Postprandial lipid effects of low-dose ritonavir vs. raltegravir in HIV-uninfected 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.


METHODS
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.


CONCLUSIONS
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.
Samaras
Katherine
K
Diabetes Program, Garvan Institute of Medical Research, and Department of Endocrinology, St Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
Richardson
Robyn
R
Carr
Andrew
A
D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018023:HIV Seronegativity; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008297:Male; D019518:Postprandial Period; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D008078:Cholesterol, LDL; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D008055:Lipids; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019438:Ritonavir