Pharmacokinetics and pharmacodynamics of valganciclovir in infants with severe HIV-associated pneumonia in Africa: a sub-study of the EMPIRICAL randomised controlled trial
Background: Cytomegalovirus (CMV) is a major unrecognised cause of morbidity and mortality in infants living with HIV. Valganciclovir, an oral prodrug of ganciclovir, treats CMV in immunocompromised patients, but pharmacokinetic data in infants living with HIV are lacking. This study evaluated exploratory valganciclovir pharmacokinetic and pharmacodynamic outcomes in infants with severe HIV-associated pneumonia. Methods: with covariates and log-change in plasma CMV viraemia were evaluated using linear regression. Infants were enrolled in this study between August 2020 and August 2022. Findings: did not correlate with plasma CMV viral load reduction. Interpretation: Approximately two-thirds of infants was not within adult pharmacokinetic targets at 16 mg/kg/dose of valganciclovir. However, ganciclovir exposure was not predictive for virologic response or toxicity, suggesting lower exposures did not affect treatment efficacy in the EMPIRICAL trial. Funding: This project is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2) program supported by the European Union (RIA2017MC-2013).
Authors
- Merunissa Gafur
- Salome Chitondo
- Alfeu Passanduca
- Muhammad Sidat (ORCID: https://orcid.org/0000-0001-8162-0102)
- Veronica Mulenga (ORCID: https://orcid.org/0000-0003-1843-8169)
- Sara Domínguez‐Rodríguez (ORCID: https://orcid.org/0000-0003-3747-9265)
- Sílvia Chaúque
- Perfect Shankalala (ORCID: https://orcid.org/0000-0001-5759-5162)
- Álvaro Ballesteros (ORCID: https://orcid.org/0009-0001-4403-1023)
- Cinta Moraleda (ORCID: https://orcid.org/0000-0002-8335-903X)
- Ivan Segawa (ORCID: https://orcid.org/0000-0002-4535-1694)
- Sharafat Nkinzi
- Andrew Kiggwe
- Wyclef Mumba
- Albert Kamugisha
- Celda Mavume
- Tom Jacobs (ORCID: https://orcid.org/0000-0001-5738-5528)
- Uneisse Cassia
- Vivian Mumbiro
- Stella Manhiça Langa (ORCID: https://orcid.org/0000-0003-0701-2971)
- Lilit Manukyan
- Judith Beinomugisha
- Dalila Rego
- John Tembo (ORCID: https://orcid.org/0000-0002-6660-9877)
- Matthew Bates (ORCID: https://orcid.org/0000-0003-0464-1529)
- Elizabeth Najjingo
- Lawrence Kakooza
- Justina Bramugy (ORCID: https://orcid.org/0000-0002-2350-5584)
- Alfredo Tagarro (ORCID: https://orcid.org/0000-0003-2860-3455)
- Muleya Inambao
- Henriator Namisanvu
- Jahit Sacarlal (ORCID: https://orcid.org/0000-0003-1059-217X)
- Damalie Nalwanga (ORCID: https://orcid.org/0000-0002-1862-8109)
- Kajal Chhaganlal
- Bwendo Nduna (ORCID: https://orcid.org/0000-0001-6613-4704)
- Amir Seni
- Natasha Namuziya (ORCID: https://orcid.org/0009-0002-6274-2993)
- Elias Manjate
- Natália Nipaco
- Sara Machava
- Anastância Chirindza
- Mércia Nhaca
- Ruth Marange
- Mulima Mukubesa
- Juliet Namwinwa
- Chalwe Chibuye
- Bwalya Simunyola
- Endreen Mankushe
- Henry Musukwa
- Davies Sondashi
- Karen Econi
- Joseph Ssessanga
- Paul Mbavu
- Bashira T Mbabazi
- Atija Salimo
- Armando Francisco Saide
- Sophie Mutesi
- Raul Atibo
- Laize Sílvia dos Anjos Botas Beca
- Denis Nansera (ORCID: https://orcid.org/0009-0008-6968-3934)
- Dália Machel
- Josam Thembo Mwesige
- W. Chris Buck
- Nancy Lajara Mark
- D. M. Burger
- Marizelina Chaves
- Shepherd Mudzingwa
- Terence Chipoya
- Franklyn N. Egbe
- Adelina Manheche
- Abbas Lugemwa
- Mutsa Bwakura-Dangarembizi
- Rito Eleutério
- Rogers Ankunda
- Idah Zulu
- Luzidina Martins
- Pablo Rojo
- Victor Musiime
- Edson Arcanjo
- Dorothy Murungu
- Hélio Brande
- Kusum J. Nathoo
- Sónia Martins
- Maria Teresa Gatoma
- Angela Colbers
- Hilda A. Mujuru
- Lola Madrid
- Moses Chitsamatanga
- Belinda Macmillan
- Chishala Chabala
- Bosco Kafufu
- Natasha Namuzizya
- Mariam Kasozi
- Aurora Mucarenga
Institutions
- Universidad Complutense de Madrid (ES)
- Radboud University Nijmegen (NL)
- University of Liverpool (GB)
- University of Zimbabwe (ZW)
- University of California, Los Angeles (US)
- Eduardo Mondlane University (MZ)
- University Teaching Hospital (ZM)
- Radboud University Medical Center (NL)
- Lúrio University (MZ)
- Catholic University of Mozambique (MZ)
- University of Zambia (ZM)
- Research Institute Hospital 12 de Octubre (ES)
- London School of Hygiene & Tropical Medicine (GB)
- Hospital Universitario 12 De Octubre (ES)
- Manhiça Health Research Centre (MZ)
- Madrid Health Service (ES)
- Tergooi (NL)
- Tropical Diseases Research Centre (ZM)
- Hospital Universitario Infanta Sofía (ES)
- Joint Clinical Research Centre (UG)
- University of Lincoln (GB)
- Makerere University (UG)
- Universidad Europea de Madrid (ES)
Publication Details
- Journal
- EClinicalMedicine
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1016/j.eclinm.2026.103899
- Primary Topic
- HIV/AIDS drug development and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- European and Developing Countries Clinical Trials Partnership