CD4/CD8 Ratio Normalization As a Predictor of Decrease Liver Damage in HIV-Infected Adults: A 16-Year Observational Cohort Study (Preprint)

BACKGROUND Background: Since more HIV-infected people are living longer, it is crucial to monitor the number of non-AIDS-related events, especially liver diseases. Liver-related deaths in HIV-infected patients occur more often in comparison with the general population. The CD4/CD8 ratio is considered an emerging biomarker for non-AIDS-related events. However, the current research was rarely designed to investigate the connection between the CD4/CD8 ratio and certain types of non-AIDS-related events, particularly liver damage. OBJECTIVE Objective: The aim of this study was to determine whether the CD4/CD8 ratio was associated with the development of liver damage in a large cohort of HIV-infected patients receiving antiretroviral treatment (ART) and to evaluate the efficacy of three antiretroviral drugs in normalizing the CD4/CD8 ratio and lowering the incidence of liver damage among this population. METHODS Methods: An observational cohort study was conducted among HIV-infected adults receiving ART from 2004 to 2020 in Guangxi, China. Propensity score matching, multivariable Cox proportional hazard and Fine-Gray competing risk regression models were constructed to determine the relationship of CD4/CD8 ratio normalization with liver damage. RESULTS Results: The incidence of liver damage was 20.12% among 2,440 eligible individuals during a median of four person-years of follow-up. Patients whose CD4/CD8 ratio did not normalize to 1.0 had a higher liver damage incidence than patients whose CD4/CD8 ratio normalized (adjusted HR = 7.90, 95% CI 4.39–14.21, P < 0.001; sub-distribution HR = 6.80, 95% CI 3.83–12.11, P < 0.001), similar to the PSM analysis (aHR = 6.94, 95% CI 3.41–14.12, P < 0.001; sHR = 5.67, 95% CI 2.74–11.73, P< 0.001). The Efavirdine-based regimen required the least time to normalize the CD4/CD8 ratio (71 months IQR 49–88) and had a lower prevalence of liver damage (4.18 /100 person-years). CONCLUSIONS Conclusions: Normalization of the CD4/CD8 ratio was associated with a decreased risk of liver damage in HIV-infected patients receiving ART, providing further evidence that the CD4/CD8 ratio might be utilized to identify people at risk of non-AIDS-related diseases. Efavirdine-based regimen was a recommended option for normalizing the CD4/CD8 ratio and reducing the risk of liver damage.