HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial.

HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial.

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.

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.