High mortality following early initiation of antiretroviral therapy in infants living with HIV from three African countries.

Background

Even with increasing access to rapid HIV diagnosis and early antiretroviral therapy (ART) initiation, infants living with HIV seem to have adverse outcomes. We assessed the probability of death, viral suppression, and other HIV-related events in the first three years of life among early-treated children with perinatally-acquired HIV in South Africa, Mozambique, and Mali.

Methods

We enrolled a cohort of infants who initiated ART within the initial 6 months of life and within 3 months of diagnosis. These children were monitored 2, 6, 12 and 24 weeks after enrolment, followed by biannual check-ups up to 4 years after enrolment. We assessed the probability of death, viral load (VL) suppression, severe immunosuppression (according to WHO guidelines), and engagement in care using Kaplan-Meier plots, and hazard ratios for these outcomes using multivariable Cox regression models.

Findings

Two hundred and fifteen infants were enrolled and monitored for a median of 34 months [IQR, 16.3; 44.1]. ART initiation occurred at a median of 34 days of age [IQR, 26.0; 73.0]. The probability of death at 1 year of ART was 10% (95% CI, 6-14), increased to 12% (95% CI, 8-17) at 2 and remained in 12% at 3 years. The main risk factor for HIV/AIDS-related mortality was baseline viral load [HR: 2.98 (95% CI, 1.25-7.12)]. Sixty-one of 146 (42%) children achieved sustained virological control below lower limit of detection for any ≥1 year period between enrolment and 4 years after enrolment. Viral suppression during follow-up was inversely associated with baseline viral load [Hazard Ratio (HR): 0.72 (95% CI, 0.58-0.89] and adverse maternal social events [HR: 0.26 (95% CI, 0.15-0.45)]. Adherence to ART was assessed as optimal in 81% of the visits. Female sex at birth, lower age at diagnosis and maternal adverse social life events were risk factors for low adherence [Odds ratio, OR 1.25 (95% CI, 1.00-1.56); 1.12 (95% CI, 1.01-1.27) and 2.52 (95% CI, 2.16-12.37), respectively].

Interpretation

Despite early ART, mortality remains high in infants. High baseline VL and adverse maternal social environment increased the risk of poor outcomes. Sustained supportive strategies are essential during and after pregnancy, to achieve better survival.

Funding

Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL) is a research consortium funded by ViiV Healthcare and led by Penta Foundation. The funder was not involved in the analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. The corresponding authors had access to all data and take final responsibility for the decision to submit.

Informations de copyright

© 2024 The Author(s).

Déclaration de conflit d'intérêts

The following institutions, to which the author-researchers belong, received funding from the sponsor (Penta Foundation) to carry out this research, who in turn received a non-competitive grant from ViiV named Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL): Fundación de Investigación Biomédica Hospital 12 de Octubre, Stellenbosch University, University of the Witwatersrand, Africa Health Research Institute, Fundação Ariel Glaser contra o SIDA Pediátrico, Centro de Investigaçao em Saude de Manhiça, Instituto Nacional de Saúde, Bambino Gesù Children's Hospital, Ragon Institute of MGH, MIT, and Harvard, University College of London, Gianni Benzi Pharmacological Research Foundation, University of Miami, Centre Hospitalier Universitaire Gabriel Touré, ISGlobal, Columbia University Irving Medical Center, University of Rome “Tor Vergata”, Penta Foundation. The authors reported no other relationships/conditions/circumstances that present a potential conflict of interest for this research. Elisa López reported being a full employee of ViiV Healthcare since April 2023. Outside the submitted work, Tacilta Nhampossa reported a grant from EDCTP Career Development Fellowships. Proposal: TMA2017CDF-1927 (2019–2022). Sheila Fernández-Luis reported a grant from Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and cofounded by European Social Fund. Paolo Palma reported a grant from NIH from 2020 to 2025 named PAVE, grant from NIH-NIAID (Targting HIV reservoirs in children with HIVIS-DNA and MVA-CMDR vaccines, and reported being the founder of Promiomics, a spin-off company of University Tor Vergata. Nicola Cotugno reported being the CRO and founder of Promiomics, a spin-off company of University Tor Vergata. Helena Rabie reported personal fees from ViiV community engagement meeting, personal fees from MSD Community engagement meeting.