TY - JOUR
T1 - Analysis of hepatitis B viral load decline under potent therapy
T2 - Complex decay profiles observed
AU - Lewin, Sharon R.
AU - Ribeiro, Ruy M.
AU - Walters, Tomos
AU - Lau, George K.
AU - Bowden, Scott
AU - Locarnini, Stephen
AU - Perelson, Alan S.
N1 - Funding Information:
Abbreviations: HIV, human immunodeficiency virus; HCV, hepatitis C virus; HBV, hepatitis B virus; LMV, lamivudine; FCV, famciclovir; HBeAG, hepatitis B e antigen; PCR, polymerase chain reaction; cccDNA, covalently closed circular DNA; ALT, alanine transaminase. From the 1Victorian Infectious Diseases Service and4Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, Parkville, Victoria, Australia; 2Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia; 3Los Alamos National Laboratory, Los Alamos, NM; 5Department of Medicine, Queen Mary Hospital, Hong Kong, People’s Republic of China. Received May 18, 2001; accepted August 6, 2001. Portions of this work were done under the auspices of the U.S. Department of Energy. Supported by NIH grant RR06555. S.R.L. is supported by the National Health and Medical Research Council of Australia, and The Ian Potter Foundation. S.R.L. and R.M.R. contributed equally to this work. Address reprint requests to: Alan S. Perelson, Ph.D., Theoretical Division, MS-K710, Los Alamos National Laboratory, Los Alamos, NM 87545. E-mail: [email protected]; fax: 505-665-3493. Copyright © 2001 by the American Association for the Study of Liver Diseases. 0270-9139/01/3405-0020$35.00/0 doi:10.1053/jhep.2001.28509
PY - 2001
Y1 - 2001
N2 - 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 (tl/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.
AB - 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 (tl/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.
UR - https://www.scopus.com/pages/publications/0034756599
U2 - 10.1053/jhep.2001.28509
DO - 10.1053/jhep.2001.28509
M3 - Article
C2 - 11679973
AN - SCOPUS:0034756599
SN - 0270-9139
VL - 34
SP - 1012
EP - 1020
JO - Hepatology
JF - Hepatology
IS - 5
ER -