 |
|
|
| |
The Impact of Raltegravir and Lopinavir/ritonavir on lipid subfractions, vascular and inflammatory markers in HIV Negative Subjects
|
| |
| |
Reported by Jules Levin
14th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV
July 19-21, 2012
Washington, D.C., USA
Akil Jackson, Paul Randell, Ana Milinkovic, Sundhiya Mandalia, Graeme Moyle
Chelsea and Westminster Hospital
London, UK
ABSTRACT
A randomized comparison of raltegravir versus lopinavir/ritonavir on lipid subfractions and highsensitivity
C-reactive protein in healthy volunteers
A Jackson1, P Randell1, A Milinkovic1, M Boffito1, G Moyle1
1Chelsea and Westminster Hospital, London, UK
Background: Inflammatory markers were associated with cardiovascular risk and may be affected with antiretroviral (ARV) agent choice. The impact of ARV on these markers may be best observed in an uninfected population.
Methodology: An open label, two-phase cross-over study in HIV-negative male subjects randomized 1:1 to receive 2 weeks of lopinavir/ritonavir 400/100 mg BID (LPV/R) followed by a 2-week washout period and 2 weeks of raltegravir 400 mg BID (RAL), or RAL initially followed by LPV/R. A hyperinsulinaemic euglycaemic clamp was performed prior to and following each 2-week phase of study medication. Fasting samples for lipids, adiponectin, leptin, vascular inflammation biomarkers and CD36 were also taken at each visit.
Results: 16 HIV-negative male subjects were dosed and completed the study. Two weeks of dosing with RAL did not significantly affect the glucose disposal rate assessed during the euglycaemic clamp, while 2 weeks of dosing with LPV/R resulted in a significant 16.1% reduction in the glucose disposal rate. Triglycerides rose significantly with LPV/R (+0.5 mmol/l, P=0.002) but were unchanged with RAL (+0.09 mmol/l, P=0.97). Total cholesterol rose significantly with LPV/R (+0.4 mmol/l, P<0.0001) but was unchanged with RAL
(-0.01 mmol/l, P=NS). High-density lipoprotein (HDL) cholesterol fractions were not significantly impacted. Proathrogenic lipid subfractions of low-density lipoprotein (LDL) cholesterol increased with LPV/R and were unaffected with RAL. LDL MPD, LDL PPD and LDL I significantly decreased with LPV/R (P<0.05), and trend of increased LDL III was detected with LPV/R (+3.7 mmol/l, P=0.06). Leptin and adiponectin were unchanged. High-sensitivity C-reactive protein (hs-CRP) declined significantly with RAL (-0.2 mg/l, P=0.043), and rose significantly with LPV/R (+0.25 mg/l, P=0.03). No significant changes in CD36 and adipophilin (ADFP) expression following either RAL or LPV/R treatment, were detected. CD36 expression non-significantly decreased with LPV/R treatment.
Conclusions: Lopinavir/ritonavir in healthy volunteers reduce insulin sensitivity and unfavourable affects lipid profile and hsCRP, whereas raltegravir is not associated with metabolic disturbance or inflammatory effects.
|
| |
|
|
|
|
|
