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Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial

Kiwuwa-Muyingo, S; Kikaire, B; Mambule, I; Musana, H; Musoro, G; Gilks, CF; Levin, J; (2014) Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial. AIDS , 28 (17) pp. 2579-2588. 10.1097/QAD.0000000000000447. Green open access

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Abstract

Objectives: We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART). Design: An open-label, multicentre, randomized trial. Methods: Peripheral neuropathy was self-reported at 12-weekly clinic visits. Cox regression models (excluding participants reporting preexisting peripheral neuropathy at ART initiation), considered sex; pre-ART WHO stage, age and CD4+ cell count; CD4+ cell count versus no CD4+ cell count monitoring; and time-updated CD4+ cell count, weight and use of stavudine, isoniazid and didanosine. Results: Four hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895 participants without preexisting peripheral neuropathy was 4.9 (4.7–5.4) years. Three hundred and fifty-four (12%) took stavudine as first-line substitution and 518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%) participants developed a new peripheral neuropathy episode, an incidence of 2.12 per 100 person-years. Eighteen (0.1%) had a grade 3/4 episode. Independent predictors of peripheral neuropathy were current stavudine use [adjusted hazard ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06–5.66], current isoniazid use [aHR 1.59 (95% CI 1.02–2.47)] and current didanosine use [aHR 1.60 (95% CI 1.19–2.14)]. Higher risks were independently associated with higher pre-ART weight [aHR (per+5 kg) 1.07 (95% CI 1.01–1.13)] and older age aHR (per 10 years older) 1.29 (95% CI 1.12–1.49), but there was no significant effect of sex (P = 0.13), pre-ART CD4+ cell count (P = 0.91) or CD4+ cell count monitoring (P = 0.73). Conclusion: Current stavudine, didanosine or isoniazid use continue to increase peripheral neuropathy risks, as does older age and weight at ART initiation; however, we found no evidence of increased risk in women in contrast to previous studies. The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended. All patients receiving isoniazid, either as part of antituberculosis (TB) chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.

Type: Article
Title: Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAD.0000000000000447
Publisher version: http://dx.doi.org/10.1097/QAD.0000000000000447
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution-Non Commercial License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/1437048
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