Background:  Peripheral neuropathy (PN) is a prevalent complication of HIV infection and occurs frequently in treatment-experienced patients because of primary HIV infection and neurotoxicity of antiretrovirals (ARV). It has been hypothesized that a mechanism of viral neurotoxicity is mediated by CCR5 neuronal receptors. We evaluate the effect of vicrivirac (VCV), a CCR5 antagonist ARV believed to cross the blood brain barrier, on PN.

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 ART and followed for 48 weeks. PN status was characterized with description of neuropathic symptoms, distal reflexes, and distal vibratory sensitivity. PN was defined as having at least mild loss of vibration bilaterally or ankle reflexes absent or hypoactive bilaterally. Symptomatic PN (SPN) was defined as having PN plus at least 1 neurological symptom:  pain, “pins and needles,” or “numbness.” We estimated the association between VCV (pooled doses) with PN using logistic GEE models with an as-treated analysis.

Results:  We randomized 118 participants (92% male, 65% white, median age 46, median baseline CD4 139, median HIV-1 RNA 4.58 log) (90 on VCV and 28 on placebo):  61% and 37% of participants had PN and SPN at baseline, respectively. The proportion of participants in the VCV arm with PN and SPN at baseline, week 24 and 48 were 60%, 52%, 49% and 39%, 31%, 30%, respectively; for placebo the proportions were 64%, 44%, 11% and 32%, 22%, 7%. VCV therapy did not result in a statistically significant difference relative to placebo in PN (OR 1.77, p = 0.36, 95%CI 0.52, 6.01) or SPN (OR 1.04, p = 0.97, 95%CI 0.17, 6.53) after controlling for baseline PN or SPN status and baseline drug use. Similar results were noted for individual neurologic signs and symptoms.

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 our results cannot rule out potentially important effects. This finding is consistent with the stability of PN in HIV patients previously reported. Alternative explanations include an insufficient power due to small sample size and that the VCV dose might have been insufficient for this use. The doses tested were lower than the currently recommended ARV dose of 30 mg.