Pharmacologic and Non-Pharmacologic Interventions for HIV-Neuropathy Pain. A Systematic Review and a Meta-Analysis

Abstract

Background and Objectives: Among HIV infection symptoms, sensory neuropathy (HIV-SN) remains a main cause of suffering, with incidence varying from 13-50%. So far, numerous pharmacological and non-pharmacological treatments have been tested, although few evidence-based analgesic options are available. We conducted an up-to-date systematic review and meta-analysis of the literature in order to evaluate the efficacy and safety of pharmacologic and non-pharmacologic treatments for pain control, in patients with HIV neuropathy. Materials and Methods: We searched MEDLINE, EMBASE, Scopus/Elsevier, The Cochrane Central Register of Controlled Trials (CENTRAL), USA Clinical Trials registry, and The International Web of Science up to April 2019. All randomized controlled trials evaluating efficacy and safety of non-pharmacologic and pharmacologic therapies were included. Efficacy was defined as pain reduction during the study period. Safety was estimated from adverse events. A meta-analysis was performed whenever possible. Results: 27 randomized controlled trials (RCTs) were included for analysis (7 evaluating non pharmacologic interventions, 20 pharmacologic therapies). Non-pharmacologic studies (n = 742) involved seven different therapeutic modalities. Only Acupuncture/Moxibustion showed pain reduction over placebo, Gracely Pain Scale Mean (SD): Acu/Moxa 0.85 (0.12), placebo 1.10 (0.09), p = 0.05. Pharmacologic studies, involving 2516 patients revealed efficacy for capsaicin 8% over placebo (mean difference -8.04 [95% CI: -14.92 -1.15], smoked cannabis (where pooling data for meta-analysis was not possible) and recombinant Nerve Growth Factor. Conclusion: Despite various modalities for pain control in HIV-SN, strongest evidence exists for capsaicin 8% and smoked cannabis, although of low methodological quality. Among non-pharmacologic modalities, only Acu/Moxa gave a marginal beneficial effect in one study, possibly limited by inherent methodological flaws.

Keywords: HIV; infectious disease; neuropathy; pain.

Figure 1

Flow diagram of the Study for the Systematic Review and Meta-analysis process [1].

Figure 2

Review authors’ judgements about each risk of bias domain item for each included non-pharmacologic study (+ corresponds to low risk of bias, − corresponds to high risk of bias? corresponds to unclear risk of bias).

Figure 3

Graphical representation of the risk of bias in RCTs assessing the effects of non-pharmacological interventions in HIV neuropathy pain.

Figure 4

Review authors’ judgements about each risk of bias domain item for each included pharmacologic study (+ corresponds to low risk of bias, − corresponds to high risk of bias, ? corresponds to unclear risk of bias).

Figure 5

Graphical representation of the risk of bias in RCTs assessing the effects of pharmacological interventions in HIV neuropathy pain.

Figure 6

(A). Pregabalin vs. placebo, NRS [0–10] reduction (B). Pregabalin vs. placebo, proportion of patients with >30% NRS reduction. (C). Pregabalin vs. placebo, proportion of patients with >50% NRS reduction.

Figure 7

(A). Capsaicin 8% over placebo, NRS 0–100 reduction, random effect. (B). Capsaicin 8% over placebo, proportion of patients with >30% NRS reduction.

Figure 8

(A). Capsaicin 8% over placebo, PGIC. (B). Capsaicin 8% over placebo, CGIC.