Journal
JOURNAL OF INFECTION
Volume 66, Issue 1, Pages 57-66Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2012.09.013
Keywords
HIV; CD4/CD8 ratio; Immune activation; Immunosenescence; Bacterial translocation; HIV-1 latent reservoir; CD4 count
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Funding
- Spanish AIDS Network Red Tematica Cooperativa de Investigacion en SIDA [RD06/0006]
- Spanish National of Health, Instituto de Salud Carlos III [FIS-PI080958, CP08/00046]
- Foundation of Investigation and prevention of AIDS [FIPSE-36-0844/09]
- Spanish Ministry of Science and Innovation (Ayudas para Contratos de Formacion en Investigacion Rio Hortega)
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Objectives: HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding. Methods: Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm(3). Laboratory measurements included T-cell activation (HLADR(+), CD38(+)) and senescence (CD57(+)), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus). Results: CD4/CD8 ratio was positively correlated with CD4 nadir (r = 0.468, p = 0.038) and accumulated ART exposure (r = 0.554, p = 0.0011), and negatively with viral load before ART initiation (r = -0.547, p = 0.013), CD4(+)HLADR(+)CD38(+) T-cells (r = -0.428, p = 0.086) and CD8(+)CD57(+) T-cells (r = -0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4(+)HLADR(+)CD38(+) T-cells and CD8(+)HLADR(+) T-cells. Conclusions: In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression. (C) 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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