No difference in effectiveness of treatment simplification to boosted or unboosted atazanavir plus lamivudine in virologically suppressed in HIV-1-infected patients

BACKGROUND: Simplification strategies of antiretroviral treatment represent effective tools for the reduction of drug-induced toxicity, resistance mutations in case of virological failure and costs. OBJECTIVES: To assess the effectiveness of simplification to atazanavir/ritonavir (ATV(rtv)) or unboosted atazanavir (ATV(400)) plus lamivudine, and if low plasma or intracellular ATV C(trough) influence virological outcomes. METHODS: Ambispective observational study in patients with undetectable HIV-RNA who were switched to ATV(rtv) or ATV(400) plus lamivudine once daily. Previous virological failures (VF) were allowed if the resistance tests showed major resistance mutation neither to ATV nor to lamivudine. VF was defined as two consecutive plasma HIV-RNA >200 copies/mL. Effectiveness was assessed by intention-to-treat and on-treatment analyses. Plasma and intracellular ATV C(trough) were measured by LC-MS/MS. RESULT: A total of 246 patients were included. At week 48, the Kaplan–Meier estimation of efficacy within the ATV(rtv) and ATV(400) groups were 85.9% [95% confidence interval, (CI(95)), 80.3–91.4%] versus 87.6% (CI(95), 80.1–94.1%) by intention-to-treat analysis (p = 0.684), and 97.7% (CI(95), 95.2–100%) versus 98.8% (CI(95), 97.0–100%) by on-treatment analysis (p = 0.546), respectively. Plasma and intracellular C(trough) were significantly higher with ATV(rtv) than with ATV(400) (geometric mean (GM), 318.3 vs. 605.9 ng/mL; p = 0.013) and (811.3 vs. 2659.2 ng/mL; p = 0.001), respectively. Only 14 patients had plasma C(trough) below the suggested effective concentration for ATV (150 ng/mL). No relationship between plasma or intracellular C(trough) and VF or blips were found. CONCLUSION: Boosted or unboosted ATV plus lamivudine is effective and safe, and the lower plasma C(trough) observed with ATV(400) do not compromise the effectiveness of these simplification regimens in long-term virologically suppressed HIV-1-infected patients.