Amino acid polymorphism in the reverse transcriptase region of hepatitis B virus and the relationship with nucleos(t)ide analogues treatment for preventing mother-to-infant transmission.
A high maternal serum hepatitis B virus (HBV) DNA level is associated with vaccine failure. The administration of nucleos(t)ide analogues (NAs) in pregnancy for decreasing serum HBV is regarded as an effective and safe method to reduce HBV perinatal transmission. However, the effect of NAs treatment is closely related to amino acid polymorphisms in the HBV reverse transcriptase (RT) region. The full-length RT coding region of 334 HBV isolates from untreated Chinese women of childbearing age with persistent HBV infection were sequenced and amino acid polymorphic analysis was performed to evaluate its impact on NAs treatment for decreasing HBV perinatal transmission. Of the 334 isolates, 36 (10.8%) harbored NAs resistance (NAr) mutations which were mainly putative drug mutations related to lamivudine. The primary drug mutation rtA181T/V was detected in three HBeAg-negative women with an HBV DNA level of <4 log IU/ml. These NAr mutations were rarely detected in women with an HBV DNA level of ≥7 log IU/ml (P = 0.014) or in women younger than 35 years (P = 0.001). The NAr mutation rate among young women (<35 years) who had a high HBV DNA level (≥7 log IU/ml) was significantly lower than in women who had lower HBV DNA levels (<7 log IU/ml) or who were older (≥35 years; P = 0.017). These results suggest that younger women with a high HBV DNA level harbor fewer NAr mutations and that this population may respond to NAs treatment for the prevention of mother-to-infant transmission.
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Jie
J
Chen
Ling
L
Yan
Feng-Cai
FC
Zhu
Jian-Xun
JX
Liu
Rong-Cheng
RC
Li
Fu-Zhen
FZ
Wang
Jie
J
Li
Hui
H
Zhuang
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002681:China; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D014644:Genetic Variation; D006509:Hepatitis B / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D006515:Hepatitis B virus / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
D000998:Antiviral Agents; D004279:DNA, Viral; D012194:RNA-Directed DNA Polymerase
hepatitis B virus; nucleos(t)ide analogues; perinatal transmission; reverse transcriptase