Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+and CD4+T lymphocytes

Author:

Oxenius Annette1,Price David A.1,Easterbrook Philippa J.1,O'Callaghan Christopher A.1,Kelleher Anthony D.1,Whelan Joseph A.1,Sontag Glenn1,Sewell Andrew K.1,Phillips Rodney E.1

Affiliation:

1. Nuffield Department of Clinical Medicine and Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; The Caldecot Centre, King's College Hospital, London, SE5 9RS, United Kingdom; and St. Stephens Centre, Chelsea and Westminster Hospital, London, SW10 9NH, United Kingdom

Abstract

Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV-1 infection without clear understanding of its immunological effects. Here, we demonstrate that early use of HAART during primary infection preserves HIV-specific CD8+T cells physically and functionally while HIV-specific T cell help is sustained. We also show that even transient administration of HAART at seroconversion can preserve HIV-specific immunity. In contrast, delayed initiation of HAART is associated with a progressive loss of HIV-specific CD8+T cells and absent HIV-specific T cell help. These results imply that HIV-specific T help is damaged during primary HIV-1 infection. Early drug treatment, which preserves this immunity, also preserves HIV-specific CD8+T cells. These results have implications for understanding the early pathogenesis of HIV-1 infection and suggest that acute HIV infection should be treated aggressively and as early as possible.

Publisher

Proceedings of the National Academy of Sciences

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