Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection.

BACKGROUND: We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients. METHODS: We analyzed pooled data from week 48 from the two studies according to sex, race or ethnic group, clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of screening, the use or nonuse of enfuvirtide in optimized background therapy (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs coadministered, the first use of selected background agents, and tropism at baseline. Changes in viral tropism and the CD4 count at treatment failure were evaluated. Data on aminotransferase levels in patients coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) were also analyzed. RESULTS: A treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline. CONCLUSIONS: Subanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.

Maraviroc for previously treated patients with R5 HIV-1 infection

Background CC chemokine receptor 5 antagonists are a new class of antiretroviral agents.Methods We conducted two double- blind, placebo- controlled, phase 3 studies - Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment- Experienced Patients ( MOTIVATE) 1 and MOTIVATE 2 - with patients who had R5 human immunodeficiency virus type 1 ( HIV- 1) only. They had been treated with or had resistance to three antiretroviral- drug classes and had HIV- 1 RNA levels of more than 5000 copies per milliliter. The patients were randomly assigned to one of three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice daily, or placebo, each of which included optimized background therapy ( OBT) based on treatment history and drug- resistance testing. Safety and efficacy were assessed after 48 weeks.Results A total of 1049 patients received the randomly assigned study drug; the mean baseline HIV- 1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48 weeks, in both studies, the mean change in HIV- 1 RNA from baseline was greater with maraviroc than with placebo: - 1.66 and - 1.82 log(10) copies per milliliter with the once- daily and twice- daily regimens, respectively, versus - 0.80 with placebo in MOTIVATE 1, and - 1.72 and - 1.87 log(10) copies per milliliter, respectively, versus - 0.76 with placebo in MOTIVATE 2. More patients receiving maraviroc once or twice daily had HIV- 1 RNA levels of less than 50 copies per milliliter ( 42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE 1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P< 0.001 for both comparisons in each study). The change from baseline in CD4 counts was also greater with maraviroc once or twice daily than with placebo ( increases of 113 and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of 122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P< 0.001 for both comparisons in each study). Frequencies of adverse events were similar among the groups.Conclusions Maraviroc, as compared with placebo, resulted in significantly greater suppression of HIV- 1 and greater increases in CD4 cell counts at 48 weeks in previously treated patients with R5 HIV- 1 who were receiving OBT. (ClinicalTrials. gov numbers, NCT00098306 and NCT00098722.)