Background
Non-nucleoside reverse transcriptase (NNRTI) inhibitor-based antiretroviral therapy is not suitable for all treatment-naïve HIV-infected persons.
Objective
Perform a rigorous evaluation of three NNRTI-sparing initial antiretroviral regimens to demonstrate equivalence for virologic efficacy and tolerability.
Design
Phase-III, 1:1:1 randomized, open label, >96 week study.
Setting
Fifty-seven sites in United States and Puerto Rico.
Patients
Treatment naïve, ≥18 years, HIV-1 RNA >1000 copies/mL, no nucleoside reverse transcriptase or protease inhibitor resistance.
Intervention
Atazanavir 300 mg with ritonavir 100 mg, daily; or raltegravir 400 mg twice daily; or darunavir 800 mg with ritonavir 100 mg, daily; plus emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg daily.
Measurements
Virologic failure defined as confirmed HIV-1 RNA >1000 copies/mL between 16 and 24 weeks, or >200 copies/mL at or after 24 weeks; tolerability failure defined as discontinuation of atazanavir, raltegravir or darunavir for toxicity. A secondary endpoint was a combination of virologic efficacy and tolerability.
Results
Among 1,809 participants all pairwise comparisons of incidence of virologic failure over 96-weeks demonstrated equivalence within ±10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and a 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir respectively, primarily due to 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 time of virologic failure was rare but more likely with raltegravir.
Limitations
Open label; ritonavir not provided
Conclusions
Over 2 years all three regimens attain high and equivalent rates of virologic control. Regimens containing raltegravir or ritonavir-boosted darunavir have superior tolerability compared to the ritonavir-boosted atazanavir regimen.
Primary Funding Source
National Institute of Allergy and Infectious Diseases
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