HIV This Week

Grunfeld C, Delaney JA, Wanke C, Currier JS, Scherzer R, Biggs ML, Tien PC, Shlipak MG, Sidney S, Polak JF, O ’ Leary D, Bacchetti P, Kronmal RA. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS. 2009 May 18. [Epub ahead of print]

Cardiovascular disease is an increasing cause of morbidity and mortality in HIV-infected patients. However, it is controversial whether HIV infection contributes to accelerated atherosclerosis independent of traditional cardiovascular disease risk factors. In a cross-sectional study of HIV-infected participants and controls without pre-existing cardiovascular disease from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) and the Multi-Ethnic Study of Atherosclerosis (MESA), preclinical atherosclerosis was assessed by carotid intima-medial thickness measurements in the internal/bulb and common regions in HIV-infected participants and controls after adjusting for traditional cardiovascular disease risk factors. For internal carotid, mean intima-medial thickness was 1.17 +/- 0.50 mm for HIV-infected participants and 1.06 +/- 0.58 mm for controls (P < 0.0001). After multivariable adjustment for demographic characteristics, the mean difference of HIV-infected participants vs. controls was 0.188 mm [95% confidence interval (CI) 0.113-0.263, P < 0.0001]. Further adjustment for traditional cardiovascular disease risk factors modestly attenuated the HIV association (0.148 mm, 95% CI 0.072-0.224, P = 0.0001). For the common carotid, HIV infection was independently associated with greater intima-medial thickness (0.033 mm, 95% CI 0.010-0.056, P = 0.005). The association of HIV infection with intima-medial thickness was similar to that of smoking, which was also associated with greater intima-medial thickness (internal 0.173 mm, common 0.020 mm). Even after adjustment for traditional cardiovascular disease risk factors, HIV infection was accompanied by more extensive atherosclerosis measured by intima-medial thickness The stronger association of HIV infection with intima-medial thickness in the internal/bulb region compared with the common carotid may explain previous discrepancies in the literature. The association of HIV infection with intima-medial thickness was similar to that of traditional cardiovascular disease risk factors, such as smoking.

Editors´note: Although HIV infection and its therapies are associated with increases in several traditional cardiovascular disease risk factors, such as decreased high-density lipoprotein (HDL cholesterol is the good one), increased non-HDL cholesterol, and diabetes, this study of carotid wall thickness suggests that HIV infection itself confers an additional effect equivalent to a 5- to 9-year increase in age. These data suggest that women are more affected – for them the effects of HIV infection on the risk of atherosclerosis are greater than those of smoking.

Plasma soluble inflammatory molecules are associated with the risk of ischaemic cardiovascular events. Calmy and colleagues investigated whether HIV replication modified the levels of these proteins in a combination antiretroviral therapy (ART) interruption trial. In 145 HIV-infected Thai patients (62% women, median CD4 cell count 271 cells/microl, median plasma HIV-RNA 4.66 log10 copies/ml) included in the Swiss-Thai-Australia Treatment Interruption Trial (STACCATO), leptin, adiponectin, C-reactive protein, soluble vascular cell adhesion molecule-1 (s-VCAM-1), P-selectin, chemokine ligand 2, chemokine ligand 3, interleukin (IL)-6, IL-10, granulocyte macrophage colony-stimulating factor and D-dimer were measured before combination antiretroviral therapy was initiated, after combination antiretroviral therapy had suppressed HIV replication to less than 50 copies/ml plasma (median 8 months) and again 12 weeks after randomization to continued combination ART (n=48) or interrupted combination antiretroviral therapy (n=97). Multiple linear regression and logistic regression were used to investigate the association between each cardiovascular marker and plasma HIV-RNA. Initiation of combination antiretroviral therapy resulted in significant declines in s-VCAM-1, P-selectin, leptin and D-dimer, whereas mediators with anti-inflammatory properties, such as adiponectin and IL-10, increased. At 12 weeks after randomization, the authors found positive associations between levels of s-VCAM-1 and chemokine ligand 2 with an increase in plasma HIV-RNA (r=0.271, P=0.001 and r=0.24, P=0.005, respectively), whereas levels of adiponectin decreased for each 1 log increase in plasma HIVRNA (r=-0.24, P=0.002). Detectable IL-10 was less likely (odds ratio = 0.64, 95% confidence interval = 0.43-0.96) for each 1 log increase in plasma HIV-RNA. Plasma levels of several inflammatory, anti-inflammatory and endothelial activation markers of cardiovascular disease are associated with HIV-RNA replication.

Editors’ note: Established cardiovascular risk factors are widely used to assess the risk of heart attacks but serum markers of endothelial activation and inflammation may also predict coronary risk. This study assessed levels of these markers before, during, and after stopping antiretroviral treatment, to tease out changes associated with HIV infection itself rather than those caused by antiretroviral drugs, some of which are known to increase heart attack risk. The association between high plasma levels of inflammatory markers and ongoing HIV-RNA replication in patients off antiretroviral treatment suggests the need to test interventions to lower these markers in people living with HIV, particularly those with detectable viral loads, to prevent cardiovascular events.