1. In HIV patients, equivalent rates of virologic control were seen between antiretroviral regimens of emtricitabine and tenofovir disproxil fumarate (TDF) paired with ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir.
2. Treatment with raltegravir or ritonavir-boosted darunavir demonstrated better tolerability compared to ritonavir-boosted atazanavir.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Two reverse transcriptase inhibitors combined with a nonnucleoside reverse transcriptase inhibitor (NNRTI), a ritonavir-boosted protease inhibitor (PI), or an integrase inhibitor are recommended for initial HIV-1-infected individuals. Traditionally, efavirenz has been the NNRTI of choice, but efavirenz is not an option for women contemplating pregnancy, patients with NNRTI resistance, or those with severe psychiatric disorders. To evaluate the efficacy and tolerability of efavirenz alternatives, adults infected with HIV-1 were randomized to receive 1 of 3 regimens: emtricitabine and TDF paired with atazanavir and ritonavir, darunavir and ritonavir, or raltegravir. All 3 regimens achieved equivalent and high rates of virologic suppression. Raltegravir proved to have a better tolerability, followed by ritonavir-boosted darunavir and then ritonavir-boosted atazanavir. However, ritonavir-boosted darunavir and atazanavir had lower likelihood of drug-resistance. This study was the first to compare NNRTI alternatives head-to-head and supports several reasonable options for initial HIV antiretroviral therapy. Limitations to the study include an open-label design chosen to reduce pill-burden, the fact that ritonavir was not directly provided to participants (co-pay reimbursement was offered to alleviate difficulties in obtaining medication), and participants were allowed to change therapy options due to an intolerant response.
In-Depth [randomized controlled trial]: A total of 1,809 participants were recruited from 57 sites and randomized in a 1:1:1 ratio to receive atazanavir 300 mg with ritonavir 100 mg once daily, darunavir 800 mg with ritonavir 100 mg once daily, or raltegravir 400 mg twice daily, each with a fixed-dose combination of TDF 300 mg plus emtricitabine 200 mg daily. Follow-up was performed for 96 weeks after enrollment, and virologic failure was defined as HIV-1 RNA level greater than 1000 copies/mL at or after 16 weeks and before 24 weeks, or less than 200 copies/mL at or after 24 weeks. Tolerability was measured as time from randomization to discontinuation due to toxicity. Equivalence was pre-defined as a 2-sided 97.5% CI on pairwise difference in 96 week cumulative incidence of each individual or composite end point falling between -10% and 10%. The cumulative probability of virolgoic failure by 96 weeks was 9.0% in the raltegravir group, 12.6% in the ritonavir-boosted atazanavir group, and 14.9% in the ritonavir-boosted darunavir group. The primary tolerability endpoint between raltegravir and ritonavir-boosted daruanvir was equivalent, but ritonavir-boosted atazanavir resulted in 12.7% (97.5%CI 9.4%-16.1%) higher incidence of discontinuation than raltegarvir and 9.2% (97.5%CI 5.5%-12.9%) more than ritonavir-boosted darunavir.
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