Authors:

Thomé, Beatriz; Pacola, Denise Peluso; Della Negra, Marinella; Durigon, Giuliana Stravinskas; de Sousa Marques, Heloisa Helena; Costa, Priscilla Ramos; Miraglia, João Luiz; Vieira, Vinicius Adriano; Jacintho, Lucas Caue; Itto, Lucas Yuji Umesaki; Avelino-Silva, Vivian I.; Abrams, Elaine J.; Kallás, Esper Georges

Abstract:

Objective:

We aimed to evaluate how age at antiretroviral treatment (ART) initiation modified immune parameters and vaccine responses in a Brazilian cohort of children with perinatally acquired HIV on long-term treatment.

Design:

Cross-sectional study including children <18 years; ART for ≥6 months; and HIV viral load <50 copies/ml.

Methods:

Data was abstracted from medical charts and blood was collected for serology and PBMC isolation. Antibody titers for hepatitis A and B, rubella, mumps and measles were measured. T cells with markers for senescence (CD57⁺), anergy (CD28^–), apoptosis (CD95⁺), activation (CD38⁺, CCR5⁺, HLA-DR⁺) and exhaustion (PD-1⁺) were analyzed by flow cytometry. Children were categorized in four groups: ART initiation <6 months; ≥6 months <1 year; ≥1 year <5 years; ≥5 years.

Results:

Fifty-five participants with a median age of 12 (8.3;15.9) years and median time on ART of 9 (5.0;13.2) years were included. Median age at ART initiation was 1.8 (0.6;3.6) years. Compared to those starting ART later, children who initiated ART earlier (<1 year of age, and especially < 6 months) had higher CD4⁺ counts, CD4⁺ nadir, and CD4⁺/CD8⁺ ratio. Earlier ART was associated with CD4⁺ and CD8⁺ profiles with lower frequencies of activation, senescence, and exhaustion markers, and higher antibody titers for mumps, measles and rubella. Activation, senescence, and exhaustion markers correlated with poorer vaccine response.

Conclusion:

Children who started ART later in life presented with worse immune outcomes even after long-term ART.