Analysis of hepatitis B viral load decline under potent therapy: complex decay profiles observed.
We used a new real-time polymerase chain reaction (PCR)-based assay that is sensitive, has a wide dynamic linear range, and is highly reproducible to quantify hepatitis B virus (HBV) DNA in the serum of infected individuals undergoing potent antiviral therapy. In addition, we made frequent measurements of viral load after initiation of treatment and maintained follow-up to about 12 weeks. To analyze the data we used a new model of HBV decay, which takes into account that existing drug treatments do not completely block de novo infection and the possibility of noncytolytic loss of infected cells. On initiation of therapy, there was a mean delay of 1.6 days followed by a biphasic or muliphasic decay of plasma HBV DNA. The slope of the first phase varied considerably, with one individual having rapid decay, corresponding to a virion half-life of 1 hour, but others showing half-lives of up to 92 hours. Individuals either had a slow second-phase decline (t((1/2)) = 7.2 +/- 1.2 days) or a flat second phase. Some individuals exhibited a complex "staircase pattern" of decay, with further phases of viral DNA decline and phases with little change in viral load.
Lewin
S R
SR
Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Ribeiro
R M
RM
Walters
T
T
Lau
G K
GK
Bowden
S
S
Locarnini
S
S
Perelson
A S
AS
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D003199:Computer Systems; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D000077595:Famciclovir; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013997:Time Factors; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015075:2-Aminopurine; D000077595:Famciclovir