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Probability of AIDS and non-AIDS-related mortality of early-treated children living with HIV-1

Title
Probability of AIDS and non-AIDS-related mortality of early-treated children living with HIV-1
Presenter
Camille Bréhin
Authors
C. Bréhin * (1), A. Tagarro (2), S.D.-R. Domínguez-Rodríguez (2), L. Kuhn (3), T. Nhampossa (4), K. Otwombe (5), A. Janse van Rensburg (6), N. Klein (7), M.G. Lain (8), A.I. Maiga (9), C. Giaquinto (10), P. Rossi (11), P. Rojo (2), EPIICAL Consortium
Institutions
(1) Toulouse University Hospital, Toulouse, France, (2) Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre, Madrid, Spain, (3) Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, United States, (4) Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique, (5) School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, (6) Tygerberg Children''s Hospital and Family Clinical Research Unit, Stellenbosch University, Cape Town, South Africa, (7) Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom, (8) Fundação Ariel Glaser Contra O Sida Pediátrico, Maputo, Mozambique, (9) SEREFO (HIV/TB Research and Training CenteHIV/TB Research and Training Center, FMOS, University of STT, Bamako, Mali, (10) PENTA Onlus, Padova, Italy, (11) Bambino Gesù Children's Hospital, Rome, Italy

BACKGROUND: The mortality of early treated children born with HIV in Sub-Saharan Africa during first years of life is still higher than baseline. We assessed the probability of AIDS-related mortality of a cohort of early treated children born with HIV, and factors related to them.
METHODS: EARTH-EPIICAL Cohort is underway in Mozambique, Mali, and South Africa. From May 1st, 2018 to May 1st, 2021, infants with HIV who started ART in the first 3 months of life, are followed up for 24 months. To describe the probability of AIDS-related death, a competing risk joint model was performed consisting of a multivariable mixed linear model for longitudinal CD4 trajectory and a survival Cox proportional model. The model was adjusted by ART initiation regimen, age at HIV diagnosis, and weight-for-age.
RESULTS: 212 participants were enrolled and followed during a median time of 17 [6.8;27.5] months; 84 reached 2 years of follow-up. ART started at 34 [26;74] days of life.
23 patients (10.8%) died, at a median of 2.5 [0.6;6.8] months of age; 12 due to AIDS-related causes . At 2 years, overall probability (P) of death was 12% (CI95%,7 to 17). The excess of mortality compared to baseline mortality was 7%; the excess of mortality due to AIDS-related causes was 5.7%, and due to non-AIDS related causes was 1.4%. According to the joint model, there was an inverse statistically significant association between the probability of AIDS-related mortality and the percentage of CD4 (%CD4) during the time to follow up and (HR:0.9 [CI95%, 0.86-0.98], p=0.046). An increase in CD4 count decrease a 10% the probability of AIDS-related mortality. Notably, these estimates had opposite sign for the non-AIDS-attributable deaths (HR:1.09 [CI95%, 1.02-1.15], p=0.003). Interestingly, baseline VL was significantly associated with non-AIDS-related mortality (HR:4.34 (CI95%, 1.84-20.7), p=0.026).
CONCLUSIONS: Despite early treatment, excess of AIDS- and non-AIDS-related mortality remains high in children living with HIV-1. Differentiating AIDS and non-AIDS related mortality in children with HIV may allow us to understand better the risk factors associated with mortality. CD4 percentage changes over time, and it impacts the probability of death. Infants with high baseline VL and low CD4% require specific attention.