Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial
Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22 % at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17 % by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29 % (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.
KeywordsHIV Peripheral neuropathy Africa Second-line ART Tuberculosis
We thank all the patients and staff from all the centres participating in the EARNEST trial. The EARNEST trial was funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) with contributions from the Medical Research Council, UK, Institito de Salud Carlos III, Spain, Irish Aid, Ireland, Swedish International Development Cooperation Agency (SIDA), Sweden, Instituto Superiore di Sanita (ISS), Italy and Merck, USA. Substantive in-kind contributions were made by the Medical Research Council Clinical Trials Unit, UK, CINECA, Bologna, Italy, Janssen Diagnostics, Mechelen, Belgium; GSK, UK; Abbott Laboratories, USA. Trial medication was donated by AbbVie, Merck, Pfizer, GSK and Gilead
Conflict of interest
NIP was the EDCTP grant recipient for this trial. NIP, ASW, MT, JT and AAP are employed by the MRC-UK. NIP, ASW and AAP have received funding support for other studies from GSK or Janssen. AM, GM and HM have received support from the Research Councils-UK for research projects. NIP has received payments for lectures from Merck, Janssen and AbbVie. AAP has received payments for lectures from Janssen. Institutional payment has been received from Gilead Sciences because of a lecture given by ASW. ASW has been DSMB member—for studies sponsored by Tibotec.
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