network survey data from hidden populations using stochastic context-free grammars. PLoS One. 2009; 4(9): 6777-6786.

The Reliability and Validity of Drug Users' Self Reports of Amphetamine Use among Primarily Heroin and Cocaine Users

Relatively few studies have addressed the psychometric properties of self-report measures of amphetamine use. This study examines the reliability and validity of the Risk Behavior Assessment's (RBA) lifetime and recent amphetamine-use questions. To evaluate validity, 4027 out-of-treatment primarily cocaine and heroin users provided urine samples that were compared to self-report data; to evaluate reliability, 218 completed the RBA at two time points, 48h apart. In the overall sample, self-reports demonstrated moderately high validity, with a 95% accuracy rate (kappa=.54). When analysis was restricted to recent amphetamine users validity was lower (71.5% accuracy; kappa=.41). Test-retest data indicated good reliability for self-reports of ever having used amphetamine (kappa=.79), and amphetamine use in the past 30 days (.75<r (.75<r<.91). Out-of-treatment drug users provided accurate self-reports of amphetamine use. Reliable and valid measures are essential for describing and predicting trends in amphetamine use, evaluating the effectiveness of interventions, and developing policies and programs. Napper L, Fisher DG, Johnson ME, Wood M. The reliability and validity of drug users' self reports of amphetamine use among primarily heroin and cocaine users. Addict Behav. 2010; 35(4): 350-354.

Examining Factorial Structure and Measurement Invariance of the Brief Symptom Inventory (BSI)-18 among Drug Users

The purpose of this study was to examine the factorial structure of the Brief Symptom Inventory 18 (BSI-18) and test its measurement invariance among different drug using populations. A total sample of 710 drug users was recruited using respondent-drive sampling (RDS) from three states: Ohio (n=248), Arkansas (n=237), and Kentucky (n=225). The results of confirmatory factor analysis (CFA) showed: 1) the BSI-18 has a three-factor structure (somatization, depression, and anxiety) with an underlying second-order factor (global severity index of distress); and 2) its factorial structure and metric (factor loadings) are invariant across populations under study. However, the scalars (intercepts) of the BSI-18 items are not invariant, and the means of the latent factors also varied across populations. The findings provide evidence of a valid factorial structure of the BSI-18 that can be readily applied to studying drug using populations. Wang J, Kelly BC, Booth BM, Falck RS, Leukefeld C, Carlson RG. Examining factorial structure and measurement invariance of the Brief Symptom Inventory (BSI)-18 among drug users. Addict Behav. 2010; 35(1): 23-29.

Opt-out Testing for Stigmatized Diseases: A Social Psychological Approach to Understanding the Potential Effect of Recommendations for Routine HIV Testing

Few studies have examined experimentally whether an opt-out policy will increase testing rates or whether this strategy is especially effective in the case of stigmatized diseases such as HIV. In this research, one study using a 2 x 2 factorial design asked 118 participants (63 men, 55 women, average age 23 years) to make moral judgments about a person's decision to test for stigmatized diseases under an opt-in versus an opt-out policy. In another study, a 2 x 2 factorial design measuring testing rates explored whether opt-out methods reduce stigma and increase testing for stigmatized diseases in a group of 79 undergraduates (32 men, 47 women, average age 19.8 years). The first study found that getting HIV tested draws suspicion regarding moral conduct in an opt-in system, whereas not getting tested draws suspicion in an opt-out system. The second study found that an opt-out policy may increase testing rates for stigmatized diseases and lessen the effects of stigma in people's reluctance to test. These findings suggest that a social psychological approach to health services can be used to show how HIV testing policies can influence both the stigmatization associated with testing and participation rates. An understanding of how HIV testing policies may affect patient decision making and behavior is imperative for creating effective testing policies. Young SD, Monin B, Owens DK. Opt-out testing for stigmatized diseases: a social psychological approach to understanding the potential effect of recommendations for routine HIV testing. Health Psychol. 2009; 28(6): 675-681.


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