Journal article
Outcomes by Sex Following Treatment Initiation With Atazanavir Plus Ritonavir or Efavirenz With Abacavir/Lamivudine or Tenofovir/Emtricitabine
Clinical infectious diseases, Vol.58(4), pp.555-563
2014
DOI: 10.1093/cid/cit747
PMCID: PMC3905755
PMID: 24253247
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.
Details
- Title: Subtitle
- Outcomes by Sex Following Treatment Initiation With Atazanavir Plus Ritonavir or Efavirenz With Abacavir/Lamivudine or Tenofovir/Emtricitabine
- Creators
- Kimberly Y SMITH - Department of Medicine Division of Infectious Diseases, Rush University Medical Center, Chicago, Illinois, United StatesCamlin TIERNEY - Statistical Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, United StatesMargaret FISCHL - Department of Internal Medicine, University of Miami, Florida, United StatesEric S DAAR - Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United StatesAnn C COLLIER - Department of Medicine, Division of Infectious Diseases, University of Washington Medical Center, Seattle, United StatesKatie MOLLAN - Statistical Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, United StatesCharles S VENUTO - Center for Human Experimental Therapeutics, University of Rochester, New York, United StatesChakra BUDHATHOKI - Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United StatesQING MA - Department of Pharmacy Practice, University of Buffalo, State University of New York, United StatesGene D MORSE - School of Pharmacy and Pharmaceutical Sciences, University of Buffalo, State University of New York, United StatesPaul SAX - Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United StatesDavid KATZENSTEIN - School of Medicine, Division of Infectious Diseases, Stanford University, California, United StatesCatherine GODFREY - Division of AIDS, National Institutes of Health, Bethesda, Maryland, United StatesAIDS Clinical Trials Group 5202 Study Team
- Contributors
- Jeffery L Meier (Contributor) - University of Iowa, Internal MedicineJack T Stapleton (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Clinical infectious diseases, Vol.58(4), pp.555-563
- Publisher
- Oxford University Press
- DOI
- 10.1093/cid/cit747
- PMID
- 24253247
- PMCID
- PMC3905755
- ISSN
- 1058-4838
- eISSN
- 1537-6591
- Language
- English
- Date published
- 2014
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Epidemiology; Internal Medicine
- Record Identifier
- 9984094375902771
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