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

• Published in: AIDS (London) Vol. 23; no. 8; pp. 929 - 939
• Main Authors: CALMY, Alexandra, GAYET-AGERON, Angèle, ANANWORANICH, Jintanat, MONTECUCCO, Fabrizio, NGUYEN, Alain, MACH, Francois, BURGER, Fabienne, UBOLYAM, Sasiwimol, CARR, Andrew, RUXUNGTHAM, Kiat, HIRSCHEL, Bernard
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 15-05-2009
• Subjects: Adult; AIDS/HIV; Anti-HIV Agents - administration & dosage; Biological and medical sciences; Biomarkers - blood; Cardiovascular Diseases - blood; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections - blood; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Risk Factors; RNA, Viral - blood; Thailand - ethnology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Thailand; Immunopathology; HIV-RNA replication; RNA; Retroviridae; Cardiovascular disease; AIDS; Inflammation; Immune deficiency; Lentivirus; Infection; Virus; HIV; Viral disease; Treatment withdrawal; marker; Cardiovascular risk; Replication; Human immunodeficiency virus
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/qad.0b013e32832995fa

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.
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) 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 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.