Single-dose nevirapine exposure does not affect response to antiretroviral therapy in HIV-infected African children aged below 3 years. (24th August 2015) - Musoke, Philippa
Abstract : Objectives: To assess the impact of exposure to single-dose nevirapine (sdNVP) on virological response in young Ugandan/Zimbabwean children (<3 years) initiating antiretroviral therapy (ART), and to investigate other predictors of response. Design: Observational analysis within the ARROW randomized trial. Methods: sdNVP exposure was ascertained by the caregiver's self-report when the child initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Viral load was assayed retrospectively over a median 4.1 years of follow-up. Multivariable logistic regression models were used to identify independent predictors of viral load below 80 copies/ml, 48 and 144 weeks after ART initiation (backwards elimination, exit P = 0.1). Results: Median (IQR) age at ART initiation was 17 (10–23) months in 78 sdNVP-exposed children vs. 21 (14–27) months in 289 non-exposed children (36 vs. 20% <12 months). At week 48, 49 of 73 (67%) sdNVP-exposed and 154 of 272 (57%) non-exposed children had viral load below 80 copies/ml [adjusted odds ratio (aOR) 2.34 (1.26–4.34), P = 0.007]; 79 and 77% had viral load below 400 copies/ml. Suppression was significantly lower in males ( P = 0.009), those with higher pre-ART viral load ( P = 0.001), taking syrups ( P = 0.05) and with lower self-reported adherence ( P = 0.04). At week 144, 55 of 73 (75%) exposed and 188 of 272 (69%) non-exposed children had less than 80 copies/ml [aOR 1.75 (0.93–3.29), P = 0.08]. There was no difference between children with and without previous sdNVP exposure in intermediate/high-level resistance to NRTIs ( P > 0.3) or NNRTIs ( P > 0.1) ( n = 88) at week 144. Conclusion: Given the limited global availability of lopinavir/ritonavir, its significant formulation challenges in young children, and the significant paediatric treatment gap, tablet fixed-dose-combination NVP-based ART remains a good alternative to syrup lopinavir-based ART for children, particularly those over 1 year and even if exposed to sdNVP. Abstract : Supplemental Digital Content is available in the text