Efficacy of Maraviroc in combination with at least one other potent new antiretroviral drug: 24-week combined analysis of the MOTIVATE 1 and 2 studies
Objectives: Maraviroc, a CCR5 antagonist, plus optimized background therapy (OBT) demonstrated statistically significantly greater virologic and immunologic efficacy and a similar safety profile compared to placebo plus OBT at 24 weeks in two double-blind studies in treatment-experienced patients – MOTIVATE 1 (USA/Canada) and MOTIVATE 2 (Europe/Australia/USA). The aim of this analysis was to evaluate efficacy of maraviroc when combined with other active drugs in the OBT.
Methods: Patients with triple-class-experience and/or -resistance, CCR5-tropic HIV-1 (Trofileä), and HIV-1-RNA ³5000 copies/mL were randomized 2:2:1 to OBT (3–6 ARVs +/- low-dose ritonavir) plus maraviroc QD, BID or placebo. Efficacy was evaluated by screening genotypic, phenotypic and overall susceptibility scores to OBT, as well as by first-time use of selected background drugs.
Results: More patients with higher susceptibility scores reached undetectable HIV-1 RNA than those with lower scores. For patients receiving maraviroc whose virus had no enfuvirtide or lopinavir/r resistance mutations detected at screening, first-time use of enfuvirtide or lopinavir/r increased the likelihood of achieving undetectable HIV-1 RNA.
| ||Placebo + OBT||Maraviroc QD + OBT||Maraviroc BID + OBT|
| ||<50 / <400 copies/mL||<50 / <400 copies/mL||<50 / <400 copies/mL|
|Total population||25% / 30% (N=207)||48% / 61% (N=408)||48% / 65% (N=419)|
|Enfuvirtide first use/no mutations||36% / 40% (N=58)||64% / 75% (N=91)||53% / 75% (N=109)|
|Lopinavir/r first use/no mutations||50% / 60% (N=10)||74% / 96% (N=27)||70% / 87% (N=23)|
Conclusions: The data demonstrate that maraviroc combined with at least one other potent new antiretroviral in the regimen is highly effective in reducing viral load to below the limit of detection. This is consistent with an additive effect of maraviroc with other antiretroviral drugs, as predicted by in vitro data.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
"vanderRystE., et al.
Efficacy of Maraviroc in combination with at least one other potent new antiretroviral drug: 24-week combined analysis of the MOTIVATE 1 and 2 studies.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: