Lamivudine

Journal of Viral Hepatitis, 2009, 16, 94–103

doi:10.1111/j.1365-2893.2008.01056.x

Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study
W.-M. Xu,1 Y.-T. Cui,2 L. Wang,3 H. Yang,4 Z.-Q. Liang,5 X.-M. Li,6 S.-L. Zhang,7 F.-Y. Qiao,8 F. Campbell,9 C.-N. Chang,10 S. Gardner10 and M.Atkins11 1Shanghai Infectious Disease Hospital, Shanghai, China;
2

Beijing United Family Hospital, Beijing, China; 3Beijing Ditan Hospital, Beijing, China; 4Beijing Youan Hospital, Beijing, China; 5Southwestern

Hospital, Chongqing, China; 6The 3rd Affiliated Hospital of Zhongshan University, Guangzhou, China; 7The 1st Affiliated Hospital of Xian Communication University, Xian, China; 8WuhanTongji Hospital, Wuhan, China; 9GlaxoSmithKline Research and Development, Greenford, UK;
10

GlaxoSmithKline Research and Development, Research Triangle Park, NC, USA; and

11

St. MaryÕs Hospital, London, UK

Received May 2008; accepted for publication July 2008

SUMMARY. This randomized, double-blind, placebo-controlled study evaluated whether lamivudine given during late pregnancy canreduce hepatitis B virus (HBV) perinatal transmission in highly viraemic mothers. Mothers were randomized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum. At birth, infants received recombinant HBV vaccine with or without HBIg and were followed until week 52. One hundred and fifty mothers, with a gestational age of 26–30 weeks and serum HBV DNA >1000 MEq/mL(bDNA assay), were treated. A total of 141 infants received immunoprophylaxis at birth. In lamivudinetreated mothers, 56 infants received vaccine + HBIg (lamivudine + vaccine + HBIg) and 26 infants received vaccine (lamivudine + vaccine). In placebo-treated mothers, 59 infants received vaccine + HBIg (placebo + vaccine + HBIg). At week 52, in the primary analyses where missing data was counted asfailures, infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of

HBsAg seropositivity (10/56, 18% vs 23/59, 39%; P = 0.014) and in detectable HBV DNA (11/56, 20% vs 27/ 59, 46%; P = 0.003) compared to infants in the placebo + vaccine + HBIg group. Sensitivity analyses to evaluate the impact of missing data at week 52 resulting from a high dropout rate (13% inthe lamivudine + vaccine + HBIg group and 31% in the placebo + vaccine + HBIg group) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers, but the differences were not statistically significant. No safety concerns were noted in the lamivudine-treated mothers or their infants. Results of this study suggestthat lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization. Keywords: chronic hepatitis B, HBIg, hepatitis B virus, lamivudine, vaccination.

INTRODUCTION
Hepatitis B virus (HBV) infection is the leading cause of chronic hepatitis with current estimates of 400 million chronically infected individuals worldwide [1]. Perinataltransmission is an important factor in the endemicity of HBV
Abbreviations: ALT, alanine aminotransferase; HBIg, hepatitis B immune globulin; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HIV, human immunodeficiency virus. Correspondence: Wei-Min Xu, MD, Shanghai Skin Disease and STD Hospital, No. 196 Wuyi Road, Shanghai 200050, China. E-mail: wmxu@sohu.com

in high-risk regionssuch as Asia. Infants born to mothers positive for both hepatitis B surface (HBsAg) and hepatitis B e antigen (HBeAg) have a 70–90% chance of acquiring perinatal HBV infection, and 85–95% of infected infants will become chronic HBV carriers [2,3]. Perinatal transmission of HBV can be prevented by HBV vaccination in 75–80% of cases if given within 24 h of birth. By co-administering passive–active...