Modeling complex decay profiles of hepatitis B virus during antiviral therapy.
Typically, hepatitis B virus (HBV) decays in patients under therapy in a biphasic manner. However, more complex decay profiles of HBV DNA (e.g., flat partial response, triphasic, and stepwise), for which we have no clear understanding, have also been observed in some treated patients. We recently introduced the notion of a critical drug efficacy, epsilon(c), such that if overall drug efficacy, epsilon(tot), is higher than the critical drug efficacy (i.e., epsilon(tot) > epsilon(c)) then viral levels will continually decline on therapy, while if epsilon(tot) < epsilon(c), then viral loads will initially decline but will ultimately stabilize at a new set point, as seen in flat partial responders. Using the idea of critical efficacy and including hepatocyte proliferation in a viral kinetic model, we can account for these complex HBV DNA decay profiles. The model predicts that complex profiles such as those exhibiting a plateau or shoulder phase, as well as a class of stepwise declines, occur only in patients in whom the majority of hepatocytes are infected before therapy.


CONCLUSIONS
We show via kinetic modeling how a variety of HBV DNA decay profiles can arise in treated patients.
Dahari
Harel
H
Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Shudo
Emi
E
Ribeiro
Ruy M
RM
Perelson
Alan S
AS
D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000187:drug effects / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral