@article{c4557a23e43c4f448b2e9d5152e89b90,
title = "Simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques",
abstract = "Worldwide, nearly two million children are infected with human immunodeficiency virus (HIV), with breastfeeding accounting for the majority of contemporary HIV transmissions. Antiretroviral therapy (ART) has reduced HIV-related morbidity and mortality but is not curative. The main barrier to a cure is persistence of latent HIV in long-lived reservoirs. However, our understanding of the cellular and anatomic sources of the HIV reservoir during infancy and childhood is limited. Here, we developed a pediatric model of ART suppression in orally simian immunodeficiency virus (SIV)-infected rhesus macaque (RM) infants, with measurement of virus persistence in blood and tissues after 6 to 9 months of ART. Cross-sectional analyses were conducted to compare SIV RNA and DNA levels in adult and infant RMs naive to treatment and on ART. We demonstrate efficient viral suppression following ART initiation in SIV-infected RM infants with sustained undetectable plasma viral loads in the setting of heterogeneous penetration of ART into lymphoid and gastrointestinal tissues and low drug levels in the brain. We further show reduction in SIV RNA and DNA on ART in lymphoid tissues of both infant and adult RMs but stable (albeit low) levels of SIV RNA and DNA in the brains of viremic and ART-suppressed infants. Finally, we report a large contribution of naive CD4+ T cells to the total CD4 reservoir of SIV in blood and lymph nodes of ART-suppressed RM infants that differs from what we show in adults. These results reveal important aspects of HIV/SIV persistence in infants and provide insight into strategic targets for cure interventions in a pediatric population.",
keywords = "Antiretroviral therapy, Infants, Rhesus macaques, SIV",
author = "Maud Mavigner and Jakob Habib and Claire Deleage and Elias Rosen and Cameron Mattingly and Katherine Bricker and Angela Kashuba and Franck Amblard and Schinazi, {Raymond F.} and Sherrie Jean and Joyce Cohen and Colleen McGary and Mirko Paiardini and Wood, {Matthew P.} and Sodora, {Donald L.} and Guido Silvestri and Jacob Estes and Ann Chahroudi",
note = "Funding Information: This work was supported in part with federal funds from the National Cancer Institute (NIH contract HHSN261200800001E). The study was funded by the Emory+Children{\textquoteright}s Pediatric Center Seed Grant Program, the Campbell Family Foundation, and R01-AI133706 (all to A.C.) and by R01-DE023047 (to D.L.S.). We also acknowledge support from the Yerkes National Primate Research Center (RR000165/OD011132) and the Emory Center for AIDS Research (P30 AI050409). Funding Information: We thank Gilead for provision of the antiretroviral drugs PMPA and FTC. This work was supported in part with federal funds from the National Cancer Institute (NIH contract HHSN261200800001E). The study was funded by the Emory-Children's Pediatric Center Seed Grant Program, the Campbell Family Foundation, and R01-AI133706 (all to A.C.) and by R01-DE023047 (to D.L.S.). We also acknowledge support from the Yerkes National Primate Research Center (RR000165/OD011132) and the Emory Center for AIDS Research (P30 AI050409). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. Publisher Copyright: {\textcopyright} 2018 American Society for Microbiology. All Rights Reserved.",
year = "2018",
month = sep,
day = "1",
doi = "10.1128/JVI.00562-18",
language = "English (US)",
volume = "92",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "18",
}