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Maraviroc Does Not Boost Stalled CD4s in Virologically Suppressed People
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Deflating expectation based on earlier study of maraviroc, this CCR5 antagonist did not crank up stalled CD4 counts in people with tight virologic control, according to results of a 34-person pilot study [1]. Maraviroc did appear to quiet immune activation.
In the MERIT trial of previously untreated people, CD4 and CD8 counts rose higher in the first 48 weeks of treatment in people randomized to maraviroc than in those randomized to efavirenz, despite better virologic control with efavirenz [2]. These findings led some to speculate that, by plugging CCR5 receptors, maraviroc slows CD4-cell migration to the gut, where CD4s may be more vulnerable to HIV [3].
This single-arm pilot study enrolled 34 people with a CD4 count under 250 and a calculated CD4 slope between -20 and +20 cells per year, despite having an undetectable viral load for at least 48 weeks. Everyone added maraviroc to their current regimen for 24 weeks. Timothy Wilkin and AIDS Clinical Trials Group (ACTG) 5256 colleagues analyzed a primary endpoint of change in CD4 count from the average of two baseline counts to the average of the week 22 and week 24 counts on maraviroc plus the baseline regimen.
Median baseline CD4 count in the 34 study participants stood at 153 and median time of viral load suppression stretched close to 3 years. Median pre-entry CD4 slope was +5.8 cells per year. These 34 people (2 of them women) had a median age of 50 years (range 41 to 64). Two people stopped maraviroc after virologic failure and were excluded from the analysis.
Only 2 people gained 50 or more CD4 cells during the 24 weeks. The median CD4 gain at weeks 22/24 was 12 cells (90% confidence interval 1 to 22). CD4 slope rose to 24.7 cells per year. The ACTG team rated that improvement "not at the magnitude expected."
Separately presented results of two phase 3 placebo-controlled trials of vicriviroc, another CCR5 antagonist, plus optimized background regimens in antiretroviral-experienced people (which NATAP will describe in another article) also showed no special CD4 advantage with the CCR5 blocker [4].
CD4 and CD8-cell activation markers (CD38 and HLA-DR) did decrease after addition of maraviroc, but those drops were not associated with better CD4-cell gains. That lack of correlation suggested to Wilkin and colleagues "that persistently low CD4 T-cell counts in this population may not be related to ongoing immune activation." But they call for further study of CCR5 antagonists as dampers of immune activation associated with chronic HIV infection and its complications.
References
1. Wilkin T, Lalama C, Tenorio A, et al. Maraviroc intensification for suboptimal CD4+ cell response despite sustained virologic suppression: ACTG 5256. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 285.
2. Saag M, Ive P, Heera J, et al. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine/lamivudine), for the treatment of antiretroviral naive subjects infected with R5 HIV-1: week 48 results of the MERIT study. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. July 22-25, 2007. Sydney. Abstract WESS104.
3. Deeks SG. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med. 2009;17:118-123. http://www.iasusa.org/pub/topics/2009/issue4/118.pdf.
4. Gathe J, Diaz R, Fatkenheuer G, et al. Phase 3 Trials of vicriviroc in treatment-experienced subjects demonstrate safety but not significantly superior efficacy over potent background regimens alone. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 54LB.
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