Long-Term Incidence of Hepatitis B Virus Resistance to Lamivudine in Human Immunodeficiency Virus-Infected Patients

Hepatology, November 1999, p. 1302-1306, Vol. 30, No. 5

Yves Benhamou1, Marie Bochet2, Vincent Thibault3, Vincent Di Martino1, Eric Caumes2, Fran┴ois Bricaire2, Pierre Opolon1, Christine Katlama2, and Thierry Poynard1

From the 1Service d'H╚pato-Gastroent╚rologie, 2Service des Maladies Infectieuses, 3Laboratoire de Virologie, H┘pital Piti╚-Salp═tri╦re, Paris, France.

Hepatitis B virus (HBV) resistance to lamivudine has not been extensively documented in human immunodeficiency virus (HIV)-infected patients. We studied the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudine therapy. Serum HBV DNA was quantified by molecular hybridization. Sequence analysis of the HBV polymerase was performed in patients who became resistant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectable in 57 patients (86.4%, 95% CI: 75.7%-93.6%). After 2 years of lamivudine, 47% ▒ 18.6% of the patients, had sustained HBV-DNA suppression. All the 22 tested patients with HBV resistance developed mutation at position 550 in the YMDD motif of the DNA polymerase. None of the following variables were associated with an increased risk of lamivudine resistance: age, associated protease inhibitor therapy, Center for Disease Control (CDC) stage C, known HIV-infection duration, serum HBV-DNA level at baseline, CD4 cell count and serum alanine transaminase levels at baseline and at HBV-replication suppression (2 months of lamivudine). Lamivudine (300 mg/d) is effective for the inhibition of HBV replication in HIV-infected patients. However, emergence of lamivudine-resistant HBV may occur in 20% of patients per year.