The profile of mutational clusters associated with lamivudine resistance can be constrained by HBV genotypes.
J Hepatol
; 50(3): 461-70, 2009 Mar.
Article
in En
| MEDLINE
| ID: mdl-19041149
ABSTRACT
BACKGROUND/AIMS:
To investigate the different clusters of mutations associated with lamivudine resistance in HBV genotypes D and A.METHODS:
HBV reverse transcriptase sequences of 89 HBV-infected patients failing lamivudine treatment were analyzed. The association of mutations with HBV genotypes was assessed by Chi-Squared test and multivariate logistic regression analysis. Covariate analysis was based on hierarchical clustering.RESULTS:
In genotype A, the rtM204V (prevalence 68.2%) was the main sign of lamivudine failure. Multivariate analysis confirmed that genotype A is the only predictor for rtM204V emergence (OR 14.5 [95% CI 1.3-158], P=0.02). Covariate analysis showed that rtM204V clusters with rtL180M, rtL229V (corresponding to sF220L in the HBsAg), and, interestingly, with HBsAg mutation sS207N (bootstrap=0.95). Both sF220L and sS207N co-localized in the fourth transmembrane HBsAg domain. In contrast, in genotype D the primary mutations rtM204V and rtM204I occurred with similar prevalence (39.1% versus 45.3%, P=0.47), and showed a distinct pattern of compensatory mutations. rtM204V clusters with mutations localized in the RT-B domain (rtV173L, rtL180M, and rtT184A/S) (bootstrap=0.94), while rtM204I clusters with mutations localized in the RT-A domain (rtS53N, rtT54Y, and rtL80I/V) (bootstrap=0.96) (without associations with HBsAg specific mutations).CONCLUSIONS:
HBV genotype plays an important role in driving RT evolution under lamivudine treatment, and thus can be relevant for therapeutic sequencing, immunological response and disease progression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatitis B virus
/
Lamivudine
/
Hepatitis B, Chronic
Type of study:
Risk_factors_studies
Limits:
Adult
/
Humans
/
Middle aged
Language:
En
Journal:
J Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2009
Document type:
Article
Affiliation country: