Further investigation of the occurrence mechanism of lipodystrophy with HIV protease inhibitors in HIV-infected patients

Abstract

Introduction: Lipodystrophy is a long-term metabolic complication in HIV infected patients on antiretroviral therapy. We aimed to determine the mechanism by which lipodystrophy occurs with HIV protease inhibitors.

Methods: We performed an in-vitro analytical study, by setting our sights on carbohydrate lipid metabolism enzymes such as alpha glucosidase, alpha amylase and lipase, the activity of which most often undergoes disorders observed in cases of lipodystrophy. The
principle of this methodology consisted in carrying out in-vitro enzyme inhibition assays by the spectrophotometric method on these enzymes, in order to determine a probable inhibition of their activity by the HIV protease inhibitors used in antiretroviral therapy. And then, to compare the inhibition obtained with the one of reference inhibitory molecules such as acarbose and orlistat.

Results: The results revealed that in the presence of HIV protease inhibitor like 59.98% with an IC50 of 3.76±0.03 mg/ml and similarly in the presence of Lopinavir 200 mg /Ritonavir 100 mg, this pancreatic lipase activity was reduced to 63.78% with an IC50 of 4.62±0.09 mg/ml. The two antiretroviral drugs presented IC50 which were statistically significant compared with the one of orlistat (p.value=0.01) with an inhibition percentage of 58.98% and IC50 of 3.62 ± 0.01 mg/ml.

Conclusion: HIV protease inhibitors, used in antiretroviral therapy exhibit an inhibitory effect on some enzymes involved in biological processes in the body, thus causing the lipodystrophy.