Search

Objectives: To explore factors associated with short and long-term hepatitis B virus (HBV) DNA suppression in a multinational cohort of HIV-HBV co-infected patients receiving HBV-active antiretrovirals., Methods: One hundred and fifteen HIV-HBV co-infected patients participating in one of the two global randomized clinical trials conducted by the Adult AIDS Clinical Trials Group of different antiretroviral regimens received either HBV monotherapy with either lamivudine or emtricitabine (N = 56), or HBV dual therapy with tenofovir disoproxil fumarate (TDF) + lamivudine or emtricitabine (N = 59). Associations of pretreatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression. HBV drug-resistance mutations were determined by pol sequencing in those with viral rebound., Results: The proportion with HBV DNA below 200 IU/ml was 60% (95% confidence interval 50-69%) at 24 weeks and 79% (95% confidence interval 69-88%) at 144 weeks. Pretreatment factors associated with the primary outcome were HBV DNA, CD4 T-cell count, and aspartate aminotransferase, but only pretreatment HBV DNA remained associated with long-term suppression (P < 0.0001). HBV therapy group was not significantly associated with the primary outcome at 24 weeks; however, longitudinally, a greater proportion in the dual-therapy group achieved HBV DNA below 200 IU/ml (P = 0.007). A higher proportion of hepatitis B e antigen-negative patients (n = 57) achieved HBV DNA below 200 IU/ml at any point, regardless of the therapy group. All 12 patients with emergence of lamivudine-resistant mutants were in the monotherapy group., Conclusions: TDF-based dual HBV-active antiretroviral therapy is preferred to treat HIV-HBV co-infected patients. In resource-limited settings in which TDF may not be universally available, lamivudine or emtricitabine HBV monotherapy is a reasonable option in patients with low HBV replication.

Background: Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART)., Methods: One hundred sixty-five HIV-HBV-coinfected individuals from the United States, Australia, and Thailand, the majority of whom were on HAART at study entry, were prospectively followed semiannually for a median of 2.8 years. Logistic regression was used to determine factors associated with detectable HBV DNA., Results: Anti-HBV regimens were TDF/emtricitabine (57%), lamivudine or emtricitabine (19%), or TDF monotherapy (13%). During follow-up, HBV DNA was detected at 21% of study visits and was independently associated with hepatitis B e antigen (HBeAg), HAART <2 years, CD4 <200 cells/mm(3), detectable HIV RNA, reporting <95% adherence, and anti-HBV regimen. TDF/emtricitabine was less likely to be associated with detectable HBV than other regimens, including TDF monotherapy (odds ratio, 2.79; P = .02). In subjects on optimal anti-HBV therapy (TDF/emtricitabine) and with undetectable HIV RNA, HBeAg, CD4 <200 mm(3), and reporting <95% adherence remained associated with detectable HBV DNA. Three main patterns of HBV viremia were observed: persistent HBV viremia, viral rebound (>1 log from nadir), and viral blips. No TDF resistance was identified., Conclusions: Tenofovir/emtricitabine was superior to other anti-HBV regimens in long-term HBV suppression. HBV viremia on therapy was identified in 1 of 3 main patterns. Suboptimal adherence was associated with detectable HBV DNA during therapy, even when HIV was undetectable.

Objective: To understand the HIV-hepatitis B virus (HBV) epidemic from a global perspective by clinically and virologically characterizing these viruses at the time of antiretroviral therapy (ART) initiation in a multinational cohort., Methods and Design: HIV-infected patients enrolled in two international studies were classified as HIV-HBV coinfected or HIV monoinfected prior to ART. HIV-HBV coinfected patients were tested for HBV characteristics, hepatitis D virus (HDV), a novel noninvasive marker of liver disease, and drug-resistant HBV. Comparisons between discrete covariates used χ or Fisher's exact tests (and Jonchkheere-Terpstra for trend tests), whereas continuous covariates were compared using Wilcoxon Rank-Sum Test., Results: Of the 2105 HIV-infected patients from 11 countries, the median age was 34 years and 63% were black. The 115 HIV-HBV coinfected patients had significantly higher alanine aminotransferase and aspartate aminotransferase values, lower BMI, and lower CD4 T-cell counts than HIV monoinfected patients (median 159 and 137 cells/μl, respectively, P = 0.04). In the coinfected patients, 49.6% had HBeAg-negative HBV, 60.2% had genotype A HBV, and 13% were HDV positive. Of the HBeAg-negative patients, 66% had HBV DNA 2000 IU/ml or less compared to 5.2% of the HBeAg-positive individuals. Drug-resistant HBV was not detected., Conclusion: Screening for HBV in HIV-infected patients in resource-limited settings is important because it is associated with lower CD4 T-cell counts. In settings in which HBV DNA is not available, HBeAg may be useful to assess the need for HBV treatment. Screening for drug-resistant HBV is not needed prior to starting ART in settings in which this study was conducted.

Screening with hepatitis B surface antigen (HBsAg) is highly recommended for at-risk individuals. Mutations in the HBsAg can result in an inability to detect the virus during routine screening. We describe a hemodialysis patient found to have high levels of hepatitis B virus (HBV) DNA and HBV antibody but negative HBsAg on two routine assays.

HIV infection has a significant impact on the natural progression of hepatitis B virus (HBV) related liver disease. In HIV-HBV co-infected patients, little is known about mutations in the HBV genome, which can influence severity of liver disease. The aim of this study was to characterize and to determine the frequency of known clinically significant mutations in the HBV genomes from HIV-HBV co-infected patients and from HBV mono-infected patients. To accomplish this, genomic length HBV sequencing was performed in highly-active anti-retroviral therapy (HAART)-naïve HIV-HBV co-infected patients (n=74) and in anti-HBV therapy-naïve HBV mono-infected patients (n=55). The frequency of HBV mutations differed between the co-infected and mono-infected patients when comparing patients with the same genotype. BCP mutations A1762T and G1764A were significantly more frequent in HBV genotype C mono-infection and the -1G frameshift was significantly more frequent in co-infection and was only observed in HBV genotype A co-infection. PreS2 deletions were observed more frequently in the setting of co-infection. Further work is needed to determine if these mutational patterns influence the differences in liver disease progression in HIV-HBV co-infected and HBV mono-infected patients., (Copyright 2010 Elsevier Inc. All rights reserved.)