Initiation of antiretroviral therapy at higher nadir CD4+ T-cell counts is associated with reduced arterial stiffness in HIV-infected individuals

Abstract

Objective: HIV infection is associated with increased rates of cardiovascular disease. We sought to evaluate whether initiation of HIV therapy at higher nadir CD4(+) T-cell counts might reduce cardiovascular risk, as measured by arterial stiffness.

Design: We conducted a cross-sectional study of 80 HIV-infected men who were antiretroviral-treated with undetectable plasma HIV RNA levels.

Methods: Participants underwent noninvasive assessment of arterial stiffness by pulse wave analysis (augmentation index normalized for heart rate of 75 bpm) and carotid-femoral pulse wave velocity, both sensitive measures of cardiovascular risk. A generalized linear model was used to determine the relationship between cardiovascular and HIV-related predictors, and arterial stiffness.

Results: In unadjusted analyses, predictors of arterial stiffness included age, blood pressure, antihypertensive medication use, and nadir CD4(+) T-cell count below 350 cells/microl (all P < 0.05). After adjusting for both cardiovascular risk factors (age, blood pressure, antihypertensive medication use, diabetes, hypercholesterolemia, and smoking) and HIV-related covariates, nadir CD4(+) T-cell count below 350 cells/microl was independently associated with a 0.41 m/s increase in pulse wave velocity (95% confidence interval 0.03-0.79, P = 0.03) and a 7.3% increase in augmentation index (augmentation index normalized for heart rate of 75 bpm; 95% confidence interval 2.6-11.9, P = 0.003). Neither duration of antiretroviral therapy nor exposure to protease inhibitors was associated with arterial stiffness.

Conclusion: Among treated HIV-infected individuals, arterial stiffness is independently associated with both traditional cardiovascular risk factors as well as a low nadir CD4(+) T-cell count. Our data suggest that cardiovascular risk among HIV-infected individuals could be reduced through early initiation of antiretroviral therapy, before CD4 T-cell counts are depressed, a concept that should be tested prospectively in future studies.

Figure 1

Correlation between nadir CD4+ T-cell count and measures of arterial stiffness as assessed by a) augmentation index normalized for a heart rate of 75 bpm (r=−0.37, p=0.0009, and b) carotid-femoral pulse wave velocity (for transformed PWV, r=0.25, p=0.03)