Background:  Peripheral neuropathies are common complications of HIV infection, affecting more than a third of patients. The pathogenesis of these neuropathies is unknown and treatment is limited to symptomatic measures. A previous study showed that prosaposin-derived peptides (PRO) was associated with a significant reduction of pain vs placebo in diabetic polyneuropathy. We examined the safety and efficacy of PRO for the treatment of painful HIV-associated sensory neuropathies (HIV-SN) and evaluated the use of an electronic diary to record HIV-associated neuropathic pain.

Methods:  NARC 009/ACTG A5180 was a prospective, randomized, double-blind, placebo-controlled, multicenter, dose ranging study that enrolled adult patients with neurologist-confirmed painful HIV-SN. Pain modulating therapy was removed prior to baseline. Subjects with at least a moderate pain rating were stratified according to sural nerve action potentials as a surrogate of baseline nerve fiber damage and randomized to 2, 4, 8, or 16 mg/day PRO or placebo administered via subcutaneous injection. The study drug was maintained for 6 weeks, and then subjects were crossed over to placebo from active arms, or 4 mg/day from placebo. Neurotoxic antiretroviral drugs were held constant. Patients were trained on the use of an electronic diary designed to capture Gracely Pain Scale data.

Results:  We report the final results based on 237 randomized subjects. There was no difference in the frequency of adverse events or laboratory toxicities between PRO and placebo . The study was stopped after a planned futility analysis revealed that statistical significance (with respect to pain changes between PRO and placebo) was unlikely to be observed with full completion of the trial. The 6-week median (IQR) Gracely pain scale changes were –0.06 (–0.37, –0.00), –0.19 (–0.45, –0.01), –0.05 (–0.30, 0.05), –0.13 –0.48, 0.01), and –0.06 (–0.33, 0.04) for the 2, 4, 8, 16 mg, and placebo arms respectively. Use of the electronic diary to collect pain data displayed similar variability of pain changes compared to trials that have used paper collection methods.

Conclusions:  Although the 6-week treatment with PRO was safe and well tolerated, it was not effective at reducing HIV-associated neuropathic pain relative to placebo. The use of an electronic diary to record neuropathic pain is novel in HIV-SN.