PA-167 Characterization of HIV-1 reservoirs in children and adolescents: a systematic review and meta-analysis toward pediatric HIV cure

• Published in: BMJ global health Vol. 8; no. Suppl 10; pp. A45 - A46
• Main Authors: Ka’e, Aude Christelle, Santoro, Maria Mercedes, Nanfack, Aubin, Jagni Semengue, Ezechiel Ngoufack, Yagai, Bouba, Nka, Alex Durand, Ambada, Georgia, Sagnia, Bertrand, Roi Togna Pabo, Willy Le, Takou, Desire, Chenwi, Collins Ambe, Sonela, Nelson, Sosso, Samuel Martin, Nkenfou, Celine, Colizzi, Vittorio, Halle- Ekane, Gregory Edie, Ndjolo, Alexis, Ceccherini-Silberstein, Francesca, Perno, Carlo-Federico, Lewin, Sharon, Tiemessen, Caroline, Fokam, Joseph
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 17.12.2023; BMJ Publishing Group LTD
• Subjects: Abstracts of Poster and e-Poster Presentations; Drug resistance; Pediatrics; Systematic review; Teenagers; Africa
• ISSN: 2059-7908
• DOI: 10.1136/bmjgh-2023-EDC.111

BackgroundThe virostatic effect of antiretroviral therapies (ART) infers viral persistence in sanctuaries, with a high likelihood of reactivation off-treatment. This systematic review and meta-analysis aimed at estimating the global burden of archived drug resistance mutations (ADRMs), the size of reservoirs and their determinants in paediatrics.MethodsWere included, randomized and non-randomized trials, cohorts and cross-sectional studies of HIV reservoirs in vertically-infected participants, published in English/French between 2002–2022. As primary outcomes, we evaluated the prevalence of ADRMs and estimated the size of reservoirs (HIV-1 DNA copies/10 6 cells) in paediatrics. Subgroup analysis were performed to further characterize the data and the meta-analysis was done through random effect models.ResultsOverall, 50 studies from 17 countries worldwide were included encompassing 2569 vertically infected participants (aged 2-days to 19-years; 52.81% females). There were limited data on the quantitative characterization of viral reservoirs in SSA, and sensitive tool as ddPCR for characterizing viral reservoirs were not implemented in the most sub-Saharan Africa (SSA) countries. Overall prevalence of ADRMs was 37.80% [95%CI: 13.89–65.17], with 48.79 [95%CI: 0–100] in Africa, 42.08% [6.68–82.71] in America, 23.88% [95%CI: 14.34–34.90] in Asia, and 20.00% [95%CI: 10.72–31.17] in Europe; without any difference between infants and adolescents (p=0.656). Starting ART before 2 months of age limited the size of HIV-1 DNA (p=0.054). Participants with long suppressed viremia (>5years) had lower rates of HIV-1 DNA (p=0.027) whereas pre-/post-ART CD4 ≤29% and pre-/post-ART viremia ≥5Log were all found associated with higher rates of HIV-1 DNA (p=0.038, p=0.047, p=0.041 and 0.035 respectively).ConclusionOur findings underscore high levels of ADRMs in paediatrics worldwide, with a higher reservoir driven by delayed ART initiation, shorter period of viral suppression and immuno-virological failures. Thus, strategies for paediatric HIV functional cure should target adolescents/children with very early ART initiation, high immunity and long-term viral suppression.