Impact of baseline antiretroviral resistance status on efficacy outcomes among patients receiving maraviroc plus optimized background therapy in the MOTIVATE 1 and 2 trials.
OBJECTIVE
The MOTIVATE studies assessed maraviroc with optimized background therapy (OBT) in treatment-experienced patients with R5 HIV-1. This post hoc analysis compared outcomes between patients with and without HIV-1 resistance to epsilon3 classes of antiretrovirals at screening (triple-class-resistant [TCR] versus not-TCR [nTCR]).


METHODS
Week 48 changes (N = 635) in HIV-1 RNA and CD4+ cells were compared between TCR and nTCR groups receiving twice-daily maraviroc+OBT or placebo+OBT.


RESULTS
HIV-1 RNA change from baseline on maraviroc was significantly greater in the nTCR group (-2.05 vs -1.74 log(10) copies/mL; 95% CI difference 0.05-0.58 log(10)) though proportions <400 or <50 copies/mL were not. Week 48 CD4 increases were significantly greater in the nTCR group overall (mean +150 vs +110 cells/mm(3); 95% CI difference 18-62 cells/mm(3)) and in those with <50 RNA copies/mL (nTCR +192 vs +126 cells/mm(3); 95% CI difference, 19-93 cells/mm(3)) or receiving > or = 2 active OBT agents (weighted score; nTCR +184 vs +125 cells/mm3; 95% CI difference 8-110 cells/mm(3)).


CONCLUSIONS
Virologic suppression on maraviroc was greater in the nTCR than the TCR group, though proportions <50 or 400 copies/mL were not significantly different. Optimal CD4 increases on maraviroc appeared to accrue from initiation before development of TCR virus.
Nelson
Mark
M
Chelsea and Westminster Hospital, London, UK. Mark.nelson@chelwest.nhs.uk
Fisher
Martin
M
Gonzalez-Garcia
Juan
J
Rockstroh
Jürgen K
JK
Weinstein
David
D
Valdez
Hernan
H
Mayer
Howard
H
van der Ryst
Elna
E
Goodrich
James M
JM
Dang
Nathalie
N
D018791:CD4 Lymphocyte Count; D017326:Clinical Trials, Phase III as Topic; D003510:Cyclohexanes / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D005260:Female; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load
D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc