Background:
Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular aging and cardiovascular (CV) disease. We evaluated relationships between HIV parameters, Framingham Risk Score (FRS)-based 10-year CV risk, vascular age and cognitive function 6 years after ART initiation during acute HIV infection (AHI).
Methods:
RV254 Thai participants were enrolled during AHI, initiated ART within days and underwent regular follow-up. FRS-based CV risk at week 288 was calculated using age, sex, lipid profile, systolic blood pressure, smoking, diabetes and antihypertensive usage status. FRS-based vascular age was defined as age with the same predicted CV risk but optimally-controlled risk factors. Vascular age deviation (VAD) was vascular age minus actual age. Cognitive performance (NPZ-4) was determined by averaging z-scores of: Color Trails 1 & 2, non-dominant hand Grooved Pegboard (GPB), and Trails Making A. Linear regression model was used to assess factors associated with VAD.
Results:
The study included 356 participants (98% male; 100% viral suppression) who completed week 288 visits between 5/2009 and 6/2022. CV risk factors are summarized in Table 1. At week 288, the actual and vascular ages were 32 (IQR 28,37) and 34 (IQR 30,40) years (p< 0.001). Vascular age was higher than actual age in 232 (65%) participants (VAD = 3(IQR -1,7) years). The 10-year CV risk was 2.3% (IQR 1.6,3.9, “low risk” ≤10%). Only one clinically-relevant CV adverse event occurred (embolic stroke) within the study period. In univariable analysis, higher week 288 CD4+ T-cell count was associated with increased VAD (b[95%CI]: 0.5 years [0.3-0.7] per 100 cell increase in CD4+ T-cell count, p< 0.001). Given a known association between smoking and CD4+ T-cell count in the literature, and that CD4+ T-cell count was 102 (95%CI 20-183) cells higher in smokers (p=0.015) in this study, stratification analysis was performed. CD4+ T-cell count remained independently associated with VAD regardless of smoking status (p< 0.05). Vascular age and VAD at week 288 were not associated with NPZ-4. There was an unexpected association between higher VAD and better z-GPB scores (b[95%CI]: 0.5 [0.01-1.02], p=0.045).
Conclusions:
In young PWH after 6 years of ART initiated during AHI, 10-year CV risk was low and CV events were rare. Higher CD4 count was associated with higher VAD even after controlling for smoking. Vascular risk after 6 years on ART did not predict cognitive test performance.
Table 1. HIV serum parameters, cardiovascular comorbidities, and cognitive test scores at acute HIV (baseline) and week 288 follow-up