HIV Neuropathy Pain Continues to Pose a Challenge


HIV-related painful neuropathy (HIV-PN) is particularly challenging and nested within the already challenging problem of neuropathic pain (NP) management. Currently available medications that consistently demonstrate evidence, albeit modest, in painful diabetic neuropathy and postherpetic neuralgia have failed to demonstrate any measurable benefit in HIV-PN [1]. Two manuscripts in this issue demonstrate efforts to address this problem in different ways. Harrison et al. applied the appealing approach of the blinded crossover study of combination analgesic therapy, an approach perhaps best demonstrated by Gilron et al. in their landmark study of morphine, gabapentin, and combination therapy in NP [2]. By contrast, Dorfman et al. used a nonpharmacologic approach, self-directed hypnosis, to treat HIV-PN. Only one can be considered a “positive” study but both are instructive.

Harrison et al. failed in their effort to complete the study of combination therapy because of inadequate subject recruitment in spite of best efforts. They speculate that this issue could be due to a broad variety of problems, including a (thankfully) smaller prevalence of HIV-PN than commonly believed, as well as several barriers to recruitment and retention of patients meeting inclusion criteria. Among these are the availability of study medication outside of the study, reluctance to washout from excluded medications and to participate in a placebo period, the stigma applied by many patients to the use of methadone and fear of addiction, and the regulatory restrictions imposed upon investigators when using a controlled substance as a study drug. All of these possibilities are reality and most likely it was combination of all of these factors. This experience illustrates the need for potential study sites to provide informed and conservative estimates of anticipated subject recruitment and for investigators to establish and adequately fund recruitment strategies as a critical component of study design. Study designs that allow adequate rescue, or use of time to failure of an intervention as an outcome measure, may alleviate concerns regarding placebo arms in pain clinical trials. In an era of increasing involvement of patient support and advocacy groups in the research process, it is also worthwhile to note that socially conscious patients may perceive a personal responsibility to participate in clinical research from which others will ultimately benefit.

In recognition of the limited benefit of pharmacologic interventions in HIV-PN, Dorfman et al. applied a self-hypnosis protocol to the treatment of HIV-PN and demonstrated benefit. They acknowledge that this was an unblinded investigation and a short-duration study. Further investigation will certainly be needed. Nonetheless, the approach is intuitively appealing not only because of the apparent benefit but also because it effectively demonstrates the value of active patient engagement in their pain management regimen and the potential for people in pain to experience a measure of control over their circumstances.

HIV-PN is still a challenge because it can cause severe pain and disrupts quality of life and because treatments that provide benefit in other pain disorders have been found consistently ineffective in HIV-PN [[3-5]]. Basic research into the mechanisms of HIV-related NP is needed. The studies in this issue of Pain Medicine should be taken as evidence of the need to meet the challenge with novel interventions, novel trial designs, and attention to the problem of subject recruitment and retention. In addition, clinical science should be able to better characterize patients with HIV-PN and define distinguishing features that separate it from other NP disorders, beyond failures to respond to specific pharmacological agents.