Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211.
OBJECTIVE
To evaluate the effect of vicriviroc (VCV) on peripheral neuropathy (PN), the most prevalent neurological complication of HIV infection in HIV-1-infected treatment- experienced population.


METHODS
A5211 is a randomized placebo- controlled trial evaluating VCV in treatment-experienced HIV participants failing current therapy. Participants were randomized to VCV (5, 10, or 15 mg) or placebo with optimized ritonavir-containing antiretroviral therapy and followed for 48 weeks. PN was defined as having at least mild loss of vibration bilaterally or ankle reflexes absent or hypoactive bilaterally. We estimated the association between VCV (pooled doses) with PN using a logistic generalized estimating equation. Additional outcomes included symptomatic neuropathy (SPN), painful neuropathy (PPN), and neuropathic signs and symptoms.


RESULTS
118 participants (92% male, 65% white, median age of 46 years, median baseline CD4 139, median HIV-1 RNA 4.58 log) were randomized (90 on VCV and 28 on placebo). VCV therapy did not result in a statistically significant difference relative to placebo in PN (OR = 1.52; P = .39; 95% CI 0.59, 3.90) after controlling for baseline PN status and baseline neurotoxic nucleoside reverse transcriptase inhibitor(s) use.


CONCLUSIONS
Treatment with VCV over 48 weeks failed to result in statistically significant effect on PN in treatment-experienced participants with HIV infection relative to placebo, however potentially important effects cannot be ruled out.
Yeh
Tzu-min
TM
Harvard School of Public Health, Boston, Massachusetts 02115, USA. tyeh@sdac.harvard.edu
Evans
Scott R
SR
Gulick
Roy M
RM
Clifford
David B
DB
D000293:Adolescent; D000328:Adult; D065100:CCR5 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000517:prevention & control; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D055815:Young Adult
D065100:CCR5 Receptor Antagonists; D010879:Piperazines; D011743:Pyrimidines; C486781:vicriviroc
Handb Clin Neurol. 2007;85:129-37
18808980
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17570119
Ann Neurol. 2003 Sep;54(3):287-96
12953261
Antimicrob Agents Chemother. 2005 Dec;49(12):4911-9
16304152
Virology. 2005 Apr 10;334(2):178-93
15780868
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jun 1;9(2):153-61
7749792
Ann Neurol. 2004 Dec;56(6):873-7
15562411