Context: The long-term adverse effects, expense, and difficulty of adherence to antiretroviral regimens have led to studies of simpler maintenance therapies. Maintenance therapy with ritonavir-boosted atazanavir alone is a possible option because of low pill burden, once-daily dosing, safety, and unique resistance profile. Objective: To assess whether simplified maintenance therapy with atazanavir-ritonavir alone after virologic suppression increases the risk of virologic failure (2 consecutive human immunodeficiency virus type 1 [HIV-1] RNA measurements of ≥200 copies/mL). Design, Setting, and Participants: Single-group, open-label, multicenter, 24-week pilot study of 36 HIV-infected adults with virologic suppression for 48 weeks or longer receiving their first protease inhibitor (PI)-based regimen. The study was conducted between September 1, 2004, and April 18, 2006, at 12 participating AIDS clinical trial units in the United States. Intervention: Participants switched PIs to atazanavir-ritonavir at entry and discontinued nucleoside analog reverse transcriptase inhibitors (NRTIs) after 6 weeks. Main Outcome Measures: Virologic failure within 24 weeks of discontinuing NRTIs. Other measures included HIV-1 drug resistance, plasma atazanavir concentrations, adverse events, CD4 cell counts, plasma lipid levels, and HIV-1 RNA levels in seminal plasma. Results: Thirty-six participants enrolled and 2 discontinued before simplification to atazanavir-ritonavir alone. Thirty-four patients were included in the analysis of the primary end point after 24 weeks: 1 withdrew voluntarily, and 33 continued the regimen. Virologic success (absence of failure) through 24 weeks of simplified therapy occurred in 91% (31 of 34 patients; lower 90% confidence interval limit=85%). Three participants experienced virologic failure 12, 14, and 20 weeks after simplification, with plasma HIV-1 RNA levels of 4730, 1285, and 28 397 copies/mL, respectively. Resistance testing at failure did not identify PI resistance mutations. Plasma atazanavir concentrations at failure were low or below detection in 2 of 3 participants experiencing failure. There were no treatment discontinuations for adverse events after simplification; no significant changes in CD4 cell counts or plasma lipid levels; and no detectable HIV-1 RNA in seminal plasma from all 8 participants tested. Conclusions: These preliminary data suggest that simplified maintenance therapy with atazanavir-ritonavir alone may be efficacious for maintaining virologic suppression in carefully selected patients with HIV infection. These findings require confirmation in larger, randomized trials of this strategy. Trial Registration: clinicaltrials.gov Identifier: NCT00084019.
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