Maraviroc Intensification of Stable Antiviral Therapy in HIV-1-Infected Patients With Poor Immune Restoration: MARIMUNO-ANRS 145 Study

Objective: To address the ability of a 24-week Maraviroc (MVC) intensification of a stable antiretroviral therapy (cART) to significantly increase the CD4 cell count slope. Methods: Patients were eligible if they had CD4 < 350 cells/mm(3), a CD4 slope < 50 cells/mm(3) per year, and sustained plasma HIV-RNA < 50 copies/mL over the last 2 years, while receiving a stable cART. Patients harboring pure X4-using viruses by a phenotypic tropism assay were excluded. MVC was added to cART for 24 weeks, at the recommended dosage per drug-drug interactions. The primary endpoint was a significant positive difference in CD4 slopes (with MVC-pre-MVC, paired t test). Results: Sixty patients (55 men), with median age 51 years, baseline CD4 238 cells/mm(3), and slope before intensification + 14.1 cells/mm(3) per year were included. CD4 nadir was < 50/mm(3) in 47% of the population. The full set of patients (N = 57) completed week 24, and the on-treatment patients (N = 48) did not discontinue MVC. The median CD4 slope difference from baseline was +22.6 cells/mm(3) per year (P = 0.08) in full set and +22.6 cells/mm(3) per year (P = 0.04) in on-treatment. Slope evolution was not different according to baseline tropism, CD4 nadir, or ongoing cART regimen. No drug-related severe adverse events were recorded during intensification. MVC plasma concentrations were significantly different depending on drug-drug interaction with ongoing cART regimen and tended to be correlated with CD4 cells increase. Conclusion: In this study, MVC intensification of stable cART over 24 weeks was able to enhance CD4 cell slopes in patients with prior insufficient immune restoration despite long-term virological control.