Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression : 48-week efficacy and safety results

Objectives:The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50copies/ml.Methods:A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: two consecutive HIV-RNA >50copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50copies/ml after 12 weeks since reintensification.Results:One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with two NRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with two NRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification=failure), treatment success was 73% in ATV/r arm and 85% in ATV/r along with two NRTIs [difference -12.1%, 95% confidence interval (95% CI) -27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92% in ATV/r arm and 85% in the ATV/r along with two NRTIs arm (difference 7.5%, 95% CI -4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P=0.003) and grade 3-4 drug-related (P=0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)-cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs.Conclusion:ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.