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Scarcity of intact HIV genomes in vertically infected Thai children who initiated ART during the first months of life

Title
Scarcity of intact HIV genomes in vertically infected Thai children who initiated ART during the first months of life
Presenter
Caroline Dufour
Authors
C. Dufour * (1), M. Massanella (1), A. Pagliuzza (1), C. Richard (1), J. Ananworanich (2), L. Leyre (1), T. Jupimai (3), J. Mitchell (4), P. Sawangsinth (5), M. de Souza (5), P. Suntarattiwong (6), K. Chokephaibulkit (7), L. Trautmann (4), T. Puthanakit (3,8,9), R. Fromentin (1), N. Chomont (1)
Institutions
(1) Université de Montréal/Centre de Recherche du CHUM, Microbiology, Infectiology and Immunology, Montreal, Canada, (2) University of Amsterdam/Amsterdam Medical Center, Department of Global Health, Amsterdam, Netherlands, the, (3) Chulalongkorn University/Center of Excellence in Pediatric Infectious Diseases and Vaccines, Bangkok, Thailand, (4) Oregon Health & Science University/Vaccine and Gene Therapy Institute, Portland, United States, (5) SEARCH/Thai Red Cross AIDS research Centre, Bangkok, Thailand, (6) Queen Sirikit National Institute of Child Health, Bangkok, Thailand, (7) Mahidol University/Siriraj Hospital, Faculty of Medicine, Department of Pediatrics, Bangkok, Thailand, (8) Chulalongkorn University, Faculty of Medicine, Department of Pediatrics, Bangkok, Thailand, (9) The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), the Thai Red Cross AIDS Research Centre (TRC-ARC), Bangkok, Thailand

BACKGROUND: Latently infected cells harboring intact HIV genomes persist in children living with HIV receiving suppressive ART. However, the dynamics of these genetically intact viral genomes over time remains unclear.
METHODS: Thai children vertically infected with HIV who initiated ART within the first 6 months of life were enrolled in the HIVNAT209 & HIVNAT194 studies and followed longitudinally. We used cross sectional blood samples collected from infants before initiation of ART (n=3) as well as in virally suppressed children on ART for 2 years (n=6), 3 years (n=5) and more than 3 years (n=5). Near-full length (NFL) proviral sequences were obtained by FLIPS on enriched CD4 T cells and PacBio sequencing.
RESULTS: We obtained a total of 939 NFL HIV genomes (200 before ART and 282, 263 and 194 after 2, 3,and­>3 years of ART, respectively). Prior to ART initiation, 48% of the viral genomes were genetically intact (Fig. 1). This proportion drastically decreased to 11%, 6% and 1% after 2, 3 and >3 years of ART, respectively, while proviruses presenting large internal deletions largely dominated (>79%). Clonally expanded proviruses (i.e., 100% identical sequences) were rare before ART initiation (7%) and observed in only 1 of the 3 samples studied. However, the proportion of identical genomes dramatically increased to 36% after 2 years of ART and remained stable afterwards (36% and 40% at 3 and >3 years of ART, respectively). None of these clonally expanded genomes during suppressive ART were genetically intact.


CONCLUSIONS: These results suggest that genetically intact HIV genomes are massively depleted during the first years of ART in children who initiated treatment during the first months of life. Although clonal expansions of defective proviruses were frequently observed during ART, genetically intact HIV genomes were scarce and always unique.