Supervisors info:
Τουλούμη Παναγιώτα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Πανταζής Νικόλαος, ΕΔΙΠ, Ιατρική Σχολή, ΕΚΠΑ
Σιάννης Φώτιος, Επίκουρος Καθηγητής, Τμήμα Μαθηματικών, ΕΚΠΑ
Summary:
Background: CD4/CD8 ratio has been identified as a valuable marker of the health of immune system in the general population. In HIV-positive people, this ratio is reversed (values < 1) and, in many cases, its normalization fails, even after several years of effective antiretroviral treatment. Furthermore, low values of CD4/CD8 ratio have been associated with high rates of morbidity and mortality. The aim of this study is to investigate the long-term evolution of the CD4/CD8 ratio in HIV positive patients after the cART initiation. At the same time, the association of levels of CD4 / CD8 ratio in time with mortality, AIDS related and non-AIDS related morbidity will be assessed.
Methodology: Data for HIV positives were derived from the multicenter cohort study AMACS. Adult HIV positive patients under cART, which started after 2000, were included in the analysis. Mixed effects models were used to see the long-term evolution of the CD4/CD8 ratio, using log-transformed ratio and time cut at two points (linear splines), 3 and 48 months. To investigate whether CD4 / CD8 ratio is a predictor of mortality and morbidity after cART initiation, Cox models were used, taking the ratio into account as a time-varying variable. In addition, sensitivity analysis was performed with competitive risks.
Results: Out of the 10275 HIV positive registered in the AMACS database, 2868 were finally included in the analysis, with median age of 36 years, 85.39% being male and 66% being homosexual. The median CD4/CD8 ratio at the time of cART initiation was 0.29. Since the start of the cART, the CD4/CD8 ratio has been increasing throughout the whole period of follow-up, but these values remained below 1. The CD4/CD8 ratio was not a significant risk factor of the first occurrence of AIDS/DEATH or SNAE, adjusted for the CD4 counts. However, the sensitivity analysis showed that the CD4/CD8 ratio was associated with the risk of cardiovascular or renal diseaseor non – AIDS defining malignancies, with values of ratio greater than 0.80 to indicate a 55% lower cause-specific risk of developing such diseases (HR = 0.45, p-value = 0.004).
Conclusions: A small proportion of HIV positive patients manage to normalize the CD4/CD8 ratio and, therefore, its overall restoration is rare. In addition, low values of CD4/CD8 ratio are associated with an increased risk of cardiovascular or renal disease events or non – AIDS defining malignancies, making the CD4/CD8 ratio a useful indicator for detecting patients at an increased risk of developing such diseases.
Keywords:
CD4/CD8 ratio, HIV, cART, SNAE
