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


RESULTS
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.


CONCLUSIONS
Plasma levels of several inflammatory, anti-inflammatory and endothelial activation markers of cardiovascular disease are associated with HIV-RNA replication.
Calmy
Alexandra
A
HIV Unit, Geneva University Hospital, 15 rue Micheli-Du-Crest, Geneva 1205, Switzerland. acalmy@gmail.com
Gayet-Ageron
Angele
A
Montecucco
Fabrizio
F
Nguyen
Alain
A
Mach
Francois
F
Burger
Fabienne
F
Ubolyam
Sasiwimol
S
Carr
Andrew
A
Ruxungtham
Kiat
K
Hirschel
Bernard
B
Ananworanich
Jintanat
J
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D012307:Risk Factors; D013785:Thailand / Q000208:ethnology
D019380:Anti-HIV Agents; D015415:Biomarkers; D012367:RNA, Viral