The study evaluated whether treatment with valganciclovir, in addition to standard care, could reduce mortality among hospitalised infants with severe HIV-associated pneumonia who were at high risk of cytomegalovirus (CMV) co-infection. The study provided important evidence that valganciclovir was associated with a reduced risk of death during the first weeks after treatment initiation, suggesting an early survival benefit among infants receiving the treatment. This effect was most pronounced during the first month after hospital admission and gradually diminished over time. Although the prespecified mortality analyses at 15 days and 1 year were not conclusive, additional analyses suggested that the survival benefit extended for several weeks beyond completion of the 15-day treatment course. Importantly, valganciclovir treatment was shown to be safe and well tolerated, with no increase in serious adverse events.

The findings address an important evidence gap in the management of CMV-associated disease in infants living with HIV, particularly in settings where access to diagnostic testing remains limited. They may also help inform future clinical guidelines and contribute to improved management of one of the leading causes of mortality among children living with HIV in sub-Saharan Africa.

Beyond its clinical findings, the trial demonstrates the value of multinational research partnerships in delivering high-quality clinical research in countries with a high burden of infectious diseases. The study strengthened collaboration between African and European investigators, reinforced clinical trial capacity across participating sites, and generated evidence that is directly relevant to policy and clinical practice in the region.

Building on the success of the EMPIRICAL trial, the consortium continues to expand its contribution to paediatric HIV research. Several consortium partners have recently been awarded two Global Health EDCTP3-funded projects, SUPPORT and ENABLE, which will further strengthen research capacity and generate evidence to improve the management of infectious diseases affecting children and other vulnerable populations in sub-Saharan Africa. The consortium is also working closely with the World Health Organization (WHO) and national health authorities to support the translation of the EMPIRICAL findings into evidence-based policies and clinical guidelines, helping to maximise the public health impact of the research.

Project information

The EMPIRICAL study received funding from the EDCTP2 programme, supported by the European Union under grant agreement RIA2017MC-2013 (EMPIRICAL), the UK National Institute for Health and Care Research (NIHR), and UK International Development. NIHR is funded by the Department of Health and Social Care (UK-DHSC). The NIHR Global Health Research portfolio supports high-quality applied health research for the direct and primary benefit of people in low- and middle-income countries, using international development funding from the UK Government. The project was coordinated by Dr Pablo Rojo (Servicio Madrileño de Salud, Spain) and brought together partners from Côte d’Ivoire, France, Italy, Malawi, Mozambique, the Netherlands, Spain, Uganda, the United Kingdom, Zambia and Zimbabwe. The consortium investigated whether empirical treatment for cytomegalovirus and tuberculosis could improve survival among infants living with HIV and severe pneumonia while strengthening clinical trial capacity across participating African sites.