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

被引:19
作者
Martin, Genevieve E. [1 ,9 ]
Pace, Matthew [1 ]
Shearer, Freya M. [2 ,10 ]
Zilber, Eva [1 ]
Hurst, Jacob [1 ]
Meyerowitz, Jodi [1 ]
Thornhill, John P. [1 ,3 ]
Lwanga, Julianne [4 ]
Brown, Helen [1 ]
Robinson, Nicola [1 ]
Hopkins, Emily [1 ]
Olejniczak, Natalia [1 ]
Nwokolo, Nneka [5 ]
Fox, Julie [4 ,6 ]
Fidler, Sarah [3 ,7 ]
Willberg, Christian B. [1 ,8 ]
Frater, John [1 ,8 ]
机构
[1] Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England
[2] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England
[3] Imperial Coll, Wright Fleming Inst, Div Med, London, England
[4] Guys & St Thomas NHS Fdn Trust, Dept Genitourinary Med & Infect Dis, London, England
[5] Chelsea & Westminster Hosp, London, England
[6] Kings Coll London, Natl Inst Hlth Res, Biomed Res Ctr, London, England
[7] Imperial Coll, Natl Inst Hlth Res, Biomed Res Ctr, London, England
[8] Natl Inst Hlth Res, Biomed Res Ctr, Oxford, England
[9] Alfred Hosp, Melbourne, Vic, Australia
[10] Univ Melbourne, Sch Populat & Global Hlth, Modelling & Simulat Unit, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
HIV; HIV reservoir; primary HIV infection; T cells; HIV-POSITIVE PATIENTS; IMMUNE ACTIVATION; ANTIRETROVIRAL THERAPY; VIRAL LOAD; RESERVOIR; PERSISTENCE; EXPRESSION; BLOOD; CD4(+); PROVIRUSES;
D O I
10.1093/infdis/jiz563
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 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.
引用
收藏
页码:1135 / 1145
页数:11
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