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

来源：

JOURNAL OF INFECTIOUS DISEASES | 2020年 / 221卷 / 07期

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

页码：1135 / 1145

页数：11