Influence of rosiglitazone on flow-mediated dilation and other markers of cardiovascular risk in HIV-infected patients with lipoatrophy.
BACKGROUND
Antiretroviral therapy for HIV infection is commonly complicated by lipoatrophy, insulin resistance and dyslipidaemia. In HIV-uninfected adults with insulin resistance or type 2 diabetes, thiazolidinediones can lower blood pressure and improve both insulin sensitivity and endothelial function. This study sought to investigate the effects of rosiglitazone on endothelial function and other markers of cardiovascular risk in patients with HIV-related lipoatrophy.


METHODS
HIV-infected, lipoatrophic adults receiving antiretroviral therapy were randomized to receive either rosiglitazone 4 mg or matched placebo, twice daily. Percentage flow-mediated forearm arterial dilation (FMD%) was measured at weeks 0, 12, 24 and 48, together with other markers of vascular risk (blood pressure, lipids, glycaemic parameters, adiponectin and leptin).


RESULTS
Out of 64 enrolled adults, 44 (69%) attended all visits (23 rosiglitazone, 21 placebo). Relative to placebo, at week 48, rosiglitazone decreased systolic blood pressure (8 mmHg, P=0.03), insulin (3 microIU/ml, P=0.02), insulin resistance (P=0.03) and leptin (0.6 ng/ml, P=0.02), whilst adiponectin was increased (3.3 microg/lml, P<0.0001). However, rosiglitazone increased total cholesterol (49.1 mg/dl, P=0.001), low-density lipoprotein cholesterol (23.5 mg/dl, P=0.01) and triglycerides (146 mg/dl, P=0.06). Mean baseline FMD% for the entire cohort was moderately impaired (4.5%). Compared with baseline, mean on-treatment FMD% increased by 0.8% with rosiglitazone and decreased by 0.3% with placebo, (mean difference 1.1%, 95% CI -0.2 to 2.5, P=0.09).


CONCLUSIONS
Rosiglitazone has minimal effect on flow-mediated dilation in HIV-infected lipoatrophic adults. However, despite worsening of the lipid profile, the overall effect of rosiglitazone on the cardiovascular risk profile in these subjects was positive.
Kovacic
Jason C
JC
Cardiology Department, HIV, Immunology and Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, Australia. jkovacic@netline.net.au
Martin
Allison
A
Carey
Dianne
D
Wand
Handan
H
Mallon
Patrick W G
PW
Feneley
Michael P
MP
Emery
Sean
S
Cooper
David A
DA
Carr
Andrew
A
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects; D001315:Australia; D002318:Cardiovascular Diseases / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D019380:Anti-HIV Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone