The protease inhibitors ritonavir and saquinavir influence lipid metabolism: a pig model for the rapid evaluation of new drugs.

BACKGROUND Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Göttingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to have similar reactions to antiretroviral drugs. METHODS The pigs were treated orally with high doses of the protease inhibitors ritonavir and saquinavir for 4 weeks. The model allows repeated concomitant biopsies from liver, muscle, adipose tissue and plasma samples. RESULTS The study showed a general decrease in polyunsaturated fatty acids; changes in both saturated and monounsaturated fatty acids were also apparent after antiretroviral treatment. The changes were observed after 4 weeks of treatment. At 4 weeks post-treatment, the levels of all fatty acids were lower compared with pretreatment levels, suggesting a prolonged effect of the antiretroviral drug treatment lasting beyond the 4 week post-treatment observation period. CONCLUSIONS The Göttingen mini-pig model is a promising animal model for rapid screening of the metabolic effects induced by antiretroviral drugs.