Kinetics of hepatitis B surface and envelope antigen and prediction of treatment response to tenofovir in antiretroviral-experienced HIV–hepatitis B virus-infected patients
- 15 May 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in AIDS
- Vol. 26 (8), 939-949
- https://doi.org/10.1097/qad.0b013e328352224d
Abstract
Hepatitis B surface (HBsAg) and envelope (HBeAg) antigen loss are the primary goals of treating chronic hepatitis B virus (HBV). Although their quantification is useful for other antivirals, such has not been the case with tenofovir disoproxil fumarate (TDF), particularly in HIV infection. Prospective, multicenter, cohort study in 143 antiretroviral-experienced HIV-HBV-co-infected patients initiating TDF. HBsAg (IU/ml) and HBeAg levels (S/CO) were measured every 6 months. HBsAg and HBeAg decline (Δ) were assessed by mixed-effect linear models. Quantification criteria were used to assess predictability of antigen loss with time-dependent receiver operating characteristic curves. After a median follow-up of 30.3 months, cumulative incidence rate of HBsAg loss was 4.0% (n = 4) in the entire study population and HBeAg loss was 21.0% (n = 17) in the 96 HBeAg-positive patients. ΔHBsAg was steady during follow-up (HBeAg-positive: -0.027; HBeAg-negative: -0.017 log(10) IU/ml per month), whereas ΔHBeAg ratio was strongly biphasic (-27.1 S/CO per month before and -6.5 S/CO per month after 18 months). Baseline HBeAg and ΔHBeAg were significantly different in patients harboring precore mutations (P < 0.01), whereas both ΔHBsAg and ΔHBeAg were significantly slower among HBeAg-positive patients with CD4(+) T-cell count less than 350 cells/μl (P < 0.05). HBeAg-ratio of 10 S/CO or less at 12 months of therapy was the optimal marker of HBeAg loss, with high sensitivity (0.82) and specificity (0.84) at 36 months. In patients with HBsAg loss, three of four (75.0%) patients had a baseline level of HBsAg of 400 IU/ml or less. During TDF treatment, HIV-induced immunosuppression and HBV genetic variability are associated with differences in HBsAg and HBeAg decline among antiretroviral-experienced, co-infected patients. Considering the decline of HBsAg level is slow, further evaluation is needed to determine its role as a marker of therapeutic efficacy.Keywords
This publication has 32 references indexed in Scilit:
- Clinical and virological outcomes in HIV-infected patients with chronic hepatitis B on long-term nucleos(t)ide analoguesAIDS, 2011
- Microarray for Hepatitis B Virus Genotyping and Detection of 994 Mutations along the GenomeJournal of Clinical Microbiology, 2010
- Six-Year Follow-Up of Hepatitis B Surface Antigen Concentrations in Tenofovir Disoproxil Fumarate Treated HIV–Hbv-Coinfected PatientsAntiviral Therapy, 2010
- Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in EuropeJournal of Antimicrobial Chemotherapy, 2010
- EASL Clinical Practice Guidelines: Management of chronic hepatitis BJournal of Hepatology, 2009
- Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis BHepatology, 2008
- Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patientsHepatology, 2008
- Impact of Highly Active Antiretroviral Therapy (HAART) on the Natural History of Hepatitis B Virus (HBV) and HIV Coinfection: Relationship between Prolonged Efficacy of HAART and HBV Surface and Early Antigen SeroconversionClinical Infectious Diseases, 2007
- Genetic characteristics of hepatitis B virus genotypes as a factor for interferon‐induced HBeAg clearanceJournal of Medical Virology, 2007
- Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy for HBeAg positive chronic hepatitis BJournal of Viral Hepatitis, 2005