Rapid and profound decay of inducible and intact HIV genomes in early treated Thai children

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 (median 9.9 weeks) and remained virally suppressed for up to 9.9 years. Only a small fraction of HIV genomes produced HIV transcripts (1.8%), viral proteins (<0.9%) or infectious virions (<0.05%). Accordingly, replication-competent virus was detected in only 15% of the participants. Despite the predominance of naïve cells in pediatric blood, most proviruses were detected in memory CD4+ T cells, especially central memory cells (contribution 41%). 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 five years. Near full-length sequencing of 1,305 HIV genomes revealed a dramatic reduction in genetically intact proviruses, from 40% pre-ART to 0.3% 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.

Authors

Institutions

Publication Details

Journal
Journal of Clinical Investigation
Published
2026-04-02
DOI
https://doi.org/10.1172/jci198054
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Rapid and profound decay of inducible and intact HIV genomes in early treated Thai children

Amélie Pagliuzza, Julie L. Mitchell, Rapisa Nantanee, Suparat Kanjanavanit et al.
Journal of Clinical Investigation
HIV Research and Treatment
article

Rapid and profound decay of inducible and intact HIV genomes in early treated Thai children

Amélie Pagliuzza, Julie L. Mitchell, Rapisa Nantanee, Suparat Kanjanavanit, Corentin Richard, Rémi Fromentin, Thitiporn Borkird, Audrée Lemieux, Louise Leyre, Thidarat Jupimai, Panadda Sawangsinth, Marta Massanella, Lydie Trautmann, Supranee Buranapraditkun, Nicolas Chomont, Caroline Dufour, Witaya Petdachai, de Souza, Thanyawee Puthanakit, Kulkanya Chokephaibulkit, Jintanat Ananworanich, Pope Kosalaraksa, Piyarat Suntarattiwong
article en

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 (median 9.9 weeks) and remained virally suppressed for up to 9.9 years. Only a small fraction of HIV genomes produced HIV transcripts (1.8%), viral proteins (<0.9%) or infectious virions (<0.05%). Accordingly, replication-competent virus was detected in only 15% of the participants. Despite the predominance of naïve cells in pediatric blood, most proviruses were detected in memory CD4+ T cells, especially central memory cells (contribution 41%). 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 five years. Near full-length sequencing of 1,305 HIV genomes revealed a dramatic reduction in genetically intact proviruses, from 40% pre-ART to 0.3% 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.

Journal of Clinical Investigation
Thai Red Cross Society (TH), Siriraj Hospital (TH), Chulalongkorn University (TH), Khon Kaen University (TH), Mahidol University (TH), Hatyai Hospital (TH), King Chulalongkorn Memorial Hospital (TH), Queen Sirikit National Institute of Child Health (TH), Phramongkutklao Hospital (TH), Amsterdam Institute for Global Health and Development (NL), Children's Cancer Therapy Development Institute (US), Centre Hospitalier de l’Université de Montréal (CA), Nakornping Hospital (TH), Walter Reed Army Institute of Research (US)
Styrelsen för Internationellt Utvecklingssamarbete, Chulalongkorn University, Thailand Science Research and Innovation, National Institutes of Health, Canadian Institutes of Health Research
Openalex Percentile: Top 29%
HIV Research and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.