Vicriviroc plus optimized background therapy for treatment-experienced subjects with CCR5 HIV-1 infection: final results of two randomized phase III trials.
BACKGROUND
Vicriviroc, a novel HIV CCR5 antagonist, demonstrated significant efficacy and favorable tolerability in phase II trials in treatment-experienced subjects, supporting further evaluation in phase III studies.


METHODS
Two identical double-blind, placebo (PBO)-controlled trials in CCR5-tropic HIV-infected subjects with documented resistance to two antiretroviral classes were conducted. Subjects were randomized to vicriviroc 30 mg QD (N = 571) or PBO (N = 286) with open-label optimized background therapy (OBT) containing ≥2 fully active antiretroviral drugs. The primary endpoint was percentage of subjects with <50 copies/mL HIV RNA at 48 weeks. It was analyzed in a logistic regression with treatment (vicriviroc + OBT/PBO + OBT), use of enfuvirtide in baseline OBT (yes/no), and baseline HIV RNA (≤100,000/>100,000 copies/mL) as covariates. In addition, a pre-planned analysis to examine other efficacy and safety endpoints was conducted.


RESULTS
Baseline characteristics of the pooled mITT population (vicriviroc, n = 486; PBO, n = 235) included mean HIV RNA of 4.6 log(10) copies/mL and mean CD4 count of 257 cells/μL. Approximately 60% of subjects received ≥3 active drugs in the OBT. The percentage of subjects with <50 copies/mL HIV RNA was not significantly different between vicriviroc and PBO at week 48 (64% vs 62%, p = 0.6). However, in subjects receiving ≤2 active drugs in their OBT, the proportion achieving <50 copies/mL HIV RNA was higher in those receiving vicriviroc compared with PBO (70% vs 55%, p = 0.02).


CONCLUSIONS
The studies failed to show significant efficacy gains when vicriviroc was added to OBT. However, given the efficacy results of earlier vicriviroc trials and other CCR5 antagonist, studies are needed to define the role of this class of drugs in the treatment of HIV. Clinical trial identifier: http://www.clinicaltrial.gov/: VICTOR-E3 (NCT00523211) and VICTOR-E4 (NCT00474370).
Hospital Guilherme Alvaro, Santos, Brazil.
Marcos M
MM
Caseiro
Mark
M
Nelson
Ricardo S
RS
Diaz
Joseph
J
Gathe
Jose L
JL
de Andrade Neto
Jihad
J
Slim
Antonio
A
Solano
Eduardo M
EM
Netto
Carmen
C
Mak
Junwa
J
Shen
Wayne
W
Greaves
Lisa M
LM
Dunkle
Regis A
RA
Vilchez
Jennifer
J
Zeinecker
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D010919:Placebos / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000821:virology
D019380:Anti-HIV Agents; D010879:Piperazines; D010919:Placebos; D011743:Pyrimidines; D012367:RNA, Viral; D019713:Receptors, CCR5; D015728:Receptors, HIV; C486781:vicriviroc