Rapid and profound decay of inducible and intact HIV genomes in early-treated Thai children
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, on behalf of the HIV Netherlands Australia Thailand Research Collaboration 209 and 194 (HIVNAT209 and HIVNAT194) study groups
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, on behalf of the HIV Netherlands Australia Thailand Research Collaboration 209 and 194 (HIVNAT209 and HIVNAT194) study groups
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Research Article AIDS/HIV Immunology Virology

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

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.

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, on behalf of the HIV Netherlands Australia Thailand Research Collaboration 209 and 194 (HIVNAT209 and HIVNAT194) study groups

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Figure 6

Integrity of the HIV reservoir over time in early-ART-treated Thai children.

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Integrity of the HIV reservoir over time in early-ART-treated Thai child...
(A) Near full-length HIV genome alignments of participant 030 at 4 time points (before ART, and after 2, 3, and 7 years on ART). Each sequence is color-coded based on its integrity. (B) Percentage of each integrity categories of the HIV reservoir of 26 samples. Each sample was composed of 1 to 15 clones. (C) Pie charts representing the proportion of each integrity categories of the HIV reservoir for all samples of each time point. The percentage of each category is shown in the legend of the pie chart. The total number of proviruses per time point is indicated in the center of the pie chart, and the number of samples per time point with intact proviruses is noted at the top. P value (Cochran-Armitage Test for Trend) indicates that the trend of a decreasing proportion of intact HIV sequences is significant (P < 0.001). (D) Frequency of defective (light gray bars) and intact (dark gray bars) proviruses sequenced per million CD4+ T cells tested. Each dot represents the value for a specific sample, and each PID is color-coded. Bar graph shows the mean value for each group. Unfilled circle corresponds to undetectable values.