HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

Autor: Sergio Serrano-Villar, Talia Sainz, Sulggi A Lee, Peter W Hunt, Elizabeth Sinclair, Barbara L Shacklett, April L Ferre, Timothy L Hayes, Ma Somsouk, Priscilla Y Hsue, Mark L Van Natta, Curtis L Meinert, Michael M Lederman, Hiroyu Hatano, Vivek Jain, Yong Huang, Frederick M Hecht, Jeffrey N Martin, Joseph M McCune, Santiago Moreno, Steven G Deeks
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS Pathogens, Vol 10, Iss 5, p e1004078 (2014)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1004078
Popis: A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.
Databáze: Directory of Open Access Journals
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