Abstract
ObjectivesImmune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell subsets after 18 months of cART and overall survival during 12 years of follow up.MethodsA cohort of 101 HIV infected patients who had undetectable plasma HIV after starting cART was included in 1997–1998. T cell subsets were analyzed by flowcytometry after 18 months of cART. Relation to survival was calculated using Kaplan-Meier curves and multiple Cox regression.ResultsSeventeen patients died during the observation period. The leading causes of death were non-AIDS cancer and cardiovascular disease. Higher levels of CD8 memory T cells (CD8+,CD45RO+,CD45RA-) showed a significant beneficiary effect on survival, HR of 0.95 (95% confidence interval 0.91–0.99, P = 0.016) when adjusted for age, nadir CD4 count, CD4 count, and AIDS and hepatitis C status. T cell activation was not associated with increased risk of death.ConclusionsLarger and longitudinal studies are needed to accurately establish prognostic factors, but overall results seem to suggest that prognostic information exists within the CD8 compartment.
Highlights
Since the discovery and implementation of combination antiretroviral therapy the prognosis of human immunodeficiency virus (HIV) infected patients has improved enormously
Probably coexistent, factors have been suggested as contributors to this, including excess of risk factors such as smoking, combination antiretroviral therapy (cART) toxicity and foremost the theory that ongoing immune activation/ dysfunction leads to chronic inflammation that causes comorbidity and mimics natural aging at the cellular level (‘‘inflamm-aging’’ or ‘‘immunosenescence’’) [1,2]
Studies in patients nor receiving cART have convincingly shown that increased levels of cellular and soluble markers of immune activation are linked to higher risk of progression to AIDS, lower CD4 counts and poorer prognosis [3,4,5,6]
Summary
Since the discovery and implementation of combination antiretroviral therapy (cART) the prognosis of human immunodeficiency virus (HIV) infected patients has improved enormously. Studies in patients nor receiving cART have convincingly shown that increased levels of cellular and soluble markers of immune activation are linked to higher risk of progression to AIDS, lower CD4 counts and poorer prognosis [3,4,5,6]. CART effectively induces viral suppression and a partial restoration of immune function and composition, but residual immune activation is the rule [9,10]. This residual immune activation has been shown to impair immune reconstitution [11,12,13,14]. The clinical importance of this residual immune activation, microbial translocation and T cell senescence remains undetermined as most of the studies addressing this crucial question are either cross-sectional, longitudinal with limited follow-up time or relies on surrogate laboratory endpoints
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