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, Rooney, James F, Seekins, Daniel, and Currier, Judith S
BackgroundNonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.ObjectiveTo evaluate 3 nonnucleoside reverse transcriptase inhibitor-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.DesignA phase 3, open-label study randomized in a 1:1:1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954).Setting57 sites in the United States and Puerto Rico.PatientsTreatment-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.InterventionAtazanavir, 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.MeasurementsVirologic 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.ResultsAmong 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.LimitationThe trial was open-label, and ritonavir was not provided.ConclusionOver 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.Primary funding sourceNational Institute of Allergy and Infectious Diseases.