SUMMARY: Treatment-experienced HIV patients who used the CCR5 antagonist maraviroc (Selzentry) achieved larger CD4 cell gains that reduced the risk of developing opportunistic infections, according to 48-week results from the MOTIVATE 1 and 2 trials published in the December 9, 2009 advance online issue of the Journal of Acquired Immune Deficiency Syndromes. These findings add to the evidence that maraviroc appears to have a beneficial effect on CD4 recovery that is greater than expected based on antiviral potency alone.

By Liz Highleyman

In the present analysis, David Asmuth from the University of California at Davis and colleagues aimed to determine factors associated with immunological response to maraviroc-containing regimens in treatment-experienced patients enrolled in the MOTIVATE 1 and 2 trials.

As previously reported, these identical Phase 3 trials (MOTIVATE 1 in the U.S. and Canada; MOTIVATE 2 in the U.S., Europe, and Australia) together included more than 1000 heavily treatment-experienced patients with documented CCR5-tropic HIV and triple-class antiretroviral drug resistance. Participants were randomly assigned to receive maraviroc at doses of 150 mg once-daily or 150 twice-daily, or else placebo, in combination with optimized background therapy.

Most study participants (90%) were men and the average age was about 45 years. Patients had relatively advanced disease, with a median CD4 cell count of 150-180 cells/mm3 and a mean HIV viral load of about 65,000 copies/mL.
This retrospective analysis included 1047 patients in the 2 trials. The investigators evaluated longitudinal changes in CD4 count, predictors of CD4 cell gains at 48 weeks, and time to AIDS-defining (category C) events.

Results

	At 48 weeks, median CD4 cell increases were significantly larger in the one-daily and twice-daily maraviroc arms compared with the placebo arm (92, 103, and 24 cells/mm3, respectively; P < 0.05).
	CD4 cell gains remained significantly larger with maraviroc when considering only patients in all treatment arms who achieved HIV RNA > 50 copies/mL (126, 125, and 96 cells/mm3, respectively; P < 0.05).
	CD4 cell increases in the maraviroc arm remained significantly larger after adjusting for other predictors of CD4 recovery including changes in HIV viral load.
	Patients in the maraviroc arms took longer on average to progress to category C events.
	In a multivariate analysis, having a higher on-treatment CD4 count -- but not maraviroc use per se -- was protective against new AIDS-defining events (hazard ratio 0.8, or 20% reduction, per additional 25 cells/mm3).

Based on these findings, the investigators concluded, "MOTIVATE patients receiving maraviroc had larger CD4 T-cell increases than those receiving placebo, even after adjusting for the greater virologic potency of maraviroc-containing regimens. This additional CD4 response was associated with a longer time to the development of AIDS-defining events on maraviroc."

University of California Davis, Sacramento, CA; Pfizer Research and Development, New London, CT; University of New South Wales, Sydney, Australia; University of California San Diego, San Diego, CA; Pfizer, Inc., New York, NY; Hospital Geneva University Hospital, Geneva, Switzerland.

1/05/10

Reference
DM Asmuth, J Goodrich, DA Cooper, and others. CD4+ T-Cell Restoration After 48 Weeks in the Maraviroc Treatment-Experienced Trials MOTIVATE 1 and 2. Journal of Acquired Immune Deficiency Syndromes (Abstract). December 9, 2009 (Epub ahead of print).