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

on behalf of the AIDS Clinical Trials Group Study A5202 Team

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3300-3310
Number of pages11
JournalJournal of Antimicrobial Chemotherapy
Volume69
Issue number12
DOIs
StatePublished - Dec 1 2014

Keywords

  • Clearance
  • Efficacy
  • Safety
  • Tolerability

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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