Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211

Abstract

Purpose: 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.

Method: 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.

Conclusion: 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.

Figures

Figure 1

CONSORT diagram. VCV = vicriviroc.

Figure 2

Effect of vicriviroc (VCV vs. placebo) on various neuropathic outcomes (odds ratios [OR] and 95% CIs), adjusted for baseline status of neuropathic outcomes and baseline neurotoxic nucleoside reverse transcriptase inhibitor(s) (RTI) use. PN = peripheral neuropathy; PPN = painful neuropathy; SPN = symptomatic neuropathy.

Figure 3

Neuropathy (PN) prevalence (using observed data by randomized treatment assignment), median CD4, and HIV RNA over time.