Switch to Ritonavir-Boosted versus Unboosted Atazanavir plus Raltegravir Dual-Drug Therapy Leads to Similar Efficacy and Safety Outcomes in Clinical Practice.

Abstract

OBJECTIVES: To assess immunovirological response, safety and pharmacokinetic of NRTI-sparing regimen dual therapy of atazanavir (ATV) and raltegravir (RAL) in maintenance strategy. METHODS: A retrospective analysis was conducted on a cohort of HIV-infected adults followed in French centers (Dat'AIDS cohort), comparing the proportions of virological and therapeutic failures between ATV + RAL and ATV/ritonavir + RAL dual therapy regimens. RESULTS: 283 patients were assessed: 185 switched for ATV + RAL and 98 for ATV/ritonavir + RAL dual therapy. Virological failure rate at week 96 was 13.8% (95% CI, 9.8-17.8), without difference between the two groups (Log-rank Test, p = 0.87). The cumulative percentages of patients remaining free of therapeutic failure at week 24, 48 and 96 of dual therapy were 74.9% (95% CI, 69.9-80.0), 65.4% (95% CI, 59.8-70.9) and 53.4% (95% CI, 47.5-59.2), respectively. Four out of 39 confirmed virological failures developed RAL resistance. By multivariate analysis, virological failure was associated with high HIV-1 RNA zenith (p = 0.02), low CD4+ T-cell count at baseline (p<0.001) and short duration on antiretroviral therapy (p<0.001). Before week 96, dual therapy was discontinued in 44 patients (16%) because of various adverse events, with no difference between the two groups. Minimal plasma levels were targeted in 84% and 87% of patients for ATV and RAL, respectively, and both were significantly higher in ritonavir-boosted regimen. CONCLUSIONS: Emerging RAL-resistance and discontinuations for adverse events resulted in moderate efficacy rates of ATV and RAL dual therapy in heavily pretreated patients.