SUMMARY: HIV positive people using today's state-of-the-art antiretroviral drugs are likely to achieve good CD4 cell recovery, but this cannot be attributed specifically to use of CCR5 antagonists such as maraviroc (Selzentry), according to a presentation at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) this week in Boston.

By Liz Highleyman

Antiretroviral therapy (ART) has improved markedly over the past decade, with medications that are more potent, more convenient, and less likely to cause serious side effects. In addition to new and improved drugs in the non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor classes, the modern armamentarium includes 2 novel drug classes, integrase inhibitors and CCR5 antagonist entry inhibitors.

Some previous studies have suggested that CCR5 antagonists -- a class that currently includes only 1 approved drug, maraviroc (Selzentry) -- may produce larger CD4 cell gains than other types of antiretroviral drugs, but findings have not been consistent.

Marie Pichenot?from University Hospital Tourcoing in France and colleagues aimed to assess the ability of a CCR5 antagonist to enhance CD4 cell recovery compared with other newer antiretroviral drugs.

The researchers performed a systemic review and meta-analysis of randomized clinical trials published in medical journals or presented at conferences since 2003 that looked at virological and immunological response to a new antiretroviral drug versus placebo in treatment-experienced patients. They included studies of maraviroc, the experimental CCR5 antagonist vicriviroc (now discontinued as an HIV candidate), the fusion inhibitor enfuvirtide (T-20, Fuzeon), the integrase inhibitor raltegravir (Isentress), the next-generation NNRTI etravirine (Intelence), and the 2 newest protease inhibitors, tipranavir (Aptivus) and darunavir (Prezista).

The investigators identified 10 studies that met the criteria for inclusion, representing a total of 6401 patients; 4 of these evaluated maraviroc. They collected information on baseline patient characteristics, rates of undetectable viral load, and changes in CD4 cell count at week 48 in groups receiving a new drug versus those receiving placebo -- that is, compared with a background regimen without the new drug.

Results

	Use of newer antiretroviral agents was associated with superior CD4 cell response at week 48 compared with placebo (pooled difference in CD4 cell count +39 cells/mm3).
	However, use of a CCR5 inhibitor rather than another type of new drug did not explain this gain (P = 0.22).
	Male sex (P = 0.014) and initial genotypic sensitivity scores (a measure of drug resistance) of 0, < 1, or < 2 (P = 0.001, 0.0017, and 0.045, respectively) were associated with larger CD4 cell gains with new agents vs placebo.
	A higher rate of undetectable viral load in the placebo group at week 48 -- indicating that the background regimen was suppressing HIV by itself -- was associated with a smaller difference in CD4 cell gains (P = 0.042).

Based on this analysis, the investigators concluded, "CCR5 [antagonists] do not allow a better CD4 cell recovery when compared to others new antiretroviral agents in treatment-experienced patients."

Investigator affiliations: Univ. Hosp., Tourcoing, France; INSERM U995, Lille, France; Univ. Hosp., Toulouse, France; 4EA2694, Lille, France.

9/17/10

Reference
M Pichenot, S Deuffic-Burban, l Cuzin, and Y Yazdanpanah. CCR5 Inhibitors and CD4 Cell Count Change in Treatment Experienced Patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-1813.

Other Source
ICAAC. Use of new antiretroviral agents to restore CD4 cell count in treatment-experienced patients. Media advisory. September 14, 2010.