CD4+ T-cell restoration after 48 weeks in the maraviroc treatment-experienced trials MOTIVATE 1 and 2.
OBJECTIVE
To determine factors associated with CD4 responses to maraviroc (MVC)-containing regimens in treatment-experienced patients.


METHODS
Forty-eight-week data from MOTIVATE 1 and 2 was used to assess MVC once or twice daily versus placebo (PBO), each with optimized background therapy (N = 1047). A repeated measures model evaluated longitudinal CD4 changes, multivariate linear regression evaluated predictors of week 48 increases, and Cox proportional hazard modeling evaluated time to category C events.


RESULTS
Median CD4 increases were greater on MVC once or twice daily than PBO (92, 103, and 24 cells/mm3, respectively; P < 0.05), and the difference remained significant among patients achieving less than 50 HIV-1 RNA copies/mL (126, 125, and 96 cells/mm3; P < 0.05) or when adjusted for other predictors of CD4 increase including change in HIV-1 RNA. Time to a category C event was longer on MVC; in multivariate models, higher on-treatment CD4 count, but not MVC treatment, was protective against new events (hazard ratio 0.8 per +25 cells/mm3; 95% confidence interval 0.78-0.87).


CONCLUSIONS
MOTIVATE patients receiving MVC had larger CD4+ T-cell increases than those receiving PBO, even after adjusting for the greater virologic potency of MVC-containing regimens. This additional CD4 response was associated with a longer time to the development of AIDS-defining events on MVC.
Asmuth
David M
DM
University of California Davis, Sacramento, CA, USA.
Goodrich
James
J
Cooper
David A
DA
Haubrich
Richard
R
Rajicic
Natasa
N
Hirschel
Bernard
B
Mayer
Howard
H
Valdez
Hernan
H
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000077592:Maraviroc; D009894:Opportunistic Infections / Q000453:epidemiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D014230:Triazoles; D000077592:Maraviroc