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

Background The 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. Methods Were 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. Results Overall, 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). Conclusion Our 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.