Xiuhong Li

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.

Incidence and epidemiology of anal cancer in the multicenter AIDS cohort study.

Objective:To examine the incidence and risk factors for anal cancer in a multicenter cohort of human immunodeficiency virus (HIV) positive and HIV-negative men who have sex with men followed between 1984 and 2006 (Multicenter AIDS Cohort Study). Methods:Prospective analysis using Poisson regression and Cox proportional hazard models and a nested case-control study using conditional logistic regression. Results:There were 28 cases of anal cancer among the 6972 men who were evaluated. The incidence rate was significantly higher in HIV-positive men than in HIV-negative men (incidence rate = 69 vs 14 per 100,000 person-years). Among HIV-positive men, anal cancer incidence was higher in the highly active antiretroviral therapy (HAART) era than the pre-HAART era (incidence rate = 137 vs 30 per 100,000 person-years). In multivariate analysis restricted to the HAART era, anal cancer risk increased significantly with HIV infection (relative hazard = 4.7, 95% confidence interval = 1.3 to 17) and increasing number of unprotected receptive anal sex partners at the first 3 study visits (P trend = 0.03). Among HIV-positive men, current HAART use did not decrease anal cancer risk. Conclusions:HIV-positive men had increased risk of anal cancer. Improved survival of HIV-positive individuals after HAART initiation may allow for sufficient time for human papillomavirus-associated anal dysplasias to develop into malignancies, thus explaining the increased incidence of anal cancer in the HAART era.

Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study

Objective:To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls. Design:Prospective cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicenter AIDS Cohort Study evaluated at 6-month intervals between 1999 and 2003. Methods:Recent ART exposure was assessed by type of treatment in the preceding 6 months [i.e., no ART, monotherapy, combination ART, or highly active antiretroviral therapy (HAART) with and without a protease inhibitor (PI)]. Cumulative exposure was determined for the three major ART classes and for individual medications within each class. Two endpoints, a modified QUICKI index, 100 × 1/[log10(glucose) + log10(insulin)] and fasting hyperinsulinemia (insulin > 15 μU/ml), were assessed. All statistical models were adjusted for age, body mass index, race, nadir CD4 cell count, hepatitis C serostatus and family history of diabetes mellitus. Results:Each of the HIV-infected groups had higher odds of hyperinsulinemia and lower mean QUICKI than the HIV-seronegative men. Each additional year of exposure to nucleoside analogue reverse transcriptase inhibitors (NRTI) was associated with increased odds of hyperinsulinemia [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02–1.13) and a lower QUICKI (−0.04; 95% CI, −0.07 to −0.01). Cumulative exposure to non-nucleoside analogue reverse transcriptase inhibitors or PI drugs was not associated with either insulin resistance marker. Of individual medications examined, stavudine was associated with the highest risk of hyperinsulinemia (OR, 1.2; 95% CI, 1.2–1.3). Conclusions:Fasting surrogate markers suggest increased insulin resistance in HIV-infected men, which is related to cumulative NRTI exposure.

Specific Sex-Drug Combinations Contribute to the Majority of Recent HIV Seroconversions Among MSM in the MACS

Background:New HIV infections are being observed among men who have sex with men (MSM). Understanding the fusion of risky sexual behaviors, stimulant and erectile dysfunction drug use with HIV seroconversion may provide direction for focused intervention. Methods:During the follow-up period (1998-2008), we identified 57 HIV seroconverters among 1667 initially HIV-seronegative men. Time to seroconversion was modeled using Cox proportional hazards regression analysis for 7 combinations of sex drugs (inhaled nitrites or “poppers”, stimulants, and erectile dysfunction drugs) used at the current or previous semiannual visit, adjusting for other risk factors including sexual behavior, alcohol and other drugs used, and depression. Model-based adjusted attributable risks were then calculated. Results:The risk of seroconversion increased linearly with the number of unprotected receptive anal sex partners (URASP), with hazard ratios ranging from 1.73 [95% confidence interval (CI): 0.75 to 4.01] for 1 partner, to 4.23 (95% CI: 1.76 to 10.17) for 2-4 partners, and to 14.21 (95% CI: 6.27 to 32.20) for 5+ partners, independent of other risk factors. After adjustment, risks for seroconversion increased from 2.99 (95% CI: 1.02 to 8.76) for men who reported using stimulants only (1 drug) to 8.45 (95% CI: 2.67 to 26.71) for men who reported using all 3 sex drugs. The use of any of the 7 possible sex drug combinations accounted for 63% of the 9-year HIV seroincidence in the Multicenter AIDS Cohort Study. When contributions of increased URASP and combination drug use were analyzed together, the total attributable risk for HIV seroconversion was 74%, with 41% attributable to URASP alone and a residual of 33% due to other direct or indirect effects of sex drug use. Conclusions:Use of poppers, stimulants, and erectile dysfunction drugs increased risk for HIV seroconversion significantly in this cohort. These data reinforce the importance of implementing interventions that target drug reduction as part of comprehensive and efficacious HIV prevention strategies.

Ten-Year Predicted Coronary Heart Disease Risk in HIV-Infected Men and Women

BACKGROUND Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. METHODS Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. RESULTS Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income <

Longitudinal changes in serum lipids among HIV‐infected men on highly active antiretroviral therapy

10,000 vs. >

Elevated Levels of Monocyte Activation Markers Are Associated With Subclinical Atherosclerosis in Men With and Those Without HIV Infection

40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]). CONCLUSIONS Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.

Age, Comorbidities, and AIDS Predict a Frailty Phenotype in Men Who Have Sex With Men

The aim of the study was to describe longitudinal changes in serum lipids among HIV‐infected men receiving highly active antiretroviral therapy (HAART) with long‐term follow‐up.

Antiretroviral therapy is associated with an atherogenic lipoprotein phenotype among HIV-1-infected men in the multicenter AIDS cohort study

BACKGROUND Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study. METHODS We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors. RESULTS Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque. CONCLUSIONS sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection.

Longitudinally preserved psychomotor performance in long-term asymptomatic HIV-infected individuals

BACKGROUND Adults aging with HIV infection are at risk for age-related comorbidities and syndromes, such as frailty. The objective of this study was to evaluate the expression and predictors of the frailty phenotype (FP) among HIV-infected (HIV+) and HIV-uninfected (HIV-) men who have sex with men. METHODS A prospective, observational cohort study was nested in the Multicenter AIDS Cohort Study from October 2007-September 2011. FP conversion was defined as the onset of FP over two consecutive study visits. Adjusted odds ratios and 95% confidence intervals ([,]) for FP conversion were estimated using logistic regression models with generalized estimating equations. RESULTS Of 10,571 completed study visits from 1,946 men who have sex with men, 12% and 9% were FP+ among HIV+ and HIV- men, respectively (p = .002). The proportion of FP+ visits increased with age regardless of HIV status, but was significantly greater in HIV+ compared to HIV- men aged 50-64 years. Of the 10,276 consecutive visit pairs contributed by participants, 5% (537) were classified as FP conversion, and 45% of the men with FP conversion had only one FP+ study visit. FP conversion was significantly associated with a history of AIDS (adjusted odds ratios = 2.26 [1.50, 3.39], but not with HIV+ alone (adjusted odds ratios = 1.26 [0.98, 1.64]). Among men who had one or more FP+ visits, 34% of HIV+ and 38% of HIV- men had less than two comorbidities. CONCLUSIONS These findings suggest that expression of the FP can be measured in men who have sex with men with and without HIV infection and reflects multisystem dysfunction in this population; further investigations are needed to better understand clinical utility.