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

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 þ cell count; CD4 þ cell count versus no CD4 þ cell count monitoring; and time-updated CD4 þ 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 personyears. 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 (perþ5 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 ¼ 0.13), pre-ART CD4 þ cell count (P ¼ 0.91) or CD4 þ cell count monitoring (P ¼ 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.

Peripheral neuropathy in patients with human immunodeficiency viral infection at a tertiary hospital in Ghana

“…Age as a risk factor for PN, however, was reported many times before and proved to be so in HIV patients above 34 years of our cohort as well (Evans et al 2011; Wadley et al 2011; Nwabueze et al 2012; Chen et al 2013; Kiwuwa-Muyingo et al 2014; Tumusiime et al 2014a, b). As possible explanation, on the one hand, aging increases vulnerability towards neuronal toxicity, on the other hand is the HIV population’s median age rapidly increasing due to continuously improved management of infected persons in Sub-Sahara Africa, and so is the prevalence of PN.…”

“…This number somewhat ranges within the ratios found in other studies performed in sub-Sahara Africa. Such studies reported prevalence of 6% and 57% in South Africa, respectively (Boulle et al 2007; Wadley et al 2011), 13% in Malawi (Beadles et al 2009), 20.7% and 36% in Kenya, respectively (Hawkins et al 2007; Mehta et al 2010), 36% in Uganda (Forna et al 2007), 24% in Uganda/Zimbabwe (Kiwuwa-Muyingo et al 2014), 59% in Rwanda (Tumusiime et al 2014a), and 28% in Cameroon (Luma et al 2012). A recent study by Benevides et al 2017 in southern Brazil unveiled 31.3% of PN prevalence in PLHIV.…”

“…With regard to the latter, in many studies, patients were enrolled whilst on NRTIs or protease inhibitors as a first-line antiretroviral medication. It was repeatedly reported that these drug groups have severe neurotoxic impact, above all stavudine, but also didanosine and zalcitabine (Forna et al 2007; Hoffmann et al 2008; Ances et al 2009; Maritz et al 2010; Evans et al 2011; Wadley et al 2011; Kamerman et al 2012; Chen et al 2013; Kiwuwa-Muyingo et al 2014; World Health Organisation 2015). In Ghana, since inception of the study, the first-line treatment is a combination of two NRTIs and one non-NRTI, followed by a second-line treatment also including a protease inhibitor.…”

Treatment outcomes in HIV infected patients older than 50 years attending an HIV clinic in Harare, Zimbabwe: A cohort study

“…Peripheral sensory polyneuropathy was the most common ART adverse effect in this study. Older age has been shown to be associated with peripheral neuropathy in both HIV infected and uninfected people [ 37 , 38 ]. Zidovudine and tenofovir disoproxil fumarate are still in use in LMIC and clinicians should continue to monitor elderly patients for adverse effects while on these medicines.…”

“…Retention in care of 71.4% after a median follow up time of 5.6 years (IQR: 2.4-9.9) was comparable with that of a younger population (74.4%) at 36 months with a median age of 35 years (IQR: [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] in the Zimbabwe National ART Program and higher than that observed in a Kenyan cohort study (54%) at 36 months [33,34]. However, unlike with this larger…”