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

Abstract

ObjectiveTo conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally-acquired HIV infection. Study designRandomized 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. ResultsOverall, 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). ConclusionThe 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.