Increased cholesterol absorption rather than synthesis is involved in boosted protease inhibitor-associated hypercholesterolaemia

AIDS. 2018 Jun 19;32(10):1309-1316. doi: 10.1097/QAD.0000000000001837.

Abstract

Objective: The aim of this study was to compare the differential effects of first-line efavirenz (EFV)-based vs. boosted lopinavir-based antiretroviral regimens on cholesterol metabolism.

Design: Multicentre, open-label, randomized clinical trial.

Methods: Forty-nine naive HIV-infected patients were randomized (1 : 1) to receive either ritonavir-boosted lopinavir (LPV/r) or EFV both in combination with tenofovir and emtricitabine (ClinicalTrials.gov: NCT00759070). Lipid profile and serum phytosterols and cholesterol precursors were determined at baseline and after 16 weeks.

Results: After 16 weeks of intervention, total and non-HDL cholesterol as well as triglyceride levels significantly increased in the LPV/r-group (+1.0 ± 0.8; +0.8 ± 0.7 and +0.8 ± 1.5 mmol/l, respectively), but not in the EFV-group (+0.4 ± 0.7; +0.4 ± 0.6 and 0.2 ± 0.5 mmol/l, respectively). Markers of cholesterol absorption (campesterol-to-cholesterol and sitosterol-to-cholesterol ratios) significantly increased in the LPV/r-group, but not in the EFV-group, whereas there were no changes in either group of the lathosterol-to-cholesterol ratio, a marker of cholesterol synthesis.

Conclusion: Treatment with an LPV/r-based therapy increased total cholesterol relative to EFV-based therapy. Our data suggest that absorption rather than synthesis is the mechanism involved in LPV/r-associated increased total cholesterol.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alkynes
  • Antiretroviral Therapy, Highly Active / methods
  • Benzoxazines / administration & dosage
  • Benzoxazines / adverse effects
  • Blood Chemical Analysis
  • Cholesterol / metabolism*
  • Cyclopropanes
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / adverse effects*
  • Humans
  • Hypercholesterolemia / chemically induced*
  • Hypercholesterolemia / physiopathology*
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / adverse effects
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects*
  • Young Adult

Substances

  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Cholesterol
  • efavirenz
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00759070