Hepatitis B virus wild-type and rtN236T populations show similar early HBV DNA
decline in adefovir refractory patients on a tenofovir-based regimen.
Author(s): Svarovskaia ES(1), Curtis M, Zhu Y, Borroto-Esoda K, Miller MD, Berg T, Lavocat
F, Zoulim F, Kitrinos KM.
Affiliation(s): Author information:
(1)Gilead Sciences Inc., Foster City, CA 94404, USA.
Publication date & source: 2013, J Viral Hepat. , 20(2):131-40
Hepatitis B virus (HBV) pol/RT mutations that confer clinical resistance to
tenofovir disoproxil fumarate (TDF) have not been detected to date. In vitro, the
rtN236T adefovir dipivoxil (ADV)-associated resistance mutation confers low-level
cross-resistance to tenofovir: 3- to 13-fold changes in EC(50) from wild type.
This study evaluated the clinical response of rtN236T mutant viruses by comparing
their early viral load decay kinetics to wild-type viruses in chronic HBV
monoinfected patients harbouring rtN236T prior to initiating TDF or emtricitabine
(FTC)/TDF therapy. Baseline samples (n = 105) from adefovir refractory patients
were tested for the presence of rtN236T using a highly sensitive allele-specific
PCR assay with an rtN236T detection cut-off of 0.5%. The rtN236T mutation was
detected at baseline in 14.3% (14/98) of analysable patient samples (0.5-93.2%,
rtN236T percentage range). The median change in total HBV DNA at week 24 was
comparable for patients with rtN236T detected at baseline (-3.7 log(10)
copies/mL, n = 14) as compared to patients with wild-type HBV (-3.2 log(10)
copies/mL, n = 90). In patients with rtN236T, wild-type and rtN236T mutant virus
showed similar rates of HBV DNA decline with no statistically significant
difference observed at week 4. Moreover, the proportion of rtN236T remained
unchanged in patients in either arm of the study during treatment. In conclusion,
the rtN236T mutant virus showed similar HBV DNA decline kinetics to wild-type
virus in adefovir refractory patients who switched to TDF or FTC/TDF. Despite low
levels of cross-resistance in vitro, TDF similarly suppresses wild-type and
rtN236T mutant viruses in vivo.
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