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Virologic Response to First-Line Efavirenz- or Nevirapine-Based Anti-Retroviral Therapy in HIV-Infected African Children

Kekitiinwa, A; Szubert, AJ; Spyer, M; Katuramu, R; Musiime, V; Mhute, T; Bakeera-Kitaka, S; ... ARROW Trial Team, .; + view all (2017) Virologic Response to First-Line Efavirenz- or Nevirapine-Based Anti-Retroviral Therapy in HIV-Infected African Children. Pediatric Infectious Disease Journal , 36 (6) pp. 588-594. 10.1097/INF.0000000000001505. Green open access

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Abstract

BACKGROUND: Poorer virologic response to nevirapine vs efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies. METHODS: We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine vs efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/ml at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (p=0.1). RESULTS: 445(53%) children received efavirenz and 391(47%) nevirapine. Children receiving efavirenz were older (median 8.6 years vs 7.5 nevirapine, p<0.001) and had higher CD4% (12% vs 10%, p=0.05) but similar pre-ART VL (p=0.17). The initial non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) was permanently discontinued for adverse events in 7/445 (2%) children initiating efavirenz vs 9/391 (2%) initiating nevirapine (p=0.46); at switch to second-line in 17 vs 23, for tuberculosis in 0 vs 26, for pregnancy in 6 vs 0, and for other reasons in 15 vs 5. Early (36-48 week) virologic suppression <80 copies/ml was superior with efavirenz, particularly in children with higher pre-ART VL (p=0.0004); longer-term suppression was superior with nevirapine in older children (p=0.05). Early suppression was poorer in the youngest and oldest children, regardless of NNRTI (p=0.02); longer-term suppression was poorer in those with higher pre-ART VL regardless of NNRTI (p=0.05). Results were broadly similar for <400 and <1000 copies/ml. CONCLUSION: Short-term VL suppression favored efavirenz, but long-term relative performance was age-dependent, with better suppression in older children with nevirapine, supporting WHO's recommendation that nevirapine remain an alternative NNRTI.

Type: Article
Title: Virologic Response to First-Line Efavirenz- or Nevirapine-Based Anti-Retroviral Therapy in HIV-Infected African Children
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/INF.0000000000001505
Publisher version: http://dx.doi.org/10.1097/INF.0000000000001505
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) (https://creativecommons.org/licenses/by-nc/4.0/), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
Keywords: HIV, children, antiretroviral therapy, viral load, NNRTI
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1519556
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