The relationship of CCR5 antagonists to CD4+ T-cell gain: a meta-regression of recent clinical trials in treatment-experienced HIV-infected patients.
OBJECTIVE
Lower CD4+ T-cell counts are related to increased morbidity and mortality despite virologic suppression. CCR5 antagonists are associated with robust CD4+ T-cell responses. We examined the relationship of CCR5 antagonists to CD4+ T-cell gains.


METHODS
Meta-regression of recent phase 2-3 trials evaluating new antiretroviral agents in treatment-experienced subjects.


METHODS
We analyzed the relationship of CCR5 antagonists to CD4+ T-cell count increase 24 weeks after initiating the new regimen using a linear model with generalized estimating equations controlling for differing rates of virologic suppression. Each treatment group was treated as a data point weighted by sample size.


RESULTS
We included 46 treatment groups from 17 trials (11 groups from 5 trials used CCR5 antagonists). Controlling for average baseline HIV-1 RNA and proportion of subjects achieving HIV-1 RNA <50 copies/mL, use of a CCR5 antagonist was associated with an additional significant CD4+ T-cell gain of +30/μL (95% CI, 19-42) at 24 weeks compared to treatment groups not using a CCR5 antagonist.


CONCLUSIONS
Use of a CCR5 antagonist was associated with an enhanced CD4+ T-cell count response independent of virologic suppression. This observation supports further evaluation of CCR5 antagonists in patients with discordant immunologic and virologic responses to ART.
Division of Infectious Diseases, Weill-Cornell Medical College, New York, New York 10011, USA. tiw2001@med.cornell.edu
Timothy J
TJ
Wilkin
Heather R
HR
Ribaudo
Allan R
AR
Tenorio
Roy M
RM
Gulick
D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents; D065100:CCR5 Receptor Antagonists
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