Relationship Between HIV Infection, Antiretroviral Therapy, Inflammatory Markers, and Cerebrovascular Endothelial Function Among Adults in Urban China.

Abstract

Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy (ART) and inflammation may contribute to higher stroke risk in HIV infection. We compared cerebral vasoreactivity-a measure of cerebrovascular endothelial function assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound-between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China, and uninfected controls. We constructed mixed-effects models to evaluate the association of HIV, ART, and inflammatory markers with cerebral vasoreactivity. In an unadjusted model, HIV infection was associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus 1.26, P = 0.079). In multivariable analyses, cholesterol modified the association between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral vasoreactivity (BHI -0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L, the reduction in cerebral vasoreactivity associated with HIV was no longer statistically significant (BHI -0.05, P = 0.64). Among HIV-infected individuals, use of lopinavir/ritonavir compared with efavirenz was associated with lower cerebral vasoreactivity (BHI -0.24, P = 0.040). We did not find a significant association between inflammatory markers and cerebral vasoreactivity. Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol. Further study of the impact of ART on cerebrovascular endothelial function is warranted to aid with ART selection in individuals at high cerebrovascular risk.