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BackgroundCD4/CD8<0.8 is a surrogate marker of immune‐activation/immunosenescence and independently predicts mortality in the HIV‐infected patients due to non‐AIDS related events. Most studies showed that patients on antiretroviral therapy (ART) often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. Primary objective of the study was to explore the impact of CD4/CD8<0.8 as independent predictor of HIV‐associated non‐AIDS (HANA) conditions and multimorbidity (MM) in HIV patients. In patients with no previous history of cardiovascular disease (CVD) a particular insight is provided in the association between impact of CD4/CD8<0.8 and risk prediction of CVD or radiological markers of subclinical CVD.Materials and Methods914 consecutive patients attending Modena Metabolic HIV Clinic were evaluated in a cross‐sectional retrospective study. Inclusion criteria: stable ART from ≥2 years; HIV‐RNA plasma levels<40 copies/mL; stable CD4 count≥350/mmc. CD4/CD8 strata (0.8) was chosen as a cut off representing the median value of the cohort. MM was defined as the presence of≥2 HANA conditions including standard defined: chronic kidney disease, hypertension, previous CVD events, osteoporosis and diabetes mellitus. Calendar year of ART initiation was defined: "PreART" (<2000); "EarlyART" (2000–2005) and "LateART" (>=2006). High CVD risk was defined for Framingham Risk Score (FRS)≥6. Subclinical CVD was defined using cardiac CT scan for calcium score (CAC)≥100. Logistic univariate and multivariable adjusted analysis were performed to assess relationships between variables.ResultsDemographic and HIV‐specific variables distribution in patients with and without MM are shown in Table 1.Figure 1 shows HANA distribution across CD4/CD8 strata: CVD prevalence only appeared to be higher in patients with no CD4/CD8>0.8.In multivariable analyses CD4/CD8<0.8 was not an independent predictor of MM (OR=1.225, CI 0.891; 1.681, p=0.211) after adjustment for age, gender and BMI. Patients with CD4/CD8<0.8 displayed higher CVD risk but not higher prevalence of subclinical CVD. At multivariable analyses CD4/CD8<0.8 remained predictor of higher CVD risk (OR=0.65, CI 0.47–0.917, p=0.014) after correction for sex, BMI, age strata and HIV infection duration.ConclusionsLow CD4/CD8 ratio was not associated with MM prevalence. Patients with CD4/CD8<0.8 ratio displayed higher prevalence of CVD. At multivariable logistic regression CD4/CD8<0.8 is an independent prepredictor of enhanced CVD risk. This may support role of immune‐activation/senescence in the pathogenesis of CVD.