Outcomes by sex following treatment initiation with atazanavir plus ritonavir or efavirenz with abacavir/lamivudine or tenofovir/emtricitabine.

TitleOutcomes by sex following treatment initiation with atazanavir plus ritonavir or efavirenz with abacavir/lamivudine or tenofovir/emtricitabine.
Publication TypeJournal Article
Year of Publication2014
AuthorsSmith KY, Tierney C, Mollan K, Venuto CS, Budhathoki C, Ma Q, Morse GD, Sax P, Katzenstein D, Godfrey C, Fischl M, Daar ES, Collier AC
Corporate AuthorsAIDS Clinical Trials Group 5202 Study Team
JournalClin Infect Dis
Volume58
Issue4
Pagination555-63
Date Published2014 Feb
ISSN1537-6591
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Puerto Rico, Sex Factors, Treatment Outcome, United States, Young Adult
Abstract

BACKGROUND: We aimed to evaluate treatment responses to atazanavir plus ritonavir (ATV/r) or efavirenz (EFV) in initial antiretroviral regimens among women and men, and determine if treatment outcomes differ by sex.

METHODS: We performed a randomized trial of open-label ATV/r or EFV combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) in 1857 human immunodeficiency virus type 1-infected, treatment-naive persons enrolled between September 2005 and November 2007 at 59 sites in the United States and Puerto Rico. Associations of sex with 3 primary study endpoints of time to virologic failure, safety, and tolerability events were analyzed using Cox proportional hazards models. Model-based population pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM version VII).

RESULTS: Of 1857 participants, 322 were women. Women assigned to ATV/r had a higher risk of virologic failure with either nucleoside reverse transcriptase inhibitor backbone than women assigned to EFV, or men assigned to ATV/r. The effects of ATV/r and EFV upon safety and tolerability risk did not differ significantly by sex. With ABC/3TC, women had a significantly higher (32%) safety risk compared to men; with TDF/FTC, the safety risk was 20% larger for women compared to men, but not statistically significant. Women had slower ATV clearance and higher predose levels of ATV compared to men. Self-reported adherence did not differ significantly by sex.

CONCLUSIONS: This is the first randomized clinical trial to identify a significantly earlier time to virologic failure in women randomized to ATV/r compared to women randomized to EFV. This finding has important clinical implications given that boosted protease inhibitors are often favored over EFV in women of childbearing potential.

CLINICAL TRIALS REGISTRATION: NCT00118898.

DOI10.1093/cid/cit747
Alternate JournalClin. Infect. Dis.
PubMed ID24253247
PubMed Central IDPMC3905755
Grant ListAI069434 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
P30 AI073961 / AI / NIAID NIH HHS / United States
P30 AI50410 / AI / NIAID NIH HHS / United States
U01 AI069418 / AI / NIAID NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069418 / AI / NIAID NIH HHS / United States
UM1 AI069470 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
UM1 AI069477 / AI / NIAID NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States