Baseline CD4+ T-cell counts predict HBV viral kinetics to adefovir treatment in lamivudine-resistant HBV-infected patients with or without HIV infection

HIV Clin Trials. 2013 Jul-Aug;14(4):149-59. doi: 10.1310/hct1404-149.

Abstract

Background: Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected persons have not been evaluated. We investigated the role of baseline CD4+ T-cell counts as a predictor of HBV response to adefovir (ADV) therapy in chronic HBV with and without HIV coinfection.

Methods: We conducted a double-blind, randomized, placebo-controlled study of HIV-infected (n = 12) and uninfected (n = 5) chronic HBV patients treated with ADV. Five HIV uninfected patients received ADV; the HIV+ patients received ADV or placebo for a total of 48 weeks. At the end of 48 weeks, all patients received open-label ADV for an additional 48 weeks. HBV, HIV viral loads, CD4+ T-cell counts, and safety labs were performed on days 0, 1, 3, 5, 7, 10, 14, and 28 and then every 4 weeks.

Results: Lower HBV slopes were observed among coinfected compared to monoinfected patients (P = .027 at 4 weeks, P = .019 at 24 weeks, and P = .045 at 48 weeks). Using a mixed model analysis, we found a significant difference between the slopes of the 2 groups at 48 weeks (P = .045). Baseline CD4+ T-cell count was the only independent predictor of HBV decline in all patients.

Conclusion: HIV coinfection is associated with slower HBV response to ADV. Baseline CD4+ T-cell count and not IL28B genotype is an independent predictor of HBV decline in all patients, emphasizing the role of immune status on clearance of HBV.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • CD4 Lymphocyte Count*
  • Coinfection / drug therapy
  • Coinfection / virology
  • Double-Blind Method
  • Drug Resistance, Viral
  • Female
  • HIV Infections / immunology
  • HIV Infections / virology*
  • Hepatitis B / drug therapy*
  • Hepatitis B / immunology
  • Hepatitis B / virology
  • Humans
  • Kinetics
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*

Substances

  • Antiviral Agents
  • Organophosphonates
  • Lamivudine
  • adefovir
  • Adenine