Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

Author:

Goswami Ria1ORCID,Nelson Ashley N.1ORCID,Tu Joshua J.1,Dennis Maria1,Feng Liqi2,Kumar Amit1,Mangold Jesse1,Mangan Riley J.1,Mattingly Cameron3,Curtis Alan D.45,Obregon-Perko Veronica3,Mavigner Maud3ORCID,Pollara Justin6,Shaw George M.7,Bar Katharine J.7,Chahroudi Ann38,De Paris Kristina45,Chan Cliburn9,Van Rompay Koen K. A.10ORCID,Permar Sallie R.111

Affiliation:

1. Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA

2. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA

3. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA

4. Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

5. Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

6. Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA

7. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

8. Emory+Children’s Center for Childhood Infections and Vaccines, Atlanta, Georgia, USA

9. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA

10. California National Primate Research Center, University of California, Davis, California, USA

11. Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA

Abstract

Novel interventions that do not rely on daily adherence to ART are needed to achieve sustained viral remission for perinatally infected children, who currently rely on lifelong ART. Considering the risks and expense associated with ART interruption trials, the identification of biomarkers of viral rebound will prioritize promising therapeutic intervention strategies, including anti-HIV Env protein therapeutics. However, comprehensive studies to identify those biomarkers are logistically challenging in human infants, demanding the need for relevant nonhuman primate models of HIV rebound. In this study, we developed an infant RM model of oral infection with simian-human immunodeficiency virus expressing clade C HIV Env and short-term ART followed by ATI, longitudinally characterizing the immune responses to viral infection during ART and after ATI. Additionally, we compared this infant RM model to an analogous adult RM rebound model and identified virologic and immunologic correlates of the time to viral rebound after ATI.

Funder

Penn Center for AIDS Research Viral and Molecular Core

HHS | National Institutes of Health

UC | UC Davis | California National Primate Research Center

Emory University | Center for AIDS Research, Emory University

UNC | UNC-CH | Center for AIDS Research, University of North Carolina at Chapel Hill

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference69 articles.

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2. UNAIDS. 2015. Access to antiretroviral therapy in Africa—status report on progress towards the 2015 targets. http://www.unaids.org/sites/default/files/media_asset/20131219_AccessARTAfricaStatusReportProgresstowards2015Targets_en_0.pdf.

3. Adherence to antiretroviral therapy in adolescents living with HIV

4. Prevalence of Primary HIV‐1 Drug Resistance among Recently Infected Adolescents: A Multicenter Adolescent Medicine Trials Network for HIV/AIDS Interventions Study

5. Metabolic complications and treatment of perinatally HIV-infected children and adolescents

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