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Characterization of HIV-1 Reservoirs in Children and Adolescents: A Systematic Review and Meta-Analysis Toward Pediatric HIV Cure

2024; Elsevier BV; Volume: 267; Linguagem: Inglês

10.1016/j.jpeds.2024.113919

1097-6833

Aude Christelle Ka’e, Maria Mercedes Santoro, Aubin Nanfack, Ezéchiel Ngoufack Jagni Semengue, Yagaï Bouba, Alex Durand Nka, Georgia Ambada, Marie-Laure Mballa Mpouel, Bertrand Sagnia, Leslie Kenou, Michelle Sanhanfo, Willy Pabo, Désiré Takou, Collins Ambe Chenwi, Nelson Sonela, Samuel Martin Sosso, Céline Nguefeu Nkenfou, Vittorio Colizzi, Gregory Halle‐Ekane, Alexis Ndjolo, Francesca Ceccherini‐Silberstein, Carlo Federico Perno, Sharon R. Lewin, Caroline T. Tiemessen, Joseph Fokam,

HIV/AIDS Research and Interventions

Objective To conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally-acquired HIV infection. Study design Randomized and non-randomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRM) and the size of reservoirs were evaluated. Subgroup analyses were performed to characterize further the data, and the meta-analysis was done through random effect models. Results Overall, 49 studies from 17 countries worldwide were included, encompassing 2356 perinatally infected participants (48.83% females). There are limited data on the quantitative characterization of viral reservoirs in sub-Saharan Africa (SSA), with sensitive methodologies such as ddPCR rarely employed. The 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 antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (p=0.054). Participants with long suppressed viremia (>5 years) had lower levels of HIV-1 DNA (p=0.027). Ppre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with higher levels of HIV-1 DNA (p=0.038, p=0.047 and p=0.041, respectively). Conclusion The pooled prevalence of ADRMs is high in perinatally infected pediatric population, with larger proviral reservoir size driven by delayed ART initiation, a shorter period of viral suppression, and immuno-virological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.