HIV and Hepatitis.com Coverage of the 15th
Conference on Retroviruses and Opportunistic Infections (CROI 2008) February
3 - 6, 2008, Boston, MA
The
material posted on HIV and Hepatitis.com about CROI 2008 is not approved by
nor is it a part of CROI 2008.
100
mg Once- and Twice-daily Ritonavir (Norvir) Decreases HDL and CD36 Expression,
but Only Twice-daily Dosing Increases Triglycerides
Norvir
Capsule
Most
current HIV protease
inhibitors (PIs) are used in combination with a low dose of ritonavir
(Norvir) to raise their levels in the blood. This has led to interest in determining
the impact of low-dose ritonavir on changes in blood lipids among patients using
boosted PIs. In the current study, presented at the 15th
Conference on Retroviruses and Opportunistic Infections (CROI 2008) last month
in Boston, researchers investigated the possible role of ritonavir in contributing
to cardiovascular disease.
Specifically,
the study explored the relationship between low-dose ritonavir plasma exposure
and short-term changes in lipids and vascular inflammatory markers in healthy,
HIV negative volunteers. Lipids measured were total cholesterol (TC), high-density
lipoprotein (HDL or "good") cholesterol, low-density lipoprotein (LDL
or "bad") cholesterol, and triglycerides (TG).
The study included
20 non-smoking healthy volunteers (10 men, 10 women). The median age was 28 years
and the median body mass index was 22. Participants were randomized to 1 of 2
study arms:
•
Arm 1: 100 mg once-daily ritonavir, followed by a washout period, then 100 twice-daily
ritonavir;
•
Arm 2: 100 mg twice-daily ritonavir, followed by a washout period, then 100 once-daily
ritonavir
All
study phases lasted 14 days. Lipid levels, CD36 expression and vascular inflammatory
markers were measured before and after 14 day of ritonavir intake by standard
validated methods. Full steady-state ritonavir pharmacokinetics was assessed on
days 14 and 43 by high performance liquid chromatography and mass spectrometry.
Results
•
Significant decreases in HDL were seen following once- and twice-daily administration
of ritonavir (6% [P = 0.010] and 10% [P < 0.001], respectively).
•
CD36 also decreased following once- and twice-daily intake (14% [P = 0.012] and
16% [P = 0.006], respectively).
•
However, a significant increase in TG was seen only when ritonavir was given twice
daily (32%; P = 0.044).
•
No changes in vascular inflammatory markers were observed.
•
There was a significant correlation between ritonavir plasma exposure and changes
in TG and HDL (R = 0.34 [P = 0.030] and R = 0.33 [P = 0.040], respectively, all
subjects).
Conclusion
Based
on these findings, the investigators concluded that in healthy volunteers, "100
mg twice-daily ritonavir, but not 100 mg once-daily ritonavir, gave rise to an
increase in TG over 2 weeks."
In addition, they noted that the increase
was related to higher ritonavir exposure. Finally, they wrote, "Reduced HDL
and CD36 expression were observed for both ritonavir dosages."
St
Stephen's Ctr, London, UK; King's College London, UK; Chelsea and Westminster
Hosp NHS Fndn Trust, London, UK; Univ of Liverpool, UK.
100
mg Once- and Twice-daily Ritonavir (Norvir) Decreases HDL and CD36 Expression,
but Only Twice-daily Dosing Increases Triglycerides 
Specifically,
the study explored the relationship between low-dose ritonavir plasma exposure
and short-term changes in lipids and vascular inflammatory markers in healthy,
HIV negative volunteers. Lipids measured were total cholesterol (TC), high-density
lipoprotein (HDL or "good") cholesterol, low-density lipoprotein (LDL
or "bad") cholesterol, and triglycerides (TG).
Results
