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Hepatitis B virus reverse transcriptase polymorphisms between treated and treatment-naive chronically infected patients.

ABSTRACT: The aim of this study was investigation of variation(s) in the Hepatitis B virus (HBV) reverse transcriptase domain. 120 patients with chronic HBV infection recruited. 104 patients were received nucleos(t)ide analogs treatments. DNA extractions were done from plasma samples. Direct sequencing and alignment of Polymerase Chain Reaction products were applied for further analysis. HBV genotypes determined by NCBI's Genotyping Tool. Polymorphism(s) were detected by using DnaSP software. Of 120 samples, 98 were sequenced. All of products were HBV genotype D. 13/98 (13.27%) of patients had M539I/V substitutions corresponding to YMDD motif. FLLAQ to FLMAQ was observed among 22/98 (22.98) patients. Two substitutions N459Y and L515M were significantly correlated (R²?=?0.486 and R²?=?0.941 respectively) with FLLAQ motif variation. Mutation ratio among treatment-received patients to treatment-naïve patients was 0.2-0.6. Drug resistance conferring substitutions (DRCSs) were rtL180M (22/98), rtA194V (11/98), rtM204V (1/98), and rtM204I (11/98). Furthermore, six variants were observed among all patients. Appearance of DRCSs in HBV polymerase is a major obstacle to the virus treatments. In the present study, it was shown that DRCSs are more prevalent among treated patients. Therefore, replacement of current anti-viral regimen with novel anti-HBV drugs is warranted in the future.

SUBMITTER: Rezanezhadi M

PROVIDER: S-EPMC6531556 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Hepatitis B virus reverse transcriptase polymorphisms between treated and treatment-naïve chronically infected patients.

Rezanezhadi Masoumeh M Mohebbi Alireza A Askari Fatemeh Sana FS Hosseini Seyyede Delafruz SD Tabarraei Alijan A

Virusdisease 20190110 2

The aim of this study was investigation of variation(s) in the Hepatitis B virus (HBV) reverse transcriptase domain. 120 patients with chronic HBV infection recruited. 104 patients were received nucleos(t)ide analogs treatments. DNA extractions were done from plasma samples. Direct sequencing and alignment of Polymerase Chain Reaction products were applied for further analysis. HBV genotypes determined by NCBI's Genotyping Tool. Polymorphism(s) were detected by using DnaSP software. Of 120 sampl ...[more]

PMID: 31179360

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Project description:BACKGROUND:The presence of drug resistance mutations (DRMs) against antiretroviral agents is one of the main concerns in the clinical management of individuals with human immunodeficiency virus-1 (HIV-1) infection, especially in regions of the world where treatment options are limited. The current study aimed at assessing the prevalence of HIV-1 DRMs among naïve and treatment-experienced HIV-1-infected patients in Iran. METHODS:From April 2013 to September 2018, the HIV-1 protease and reverse transcriptase genes were amplified and sequenced in plasma specimens of 60 newly diagnosed antiretroviral-naive individuals and 46 participants receiving antiretroviral therapies (ARTs) for at least six months with an HIV viral load of more than 1000 IU/mL to determine the HIV-1 DRMs and subtypes. RESULTS:Among the 60 treatment-naïve HIV-1-infected participants, 8.3% were infected with HIV-1 variants with surveillance DRMs (SDRMs). The SDRMs, D67N and D67E, belonged to the NRTIs class in two patients and K103N and V106A belonged to the NNRTIs class in three patients. The phylogenetic analysis showed that 91.7% of the subjects were infected with subtype CRF35_AD, followed by subtype B (5.0%) and CRF01_AE (3.3%). Among the 46 ART-experienced participants, 33 (71.7%) carried HIV-1 variants with SDRMs (9.1% against PIs, 78.8% against NRTIs, and 100% against NNRTIs). M46I and I47V were the most common mutations for PIs, M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. Phylogenetic analysis of the polymerase region showed that all of the 46 HIV-1-infected patients who failed on ART carried CRF35_AD. CONCLUSIONS:The moderate prevalence of SDRMs (8.3%) in treatment-naïve and ART-failed (77.1%) Iranian patients with HIV-1-infection emphasizes the need for systematic viral load monitoring, expanding drug resistance testing, carefully surveilling individuals on ART regimens, and facilitating access to new antiretrovirals by health authorities.

Dataset Information

Hepatitis B virus reverse transcriptase polymorphisms between treated and treatment-naive chronically infected patients.

Publications

Hepatitis B virus reverse transcriptase polymorphisms between treated and treatment-naïve chronically infected patients.

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