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PA-167 Characterization of HIV-1 reservoirs in children and adolescents: a systematic review and meta-analysis toward pediatric HIV cure
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  1. Aude Christelle Ka’e1,2,
  2. Maria Mercedes Santoro2,
  3. Aubin Nanfack1,
  4. Ezechiel Ngoufack Jagni Semengue1,
  5. Bouba Yagai3,
  6. Alex Durand Nka1,
  7. Georgia Ambada1,
  8. Bertrand Sagnia1,
  9. Willy Le Roi Togna Pabo1,
  10. Desire Takou1,
  11. Collins Ambe Chenwi1,2,
  12. Nelson Sonela1,
  13. Samuel Martin Sosso1,
  14. Celine Nkenfou1,
  15. Vittorio Colizzi4,
  16. Gregory Edie Halle- Ekane5,
  17. Alexis Ndjolo1,
  18. Francesca Ceccherini-Silberstein2,
  19. Carlo-Federico Perno6,
  20. Sharon Lewin7,
  21. Caroline Tiemessen8,
  22. Joseph Fokam1
  1. 1Chantal Biya International Reference Centre For Research on HIV/AIDS Prevention and Management (CIRCB), Cameroon
  2. 2University of Rome Tor Vergata, Italy
  3. 3Central Technical Group, National AIDS Control Committee (NACC), Cameroon
  4. 4UNESCO Chair of Biotechnology, Immunology and Molecular Medicine, University of Rome Tor Vergata, Italy
  5. 5Faculty of Sciences, University of Buea, Cameroon
  6. 6Bambino Gesu Pediatric Hospital, Italy
  7. 7University of Melbourne, Australia
  8. 8National Institute for Communicable Diseases and Faculty of Health Sciences, University of the Witwatersrand, South Africa

Abstract

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.

https://doi.org/10.1136/bmjgh-2023-EDC.111

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