High frequency of lamivudine resistance mutations in Brazilian patients co‐infected with HIV and hepatitis B

Abstract

This study analyzed the genotype distribution and frequency of lamivudine (LAM) and tenofovir (TDF) resistance mutations in a group of patients co-infected with HIV and hepatitis B virus (HBV). A cross-sectional study of 847 patients with HIV was conducted. Patients provided blood samples for HBsAg detection. The load of HBV was determined using an "in-house" real-time polymerase chain reaction. HBV genotypes/subgenotypes, antiviral resistance, basal core promoter (BCP), and precore mutations were detected by DNA sequencing. Twenty-eight patients with co-infection were identified. The distribution of HBV genotypes among these patients was A (n = 9; 50%), D (n = 4; 22.2%), G (n = 3; 16.7%), and F (n = 2; 11.1%). Eighteen patients were treated with LAM and six patients were treated with LAM plus TDF. The length of exposure to LAM and TDF varied from 4 to 216 months. LAM resistance substitutions (rtL180M + rtM204V) were detected in 10 (50%) of the 20 patients with viremia. This pattern and an accompanying rtV173L mutation was found in four patients. Three patients with the triple polymerase substitution pattern (rtV173L + rtL180M + rtM204V) had associated changes in the envelope gene (sE164D + sI195M). Mutations in the BCP region (A1762T, G1764A) and in the precore region (G1896A, G1899A) were also found. No putative TDF resistance substitution was detected. The data suggest that prolonged LAM use is associated with the emergence of particular changes in the HBV genome, including substitutions that may elicit a vaccine escape phenotype. No putative TDF resistance change was detected after prolonged use of TDF.

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

“…The prevalence in 3TC monotreatment is about 40–77.8% among those who receive 3TC treatment for 1 year or longer [22, 23]. 3TC resistance may occur in a small proportion of patients during 3TC plus TDF treatment [24, 25]. In this study, a very high prevalence (76.4%) of 3TC resistance was found in patients on HAART, including 3TC plus TDF.…”

“…However, certain co-infected patients exhibit incomplete viral suppression, with persistent, and sometimes transient bouts of HBV replication [27, 28]. Up to 17% of patients developed virological breakthrough during 3TC plus TDF treatment [24, 25, 29]. In this study, 8.8% of patients on HAART developed virological breakthrough.…”

Hepatitis B genotype G and high frequency of lamivudine-resistance mutations among human immunodeficiencyvirus/hepatitis B virus co-infected patients in Brazil

“…We do not know whether the HBV strains that showed decreased antigenicity could escape the neutralizing action of the anti-HBs antibodies induced by vaccination and cause infection in previously vaccinated individuals (Torresi et al 2002, Matthews et al 2006. Various studies in HBV-HIV co-infected patient populations have evaluated the presence and clinical importance of these mutations (Matthews et al 2006), but in Brazil few studies have evaluated this matter (Santos et al 2004, Sucupira et al 2006, Mendes-Correa et al 2008. If these mutations are indeed associated with vaccine escape, they would have an important impact on public health.…”

“…In Brazil, the presence of genotype G has been rarely seen (Lobato et al 2006, Mendes-Correa et al 2008. Bottecchia et al (2008) identified genotype G in a patient infected with HBV only and in two patients co-infected with HIV.…”

Estudos sobre infecções pelos vírus da hepatite B (HBV), hepatite C (HCV), hepatite delta (HDV) e vírus GB-C (GBV-C) em diferentes regiões da América do Sul

“…Genotype D is the most frequent in Southern Brazil, whereas genotype A is the most frequent in all other regions [67,68]. In Italy, genotype D is largely the most frequent and is found in 73 to 80% of the patients infected with HBV [69,70] Genotype F is the most divergent and considered indigenous in the Americas.…”