Long-term incidence of hepatitis B virus resistance to lamivudine in humanimmunodeficiency virus-infected patients

Hepatitis B virus (HBV) resistance to lamivudine has not been extensively d ocumented in human immunodeficiency virus (HIV)-infected patients. We studi ed the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receivin g lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudin e therapy. Serum HBV DNA was quantified by molecular hybridization. Sequenc e analysis of the HBV polymerase was performed in patients who became resis tant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectab le 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 we re associated with an increased risk of lamivudine resistance: age, associa ted protease inhibitor therapy, Center for Disease Control (CDC) stage C, k nown HIV-infection duration, serum HBV-DNA level at baseline, CD4 cell coun t and serum alanine transaminase levels at baseline and at HBV;replication suppression (2 months of lamivudine). Lamivudine (300 mg/d) is effective fo r the inhibition of HBV replication in HIV-infected patients. However, emer gence of lamivudine-resistant HBV may occur in 20% of patients per year.