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Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression
Author(s) -
Keoshkerian Elizabeth,
Ashton Lesley J.,
Smith Danielle G.,
Ziegler John B.,
Kaldor John M.,
Cooper David A.,
Stewart Graeme J.,
Ffrench Rosemary A.
Publication year - 2003
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.10525
Subject(s) - ctl* , cytotoxic t cell , biology , immunology , cd8 , immune system , virology , effector , ex vivo , viral load , antigen , virus , in vivo , in vitro , biochemistry , microbiology and biotechnology
Ex vivo effector cytotoxic T‐lymphocyte (CTL) activity was assessed in 27 members of the Australian Long‐Term Nonprogressor cohort and correlated with genetic, virological, and immunological markers. The 27 individuals were antiretroviral naive with CD4 + T‐cell counts of >500 cells/μl for more than 8 years after human immunodeficiency virus type 1 (HIV‐1) infection. Effector CTL activity was determined using a standard ex vivo chromium release assay. Individuals with CTL activity (HIV‐1 env IIIB or pol or gag) were then compared to those without CTL activity in relation to plasma HIV‐1 RNA, ICD p24 antigen, β 2 ‐microglobulin, CD4 and CD8 T‐cell counts, CCR5 and CCR2b genotypes, and progression to CD4 <500 cells/μl or commencement of antiretroviral treatment. Of the 27 individuals examined, 19 had no detectable effector CTL activity. The eight individuals with detectable CTL activity had significantly higher plasma levels of HIV‐1 RNA ( P = 0.014), immune complex dissociated p24 antigen ( P = 0.006), and β 2 ‐microglobulin ( P = 0.009). There was increased risk of progression within 4 years of study entry in individuals with detectable effector CTL activity, higher plasma levels of HIV‐1 RNA, higher β 2 ‐microglobulin levels, and higher immune complex dissociated p24 antigen levels at enrollment ( P = 0.017, P = 0.004, P = 0.027, P = 0.008 respectively). Multivariate analysis demonstrated viral load remained the strongest predictor of disease progression within this group ( P = 0.017). There were no significant associations between CTL response and chemokine receptor genotype. These findings demonstrate the importance of HIV replication in generating an effector CTL response and show that effector CTL activity may be an early predictor of progression in people with long‐term asymptomatic HIV infection. J. Med. Virol. 71:483–491, 2003. © 2003 Wiley‐Liss, Inc.