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.

• Authors: Charles S Venuto, Katie Mollan, Qing Ma, Eric S Daar, Paul E Sax, Margaret Fischl, Ann C Collier, Kimberly Y Smith, Camlin Tierney, Gene D Morse
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 12 Pg. 3300-10 (Dec 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 25159623 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Anti-HIV Agents
• Oligopeptides
• Pyridines
• Atazanavir Sulfate
• Ritonavir

Topics

• Adult
• Anti-HIV Agents (administration & dosage, adverse effects, pharmacokinetics)
• Atazanavir Sulfate
• Female
• HIV Infections (drug therapy)
• Humans
• Male
• Metabolic Clearance Rate
• Middle Aged
• Oligopeptides (administration & dosage, adverse effects, pharmacokinetics)
• Plasma (chemistry)
• Pyridines (administration & dosage, adverse effects, pharmacokinetics)
• Ritonavir (administration & dosage, adverse effects)
• Sex Characteristics
• Time Factors
• Treatment Failure
• Treatment Outcome