Rapid and profound decay of inducible and intact HIV genomes in early-treated Thai children
Year: 2026
Type: article
Study design: Observational Study
Abstract: Early initiation of antiretroviral therapy (ART) in perinatally HIV-infected children significantly limits the establishment of the viral reservoir. However, the long-term impact of this intervention remains unclear. We measured the frequency of inducible, translation-competent, and replication-competent proviruses in samples from 62 children who initiated ART early and remained virally suppressed for up to 9.9 years. Only a small fraction of HIV genomes produced HIV transcripts, viral proteins, or infectious virions. Accordingly, replication-competent virus was detected in only 11% of the participants. Despite the predominance of naive cells in pediatric blood, most proviruses were detected in memory CD4+ T cells, especially central memory cells. Longitudinal analysis revealed a biphasic decay in HIV DNA: an initial decline followed by long-term stability, which was associated with extensive expansions of infected T cell clones. In contrast, inducible proviruses declined continuously and became undetectable in most children after 5 years. Near full-length sequencing of 1,305 HIV genomes revealed a dramatic reduction in genetically intact proviruses, from pre-ART to after 7 years of ART. Together, these findings suggest that the intact viral reservoir rapidly decays in early-treated children, offering critical insights for pediatric HIV cure strategies.
DOI: 10.1172/jci198054
Authors: Marta Massanella, Caroline Dufour, Amélie Pagliuzza, Audrée Lemieux, Corentin Richard, Jintanat Ananworanich, Louise Leyre, Thidarat Jupimai, Supranee Buranapraditkun, Rapisa Nantanee, Julie L. Mitchell, Panadda Sawangsinth, Mark de Souza, Piyarat Suntarattiwong, Suparat Kanjanavanit, Pope Kosalaraksa, Thitiporn Borkird, Witaya Petdachai, Kulkanya Chokephaibulkit, Lydie Trautmann, Rémi Fromentin, Thanyawee Puthanakit, Nicolas Chomont
Institutions: Centre Hospitalier de l’Université de Montréal, Université de Montréal, Amsterdam University Medical Centers, University of Amsterdam, Chulalongkorn University, Thai Red Cross Society, King Chulalongkorn Memorial Hospital, Oregon Health & Science University, Vaccine and Gene Therapy Institute, Queen Sirikit National Institute of Child Health, Nakornping Hospital, Khon Kaen University, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Hatyai Hospital, King Mongkut Memorial Hospital, Siriraj Hospital, Mahidol University, Henry M. Jackson Foundation, Walter Reed Army Institute of Research, HIV Netherlands Australia Thailand Research Collaboration
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1116841569, G9000293476
OpenAlex ID: W7148465003