TY - JOUR
T1 - Nevirapine Increases High-Density Lipoprotein Cholesterol Concentration by Stimulation of Apolipoprotein A-I Production
AU - Franssen, Remco
AU - Sankatsing, Raaj R.
AU - Hassink, Elly
AU - Hutten, Barbara
AU - Ackermans, Mariette T.
AU - Brinkman, Kees
AU - Oesterholt, René
AU - Arenas-Pinto, Alejandro
AU - Storfer, Stephen P.
AU - Kastelein, John J.
AU - Sauerwein, Hans P.
AU - Reiss, Peter
AU - Stroes, Erik S.
PY - 2009
Y1 - 2009
N2 - Objective-The purpose of this study was to investigate the mechanism by which the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP) increases high-density lipoprotein cholesterol (HDLc) in treatment-experienced human immunodeficiency virus-1 (HIV-1)-infected patients. Methods and Results-Twelve HIV-1 infected patients, with stably suppressed HIV-1 viral load using AZT/3TC/abacavir for >= 6 months, added NVP to their current antiretroviral regimen. Patients received a primed bolus infusion of the stable isotope L-[1-C-13]-valine for 12 hours before, as well as 6 and 24 weeks after, the addition of NVP to study apolipoprotein A-I (apoA-I) kinetics. Absolute production rate (APR) and fractional catabolic rate (FCR) of apoA-I were calculated using SAAM-II modeling. Major HDLc-modulating enzymes were assessed. Plasma apoA-I and HDLc levels increased significantly after 24 weeks of treatment by, respectively, 13 +/- 4% (P=0.01) and 16 +/- 6% (P=0.015). Concomitantly, apoA-I production rate at 24 weeks increased by 17 +/- 7% (P=0.04). ApoA-I catabolism did not change. A modest increase of lecithin: cholesterol acyltransferase and cholesteryl ester transfer protein activity was observed. Conclusions-NVP increases apoA-I production, which contributes to the HDLc increase after introduction of NVP-containing regimens. In view of the potent antiatherogenic effects of apoA-I, the observed increase may contribute to the favorable cardiovascular profile of NVP. (Arterioscler Thromb Vasc Biol. 2009;29:1336-1341.)
AB - Objective-The purpose of this study was to investigate the mechanism by which the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (NVP) increases high-density lipoprotein cholesterol (HDLc) in treatment-experienced human immunodeficiency virus-1 (HIV-1)-infected patients. Methods and Results-Twelve HIV-1 infected patients, with stably suppressed HIV-1 viral load using AZT/3TC/abacavir for >= 6 months, added NVP to their current antiretroviral regimen. Patients received a primed bolus infusion of the stable isotope L-[1-C-13]-valine for 12 hours before, as well as 6 and 24 weeks after, the addition of NVP to study apolipoprotein A-I (apoA-I) kinetics. Absolute production rate (APR) and fractional catabolic rate (FCR) of apoA-I were calculated using SAAM-II modeling. Major HDLc-modulating enzymes were assessed. Plasma apoA-I and HDLc levels increased significantly after 24 weeks of treatment by, respectively, 13 +/- 4% (P=0.01) and 16 +/- 6% (P=0.015). Concomitantly, apoA-I production rate at 24 weeks increased by 17 +/- 7% (P=0.04). ApoA-I catabolism did not change. A modest increase of lecithin: cholesterol acyltransferase and cholesteryl ester transfer protein activity was observed. Conclusions-NVP increases apoA-I production, which contributes to the HDLc increase after introduction of NVP-containing regimens. In view of the potent antiatherogenic effects of apoA-I, the observed increase may contribute to the favorable cardiovascular profile of NVP. (Arterioscler Thromb Vasc Biol. 2009;29:1336-1341.)
U2 - https://doi.org/10.1161/ATVBAHA.109.192088
DO - https://doi.org/10.1161/ATVBAHA.109.192088
M3 - Article
C2 - 19667106
SN - 1079-5642
VL - 29
SP - 1336
EP - 1341
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 9
ER -