Hepatotoxicity During Isoniazid Preventive Therapy and Antiretroviral Therapy in People Living With HIV With Severe Immunosuppression: A Secondary Analysis of a Multi-Country Open-Label Randomized Controlled Clinical Trial.

BACKGROUND: Hepatotoxicity associated with isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) has not been well studied in severely immunosuppressed people with HIV. Our objective was to determine risk factors for hepatotoxicity in severely immunosuppressed individuals taking IPT and ART. SETTING: Multicenter study in resource-limited settings with high burden of tuberculosis. METHODS: We conducted a secondary analysis of data from 1 randomized arm of the REMEMBER trial. The analysis includes participants with pre-ART CD4 cell counts of <50 cells/µL receiving IPT and ART for 24 weeks. Hepatotoxicity was defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 × upper limit of normal or symptomatic hepatitis during IPT and ART. Logistic regression was used to identify baseline risk factors for hepatotoxicity. Time to occurrence of hepatotoxicity was estimated by the Kaplan-Meier method. RESULTS: Among 426 participants (53% male, median age 35 years, median CD4 count 19 cells/µL), 31 developed hepatotoxicity (7.3%). Raised pretreatment AST/ALT (odds ratio [OR] 3.6, 95% confidence interval [CI]: 1.7 to 7.7) and hepatitis B surface antigen (HBsAg) seropositivity at baseline (OR 4.7, 95% CI: 1.7 to 12.9) were significantly associated with an increased risk of developing hepatotoxicity. Participants with both raised AST/ALT and positive HBsAg had a higher risk (OR 19.9, 95% CI: 5.3 to 74.3) and earlier onset of hepatotoxicity than participants who did not have these conditions at baseline. CONCLUSIONS: The incidence of hepatotoxicity during IPT and ART was high. Severely immunosuppressed individuals with raised pretreatment AST/ALT or HBsAg seropositivity need closer monitoring for hepatotoxicity.

Quality of life among HIV-infected individuals failing first-line antiretroviral therapy in resource-limited settings.

We evaluated health-related quality of life (QoL) in HIV infection participants with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9 resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical functioning (PF), role functioning (RF), social functioning (SF), cognitive functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each was scored between 0 (worst) to 100 (best). Mean QoL scores ranged from 67 (GHP) to 91 (PF, SF, CF). QoL varied by country; high VL and low CD4 were associated with worse QoL in most domains, except RF (VL only), SF (CD4 only) and CF (neither). Number of comorbidities, BMI and history of AIDS were associated with some domains. Relationships between QoL and VL varied among countries for all domains. The association of worse disease status with worse QoL may reflect low QoL when ART was initiated and/or deterioration associated with VF.

Binge drinking is associated with differences in weekday and weekend adherence in HIV-infected individuals.

BACKGROUND: Understanding patterns of antiretroviral adherence and its predictors is important for designing tailored interventions. Alcohol use is associated with non-adherence. This study aimed to evaluate: (1) if there was a difference in weekday compared with weekend adherence in HIV-infected individuals from low and middle income countries (LMIC), and (2) whether binge drinking was associated with this difference. METHODS: Data from a randomized trial conducted at 9 sites in 8 LMIC were analyzed. Microelectronic monitors were used to measure adherence. Differences between weekday and weekend adherence in each quarter (successive 12-week periods) were compared using Wilcoxon signed rank tests and predictors of adherence, including baseline binge drinking, were evaluated using Generalized Estimating Equations. RESULTS: Data from 255 participants were analyzed: 49.8% were male, median age was 37 years and 28.6% enrolled in Haiti. At study entry, only 2.7% reported illicit substance use, but 22.3% reported binge drinking at least once in the 30 days prior to enrollment. Adherence was higher on weekdays than weekends (median percent doses taken: 96.0% vs 94.4%; 93.7% vs 91.7%; 92.6% vs 89.7% and 93.7% vs 89.7% in quarters 1-4 respectively, all p<0.001). Binge drinking at baseline and time on study were both associated with greater differences between weekday and weekend adherence. CONCLUSIONS: Adherence was worse on weekends compared to weekdays: difference was small at treatment initiation, increased over time and was associated with binge drinking. Screening and new interventions to address binge drinking, a potentially modifiable behavior, may improve adherence in HIV-infected individuals in LMIC.

Relationship between sexual function and quality of life in obese persons seeking weight reduction.

OBJECTIVE: This study investigated sexual functioning in persons with obesity and seeking weight loss, and the associations of sexual functioning with relevant demographic and clinical variables as well as quality of life were investigated. DESIGN AND METHODS: Participants were enrolled in a two-year randomized clinical trial. Participants were obese and had at least two components of metabolic syndrome. Male and female sexual functioning was assessed by the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI) respectively. RESULTS: The rate of female sexual dysfunction was 29%. The rate of erectile dysfunction (ED) was 45%. Of the characteristics considered, FSD was associated with age (P = 0.002). ED was significantly associated with age and physical functioning (both P < 0.01). CONCLUSIONS: A large minority of patients with obesity reported sexual dysfunction. The occurrence of sexual dysfunction was associated with age, but, surprisingly, not weight-related comorbidities. This may be the result of the nature of the study sample or the methods used to administer the questionnaires that assessed sexual functioning.