HIV-1 DNA predicts disease progression and post-treatment virological control

Author:

Williams James P1,Hurst Jacob12,Stöhr Wolfgang3,Robinson Nicola124,Brown Helen124,Fisher Martin5,Kinloch Sabine6,Cooper David7,Schechter Mauro8,Tambussi Giuseppe9,Fidler Sarah10,Carrington Mary1112,Babiker Abdel3,Weber Jonathan10,Koelsch Kersten K713,Kelleher Anthony D713,Phillips Rodney E124,Frater John124,

Affiliation:

1. Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom

2. The Oxford Martin School, Institute for Emerging Infections, Oxford, United Kingdom

3. Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom

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

5. Department of Sexual Health and HIV, Brighton and Sussex University Hospitals, Brighton, United Kingdom

6. Division of Infection and Immunity, School for Life Sciences, University College London, London, United Kingdom

7. The Kirby Institute of New South Wales, Sydney, Australia

8. Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

9. Department of Infectious Diseases, Ospedale San Raffaele, Milan, Italy

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

11. Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, United States

12. Ragon Institute of MGH, MIT and Harvard, Cambridge, United States

13. St Vincent's Centre for Applied Medical Research, Sydney, Australia

Abstract

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20

Funder

Oxford Martin School, University of Oxford

National Institute of Health Research, Oxford BRC

Nuffield Department of Medicine

Wellcome Trust

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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