CYP3A induction and inhibition by different antiretroviral regimens reflected by changes in plasma 4 beta-hydroxycholesterol levels

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Objective and methods A member of the major human cytochrome P450 superfamily of hemoproteins, CYP3A4/5, converts cholesterol into 4 beta-hydroxycholesterol. We studied plasma 4 beta-hydroxycholesterol levels prior to and 4 weeks after initiating antiretroviral therapy that included efavirenz, ritonavir-boosted atazanavir or ritonavir-boosted lopinavir with the aim of exploring the usefulness of plasma 4 beta-hydroxycholesterol levels as an endogenous biomarker of CYP3A activity. Efavirenz is an inducer of CYP3A, whereas the ritonavir-boosted regimens are net inhibitors of CYP3A. Results In patients treated with efavirenz, the median plasma 4 beta-hydroxycholesterol level increased by 46 ng/mL (p=0.004; n=11). In contast, patients given ritonavir-boosted atazanavir showed a median decrease in plasma 4 beta-hydroxycholesterol of -9.4 ng/mL (p=0.0003; n=22), and those given ritonavir-boosted lopinavir showed a median change from baseline of -5.8 ng/mL (p=0.38; n=19). There were significant between-group differences in the effects of antiretroviral treatment on plasma 4 beta-hydroxycholesterol levels (p < 0.0001). Conclusion Changes in plasma 4 beta-hydroxycholesterol following the initiation of efavirenz- or atazanavir/ritonavir-based antiretroviral therapy reflected the respective net increase and decrease of CYP3A activity of these regimens. The plasma 4 beta-hydroxycholesterol level did not indicate a net CYP3A inhibition in the lopinavir/ritonavir arm, possibly because of concomitant enzyme induction.


  • F Josephson
  • L Bertilsson
  • Y Bottiger
  • Leo Flamholc
  • M Gisslen
  • V Ormaasen
  • A Sonnerborg
  • U Diczfalusy

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi


Sidor (från-till)775-781
TidskriftEuropean Journal of Clinical Pharmacology
StatusPublished - 2008
Peer review utfördJa