Treatment of pain in DSP and ATN

There are still only a small number of robust randomized controlled trials which specifically assessed peripheral neuropathic pain therapies in the context of HIV. Most include patients with both DSP and ATN as they are clinically indistinguishable. In the absence of trials specific to HIV, the practice has been to extrapolate from the wider body of evidence in the treatment of non-HIV peripheral neuropathic pain.28,29,30 Care must be taken to avoid drugs which exhibit significant known interactions with antiretroviral drugs. The most obvious example is carbamazepine which should be avoided in all patients on treatment as it interacts with protease inhibitors and some NNRTIs (see

Two randomized, double-blind studies found no significant difference in efficacy between amitriptyline and placebo in HIV-related peripheral neuropathy.31,32[I] Both studies were of sufficient quality to be included in a systematic review.28 Both studies involved comparisons between several different treatments. Kieburtz et al.31 compared amitriptyline, mexiletine, and placebo in 145 patients. Neither active treatment was superior to placebo in terms of efficacy. The authors comment that the study sample size was smaller than originally planned. Study enrolment was discontinued on the recommendation of the safety committee that suggested that even with full enrolment the trial would not be able to demonstrate a statistically significant benefit of either intervention. The study by Shlay et al.32 was an unusual design in that it compared acupuncture to amitriptyline or placebo, acupuncture versus sham acupuncture, or amitriptyline versus placebo. The study design was modified during recruitment to improve accrual. A total of 250 patients was recruited of whom 71 received amitriptyline. Power calculations suggested 260 patients needed to be randomized to each group to detect a significant difference. We were unable to locate any published trials which indicate efficacy of amitriptyline or other tricyclic antidepressants in HIV neuropathy, a feature which stands in marked contrast to the broad efficacy of tricyclic antidepressants in other neuropathic pain scenarios.28,29,30[I] We could locate no reports evaluating the use of other anti-depressants including duloxetine or opioids in DSP or ATN.

Gabapentin and pregabalin are yet to be adequately tested for effectiveness in the symptomatic treatment of DSP and ATN. One very small placebo-controlled trial showed an initial modest efficacy for gabapentin compared to placebo, but this difference was not significant at the end of the four-week treatment period.33[III] However, given the grade I evidence for the efficacy of gabapentin and pregabalin in other peripheral neuropathic pain conditions,2829 30[I] a reasoned argument might be made for their continued use in HIV-related peripheral neuropathic pain, pending the publication of substantive evidence supporting or refuting this practice.

Lamotrigine appeared to show promise in the relief of DSP and ATN in a small randomized trial,34[II] but superiority over placebo was not demonstrated in a larger trial.35[II]

Recombinant human growth factor (rhNGF) appeared to be effective at improving symptoms of HIV-related neuropathy in a phase II clinical study,36[II] and two-year follow up in an open label design showed sustained benefit.37[IV] However, adverse effects were problematic with rhNGF and it would appear that rhNGF is not being further developed for this indication.

A systematic review revealed that, on the basis of available evidence, mexilitine, capsaicin cream, and lido-caine gel are not efficacious in HIV peripheral neuropathic pain.28[I] There is also no efficacy for intranasal peptide T38[II] or memantidine.39[II]

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