Assessing the impact of autologous virus neutralizing antibodies on viral rebound time in postnatally SHIV-infected ART-treated infant rhesus macaques.

Autor:	Mainou E; Department of Biology, Pennsylvania State University, University Park, PA, USA. Electronic address: ejm6007@psu.edu., Berendam SJ; GlaxoKlineSmith, Rockville, MD, USA., Obregon-Perko V; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA., Uffman EA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Phan CT; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA., Shaw GM; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Bar KJ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Kumar MR; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Fray EJ; Department of Biochemistry and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Siliciano JM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Siliciano RF; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Silvestri G; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA., Permar SR; Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA., Fouda GG; Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA., McCarthy J; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA., Chahroudi A; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA., Conway JM; Department of Mathematics, Pennsylvania State University, University Park, PA, USA., Chan C; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
Jazyk:	angličtina
Zdroj:	Epidemics [Epidemics] 2024 Sep; Vol. 48, pp. 100780. Date of Electronic Publication: 2024 Jun 27.
DOI:	10.1016/j.epidem.2024.100780
Abstrakt:	While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early initiation is not always possible in postnatal pediatric HIV infections. The timing of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear and has never been modeled in infants. To investigate this question we used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. To gain insight into early after analytic treatment interruption (ATI), we constructed mathematical models to investigate the effect of time of ART initiation in delaying viral rebound when treatment is interrupted, focusing on the relative contributions of latent reservoir size and autologous virus neutralizing antibody responses. We developed a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound for RMs rebounding up to 60 days post-ATI. We find that the latent reservoir size is an important determinant in explaining time to viral rebound in infant macaques by affecting the growth rate of the virus. The presence of neutralizing antibodies can also delay rebound, but we find this effect for high potency antibody responses only. Finally, we discuss the therapeutic implications of our findings. Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Conway has served as a consultant for Excision BioTherapeutics and Merck. Dr. Permar serves a consultant for Moderna, Merck, Pfizer, GSK, Dynavax, and Hoopika on their CMV vaccine program and has led a sponsored program with Moderna and Merck on CMV vaccines. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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