A meta-analysis of the efficacy and safety of unboosted atazanavir compared with ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults with established virological suppression after induction

Abstract

Objectives: Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a viable option for long-term antiretroviral therapy. To evaluate the clinical evidence for this approach, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating efficacy and safety in patients with established virological suppression. Methods: Several databases were searched without limits on time or language. Searches of conferences were also conducted. RCTs were included if they compared a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta-analysis was conducted using a random effects model for the proportion achieving virological suppression (i.e. HIV RNA<50 and <400 HIV-1 RNA copies/mL), CD4 cell counts, lipid levels and liver function tests. Dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs). Results: Five studies (n=1249) met the inclusion criteria. The meta-analysis demonstrated no statistically significant difference in efficacy (i.e. HIV RNA<50copies/mL) between PI/RTV and unboosted atazanavir [RR=1.04; 95% confidence interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a subanalysis of studies where atazanavir/RTV was the only PI/RTV used during induction. Additional efficacy results support these findings. A significant reduction in total cholesterol (P<0.00001), triglycerides (P=0.0002), low-density lipoprotein (LDL) cholesterol (P=0.009) and hyperbilirubinaemia (P=0.02) was observed with unboosted atazanavir vs.PI/RTV. Conclusions: The meta-analysis demonstrated that switching patients with virological suppression from an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e. blood parameter abnormalities) without sacrificing virological efficacy. © 2013 British HIV Association.