[O16] Plasma exposure of 100 mg once (OD) and twice daily (BID) decreases HDL and CD36 expression but only BID dosing increases triglycerides (TG): potential impact of RTV on cardiovascular disease (CVD)

14th Annual Conference of the British HIV Association

23–25 April 2008, Belfast

PLASMA EXPOSURE OF 100 MG ONCE (OD) AND TWICE DAILY (BID) DECREASES HDL AND CD36 EXPRESSION BUT ONLY BID DOSING INCREASES TRIGLYCERIDES (TG): POTENTIAL IMPACT OF RTV ON CARDIOVASCULAR DISEASE (CVD)

HIV Med 2008; 9(Suppl. 1):5 (abstract no. O16)

C Fletcher¹, M Boffito¹, S Collot-Teixeira², F De Lorenzo³, L Waters¹, D Back⁴, S Mandalia¹, A Pozniak¹, JL McGregor^2,5 and B Gazzard¹
¹St Stephen’s AIDS Trust, London, UK, ²King’s College, London, UK, ³Beta Cell Diabetes Centre, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK, ⁴University of Liverpool, Liverpool, UK, ⁵Inserm U689, Paris, France

BACKGROUND: Whether RTV induces CVD is unclear. We investigated the relationship between low-dose RTV exposure and short-term changes in lipids [total cholesterol (TC), HDL, LDL, TG], monocyte scavenger receptor (CD36), vascular inflammation markers (VIM=hsCRP, sICAM-1, sCD40L).

METHODS: Non-smoking male and female healthy volunteers were randomized to: arm 1 (RTV 100 mg OD-washout-RTV 100 mg BID) or arm 2 (RTV 100 mg BID-washout-RTV 100 mg OD), all study phases lasted 14 days. Lipids, CD36 expression and VIM were measured before and after RTV 14-day intake by standard validated methods. Full steady- state RTV PK was assessed on days 14 and 43 by hplc-MS/MS. Paired-t test and Pearson’s correlation were used for statistical analysis.

RESULTS: Twenty subjects (10 females) completed the study. Median (range) age and BMI were 28 (19–45) and 22 (18–26). Median (range) RTV AUC_0-24 (ng.h/mL) and C_max (ng/mL) for OD and BID were 5773 (2466–18848) and 751 (298–1896), and 14525 (6862–46370) and 1431 (597-3874). Significant decreases in HDL (6% p=0.010 and 10% p<0.001) and CD36 (14% p=0.012 and 16% p=0.006) were seen following RTV OD and BID intake. However, a significant increase in TG was seen only when RTV was given BID (32% p=0.044). No changes in VIM were observed. 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).

CONCLUSIONS: Hundred milligrams BID RTV but not 100mg OD RTV gave rise to an increase in TG over 2 weeks in healthy volunteers; the increase was related to higher RTV exposure. Reduced HDL and CD36 expression were observed for both RTV dosages.

2008-04-23
O16

Copyright © 2008 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD