Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor-Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

• Type of Material: Article
• Authors: Jeffrey Lennox, Emory University; Raphael L. Landovitz, Grady Memorial Hospital; Heather J. Ribaudo, Harvard School of Public Health; Ighovwerha Ofotokun, Emory University; Lumine H. Na, Harvard School of Public Health; Catherine Godfrey, National Institute of Allergy and Infectious Diseases; Daniel R. Kuritzkes, Brigham and Women’s Hospital and Harvard Medical School; Manish Sagar, Boston University School of Medicine; Todd T. Brown, Johns Hopkins University; Susan E. Cohn, Northwestern University; Grace A. McComsey, Case Western Reserve University; Francesca Aweeka, University of California San Francisco; Carl J. Fichtenbaum, University of Cincinnati; Rachel M. Presti, Washington University; Susan L. Koletar, Ohio State University College of Medicin; David W. Haas, Vanderbilt University; Kristine B. Patterson, University of North Carolina School of Medicine; Constance A. Benson, University of California San Diego; Bryan P. Baugh, Janssen Scientific Affairs; Randi Y. Leavitt, Merck and Co., Inc.; James F. Rooney, Gilead Sciences; Daniel Seekins, Bristol-Myers Squibb; Judith S. Currier, University of California Los Angeles
• Language: English
• Date: 2014-10-07
• Publisher: American College of Physicians
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 American College of Physicians.
• Final Published Version (URL): http://dx.doi.org/10.7326/M14-1084
• Title of Journal or Parent Work: Annals of Internal Medicine
• Volume: 161
• Issue: 7
• Start Page: 461
• End Page: 471
• Grant/Funding Information: The project described was supported by Award Number UM1AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR).; See publication for full funding statement.
• Keywords: THERAPY; RITONAVIR; TRIAL; General & Internal Medicine; DISOPROXIL FUMARATE; COBICISTAT; Medicine, General & Internal; Science & Technology; Life Sciences & Biomedicine; RISK; INDIVIDUALS
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Objective: To evaluate 3 nonnucleoside reverse transcriptase inhibitor-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability. Background: Nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIVinfected persons. Primary Funding Source: National Institute of Allergy and Infectious Diseases. Limitation: The trial was open-label, and ritonavir was not provided. Results: Among 1809 participants, all pairwise comparisons of incidence of virologic failure over 96 weeks showed equivalence within a margin of equivalence defined as-10% to 10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilirubinemia. For combined virologic efficacy and tolerability, ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at the time of virologic failure was rare but more frequent with raltegravir. Conclusion: Over 2 years, all 3 regimens attained high and equivalent rates of virologic control. Tolerability of regimens containing raltegravir or ritonavir-boosted darunavir was superior to that of the ritonavir-boosted atazanavir regimen. Design: A phase 3, open-label study randomized in a 1:1:1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954) Setting: 57 sites in the United States and Puerto Rico. Patients: Treatment-naive persons aged 18 years or older with HIV-1 RNA levels greater than 1000 copies/mL without resistance to nucleoside reverse transcriptase inhibitors or protease inhibitors. Intervention: Atazanavir, 300 mg/d, with ritonavir, 100 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d, with ritonavir, 100 mg/d, plus combination emtricitabine, 200 mg/d, and tenofovir disoproxil fumarate, 300 mg/d.Measurements: Virologic failure, defined as a confirmed HIV-1 RNA level greater than 1000 copies/mL at or after 16 weeks and before 24 weeks or greater than 200 copies/mL at or after 24 weeks, and tolerability failure, defined as discontinuation of atazanavir, raltegravir, or darunavir for toxicity. A secondary end point was a combination of virologic efficacy and tolerability.