Abstract
Introduction:
T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection.
Patients and methods:
96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored.
Results:
Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035).
Conclusions:
Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Anti-HIV Agents / therapeutic use*
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Biomarkers / metabolism
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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Disease Progression
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Female
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Follow-Up Studies
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HIV Infections / drug therapy*
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HIV Infections / immunology*
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Hepatitis A Virus Cellular Receptor 2 / metabolism*
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Humans
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Longitudinal Studies
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Male
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Middle Aged
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Multivariate Analysis
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Programmed Cell Death 1 Receptor / metabolism*
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Retrospective Studies
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Treatment Outcome
Substances
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Anti-HIV Agents
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Biomarkers
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HAVCR2 protein, human
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Hepatitis A Virus Cellular Receptor 2
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
Grants and funding
This study has been funded by the RD12/0017/0031, RD16/0025/0013 and PI14/00518 projects as part of the Health Research and Development Strategy, State Plan for Scientific and Technical Research and Innovation (2008-2011; 2013-2016) and cofinanced by Institute of Health Carlos III, ISCIII – Sub- Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). Norma Rallón is a Miguel Servet investigator from the ISCIII (CP14/00198), Madrid, Spain. M García is a predoctoral student co-funded by CP14/00198 project and Intramural Research Scholarship from IIS-FJD, and Clara Restrepo was funded by project RD12/0017/0031 and is currently funded by project RD16/0025/0013. There was no additional external funding received for this study.