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Postprandial lipid effects of raltegravir vs low-dose ritonavir in HIV-negative adults


OBJECTIVE: Protease inhibitor therapy is associated with an increased risk of myocardial infarction. Half this risk appears attributable to fasting dyslipidemia, but half remains unexplained. We compared the fasting and postprandial effects of low-dose ritonavir and raltegravir on cardiovascular and metabolic risk factors. DESIGN: Randomized (1: 1), open-label study. METHODS: Twenty HIV-uninfected volunteers (14 women, mean age 32 years) received low-dose ritonavir (100 mg daily) or raltegravir (400 mg twice daily) for 4 weeks. We administered a standardized meal (3.6 MJ, 76% fat, 10% carbohydrates) at baseline and at week 4, with hourly assessments for 6 h after each meal. The primary outcome measure was incremental area under the curve (iAUC) change in postprandial lipids. RESULTS: Ritonavir induced significantly higher postprandial iAUC excursions in low-density lipoprotein (LDL) cholesterol than raltegravir, mostly in the first 3 h after food (P < 0.05). The ritonavir-related postprandial increases in LDL cholesterol at 1, 2, and 3 h were 30-65% greater than the ritonavir-related increase in fasting LDL cholesterol (0.34-0.43 vs. 0.26 mmol/l, P < 0.05 for each comparison). The postprandial iAUC and fasting LDL cholesterol changes at week 4 were significantly correlated (r = 0.64; P = 0.003). There was no between-group difference for other postprandial parameters. CONCLUSION: In HIV-uninfected adults, postprandial LDL cholesterol excursions with low-dose ritonavir were significantly greater than those with raltegravir. This postprandial effect of ritonavir increased by about 50% the previously observed adverse effect of ritonavir on fasting LDL cholesterol, and so may explain some of the hitherto unexplained association of protease inhibitor-based therapy with cardiovascular disease.

Type Journal
ISBN 1473-5571 (Electronic) 0269-9370 (Linking)
Authors Samaras, K.; Richardson, R.; Carr, R.
Responsible Garvan Author Prof Katherine Samaras
Publisher Name AIDS
Published Date 2010-07-01
Published Volume 24
Published Issue 11
Published Pages 1727-31
Status Published in-print
DOI 10.1097/QAD.0b013e32833ac7be 00002030-201007170-00013 [pii]
URL link to publisher's version
OpenAccess link to author's accepted manuscript version