HIV CO-INFECTION IS AN INDEPENDENT FACTOR IN DETERMINING VACCINE SCAPE MUTANTS AMONG HEPATITIS B CHRONIC PATIENTS IN BRAZIL

Abstract

Background: Prolonged lamivudine (LAM) therapy has been associated with different mutations in the hepatitis B virus (HBV) genome. The aims of this study were: (1) to compare lamivudine-resistance mutation patterns after prolonged LAM use between patients with chronic hepatitis B infection (CHB) with or without human immunodeficiency virus (HIV) co-infection; (2) to evaluate the incidence and factors associated with the presence of mutations in the envelope gene among these patients. Methods: We included patients with CHB treated with LAM and with detectable HBV-DNA (>50IU/mL) after at least six months of LAM use. HBV load was determined using an “in-house” real-time polymerase chain reaction. HBV mutation status analysis were carried out by amplification and sequencing the complete HBV RT-domain. Results: Ninety-one patients infected only with HBV and 34 HIV-HBV co-infected patients were included. The time of exposure to LAM varied from 7 to 140 months among HBV infected patients and from 12 to 182 months among co-infected patients. Mutations associated with resistance to LAM were observed in 42.9% of HBV infected patients and in 67.6% of HIV-HBV co-infected patients. In this latter group, the frequency of the rtV173L + rtL180M + rtM204V triple mutation was 32.0% versus 7.6% observed among patients infected only with HBV. All patients with this triple mutational pattern also showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that time of exposure to lamivudine superior of 32 months (adjusted PR 1.51, 95%CI 1.10–2.06) was an independent variable associated with the chance of harboring mutations in the polymerase gene. Multivariate analysis also demonstrated that HIV co-infection (adjusted PR 1.40, 95%CI 1.10–1.78) was the only independent variable associated with the chance of harboring sE164D or I195M changes in the envelope gene (vaccine escape phenotype). Conclusions: Prolonged use of LAM may be associated with multiple changes in the pol gene, among mono or co-infected patients; 2-HIV co-infection is an independent factor in determining sE164D and I195M changes in the envelope gene, a vaccine escape phenotype.