of CCR5 Antagonist Does Not Explain Better CD4 Cell Recovery with Newer
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.
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
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
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.
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).
use of a CCR5 inhibitor rather than another type of new drug did
not explain this gain (P = 0.22).
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).
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,
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
ICAAC. Use of new antiretroviral agents to restore CD4 cell count in
treatment-experienced patients. Media advisory. September 14, 2010.