Persistent immunological repercussions of late antiretroviral initiation in children with HIV

Area of Science:

• Immunology
• Pediatric HIV Research
• Vaccinology

Background:

• Perinatally acquired HIV infection in children can lead to long-term immune compromise.
• Antiretroviral treatment (ART) is crucial for managing HIV, but the optimal timing for initiation remains a key question.
• Immune system development and response to vaccination can be significantly impacted by the timing of ART initiation.

Purpose of the Study:

• To investigate how the age of initiating antiretroviral treatment (ART) affects immune parameters and vaccine responses.
• To evaluate long-term immune outcomes in children with perinatally acquired HIV based on their age at ART initiation.
• To analyze the relationship between early ART and immune cell profiles, including markers of senescence, anergy, activation, and exhaustion.

Main Methods:

• A cross-sectional study was conducted on children under 18 years old with HIV, on ART for at least 6 months, and with suppressed viral loads (<50 copies/mL).
• Data were collected from medical charts, and blood samples were analyzed for antibody titers (Hepatitis A, B, rubella, mumps, measles) and T cell immunophenotyping via flow cytometry.
• Participants were categorized into four groups based on age at ART initiation: <6 months, 6 months to <1 year, 1 year to <5 years, and ≥5 years.

Main Results:

• Children initiating ART earlier (<1 year, especially <6 months) exhibited higher CD4+ counts, CD4+ nadir, and CD4+/CD8+ ratios compared to those starting ART later.
• Earlier ART initiation was associated with CD4+ and CD8+ T cell profiles showing lower frequencies of activation, senescence, and exhaustion markers.
• Higher antibody titers for mumps, measles, and rubella were observed in children who started ART earlier; these immune markers correlated with better vaccine responses.

Conclusions:

• Later initiation of ART in children with perinatally acquired HIV is linked to poorer immune outcomes, persisting even after prolonged treatment.
• Early ART intervention is critical for optimizing immune reconstitution and vaccine efficacy in this population.
• Age at ART initiation is a significant factor influencing long-term immune health and response to infections and vaccinations in children living with HIV.