Although the prevalence of distal sensory peripheral neuropathy decreased following initiation of combination antiretroviral therapy (cART) in people living with HIV (PLWHIV) in resource-limiting settings, better strategies are needed to prevent or ameliorate residual distal sensory peripheral neuropathy after cART initiation, according to research results published in Clinical Infectious Diseases.

In a prospective, observational study from 7 urban resource-limited settings, distal sensory peripheral neuropathy prevalence was estimated in a cohort of PLWHIV aged ≥18 years with a CD4+ count <300 cells/mm3 matched with participants without HIV as well as PLWHIV who had demonstrated viral suppression on 1 of 3 cART regimens:

  • Lamivudine/zidovudine and efavirenz
  • Emtricitabine + atazanavir and didanosine enteric coated
  • Emtricitabine/tenofovir and efavirenz

Participants and matched individuals without HIV received standardized neurologic examination and functional status assessments before starting cART, every 24 weeks (until 192 weeks), and after terminating cART.

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A total of 860 participants with HIV were enrolled in the study. Before beginning cART, 21.3% of PLWHIV had distal sensory peripheral neuropathy compared with 8.5% of people without HIV (n=2400; P =.008).

Before beginning cART, compared with PLWHIV without distal sensory peripheral neuropathy, PLWHIV with prevalent distal sensory peripheral neuropathy were more likely to report loss of functional ability to work (P =.001), unemployment (P =.0005), low energy levels (P =.0005), feeling depressed (P =.003), and a loss in social interest (P =.0001).

After cART initiation, the overall prevalence of distal sensory peripheral neuropathy among PLWHIV decreased after virologic suppression was achieved: 20.3% at week 48, 17.5% at week 96, 15.3% at week 144, and 10.3% at week 192. Of the 178 PLWHIV with distal sensory peripheral neuropathy before cART, 57% of cases resolved by the patient’s last visit. Incident distal sensory peripheral neuropathy was seen in 127 participants during the course of the study.

Longitudinally, distal sensory peripheral neuropathy was more likely in older individuals and in those with less education, and was less likely with increased time on cART. Gender, cART regimen, pretreatment HIV-1 RNA, and screening CD4 or CD4 count during the course of the study did not influence the likelihood of distal sensory peripheral neuropathy. Moreover, there was no significant association between cART regimen and distal sensory peripheral neuropathy.

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Researchers noted that although the overall prevalence of distal sensory peripheral neuropathy decreased following the initiation of cART, “more than one-third of the virally suppressed participants still had distal sensory peripheral neuropathy at their last visit, suggesting that the remaining cases of neuropathy are a legacy effect of early, irreversible, HIV-induced nerve damage.” They stressed, “The sizable number of individuals with persistent [distal sensory peripheral neuropathy] warrants further investigation and better treatment options.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Vecchio AC, Marra CM, Schouten J, et al. Distal sensory peripheral neuropathy in human immunodeficiency virus type 1-positive individuals before and after antiretroviral therapy initiation in diverse resource-limited settings [published online August 12, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz745