Pharmacological Treatment of Painful HIV-Associated Sensory Neuropathy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

BackgroundSignificant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition.Method and Findings Objective: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. Design: Systematic review and meta-analysis. Data sources: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. Selection criteria: Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. Review methods: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥30% and ≥50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values.ResultsOf 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4g/day), pregabalin (1200mg/day), prosaptide (16mg/day), peptide-T (6mg/day), acetyl-L-carnitine (1g/day), mexilitine (600mg/day), lamotrigine (600mg/day) and topical capsaicin (0.075% q.d.s.).ConclusionsEvidence of efficacy exists only for capsaicin 8%, smoked cannabis and rhNGF. However,rhNGF is clinically unavailable and smoked cannabis cannot be recommended as routine therapy. Evaluation of novel management strategies for painful HIV-SN is urgently needed.

Clinical practice guidelines for management of neuropathic pain: Expert panel recommendations for South Africa

“…13,14 Added to these challenges, which are not necessarily unique to South Africa, is the high rate of HIV in this country and the paucity of evidence for treating painful HIV-related neuropathy. 15 Clinical practice guidelines for management of neuropathic pain: expert panel recommendations for South Africa S Chetty, E Baalbergen, A I Bhigjee, P Kamerman, J Ouma, R Raath, M Raff, S Salduker…”

Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans

“…Importantly, improving our understanding of SN pathogenesis may lead to effective preventative strategies, or even pathogenesis-based treatments for a condition that currently lacks effective analgesic options. 8 Of the individual SNPs associated with neuropathy, allele 2 was associated with reduced risk in each case (Table 1). The FV18_ext1 haplotype was associated with increased risk of HIV-SN.…”

“…6,7 While not fatal, HIV-SN has a significant negative impact on psychological, social and economic well-being 4 and there are no proven treatments for the pain. 8 The pathogenesis of HIV-SN has not been fully explained, but human [9][10][11] and animal studies 12 indicate that inflammation plays a central role. Genetic studies support an inflammatory etiology, providing evidence of associations with polymorphisms in TNFA, IL4 and IL10.…”

Prescribing medical cannabis in Canada: Are we being too cautious?

“…A recent meta-analysis found that smoked cannabis was significantly more effective than placebo in providing pain relief to patients with HIV-related neuropathy, while the efficacy of more commonly prescribed drugs, such as gabapentin and pregabalin, did not differ significantly from placebo. 11 Concerns regarding the prescribing of medical cannabis have also been expressed on the basis of a perceived lack of information related to its mechanism of action. Applying this model more generally, it could be argued that physicians should be discouraged from prescribing a host of routine pharmacological treatments, including gabapentin and pregabalin, whose mechanisms of action are still largely unclear.…”