Michael Plankey

The relationship between methamphetamine and popper use and risk of HIV seroconversion in the multicenter AIDS cohort study

Background:The association between methamphetamine use and HIV seroconversion for men who have sex with men (MSM) was examined using longitudinal data from the Multicenter AIDS Cohort Study. Methods:Seronegative (n = 4003) men enrolled in 1984 to 1985, 1987 to 1991, and 2001 to 2003 were identified. Recent methamphetamine and popper use was determined at the current or previous visit. Time to HIV seroconversion was the outcome of interest. Covariates included race/ethnicity, cohort, study site, educational level, number of sexual partners, number of unprotected insertive anal sexual partners, number of unprotected receptive anal sexual partners, insertive rimming, cocaine use at the current or last visit, ecstasy use at the current or last visit, any needle use since the last visit, Center for Epidemiologic Study of Depression symptom checklist score >16 since the last visit, and alcohol consumption. Results:After adjusting for covariates, there was a 1.46 (95% confidence interval [CI]: 1.12 to 1.92) increased relative hazard of HIV seroconversion associated with methamphetamine use. The relative hazard associated with popper use was 2.10 (95% CI: 1.63 to 2.70). The relative hazard of HIV seroconversion increased with the number of unprotected receptive anal sexual partners, ranging from 1.87 (95% CI: 1.40 to 2.51) for 1 partner to 9.32 (95% CI: 6.21 to 13.98) for 5+ partners. The joint relative hazard for methamphetamine and popper use was 3.05 (95% CI: 2.12 to 4.37). There was a significant joint relative hazard for methamphetamine use and number of unprotected receptive anal sexual partners of 2.71 (95% CI: 1.81 to 4.04) for men with 1 unprotected receptive anal sexual partner, which increased in a dose-dependent manner for >1 partners. Conclusions:Further examination of the mechanisms underlying the synergism of drug use and sexual risk behaviors on rates of HIV seroconversion is necessary for the development of new targeted HIV prevention strategies for nonmonogamous drug-using MSM.

Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women.

Background:Longitudinal associations between patterns of crack cocaine use and progression of HIV-1 disease are poorly understood, especially among women. This study explores relationships between crack use and HIV-1 disease outcomes in a multicenter cohort of infected women. Methods:Subjects were 1686 HIV-seropositive women enrolled at six US research centers in the Womens Interagency HIV Study. Approximately 80% were non-white and 29% used crack during the study period. Cox survival and random regression analysis examined biannual observations made April 1996 through September 2004. Outcome measures included death due to AIDS-related causes, CD4 cell count, HIV-1 RNA level, and newly acquired AIDS-defining illnesses. Results:Persistent crack users were over three times as likely as non-users to die from AIDS-related causes, controlling for use of HAART self-reported at 95% or higher adherence, problem drinking, age, race, income, education, illness duration, study site, and baseline virologic and immunologic indicators. Persistent crack users and intermittent users in active and abstinent phases showed greater CD4 cell loss and higher HIV-1 RNA levels controlling for the same covariates. Persistent and intermittent crack users were more likely than non-users to develop new AIDS-defining illnesses controlling for identical confounds. These results persisted when controlling for heroin use, tobacco smoking, depressive symptoms, hepatitis C virus coinfection, and injection drug use. Conclusion:Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women.

Application of syndemic theory to black men who have sex with men in the Multicenter AIDS Cohort Study.

This study analyzed data from a large prospective epidemiologic cohort study among men who have sex with men (MSM), the Multicenter AIDS Cohort Study, to assess syndemic relationships among Black MSM in the cohort (N = 301). We hypothesized that multiple interconnections among psychosocial health conditions would be found among these men, defining syndemic conditions. Constituents of syndemic conditions measured included reported depression symptoms, sexual compulsiveness, substance use, intimate partner violence (IPV), and stress. We found significant evidence of syndemics among these Black men: depression symptoms were independently associated with sexual compulsiveness (odds ratios [OR]: 1.88, 95% CI = 1.1, 3.3) and stress (OR: 2.67, 95% CI = 1.5, 4.7); sexual compulsiveness was independently associated with stress (OR: 2.04, 95% CI = 1.2, 3.5); substance misuse was independently associated with IPV (OR: 2.57, 95% CI = 1.4, 4.8); stress independently was associated with depression symptoms (OR: 2.67, 95% CI = 1.5, 4.7), sexual compulsiveness (OR: 2.04, 95% CI = 1.2, 3.5) and IPV (OR: 2.84, 95% CI = 1.6, 4.9). Moreover, men who reported higher numbers of syndemic constituents (three or more conditions) reportedly engaged in more unprotected anal intercourse compared to men who had two or fewer health conditions (OR: 3.46, 95% CI = 1.4–8.3). Findings support the concept of syndemics in Black MSM and suggest that syndemic theory may help explain complexities that sustain HIV-related sexual transmission behaviors in this group.

