Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion

Author:

Martin Genevieve E1ORCID,Pace Matthew1,Shearer Freya M2,Zilber Eva1,Hurst Jacob1,Meyerowitz Jodi1,Thornhill John P13,Lwanga Julianne4,Brown Helen1,Robinson Nicola1,Hopkins Emily1,Olejniczak Natalia1,Nwokolo Nneka5,Fox Julie46,Fidler Sarah37,Willberg Christian B18,Frater John18

Affiliation:

1. Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

2. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom

3. Division of Medicine, Wright Fleming Institute, Imperial College, London, United Kingdom

4. Department of Genitourinary Medicine and Infectious Disease, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom

5. Chelsea and Westminster Hospital, London, United Kingdom

6. King’s College National Institute for Health Research Biomedical Research Centre, London, United Kingdom

7. Imperial College National Institute for Health Research Biomedical Research Centre, London, United Kingdom

8. National Institute of Health Research Biomedical Research Centre, Oxford, United Kingdom

Abstract

AbstractInitiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet−Eomes− subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

Funder

Medical Research Council

National Institute of Health Research Oxford Biomedical Research Centre

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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