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.
RCT Entities:
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.
Authors: Rajesh T Gandhi; John Spritzler; Ellen Chan; David M Asmuth; Benigno Rodriguez; Thomas C Merigan; Martin S Hirsch; Robert W Shafer; Gregory K Robbins; Richard B Pollard Journal: J Acquir Immune Defic Syndr Date: 2006-08-01 Impact factor: 3.731
Authors: Bruce R Schackman; Heather J Ribaudo; Amy Krambrink; Valery Hughes; Daniel R Kuritzkes; Roy M Gulick Journal: J Acquir Immune Defic Syndr Date: 2007-12-15 Impact factor: 3.731
Authors: Ronald J Bosch; Kara Bennett; Ann C Collier; Robert Zackin; Constance A Benson Journal: J Acquir Immune Defic Syndr Date: 2007-03-01 Impact factor: 3.731
Authors: Kim Keil; Jill Hochreitter; Robin DiFrancesco; Barry S Zingman; Richard C Reichman; Margaret A Fischl; Barbara Gripshover; Gene D Morse Journal: Ther Drug Monit Date: 2007-02 Impact factor: 3.681
Authors: Antonia L Moore; Ole Kirk; Anne M Johnson; Christine Katlama; Anders Blaxhult; Manfred Dietrich; Robert Colebunders; Antonio Chiesi; Jens D Lungren; Andrew N Phillips Journal: J Acquir Immune Defic Syndr Date: 2003-04-01 Impact factor: 3.731
Authors: Gregory K Robbins; Victor De Gruttola; Robert W Shafer; Laura M Smeaton; Sally W Snyder; Carla Pettinelli; Michael P Dubé; Margaret A Fischl; Richard B Pollard; Robert Delapenha; Linda Gedeon; Charles van der Horst; Robert L Murphy; Mark I Becker; Richard T D'Aquila; Stefano Vella; Thomas C Merigan; Martin S Hirsch Journal: N Engl J Med Date: 2003-12-11 Impact factor: 91.245
Authors: Sharon A Riddler; Richard Haubrich; A Gregory DiRienzo; Lynne Peeples; William G Powderly; Karin L Klingman; Kevin W Garren; Tania George; James F Rooney; Barbara Brizz; Umesh G Lalloo; Robert L Murphy; Susan Swindells; Diane Havlir; John W Mellors Journal: N Engl J Med Date: 2008-05-15 Impact factor: 91.245
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: J Antimicrob Chemother Date: 2014-08-25 Impact factor: 5.790
Authors: David W Haas; Yuki Bradford; Anurag Verma; Shefali S Verma; Joseph J Eron; Roy M Gulick; Sharon A Riddler; Paul E Sax; Eric S Daar; Gene D Morse; Edward P Acosta; Marylyn D Ritchie Journal: Pharmacogenet Genomics Date: 2018-07 Impact factor: 2.089
Authors: Cynthia Firnhaber; Laura M Smeaton; Beatriz Grinsztejn; Umesh Lalloo; Sharla Faesen; Wadzanai Samaneka; Rosa Infante; Aadia Rana; Nagalingeswaran Kumarasamy; James Hakim; Thomas B Campbell Journal: HIV Clin Trials Date: 2015-05-15
Authors: Cindy J Bednasz; Charles S Venuto; Qing Ma; Eric S Daar; Paul E Sax; Margaret A Fischl; Ann C Collier; Kimberly Y Smith; Camlin Tierney; Yang Yang; Gregory E Wilding; Gene D Morse Journal: Ther Drug Monit Date: 2017-12 Impact factor: 3.681
Authors: J D Baxter; D Dunn; E White; S Sharma; A M Geretti; M J Kozal; M A Johnson; S Jacoby; J M Llibre; J Lundgren Journal: HIV Med Date: 2015-04 Impact factor: 3.180
Authors: Viviane D Lima; Mark Hull; David McVea; William Chau; P Richard Harrigan; Julio Sg Montaner Journal: J Int AIDS Soc Date: 2016-08-05 Impact factor: 5.396
Authors: Catherine Godfrey; Michael D Hughes; Justin Ritz; Lara Coelho; Robert Gross; Robert Salata; Rosie Mngqibisa; Carole L Wallis; Makanga E Mumbi; Mitch Matoga; Selvamuthu Poongulali; Marije Van Schalkwyk; Evelyn Hogg; Courtney V Fletcher; Beatriz Grinsztejn; Ann C Collier Journal: J Acquir Immune Defic Syndr Date: 2020-06-01 Impact factor: 3.771