Antiretroviral Treatment-Induced Galectin-9 Might Impact HIV Viremia in Addition to Contributing to Inflammaging

Background: Galectin-9 induces HIV reactivation and also contributes to non-AIDS events through inflammaging. Hence, it is important to assess its levels in HIV-infected individuals to determine their association with HIV viremia and other comorbidities. Methods: Plasma galectin-9 levels were estimated in viremic (n = 152) and aviremic (n = 395) individuals on first-line antiretroviral therapy (ART). They were assessed for correlation with HIV-1 viral load (VL), CD4 count, and ART duration, as well as for receiver operating characteristic curve analysis. Result: Plasma galectin-9 levels correlated positively with VL (r = 0.507, p < 0.0001) and ART duration (r = 0.308, p = 0.002) and negatively with CD4 count (r = −0.186, p < 0.0001). Area under the curve for galectin-9/CD4 count ratio for identifying viremic individuals was 0.906. Sensitivity and specificity of the ratio at a cutoff of 14.47 were 90.13% and 70.05%, respectively, for detecting viremic individuals. Further, galectin-9 levels correlated with cystatin C (r = 0.239, p = 0.0183), IL-18 (r = 0.311, p = 0.006), and systolic blood pressure (r = 0.220, p = 0.0355). Galectin-9-induced HIV reactivation was significantly lower in individuals on long-term ART than those on short-term ART. Conclusion: The galectin-9-to-CD4 count ratio indicated the potential of galectin-9 as a cheaper monitoring tool to detect HIV viremia. Strategies for countering the effects of galectin-9 for controlling HIV viremia and non-AIDS events are urgently warranted.