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

Intervirology. 2018;61(3):123-132. doi: 10.1159/000493797. Epub 2018 Oct 26.

Abstract

Objectives: We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China.

Methods: Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed.

Results: The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3-96.7) was significantly higher than that in group 1 (1.4%, 95% CI -1.4 to 4.2; χ2 = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 106 copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations.

Conclusion: Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.

Keywords: Antiviral therapy; Co-infection; Drug-resistant mutations; Hepatitis B virus; Human immunodeficiency virus; Prevalence.

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • China / epidemiology
  • Coinfection / drug therapy
  • Coinfection / epidemiology*
  • Coinfection / virology
  • DNA-Directed DNA Polymerase / genetics
  • Drug Resistance, Multiple, Viral / genetics*
  • Female
  • HIV / drug effects
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • Hepatitis B / drug therapy*
  • Hepatitis B / epidemiology
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Multivariate Analysis
  • Mutation
  • Prevalence
  • Tenofovir / therapeutic use
  • Viral Load

Substances

  • Anti-HIV Agents
  • Lamivudine
  • Tenofovir
  • DNA-Directed DNA Polymerase