Outbreak of hepatitis B virus genotype A and transmission of genetic drug resistance in cases coinfected with HIV-1 in Japan

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http://jcm.asm.org/cgi/content/abstract/JCM.02149-10v1

J. Clin. Microbiol. doi:10.1128/JCM.02149-10

Copyright © 2011, American Society for Microbiology and/or the Listed

Authors/Institutions. .

Outbreak of hepatitis B virus genotype A and transmission of genetic drug

resistance in cases coinfected with HIV-1 in Japan

Seiichiro Fujisaki, Yoshiyuki Yokomaku, Teiichiro Shiino, Tomohiko Koibuchi,

Junko Hattori, Shiro Ibe, Yasumasa Iwatani, Aikichi Iwamoto, Takuma Shirasaka,

Motohiro Hamaguchi, and Wataru Sugiura*

Department of Infectious Diseases and Immunology, Clinical Research Center,

National Hospital Organization Nagoya Medical Center, Nagoya, Japan; Infectious

Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo,

Japan; The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;

Department of AIDS Research, Nagoya University Graduate School of Medicine,

Nagoya, Japan; AIDS Medical Center, National Hospital Organization Osaka

National Hospital, Osaka, Japan; Aichi Blood Center, Japanese Red Cross Society,

Nagoya, Japan

* To whom correspondence should be addressed. Email: wsugiura@....

Abstract

The major route of hepatitis B virus (HBV) infection in Japan has been

mother-to-child transmission (MTCT) and blood transfusion. However, HBV cases

transmitted through sexual contact are increasing, especially among HIV-1

seropositive patients. To understand the molecular epidemiology of HBV in

HBV/HIV-1 coinfection, we analyzed HBV genotypes and HIV-1 subtypes of

HBV/HIV-1-coinfected cases at Nagoya Medical Center from 2003 to 2007. Among 394

HIV-1-infected Japanese men having sex with men (MSM) newly diagnosed during the

study period, 31 (7.9%) tested positive for the hepatitis B surface antigen. HBV

sequence analyses were successful in 26 cases, with 21 (80.7%) and 5 (19.3%)

cases determined as genotypes A and C, respectively. Our finding that HBV

genotype A was dominant in HIV-1-seropositive patients alerts clinicians to an

alternative outbreak of HBV genotype A in the HIV-1-infected MSM population, and

a shift in HBV genotype from C to A in Japan. The narrow genetic diversity in

genotype A cases suggests that genotype A has been recently introduced into the

MSM population, and sexual contacts within MSM were more active than speculated

from HIV-1 tree analyses. In addition, we found a lamivudine-resistant mutation

in 1 naïve case, suggesting a risk of drug-resistant HBV transmission. As

genotype A infection has a higher risk than other genotypes for individuals to

become HBV carriers, prevention programs are urgently needed for the target

population.