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Early Initiation of Antiretroviral Therapy in HIV-Infected Individuals Is Associated with Reduced Arterial Stiffness: a low nadir CD4+ T-cell counts are associated with arterial stiffness as assessed by Aix and PWV
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Reported by Jules Levin
CROI Feb 16-19 2010 SF
Jennifer E. Ho, Steven G. Deeks, Frederick M. Hecht, Yu Xie, Amanda Schnell, Jeffrey N. Martin, Peter Ganz, and Priscilla Y. Hsue
University of California, San Francisco
"we cannot sit around and do the usual gold standard studies (ie clinical interventional studies using CV events as endpoints) in HIV pts because the pt population is relatively young and the number of events are low. These studies would require thousands of individuals and likely take over 10 years to do. This is where the surrogate imaging studies are helpful – ie looking at subclinical atherosclerosis or vascular function help us identify individuals who are at risk and also help yield insight into mechanism". Priscila Hsue
In unadjusted analyses, predictors of arterial stiffness included age, blood pressure (BP), diabetes, current and nadir CD4+ T-cell count < 350 (all p < 0.05). After adjusting for both CV risk factors (age, systolic and diastolic BP, hypertension, diabetes, hypercholesterolemia, smoking) and HIV-related covariates, nadir CD4+ T-cell count < 350 was independently associated with a 0.58 m/s increase in PWV (95% CI 0.15-1.01, p=0.008) and a 7.2% increase in Aix@75 (95% CI 2.6- 11.8, p=0.002). Neither duration of antiretroviral therapy, nor exposure to protease inhibitors was associated with arterial stiffness.
CONCLUSIONS: Among treated HIV-infected individuals, both traditional cardiovascular risk factors as well as a low nadir CD4+ T-cell counts are associated with arterial stiffness as assessed by Aix and PWV. Our data suggest that CV risk among HIV-infected individuals could be reduced through early initiation of antiretroviral therapy, before CD4+ T-cell counts are depressed. This concept should be tested prospectively in future studies.
Background
Recent studies suggest that HIV-infected patients are at increased risk for cardiovascular events. This may be due to both HIV disease-related factors (including inflammation) and treatment-related factors. Assessment of arterial stiffness via pulse wave velocity (PWV) is strongly associated with cardiovascular risk, and prior studies have shown that HIV-infected patients have higher stiffness compared to controls. Current treatment guidelines recommend initiation of antiretroviral therapy at a CD4 T cell count of 350 cells/ul. Whether earlier initiation of HIV therapy has any effect on cardiovascular risk as assessed by PWV is unknown. We investigated the association of earlier initiation of HAART at higher CD4+ T-cell count thresholds with improved CV risk as measured by arterial stiffness as compared to delayed initiation at lower CD4+ T-cell counts.
Methods
Patient selection - We conducted a cross-sectional study of 80 HIV-infected men who were antiretroviral-treated with undetectable plasma HIV RNA levels. Patients were chosen from the SCOPE study in which patients start antiretroviral therapy in the chronic phase of HIV infection and the OPTIONS study in which patients begin antiretroviral therapy within 6 months of HIV diagnosis.
Assessment of arterial stiffness– Assessment of arterial stiffness was measured by pulse wave analysis to assess the augmentation index (Aix@75) and carotid-femoral pulse wave velocity (PWV). Blood pressure (BP) was taken as the average of 3 consecutive readings. Arterial stiffness was assessed noninvasively using the SphygmoCor System (AtCor Medical, Australia). For pulse wave analysis, 10 sequential peripheral pressure waveforms were recorded from the right radial artery using application tonometry. Pulse wave velocity (PWV) was then obtained using ECG-gated pulse waveforms over the common carotid and femoral arteries. PWV was calculated as the distance between recording sites measured over the surface of the body, divided by the time interval between the feet of the pressure waves. All measurements were performed by a single observer. Intra-observer reproducibility measurements were performed on 16 randomly selected subjects, with an intra-class correlation coefficient ranging between 93-94%.
Statistical Analysis
Univariate and multivariate linear models were used to identify predictors of arterial stiffness. We adjusted for traditional cardiovascular risk factors and HIV disease characteristics including current CD4 count, nadir CD4 count, and duration and type of antiretroviral therapy.
RESULTS
Table 1: Baseline Clinical and HIV Characteristics by Nadir CD4 Count
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