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

Calmy, Alexandraa; Gayet-Ageron, Angèlea; Montecucco, Fabriziob; Nguyen, Alaina; Mach, Francoisb; Burger, Fabienneb; Ubolyam, Sasiwimolc; Carr, Andrewd; Ruxungtham, Kiatc,e; Hirschel, Bernarda; Ananworanich, Jintanatc,f; on behalf of the STACCATO Study Group

doi: 10.1097/QAD.0b013e32832995fa
Clinical Science

Objectives: Plasma soluble inflammatory molecules are associated with the risk of ischaemic cardiovascular events. We investigated whether HIV replication modified the levels of these proteins in a combination antiretroviral therapy (cART) interruption trial.

Method and results: In 145 HIV-infected Thai patients (62% women, median CD4 cell count 271 cells/μl, median plasma HIV-RNA 4.66 log10 copies/ml) included in the Swiss–Thai–Australia Treatment Interruption Trial (STACCATO) trial, 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 cART was initiated, after cART had suppressed HIV replication to less than 50 copies/ml plasma (median 8 months) and again 12 weeks after randomization to continued cART (n = 48) or interrupted cART (n = 97). Multiple linear regression and logistic regression were used to investigate the association between each cardiovascular marker and plasma HIV-RNA. Initiation of cART 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, we 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 HIV-RNA (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.

Conclusion: Plasma levels of several inflammatory, anti-inflammatory and endothelial activation markers of cardiovascular disease are associated with HIV-RNA replication.

aHIV Unit, Switzerland

bFoundation for Medical Research, Cardiology Division, Geneva University Hospital, Geneva, Switzerland

cHIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand

dSt. Vincent's Hospital, Sydney, New South Wales, Australia

eDepartment of Medicine, Faculty of Medicine, Chulalongkorn University, Thailand

fSouth East Asia Research Collaboration with Hawaii, Bangkok, Thailand.

Received 9 October, 2008

Revised 10 December, 2008

Accepted 22 January, 2009

Correspondence to Alexandra Calmy, MD, HIV Unit, Geneva University Hospital, 15 rue Micheli-Du-Crest, 1205 Geneva, Switzerland. Tel: +41 22 3729808; fax: +41 22 3729599; e-mail: acalmy@gmail.com

© 2009 Lippincott Williams & Wilkins, Inc.