Giving valganciclovir before the precise cause of pneumonia was known reduced mortality by 40% within 15 days. Radboudumc researchers helped determine the appropriate dosing and assessed interactions with HIV medication.
Infants living with HIV who are hospitalized with severe pneumonia have a substantially better chance of survival when treated with the antiviral drug valganciclovir. An international clinical trial conducted in six African countries found that the treatment reduced mortality by 40% within 15 days. The results have been published in The Lancet.
Despite effective methods to prevent HIV transmission from mother to child, around 120,000 children are still infected with HIV each year. Approximately 75,000 children die annually from HIV-related causes. Most live in Africa and many die during their first year of life, often after developing severe pneumonia.
Treatment before the cause is confirmed
In the EMPIRICAL trial, infants living with HIV and severe pneumonia received valganciclovir in addition to standard care. The drug was given empirically, meaning that treatment began before doctors had confirmed the specific infection causing the pneumonia.
After 15 days, mortality was 40% lower among infants who received valganciclovir than among those who did not.
The study also investigated whether starting tuberculosis treatment before confirming a diagnosis would improve survival. This treatment did not reduce mortality.
Determining the correct dose
The dose of valganciclovir used in the trial was based on previous experience in children with congenital viral infections and patients who had received an organ transplant. However, little information was available about how the drug behaves in infants living with HIV who are seriously ill with pneumonia.
Tom Jacobs and David Burger from Radboudumc’s Department of Pharmacy, Pharmacology and Toxicology therefore studied the pharmacokinetics of ganciclovir, the active component of valganciclovir. They examined how the infants absorbed, processed and eliminated the drug. They also assessed whether valganciclovir interacted with the medicines used to treat HIV.
This work helped evaluate whether the infants received an effective and safe dose alongside their HIV treatment.
Longer treatment may further improve survival
The researchers are now developing a follow-up project in which valganciclovir treatment would be extended from 14 days to six months. The first doses may be administered intravenously to ensure that critically ill infants receive sufficient medication during the first days of treatment.
The aim is to determine whether a longer and more intensive treatment strategy can further reduce mortality in this particularly vulnerable group.
The EMPIRICAL trial was carried out in six African countries and coordinated by Pablo Rojo and his team in Madrid, Spain. The study was funded by the European and Developing Countries Clinical Trials Partnership.
About the publication
Moraleda C, Tagarro A, Domínguez-Rodríguez S, et al. (2026). Empirical treatment with valganciclovir in infants living with HIV and hospitalised with severe pneumonia in Africa: a multicentre, open-label, factorial, randomised, controlled, superiority trial. DOI: 10.1016/S0140-6736(26)00754-3.
