Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202.

ABSTRACT: OBJECTIVES:It is uncertain whether HIV-1 antiretroviral exposure and clinical response varies between males and females or different race/ethnic groups. We describe ritonavir-enhanced atazanavir pharmacokinetics in relation to virological failure, safety and tolerability in treatment-naive individuals to investigate potential differences. METHODS:Plasma samples were collected from participants in AIDS Clinical Trials Group Study A5202 for measurement of antiretroviral concentrations. Individual estimates of apparent oral clearance of atazanavir (L/h) were calculated from a one-compartment model and divided into tertiles as slow (<7), middle (7 to <9; reference group) and fast (?9). Associations between atazanavir clearance and clinical outcomes were estimated with a hazard ratio (HR) from Cox proportional hazards models. Interactions between atazanavir clearance and sex, race/ethnicity and NRTIs were investigated for each of the outcomes. RESULTS:Among 786 participants, average atazanavir clearance was slower in females (n = 131) than males (n = 655). Atazanavir clearance was associated with time to virological failure (P = 0.053) and this relationship differed significantly by sex (P = 0.003). Females in the fast atazanavir clearance group had shorter time to virological failure (HR 3.49; 95% CI 1.24-9.84) compared with the middle (reference) atazanavir clearance group. Among males, the slow atazanavir clearance group had a higher risk of virological failure (HR 2.10; 95% CI 1.16-3.77). CONCLUSIONS:Atazanavir clearance differed by sex. Females with fast clearance and males with slow clearance had increased risk of virological failure.

SUBMITTER: Venuto CS 

PROVIDER: S-EPMC4228779 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature