Two-Year Safety and Virologic Efficacy of Maraviroc in Treatment-Experienced Patients With CCR5-Tropic HIV-1 Infection: 96-Week Combined Analysis of MOTIVATE 1 and 2

Abstract

Background Maraviroc, the first approved CCR5 antagonist, demonstrated 48-week safety and virologic efficacy in CCR5-tropic HIV-infected, treatment-experienced patients; however, critical longer-term safety and durability of responses are unknown. Methods Two-year follow-up of 2 prospective, randomized, blinded studies of maraviroc once daily or twice daily, or placebo in treatment-experienced patients with R5-tropic HIV-1 receiving an optimized background regimen. Unblinding occurred after the week-48 visit of the last enrolled patient. Safety and virologic parameters were assessed through week 96. Results One thousand forty-nine patients were randomized and received study drugs. HIV-1 RNA was <50 copies per milliliter at week 96 in 39% and 41% of patients receiving maraviroc every day or twice a day, respectively. Among patients with HIV-1 RNA <50 copies per milliliter at week 48, 81% and 87% of patients receiving maraviroc every day or twice a day, respectively, maintained this response at week 96. At week 96, median CD4+ T-cell counts increased from baseline by 89 and 113 cells per cubic millimeter with maraviroc every day and twice a day, respectively. Exposure-adjusted rates of adverse events were similar with maraviroc or placebo. No new or unexpected events were observed after week 48. Conclusions Maraviroc-containing antiretroviral regimens maintained durable responses in treatment-experienced patients with R5 HIV-1 through 96 weeks of treatment with a safety profile similar to placebo.

The maraviroc expanded access program — safety and efficacy data from an open-label study

“…[3][4][5] Consistent with data from other studies, 7,8,13,14 subgroup analysis demonstrated that virologic response rates increased with the number of active drugs in the ARV regimen. 4,6 Current guidelines recommend the use of at least two, and preferably three, fully active agents in a new regimen in patients with evidence of virologic resistance.…”

“…The incidence of Category C AIDS-defining events and non-AIDSdefining malignancies was very low. This, together with data from the 96-week follow-up of the MOTIV-ATE studies 5 is reassuring in light of the lymphomas (and other cancers) reported in prior studies with another CCR5 antagonist. 17 Although individuals with the CCR5 delta 32 mutation are generally healthy, some immunological effects have been described, [18][19][20] raising concern at the time regarding the long-term safety of CCR5 antagonists.…”

Closing the door to human immunodeficiency virus

“…At week 48, a similar proportion of patients with less than 50 copies HIV RNA/mL was achieved in the Maraviroc-treated group, as compare with that in the Efavirenz group (a reverse transcriptase inhibitor), but CD4 + cell count rebound was greater in patients received Maraviroc (Cooper et al, 2010). These observations were confirmed by week 96 analysis (Hardy et al, 2010;Sierra-Madero et al, 2010). The emergence of pre-existing CXCR4-tropic HIV-1 that failed to be detected in pre-treatment screening was related to virologic failure (Fatkenheuer et al, 2008;Cooper et al, 2010).…”

A Review of the Toxicity of HIV Medications

“…In clinical trials, there was no statistically significant difference in these effects noted between placebo and maraviroc arms [113]. Increased aminotransferases were observed in maraviroc patients as compared with patients on non-maraviroc therapy, but no significant difference in the number of patients with large aminotransferase elevations.…”