Adversity and Syndemic Production Among Men Participating in the Multicenter AIDS Cohort Study: A Life-Course Approach

OBJECTIVES We tested a theory of syndemic production among men who have sex with men (MSM) using data from a large cohort study. METHODS Participants were 1551 men from the Multicenter AIDS Cohort Study enrolled at 4 study sites: Baltimore, Maryland-Washington, DC; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Participants who attended semiannual visits from April 1, 2008, to March 31, 2009, completed an additional survey that captured data about events throughout their life course thought to be related to syndemic production. RESULTS Using multivariate analysis, we found that the majority of life-course predictor variables (e.g., victimization, internalized homophobia) were significantly associated with both the syndemic condition and the component psychosocial health outcomes (depressive symptoms, stress, stimulant use, sexual compulsivity, intimate partner violence). A nested negative binomial analysis showed that the overall life course significantly explained variability in the syndemic outcomes (χ(2) = 247.94; P < .001; df = 22). CONCLUSIONS We identified life-course events and conditions related to syndemic production that may help to inform innovative interventions that will effectively disentangle interconnecting health problems and promote health among MSM.

It Gets Better: Resolution of Internalized Homophobia Over Time and Associations with Positive Health Outcomes Among MSM

Health disparities research among gay and bisexual men has focused primarily on risk and deficits. However, a focus on resiliencies within this population may greatly benefit health promotion. We describe a pattern of resilience (internalized homophobia (IHP) resolution) over the life-course and its associations with current health outcomes. 1,541 gay and bisexual men from the Multi-Center AIDS Cohort study, an ongoing prospective study of the natural and treated histories of HIV, completed a survey about life-course events thought to be related to health. The majority of men resolved IHP over time independent of demographics. Men who resolved IHP had significantly higher odds of positive health outcomes compared to those who did not. These results provide evidence of resilience among participants that is associated with positive health outcomes. Understanding resiliencies and incorporating them into interventions may help to promote health and well-being among gay and bisexual men.

Marginal and Mixed-Effects Models in the Analysis of Human Papillomavirus Natural History Data

Human papillomavirus (HPV) natural history has several characteristics that, at least from a statistical perspective, are not often encountered elsewhere in infectious disease and cancer research. There are, for example, multiple HPV types, and infection by each HPV type may be considered separate events. Although concurrent infections are common, the prevalence, incidence, and duration/persistence of each individual HPV can be separately measured. However, repeated measures involving the same subject tend to be correlated. The probability of detecting any given HPV type, for example, is greater among individuals who are currently positive for at least one other HPV type. Serial testing for HPV over time represents a second form of repeated measures. Statistical inferences that fail to take these correlations into account would be invalid. However, methods that do not use all the data would be inefficient. Marginal and mixed-effects models can address these issues but are not frequently used in HPV research. The current study provides an overview of these methods and then uses HPV data from a cohort of HIV-positive women to illustrate how they may be applied, and compare their results. The findings show the greater efficiency of these models compared with standard logistic regression and Cox models. Because mixed-effects models estimate subject-specific associations, they sometimes gave much higher effect estimates than marginal models, which estimate population-averaged associations. Overall, the results show that marginal and mixed-effects models are efficient for studying HPV natural history, but also highlight the importance of understanding how these models differ. Cancer Epidemiol Biomakers Prev; 19(1); 159–69

Prevalence and predictors of metabolic syndrome among HIV-infected and HIV-uninfected women in the women's interagency HIV Study

