ORCID Profile
0000-0002-5703-3984
Current Organisation
University of Oxford
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Publisher: Oxford University Press (OUP)
Date: 28-11-2019
Abstract: Initiation 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 in iduals 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 in iduals 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.
Publisher: Springer Science and Business Media LLC
Date: 09-10-2015
DOI: 10.1038/NCOMMS9495
Abstract: Treatment 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2018
Publisher: Frontiers Media SA
Date: 04-05-2018
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1038/S41385-019-0180-2
Abstract: Gut-associated lymphoid tissue (GALT) is a key location for the HIV reservoir. The observation that B-cell-T-cell doublets are enriched for CD32a (a low-affinity IgG receptor) in peripheral blood raises interesting questions, especially as these cells have been associated with HIV DNA in some studies. We sought to determine if similar doublets were present in GALT, the significance of these doublets, and their implications for the HIV reservoir. Given the importance of GALT as a reservoir for HIV, we looked for expression of CD32 on gut CD4 T cells and for evidence of doublets, and any relationship with HIV DNA in HIV + in iduals initiated on antiretroviral therapy (ART) during primary HIV infection (PHI). Tonsil tissue was also available for one in idual. As previously shown for blood, CD32
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Matthew Pace.