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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.
- 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;
- Currier, Judith S
- et al.
Published Web Locationhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412467/pdf/nihms637050.pdf
No data is associated with this publication.
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.
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