Postprandial lipid effects of low-dose ritonavir vs. raltegravir in
HIV-uninfected adults.
Author(s): Samaras K, Richardson R, Carr A.
Affiliation(s): Diabetes Program, Garvan Institute of Medical Research, and Department of
Endocrinology, St Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
Publication date & source: 2010, AIDS. , 24(11):1727-31
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.
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