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- Title
Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial.
- Authors
Lennox, Jeffrey L; Landovitz, Raphael J; Ribaudo, Heather J; Ofotokun, Ighovwerha; Na, Lumine H; Godfrey, Catherine; Kuritzkes, Daniel R; Sagar, Manish; Brown, Todd T; Cohn, Susan E; McComsey, Grace A; Aweeka, Francesca; Fichtenbaum, Carl J; Presti, Rachel M; Koletar, Susan L; Haas, David W; Patterson, Kristine B; Benson, Constance A; Baugh, Bryan P; Leavitt, Randi Y
- Abstract
<bold>Background: </bold>Nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.<bold>Objective: </bold>To evaluate 3 nonnucleoside reverse transcriptase inhibitor-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.<bold>Design: </bold>A phase 3, open-label study randomized in a 1:1:1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954).<bold>Setting: </bold>57 sites in the United States and Puerto Rico.<bold>Patients: </bold>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.<bold>Intervention: </bold>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.<bold>Measurements: </bold>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.<bold>Results: </bold>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.<bold>Limitation: </bold>The trial was open-label, and ritonavir was not provided.<bold>Conclusion: </bold>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.<bold>Primary Funding Source: </bold>National Institute of Allergy and Infectious Diseases.
- Publication
Annals of Internal Medicine, 2014, Vol 161, Issue 7, p461
- ISSN
0003-4819
- Publication type
journal article
- DOI
10.7326/M14-1084