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.

DOI: 10.1093/jac/dku303

Statistics

0200040002017
Citations per Year

694 Citations

Semantic Scholar estimates that this publication has 694 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Venuto2014SexDI, title={Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202.}, author={Charles S. Venuto and Katie R. Mollan and Qing Ma and Eric S Daar and Paul Edward Sax and Margaret A. Fischl and Ann C Collier and Kimberly Y Smith and Camlin Tierney and Gene D. Morse}, journal={The Journal of antimicrobial chemotherapy}, year={2014}, volume={69 12}, pages={3300-10} }