title: 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.
authors.affiliation: Infectious Diseases Research Unit, ABC Foundation-Medical School, São Paulo, Brazil. cassiamc@uol.com.br
authors.forename: M C
authors.initials: MC
authors.lastname: Mendes-Correa
authors.forename: J R R
authors.initials: JR
authors.lastname: Pinho
authors.forename: S
authors.initials: S
authors.lastname: Locarnini
authors.forename: L
authors.initials: L
authors.lastname: Yuen
authors.forename: R
authors.initials: R
authors.lastname: Sitnik
authors.forename: R A F
authors.initials: RA
authors.lastname: Santana
authors.forename: M S
authors.initials: MS
authors.lastname: Gomes-Gouvêa
authors.forename: O M
authors.initials: OM
authors.lastname: Leite
authors.forename: L G
authors.initials: LG
authors.lastname: Martins
authors.forename: M H
authors.initials: MH
authors.lastname: Silva
authors.forename: R J
authors.initials: RJ
authors.lastname: Gianini
authors.forename: D E
authors.initials: DE
authors.lastname: Uip
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil / Q000453:epidemiology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006509:Hepatitis B / Q000453:epidemiology / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D014758:Viral Core Proteins / Q000235:genetics; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D014758:Viral Core Proteins; D014764:Viral Proteins; D019259:Lamivudine; D000068698:Tenofovir; D004259:DNA-Directed DNA Polymerase; D000225:Adenine