Use of hepatitis B surface and "e" antigen quantification during extensive treatment with tenofovir in patients co-infected with HIV-HBV

Liver Int. 2015 Mar;35(3):795-804. doi: 10.1111/liv.12521. Epub 2014 Mar 31.

Abstract

Background & aims: In patients infected with hepatitis B virus (HBV) and HIV, hepatitis B 'e' antigen (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) may be used to predict short-term HBeAg and HBsAg loss, respectively. To determine if these quantifiable markers also provide accurate prediction of antigen loss during long-term, extensive tenofovir (TDF) treatment and to further establish qHBsAg profiles associated with HBsAg seroconversion.

Methods: Prospective study of 111 co-infected, antiretroviral-experienced patients undergoing a TDF-containing regimen for >12 months. HBV-DNA viral load, qHBeAg [Paul Ehrlich Institute Units (PEIU)/ml] and qHBsAg were quantified at baseline and every 6-12 months. Sensitivity (Se) and specificity (Sp) of qHBeAg criteria were calculated using a time-dependent receiver operator characteristic curve, and qHBsAg profiles were developed using a group-based trajectory model.

Results: After a median 74.2 months (IQR: 33.1-94.7) of TDF treatment, four patients had HBsAg seroconversion. Among the 78 (70.3%) HBeAg-positive patients, cumulative proportion with HBeAg loss was 42.0% (n = 23) at month 96. Baseline qHBeAg ≤100 PEIU/ml was the only significant factor for HBeAg loss (adjusted-HR = 2.36, 95% CI: 1.02-5.46) in multivariable analysis. In terms of predicting HBeAg-loss until month 96, qHBeAg ≤10 PEIU/ml was more accurate when evaluated at month 24 (Se = 0.73, Sp = 0.80) than month 12 (Se = 0.48, Sp = 0.90). All four patients with HBsAg seroconversion had profiles with large decreases in qHBsAg (>2 log10 IU/ml), not necessarily occurring during the first 12 months, which was infrequent in patients without seroconversion (8.4%, P < 0.001).

Conclusions: Quantifying hepatitis 'e' antigen during the first 2 years of TDF treatment is a practical tool in predicting long-term HBeAg loss. Non time-specific declines in qHBsAg may be a useful indicator of HBsAg seroconversion.

Keywords: hepatitis B surface antigen quantification; hepatitis B virus; human immunodeficiency virus; tenofovir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Coinfection / drug therapy
  • DNA, Viral / isolation & purification
  • Female
  • HIV Infections / drug therapy*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / blood*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Organophosphonates / therapeutic use*
  • Prospective Studies
  • Sensitivity and Specificity
  • Tenofovir
  • Viral Load

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Organophosphonates
  • Tenofovir
  • Adenine