Impact of Baseline Antiretroviral Resistance Status on Efficacy Outcomes Among Patients Receiving Maraviroc Plus Optimized Background Therapy in the MOTIVATE 1 and 2 Trials

Abstract

Purpose: The MOTIVATE studies assessed maraviroc with optimized background therapy (OBT) in treatment-experienced patients with R5 HIV-1. This post hoc analysis compared outcomes between patients with and without HIV-1 resistance to ε3 classes of antiretrovirals at screening (triple-class-resistant [TCR] versus not-TCR [nTCR]). Methods: Week 48 changes (N = 635) in HIV-1 RNA and CD4 + cells were compared between TCR and nTCR groups receiving twice-daily maraviroc+OBT or placebo+OBT. Results: HIV-1 RNA change from baseline on maraviroc was significantly greater in the nTCR group (–2.05 vs –1.74 log₁₀ copies/mL; 95% CI difference 0.05–0.58 log₁₀) though proportions <400 or <50 copies/mL were not. Week 48 CD4 increases were significantly greater in the nTCR group overall (mean +150 vs +110 cells/mm³; 95% CI difference 18–62 cells/mm³) and in those with <50 RNA copies/mL (nTCR +192 vs +126 cells/mm³; 95% CI difference, 19–93 cells/mm³) or receiving ε2 active OBT agents (weighted score; nTCR +184 vs +125 cells/mm³; 95% CI difference 8–110 cells/mm³). Conclusions: Virologic suppression on maraviroc was greater in the nTCR than the TCR group, though proportions <50 or 400 copies/mL were not significantly different. Optimal CD4 increases on maraviroc appeared to accrue from initiation before development of TCR virus.

Keywords:

• antiretroviral therapy
• drug resistance
• maraviroc