Maraviroc for Initial Treatment of HIV Infection -- MERIT Reexamined
Maraviroc for Initial Treatment of HIV Infection -- MERIT Reexamined
Maraviroc proved noninferior to efavirenz among treatment-naive patients but is still unlikely to see much use in this population.
The FDA recently approved the CCR5 inhibitor maraviroc for HIV-infected treatment-naive patients (JW AIDS Clin Care Dec 7 2009) based on data from the manufacturer-sponsored MERIT trial. These data were previously reported at two major conferences (JW AIDS Clin Care Sep 10 2007 and Nov 10 2008) and have now been published.
The MERIT trial was a randomized comparison of once-daily maraviroc, twice-daily maraviroc, and efavirenz, each in combination with AZT/3TC. Patients were eligible for participation if they were treatment-naive and had only CCR5-tropic virus at screening, as determined by the first-generation coreceptor tropism assay.
Of 1730 patients screened, 26% did not have an evaluable tropism result, and an additional 13% had CXCR4-using virus. A total of 895 patients received at least one dose of study medication. At 16 weeks, the once-daily maraviroc arm was discontinued for not meeting the noninferiority criteria, leaving a total of 721 patients for the primary analysis.
Approximately 27% of maraviroc recipients discontinued the study drugs (primarily for lack of efficacy), as did 25% of efavirenz recipients (primarily because of adverse events). By week 48, 65.3% of maraviroc recipients had achieved viral loads <50 copies/mL, compared with 69.3% of efavirenz recipients. Based on these results, maraviroc did not meet the criteria for noninferiority.
In a post hoc analysis, investigators retested all the screening study specimens using an enhanced-sensitivity assay that can reliably detect CXCR4-using virus when it is present in as little as 0.3% of the virus population. They found that 107 study participants actually had dual mixed-tropic virus at screening. These patients were excluded from the post hoc analysis, leaving a new study sample of 614 individuals. In this population, maraviroc did meet the criteria for noninferiority, with 68.5% of maraviroc recipients and 68.3% of efavirenz recipients reaching viral loads <50 copies/mL by week 48.
Abstract and Introduction
Abstract
Maraviroc proved noninferior to efavirenz among treatment-naive patients but is still unlikely to see much use in this population.
Introduction
The FDA recently approved the CCR5 inhibitor maraviroc for HIV-infected treatment-naive patients (JW AIDS Clin Care Dec 7 2009) based on data from the manufacturer-sponsored MERIT trial. These data were previously reported at two major conferences (JW AIDS Clin Care Sep 10 2007 and Nov 10 2008) and have now been published.
The MERIT trial was a randomized comparison of once-daily maraviroc, twice-daily maraviroc, and efavirenz, each in combination with AZT/3TC. Patients were eligible for participation if they were treatment-naive and had only CCR5-tropic virus at screening, as determined by the first-generation coreceptor tropism assay.
Of 1730 patients screened, 26% did not have an evaluable tropism result, and an additional 13% had CXCR4-using virus. A total of 895 patients received at least one dose of study medication. At 16 weeks, the once-daily maraviroc arm was discontinued for not meeting the noninferiority criteria, leaving a total of 721 patients for the primary analysis.
Approximately 27% of maraviroc recipients discontinued the study drugs (primarily for lack of efficacy), as did 25% of efavirenz recipients (primarily because of adverse events). By week 48, 65.3% of maraviroc recipients had achieved viral loads <50 copies/mL, compared with 69.3% of efavirenz recipients. Based on these results, maraviroc did not meet the criteria for noninferiority.
In a post hoc analysis, investigators retested all the screening study specimens using an enhanced-sensitivity assay that can reliably detect CXCR4-using virus when it is present in as little as 0.3% of the virus population. They found that 107 study participants actually had dual mixed-tropic virus at screening. These patients were excluded from the post hoc analysis, leaving a new study sample of 614 individuals. In this population, maraviroc did meet the criteria for noninferiority, with 68.5% of maraviroc recipients and 68.3% of efavirenz recipients reaching viral loads <50 copies/mL by week 48.