Objective: This study was performed to evaluate a once-daily dual-therapy regimen, maraviroc (MVC) + atazanavir/ritonavir (ATV/r), in treatment-naive patients.
Design: A phase 2b, randomized, open-label pilot study.
Methods: In Study A4001078 (NCT00827112), treatment-naive patients with CCR5-tropic HIV-1 (HIV-1 RNA ≥1000 copies/mL; CD4 cell count ≥100 cells/mm3) were randomized to receive either MVC 150 mg once daily (n = 60) or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily (n = 61) + ATV/r 300/100 mg once daily. Primary endpoint was proportion of patients with HIV-1 RNA <50 copies per milliliter at week 48.
Results: At week 48, 44 (74.6%) and 51 (83.6%) patients in the MVC and TDF/FTC treatment groups, respectively, had plasma HIV-1 RNA <50 copies per milliliter. Median change from baseline in CD4 cell count at week 48 was +173 and +187 cells per cubic millimeter with MVC and TDF/FTC, respectively. Seven patients discontinued from each arm; there were no deaths. The incidence of serious adverse events (AEs) was similar in each group; however, there were more grade 3/4 AEs in the MVC group (18 vs 11), mostly due to hyperbilirubinemia. Three patients in each arm were evaluable for virological analysis at discontinuation or failure (HIV-1 RNA >500 copies/mL); no genotypic resistance, change in tropism, or loss of susceptibility relevant to treatment was observed.
Conclusions: The virological activity and immunological benefit of once-daily MVC + ATV/r were confirmed. Indirect hyperbilirubinemia and associated signs were the most commonly reported AEs in both study treatment groups and were not associated with significant transaminase increases. No drug resistance occurred.