The impact of viraemia on inflammatory biomarkers and CD4+ cell subpopulations in HIV-infected children in sub-Saharan Africa
Year: 2021
Type: article
Abstract: OBJECTIVE: To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. DESIGN: Longitudinal cohort study. METHODS: In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (IL-6), soluble CD14) and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level viral load or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate the incidence of clinical events. RESULTS: Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viraemia occurred in one-third of children and prevented further immune reconstitution, but had little impact on inflammatory biomarkers. Virological rebound to ≥5000 copies/ml was associated with arrested immune reconstitution, rising IL-6 and increased risk of clinical disease progression. CONCLUSIONS: As viral load testing becomes more available in sub-Saharan Africa, repeat testing algorithms will be required to identify those with virological rebound, who need switching to prevent disease progression, whilst preventing unnecessary second-line regimen initiation in the majority of children with detectable viraemia who remain at low risk of disease progression.
Source: AIDS
Authors: Andrew J. Prendergast, Alexander J. Szubert, Godfrey Pimundu, Chipo Berejena, Pietro Pala, Annie Shonhai, Patricia Hunter, Francesca I.F. Arrigoni, Victor Musiime, Mutsa Bwakura-Dangarembizi, Philippa Musoke, Hannah Poulsom, Macklyn Kihembo, Paula Munderi, Diana M. Gibb, Moira J. Spyer, A. Sarah Walker, Nigel Klein
Institutions: Queen Mary University of London, MRC Clinical Trials Unit at UCL, Blizard Institute, University College London, Joint Clinical Research Centre, University of Zimbabwe, MRC/UVRI & LSHTM Uganda Research Unit, Uganda Virus Research Institute, Kingston University London, Makerere University, Mulago Hospital
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W3138856015