Objectives:To assess the prevalence of metabolic syndrome (MetSynd) among participants of the Womens Interagency HIV Study and to describe the association of MetSynd with HIV infection, antiretroviral therapies, and sociodemographic factors. Methods:Prevalence of MetSynd, defined by updated Adult Treatment Panel III guidelines, was assessed among 2393 (1725 seropositive and 668 seronegative) participants from the Womens Interagency HIV Study seen between October 2000 and October 2004. Results:HIV-1 infection was independently associated with MetSynd [33% vs 22%, P < 0.0001 in HIV-seropositive compared with HIV-seronegative women; adjusted odds ratio (OR) 1.79 (95% confidence interval 1.48, 2.16)]. HIV-infected women had higher mean triglyceride (154 vs 101 mg/dL, P < 0.0001) and lower mean high-density lipoprotein cholesterol levels (46 vs 55 mg/dL, P < 0.0001). Most notable factors associated with higher prevalence of MetSynd among HIV-infected women included older age (OR = 1.38 per 5 year increase, P < 0.0001); higher body mass index; current smoking; HIV-1 RNA (OR = 1.36, P = 0.019, for >50,000 vs <80 copies/mL); and use of stavudine (OR = 1.28, P = 0.009). Nevirapine use was protective (OR = 0.75, P = 0.016). There was no significant association of MetSynd with ritonavir-boosted protease inhibitors (OR = 1.15, P = 0.134). Conclusions:MetSynd is more prevalent in HIV-seropositive than HIV-seronegative women. This increased prevalence was due to dyslipidemias rather than higher blood pressure, glucose, or waist circumference.

Association of the IFNL4-ΔG Allele With Impaired Spontaneous Clearance of Hepatitis C Virus

Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Womens Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10(-5)) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P = .86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10(-14)) for IFNL4-TT/TT and 1.44 (P = .03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.

Effects of syndemics on HIV viral load and medication adherence in the multicentre AIDS cohort study.

Objectives:The objective of this study is to determine associations between intertwining epidemics (syndemics) and HIV medication adherence and viral load levels among HIV-positive MSM and to test whether adherence mediates the relationship between syndemics and viral load. Design:We analysed participant data collected between 2003 and 2009 from the Multicenter AIDS Cohort Study, a prospective HIV/AIDS cohort study in four U.S. cities. Methods:We conducted longitudinal analyses (repeated measures mixed models) to assess whether differences in viral load levels, undetectable viral load and self-reported HIV medication adherence were associated with count of syndemic conditions (substance use, depression symptoms and sexual risk behaviour, range 0–3), adjusting for race/ethnicity, age and income. Mediation analyses were conducted using structural equation modelling and the SAS %mediate macro. Results:Syndemics count was associated with higher viral loads (P < 0.0001) and lower adherence (P < 0.0001). Increased counts of concomitant syndemics were associated with viral load (P < 0.01), detectable viral load (P < 0.05) and adherence (P < 0.001). Black MSM experienced worse outcomes across domains than white MSM (P < 0.0001) and experienced higher overall rates of syndemics (P < 0.01). Adherence significantly mediated the relationship between syndemics and viral load, accounting for an estimated 32.3% of the effect (P < 0.05). Conclusion:Effectively lowering viral load levels among MSM has implications for both HIV/AIDS prevention and care. Our findings suggest that integrating substance use interventions, mental healthcare and sexual risk prevention into standard HIV care may be necessary to optimize treatment and Treatment as Prevention (TasP) models.

Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis.

Objective:Co-infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in HIV-infected individuals. However, predictors of mortality are poorly defined and most studies have focused predominantly on co-infection in men. We evaluated whether two indirect markers of hepatic fibrosis, aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co-infected women on HAART. Methods:HCV/HIV-co-infected women on antiretroviral therapy enrolled in Womens Interagency HIV Study (WIHS), a National Institutes of Health-funded prospective, multicenter, cohort study of women with and at risk for HIV infection were included. Using Cox regression analysis, associations between APRI and FIB-4 with all-cause mortality were assessed. Results:Four hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or FIB-4 levels, severe fibrosis was significantly associated with an increased risk of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI) 1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per 1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3 for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly, both APRI and FIB-4 increased during the 5 years prior to death for all women: the slope of increase was greater for women dying a liver-related death compared with nonliver-related death. Conclusion:Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV-co-infected women and may have clinical prognostic utility among women with HIV and HCV.