Sixth International Congress Drug Therapy in HIV Infection 17-21 November, 2002 Glasgow, UK

Hepatitis B virus (HBV) infection is common in HIV-positive individuals, due to shared routes of transmission of both viruses. Chronic HBV infection (as defined by positivity for serum HBsAg) affects overall 8% of HIV-positive persons in western countries. As HBV causes liver damage through an immune-mediated mechanism, the immunodeficiency produced by HIV is associated with a reduction in aminotransferase levels despite an enhancement in HBV replication. Conversely, this fact explains that the improvement in the immune status following a successful antiretroviral intervention, might occasionally be associated with episodes of acute hepatitis in chronic HBV carriers, reflecting an acute cytotoxic T lymphocyte reaction against HBV antigens exposed on the hepatocyte surface. Immune restoration can also improve the rate of HBV clearance, especially when 3TC is used, since it has direct anti-HBV activity.

Over the last 5 years we have had the opportunity to investigate the impact of HAART on the outcome of HIV/HBsAg+ carriers in our institution. A total of 37 HIV-infected patients with HBsAg+ have began HAART in the last 3 years. Eight of them were co-infected with Hepatitis D virus, and 18 with HCV; being 5 patients B+C+D. All but 5 individuals were treated with 3TC-containing regimens, and after a follow-up >6 months, clearance of serum HBV DNA was recognized in >80% of them. Moreover, seroconversion from HBsAg to anti-HBs occurred in 3 (8.1%) of them. Another 4 seroconverted from HBeAg to anti-HBe. One patient developed a clinically symptomatic hepatitis without any seroconversion, most likely reflecting the inflammatory immune recovery syndrome described after beginning HAART. Another person developed a symptomatic hepatitis after stopping 3TC, most likely due to an acute rebound of HBV replication.

Interestingly, 3 patients with serological markers of past exposure to HBV (anti-HBc+, HBsAg-neg, HBV DNA neg), and experiencing a good response to HAART for a while (in one case including 3TC), developed a severe symptomatic acute hepatitis B. All became HBsAg+ and HBV DNA+, in two even with HBeAg+. Since all had >200 CD4+ cells/ul at the time of the episode, reactivation in the context of immunodeficiency seems unlikely. Reactivation in subjects with an "occult" HBV infection (defined by the presence of low levels of serum HBV-DNA in the absence of HBsAg) might hypothetically explain this circumstance. However, in a cross-sectional study conducted on 85 HIV-infected subjects with anti-HBc antibodies but negative serum HBsAg, none harboured detectable levels of HBV-DNA even using an ultrasensitive PCR test (detection limit 400 copies/ml).

Conclusion: The evolution of HBV infection in HIV-positive subjects receiving HAART varies widely. Symptomatic hepatitis can develop as result of: i) direct hepatotoxicity of antiretroviral drugs, ii) acute immune restoration syndrome, iii) after 3TC or tenofovir withdrawal or emergence of resistance, and iv) coincident with either HBsAg or HBeAg seroconversion. Moreover, the development of severe hepatitis associated with reactivation of HBV in HIV-infected persons on HAART with serum markers of past HBV exposure is a new entity, which merits further studies.

Presenting author:Vincent Sorian

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1 Department of Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain.

2002-11-17
PL10-3

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