HIV-1 status is independently associated with decreased erectile function among middle-aged MSM in the era of combination antiretroviral therapy.

INTRODUCTION: HIV-1-infected MSM more often experience sexual dysfunctions than the general population. We assessed associations between HIV-1 status and decreased sexual functioning among MSM. METHODS: We used cross-sectional data from 399 HIV-1-infected MSM mostly on combination antiretroviral therapy (cART) and 366 HIV-1-uninfected MSM aged at least 45 years participating in the AGEhIV Cohort Study. The study questionnaire included questions on erectile function, sexual satisfaction, and sexual desire. Multivariable logistic regression models were constructed to assess the association between HIV-1 status and these three sexual domains. We also explored HIV-1-related and ART-related parameters in multivariable models among HIV-1-infected participants. RESULTS: Decreased erectile function (13.0 vs. 3.4%, P < 0.001), decreased satisfaction (17.8 vs. 11.8%, P = 0.02), and decreased desire (7.0 vs. 3.6% P = 0.03) were each more prevalent in HIV-1-infected than in HIV-1-uninfected participants. In multivariable models adjusted for age, ethnicity, waist-to-hip ratio, age-associated comorbidities, depression, frailty, use of antihypertensive and antidepressant medication, we found HIV-1 status significantly associated with decreased erectile function [adjusted odds ratio (aOR) 2.53, 95% CI 1.23-5.20], but not with decreased satisfaction (aOR 1.34, 95% CI 0.83-2.16), or decreased desire (aOR 1.77, 95% CI 0.80-3.91). Among HIV-1-infected participants, current exposure (aOR 5.39, 95% CI 2.09-13.92) and cumulative duration of exposure (aOR per year 1.20, 95% CI 1.07-1.35) to lopinavir/ritonavir were significantly associated with decreased erectile function in multivariable analysis. CONCLUSION: Among MSM aged at least 45 years, HIV-1 status was independently associated with decreased erectile function. Exposure to lopinavir/ritonavir appeared to be an independent risk factor for decreased erectile function among MSM with HIV-1.

Relationships between drug exposure, changes in metabolic parameters and body fat in HIV-infected patients switched to a nucleoside sparing regimen.

BACKGROUND: The pathogenesis of metabolic disturbances in treated HIV infection is incompletely understood. METHODS: Relationships between fasted metabolic parameters, body composition, and drug plasma concentrations were investigated in 59 patients who switched from failed nucleoside analogue treatment to ritonavir-boosted indinavir and efavirenz therapy. Metabolic parameters, peripheral fat, visceral adipose tissue (VAT) and drug plasma concentrations were measured prospectively. RESULTS: Ritonavir exposure was found to be negatively correlated with high-density lipoprotein cholesterol (HDL-c) changes, with a 2.4% decrease in HDL-c for each unit increase in ritonavir concentration ratio. Significant associations between indinavir or efavirenz concentrations and metabolic disturbances were not observed. Total cholesterol (TC) correlated positively with high body mass index (BMI) and negatively with baseline limb fat mass: each unit increase in BMI and each kilogram reduction in baseline limb fat corresponded with a TC increase of 2.4% and 4.1%, respectively. Baseline triglyceride levels were lower in those patients with relatively greater limb fat mass: each kilogram reduction of total limb fat mass was associated with a 15.7% increase in triglyceride concentration. Changes in VAT were positively correlated with TC: for every unit TC increase a 0.3% VAT increase was observed (over 48 weeks). CONCLUSIONS: Reduced limb fat mass at the start of the study treatment, increases in VAT mass, and higher plasma concentrations of ritonavir on study treatment were each--to varying degrees--associated with various metabolic disturbances.

Race is not associated with nevirapine pharmacokinetics.

The effect of race on the pharmacokinetics of nevirapine was investigated in a nonselected population. Included patients were ambulatory HIV-1-infected patients from the outpatient clinics of the Academic Medical Center and the Slotervaart Hospital, Amsterdam, The Netherlands. All patients were using nevirapine as part of their antiretroviral regimen and had at least one plasma concentration available for analysis. From the included patients, gender, age, race, hepatitis C status, baseline ASAT value, and body weight were obtained. The nonlinear mixed-effect modeling program (NONMEM) version V 1.1 was used for all analyses. Population pharmacokinetic parameters [clearance (CL/F), volume of distribution (V/F), absorption rate constant (ka)] and interindividual (IIV) and interoccasion variability (IOV) were estimated. The influence of race on the CL/F of nevirapine was tested as Negroid race versus the other races, Asian race versus the other races, and the Negroid and the Asian races as separate variables versus the Caucasian race. A database of 1732 nevirapine plasma concentrations of 383 HIV-1-infected individuals collected during 1186 outpatient clinic visits was available for this analysis. The conclusion of this study is that race is not associated with the pharmacokinetics of nevirapine, and thus requires no dose adaptations.