Immunological biomarkers predict HIV-1 viral rebound after treatment interruption

• DOI: 10.1038/ncomms9495
• Publication Date: 2015-10-09T11:18:00Z
• Authors: Jacob Hurst; Matthias Hoffmann; Matthew Pace; James P. Williams; John Thornhill; Elizabeth Hamlyn; Jodi Meyerowitz; Chris Willberg; Kersten K. Koelsch; Nicola Robinson; Helen Brown; Martin Fisher; Sabine Kinloch; David A. Cooper; Mauro Schechter; Giuseppe Tambussi; Sarah Fidler; Abdel Babiker; Jonathan Weber; Anthony D. Kelleher; Rodney E. Phillips; John Frater
• Keywords: HLA CLASS-I; EXPRESSION; 0301 basic medicine; Anti-HIV Agents; 3207 Medical Microbiology; 32 Biomedical and Clinical Sciences; HIV Infections; DETERMINANTS; 613; Article; 03 medical and health sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; ANTIRETROVIRAL THERAPY; 616; 2.1 Biological and endogenous factors; Humans; anzsrc-for: 3207 Medical Microbiology; POPULATION; anzsrc-for: 3204 Immunology; Science & Technology; MORTALITY; DISEASE PROGRESSION; 3 Good Health and Well Being; Viral Load; INFECTED INDIVIDUALS; CD4 Lymphocyte Count; 3. Good health; 3204 Immunology; Multidisciplinary Sciences; Infectious Diseases; Withholding Treatment; T-CELLS; HIV-1; HIV/AIDS; Sexually Transmitted Infections; Science & Technology - Other Topics; Infection; Biomarkers; RESPONSES

AbstractTreatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of ‘post-treatment control’ (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication.