Effect of 100mg ritonavir once- and twice-daily on lipids and cardiovascular markers in HIV-negative volunteers

Simon Collins, HIV i-Base

Carl Fletcher presented results from a study from the Chelsea and Westminster Hospital looking at the short-term impact of low-dose ritonavir on lipids, CD36 and other vascular inflammation markers (VIM) in 20 HIV-negative volunteers. The study looked at the relationship between drug exposure and these parameters.

Twenty HIV-negative volunteers (10 men and 10 women) were randomised volunteers to receive 100 mg ritonavir either once-daily (OD) or twice-daily (BID) for 14 days, and then, after a short wash-out period, switched to the alternative dose for a further 14 days. Median age and BMI were 28 years (range 19-45) and 22 kg/m2 (range 18-26).

CD36 is a receptor with a role in cholesterol accumulation and atherosclerosis pathogenesis, that is upregulated by some PIs including full-dose ritonavir. PIs can decrease monocyte CD36 levels in HIV-positive patients. Vascular markers were hsCRP, sICAM-1 and sCD40L. Lipid parameters included TC, HDL, LDL and TG.

They reported significant decreases in HDL and CD36 expression for OD and BID dosing (see Table 1) but only a significant increase in triglycerides with the BID dose. No changes in hs-CRP and VIM were observed. Drug levels showed a wide range of inter-patient variability, but there was a significant correlation between RTV plasma exposure and the change in TG and HDL (r = 0.34, p = 0.030 and r = 0.33, p = 0.040, all subjects).

Table 1: Ritonavir exposure and impact on lipids and other markers

100mg RTV OD 100mg RTV BID
AUC (ng.h/mL) median (range) 5773 (2,466-18,848) 14525 (6,862-46,370)
Cmax (ng/mL) median (range) 751 (298-1896) 1431 (597-3,874)
HDL change -6% (p = 0.010) 10% (p < 0.001)
CD36 change -14% (p = 0.012) -16% (p = 0.006)
TG change NS +32% (p = 0.044)

This study was also presented at the Retrovirus conference in Boston in February.


Fletcher C et al. Plasma exposure of 100mg once (OD) and Twice (BID) decreases HDL and CD36 expression but only BID dosing increases triglycerides: potential impact of RTV on cardiovascular disease. Oral abstract 16.

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