A novel hepatitis B virus mutation with resistance to adefovir but not to tenofovir in an HIV-hepatitis B virus-co-infected patient.
ABSTRACT A molecular virology analysis performed in an HIV-hepatitis B virus (HBV) co-infected patient showed the emergence of an unusual HBV polymerase gene mutation (rt A181T) under adefovir therapy, conferring resistance to adefovir but not to tenofovir, as proved by in-vitro phenotypic analysis. This observation suggests that careful monitoring of co-infected patients is required to diagnose HBV resistance to nucleos(t)ide analogues, and that tenofovir may be active at least against some of the adefovir-resistant strains.
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ABSTRACT: Drug resistance to nucleoside analogs is a serious problem worldwide. Both drug resistance gene mutation detection and HBV genotyping are helpful for guiding clinical treatment. Total HBV DNA from 395 patients who were treated with single or multiple drugs including Lamivudine, Adefovir, Entecavir, Telbivudine, Tenofovir and Emtricitabine were sequenced using the HiSeq 2000 sequencing system and validated using the 3730 sequencing system. In addition, a mixed sample of HBV plasmid DNA was used to determine the cutoff value for HiSeq-sequencing, and 52 of the 395 samples were sequenced three times to evaluate the repeatability and stability of this technology. Of the 395 samples sequenced using both HiSeq and 3730 sequencing, the results from 346 were consistent, and the results from 49 were inconsistent. Among the 49 inconsistent results, 13 samples were detected as drug-resistance-positive using HiSeq but negative using 3730, and the other 36 samples showed a higher number of drug-resistance-positive gene mutations using HiSeq 2000 than using 3730. Gene mutations had an apparent frequency of 1% as assessed by the plasmid testing. Therefore, a 1% cutoff value was adopted. Furthermore, the experiment was repeated three times, and the same results were obtained in 49/52 samples using the HiSeq sequencing system. HiSeq sequencing can be used to analyze HBV gene mutations with high sensitivity, high fidelity, high throughput and automation and is a potential method for hepatitis B virus gene mutation detection and genotyping.Journal of virological methods 06/2013; · 2.13 Impact Factor
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ABSTRACT: Hepatitis B virus (HBV) infection is an international public health concern, and chronic infection can lead to the development of cirrhosis, liver failure, or hepatocellular carcinoma as well as the need for liver transplantation. The recurrence of HBV infection following liver transplantation was disproportionately high prior to the introduction of proper prophylactic treatment. Risk factors associated with the recurrence of HBV infection post-transplant include hepatitis B e antigen positivity, high levels of serum HBV DNA, and the presence of an antiviral drug-resistant strain prior to transplantation. The prevention of HBV recurrence began with the introduction of hepatitis B immunoglobulin (HBIG) in the early 1 990s. Nucleos(t)ide analog (NA) antiviral drugs were next to be introduced and, in combination with HBIG, are considered to be extremely effective for the prevention of recurrence. Because of concerns with HBIG, whether HBIG can be used for a short time or discontinued altogether is under debate. All of the NA antiviral drugs have been proven to be effective against HBV, at least in the pretransplant setting, and can be used safely posttransplant. Further investigation is still needed to standardize treatment in the posttransplant setting.Gastroenterology and Hepatology 03/2014; 10(3):175-9.
- Hospital Pharmacy - HOSP PHARM. 01/2009; 44(2):165-178.