Baseline CD4/CD8 T-Cell Ratio Predicts Prompt Immune Restoration Upon cART Initiation.

Abstract

The reversal of CD4/CD8 ratio is considered an independent predictor of death in the general population, where the ratio physiologically decreases with aging. Despite effective cART, CD4/CD8 normalization does not always occur in HIV-positive subjects. In the setting of HIV, low CD4/CD8 T-cell ratio correlates with immune activation and non-AIDS events. The aim of the study was to evaluate the rate and predictors of CD4/CD8 ratio normalization in a cohort of HIV-positive subjects starting combination antiretroviral therapy (cART). This is a retrospective-prospective observational cohort study conducted at the Unit of Infectious Diseases of the University of Catania. Our cohort included naive individuals who initiated cART from January 2007 to December 2013. A total of 123 individuals were enrolled. The median age was 38 years (IQR 29-44). The median baseline CD4+ T-cell count was 288 cells/μl (IQR 105-400). 83 (67.5%) had a CD4+ T-cell count <350/μl; baseline median CD4/CD8 ratio was 0.24 (IQR 0.13-0.4); 65 patients (52.8%) had a HIV viral load >100,000 copies/ml. At 24 months, 33 individuals (26.8%) normalized their CD4/CD8 ratio, with a median time to CD4/CD8 ratio normalization of 17 months (IQR 12-30). In univariate analysis, a baseline CD4+ T-cell count >350/μl (p <0.01), a baseline CD4/CD8 ratio >0.5 (p <0.01), CDC stage A (p<0.01) and an efavirenz-based first-line regimen (p<0.05) were associated with CD4/CD8 ratio normalization. In multivariate logistic analysis, the only predictor of CD4/CD8 normalization was a baseline ratio >0.5 (OR 4.3 (1.7-11.2), p=0.003). Starting cART with a ratio >0.5 is associated with an increased likelihood to normalize CD4/CD8 ratio. Early diagnosis should be encouraged in order to treat patients promptly and favor a more robust immunological reconstitution.