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Characterization of HIV-1 Reservoirs in Children and Adolescents: A Systematic Review and Meta-Analysis Toward
Aude Christelle Ka'e1, Maria Mercedes Santoro2, Aubin Nanfack3
1Departments of Virology and Immunology, Chantal Biya International Reference Centre for Research on HIV/AIDS Prevention and Management (CIRCB), Yaounde, Cameroon; Department of Experimental Medicine, PhD Course in Microbiology, Immunology, Infectious Diseases and Transplants (MIMIT), University of Rome "Tor Vergata", Rome, Italy.
Insights
Early antiretroviral therapy (ART) initiation is crucial for reducing HIV-1 reservoirs in children. Delayed treatment and shorter viral suppression periods are linked to larger viral reservoirs, impacting treatment strategies for a pediatric HIV cure.
Area of Science:
- Virology
- Immunology
- Pediatric Infectious Diseases
Background:
- Perinatally acquired HIV infection establishes persistent viral reservoirs in children and adolescents.
- Understanding the characteristics of these reservoirs is critical for developing effective treatment and cure strategies.
- Limited data exist on quantitative viral reservoir profiles in pediatric populations, particularly in sub-Saharan Africa.
Conclusions:
- The pooled prevalence of ADRMs is high in perinatally HIV-infected children and adolescents.
- Larger proviral reservoir size is associated with delayed ART initiation, shorter viral suppression, and immunovirological failures.
- Strategies for pediatric HIV functional cure should prioritize early ART initiation, immunocompetence, and long-term viral suppression.
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 nonrandomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRMs) 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, with sensitive methodologies such as droplet digital polymerase chain reaction 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% (95% CI 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 = .656). Starting antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (P = .054). Participants with long-suppressed viremia (>5 years) had lower levels of HIV-1 DNA (P = .027). Pre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with greater levels of HIV-1 DNA (P = .038, P = .047, and P = .041, respectively).
Conclusions:
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 immunovirological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.
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