Background:  Before the advent of combination ART (cART), HIV distal sensory polyneuropathy (DSPN) was frequent, its clinical impact high and dideoxynucleoside-containing drugs contributed significantly to the problem. Improvements in ART have transformed HIV from a fatal to a chronic, manageable disease, while reducing toxicities. Our objective was to provide updated estimates of the prevalence and clinical effect of DSPN in the cART era.

Methods:  Baseline prevalence of DSPN and clinical correlates were assessed in 1539 HIV-infected individuals enrolled in a prospective, observational study at 6 US sites. DSPN was defined as at least 1 clinical sign in a symmetrical, bilateral pattern on neurological exam. Signs included diminished distal vibratory sensation, inability to discriminate sharp from dull, and reduced ankle reflexes. Correlates of DSPN evaluated in uni- and multivariate models were age, cART and dideoxynucleoside-containing drug use, HIV disease markers (current and nadir CD4, plasma viral load), hepatitis C virus (HCV), and substance use disorders (alcohol, opiates). Pain and its effect on quality of life were assessed using the MOS-HIV Health Survey.

Results:  DSPN prevalence was 57% (881 of 1539). DSPN subjects experienced more pain (219 of 881 [25%] vs 53 of 658 [8%]; p <0.01) and were significantly more impaired in MOS pain function scores (median [interquartile range], 66 [44 to 89] vs 78 [44 to 89]; p <0.01) and overall physical health (43 [33 to 54] vs 49 [39 to 58]; p <0.01) compared to those without DSPN. DSPN was more common in those currently taking cART (711 of 1095 [65%]) as compared to ARV-naïve subjects (71 of 234 [30%]) or to those who previously took ARV but stopped (99 of 210 [47%]). Among cART-treated subjects with DSPN, 68% (483) had been exposed to dideoxynucleoside-containing drugs (median exposure 41 months [17 to 72]). In multivariate analysis, significant predictors of DSPN included older age (OR 2.1 per 10-year increase, 95%CI 1.8 to 2.4), lower CD4 nadir (OR 1.2 per 100 cell decrease, 95%CI 1.1 to 1.2), current ARV use (OR 1.6, 95%CI 1.5 to 1.7), past dideoxynucleoside-containing drug use (OR 1.9, 95%CI 1.7 to 2.2), and history of opiate abuse or dependence (OR 1.4, 95%CI 1.3 to 1.4) (n = 267; median years since last met criteria 6 [0.9 to 15]).

Conclusions:  DSPN remains highly prevalent in the era of cART. Neuropathic pain leads to substantial self-reported disability, reduced quality of life and a need for costly analgesic medications that increase the burden of treatment, raising the potential for adverse drug-drug interactions. In addition to HIV and cART, advancing age, and co-morbidities such as opiate abuse may amplify the clinical impact of DSPN.