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 seroconversion

Hôtel-Dieu, Service d'Hépatologie et de Gastroentérologie, Lyon, France.
Clinical Infectious Diseases (Impact Factor: 9.42). 10/2007; 45(5):624-32. DOI: 10.1086/520752
Source: PubMed

ABSTRACT Coinfection with hepatitis B virus (HBV) in human immunodeficiency virus (HIV)-infected patients is common. However, little is known about the natural history of chronic hepatitis B in HIV-infected populations, especially the impact of highly active antiretroviral therapy (HAART) on the outcome of HBV early antigen (HBeAg) and HBV surface antigen (HBsAg) status.
The characteristics of 92 patients coinfected with HIV and HBV were retrospectively assessed before and after HAART and lamivudine treatment to determine the impact of treatment on chronic hepatitis B and factors associated with HBeAg and/or HBsAg seroconversion.
During follow-up, 82 patients received antiretroviral therapy, 79 of whom received HAART. Twenty-eight of the 76 patients who were administered lamivudine therapy developed lamivudine resistance mutations. While receiving antiretroviral therapy, 10 of 59 HBeAg-positive patients developed antibody to HBeAg, 3 of 10 cleared HBsAg, and 2 of 3 developed antibody to HBsAg. Two of 23 HBeAg-negative patients cleared HBsAg and developed antibody to HBsAg. HBeAg and/or HBsAg seroconversion combined with an undetectable HBV DNA level (i.e., an HBV response) correlated with a sustained HIV response (P=.001), shorter duration of antiretroviral therapy (P=.058), and more-severe disease, as evaluated by Centers for Disease Control and Prevention staging (for stage B vs. stage A, P=.029; for stage C vs. stage A, P=.069). For patients with elevated baseline alanine aminotransferase levels, the HBV response correlated significantly with a greater increase in CD4 cell count while receiving HAART.
In HIV-HBV-coinfected patients, HBV response correlated with a sustained HIV response to antiretroviral therapy, usually HAART including lamivudine.

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    ABSTRACT: Métodos: Se realizó un perfil serológico para Hepatitis B en los pacientes VIH posi-tivos, consistente en: HBs Ag, Anticore IgG. Estos exámenes se practicaron entre el mes de junio del 2007 hasta julio del 2009. Resultados: En 24 meses se realizaron exámenes para la detección de Hepatitis B en 103 pacientes VIH positivos. Hubo una prevalencia del 3,1% (tres pacientes) con Hepatitis B crónica. Cuatro pacientes falle-cieron durante el período del estudio, nin-guno positivo para infección por Hepatitis B. Se detectaron 6 pacientes con Ig G core para VHB positivo aislado, es decir con sospecha de Hepatitis B oculta, la cual se confirmó solo en un paciente con carga viral para ADN de VHB positiva (158 copias/ml). Este paciente no se hallaba usando lamivudina en el momento del examen. Conclusión: La prevalencia de Hepatitis B en nuestros pacientes corresponde a la reportada en todo el territorio nacional. La búsqueda de infección oculta por Virus de Hepatitis B en los pacientes VIH positivos asistentes a nuestra institución arrojó como resultado un solo pa-ciente con esta patología y con una baja carga viral. La estrategia para el diagnóstico la infec-ción oculta por VHB en los pacientes usando lamivudina debe ser más estudiada.
    03/2010; 14(1). DOI:10.1016/S0123-9392(10)70091-6
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    ABSTRACT: Background Hepatitis-related liver diseases are a leading cause of mortality and morbidity among people with HIV/AIDS taking combination antiretroviral therapy. We assessed the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection on HIV outcomes in patients in China. Methods We did a nationwide retrospective observational cohort study with data from the China National Free Antiretroviral Treatment Program from 2010–11. Patients older than 18 years starting standard antiretroviral therapy for HIV who had tested positive for HBV and HCV were followed up to Dec 31, 2012. We used Kaplan-Meier analysis and Cox proportional hazard models to evaluate survival, and logistic regression models to estimate virological failure, immunological response, and retention in care. Findings 33 861 patients with HIV met eligibility criteria. 2958 (8·7%) participants had HBV co-infection, 6149 (18·2%) had HCV co-infection, and 1114 (3·3%) had triple infection. All-cause mortality was higher in participants with triple infection (adjusted hazard ratio 1·90, 95% CI 1·53–2·37) and HCV co-infection (1·46, 1·25–1·70) than in those with HIV only, but not in those with HBV co-infection (1·06, 0·89–1·26). People with triple infection were also more likely to have virological failure (adjusted odds ratio [OR] 1·26, 95% CI 1·02–1·56) than were those with HIV only, whereas the difference was not significant for those with HBV co-infection (0·93, 0·80–1·10) or HCV co-infection (1·10, 0·97–1·26). No co-infection was significantly associated with a difference in CD4 cell count after 1 year of treatment. Loss to follow-up was more common among participants with triple infection (OR 1·37, 95% CI 1·16–1·62) and HCV co-infection (1·30, 1·17–1·45), but not HBV co-infection (0·93, 0·82–1·05), than among those with HIV only. Interpretation Screening for viral hepatitis is important in individuals diagnosed as HIV positive. Effective management for viral hepatitis should be integrated into HIV treatment programmes. Long-term data are needed about the effect of hepatitis co-infection on HIV disease progression. Funding The National Center for AIDS/STD Control and Prevention, China Center for Disease Control and Prevention.
    The Lancet Infectious Diseases 10/2014; 14(11). DOI:10.1016/S1473-3099(14)70946-6 · 19.45 Impact Factor
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    ABSTRACT: Background & Aims: In hepatitis B e antigen (HBeAg) positive-HIV co-infected patients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed. Methods: A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infected patients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72). Results: Fifty-one patients (49 men, median age 46 years, range: 32-65), were included. Median duration of HIV, HBV infections and TDF therapy was 10.3 (0.6-22), 9.8 (0.5-16), and 3.3 (0.5-6.8) years, respectively. Median baseline CD4 count was 506 (175-1316)/mm(3). HIV viral load was <50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four (8%) patients had a HBV sustained, response. No HBs seroconversion was observed. Only patients with more than 350 CD4/mm(3) at baseline achieved HBe loss. HBeAg level >10 PEI U/ml at W12 or a quantitative HBsAg decline <0.5 log IU/ml at W24 had 100% and 84% negative predictive values for response, respectively. Conclusions: 48-week PegIFN additional therapy to cART including TDF did not significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20% of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring and optimising this strategy.
    Journal of Hepatology 05/2014; 61(4). DOI:10.1016/j.jhep.2014.05.030 · 10.40 Impact Factor


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