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The Journal of International Medical... Dec 2023Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic... (Review)
Review
Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic hepatitis B virus (HBV) infection. Following diagnosis by electromyography (EMG), magnetic resonance image (MRI) scans and laboratory data (i.e., elevated serum creatinine kinase (CK) and myoglobin) telbivudine was discontinued and the patient was treated with methylprednisolone. While his CK and myoglobin levels decreased rapidly, his muscle weakness and pain improved slowly. Learning points include: patients undergoing haemodialysis and concomitantly receiving antiviral treatment for HBV, should have their serum levels of CK and myoglobin monitored regularly; treatment with corticosteroids maybe required; relief from rhabdomyolysis-induced muscle weakness and pain may be slow due to nerve fibre damage.
Topics: Male; Humans; Telbivudine; Hepatitis B, Chronic; Antiviral Agents; Myoglobin; Thymidine; Rhabdomyolysis; Renal Dialysis; Pain; Muscle Weakness
PubMed: 38140948
DOI: 10.1177/03000605231222244 -
Frontiers in Microbiology 2023Hepatitis B virus (HBV) antiviral Resistance-Associated Mutations (RAMs) in human immunodeficiency virus (HIV) coinfected patients undergoing highly active...
High frequency of Lamivudine and Telbivudine resistance mutations in hepatitis B virus isolates from human immunodeficiency virus co-infected patients on highly active antiretroviral therapy in Bucaramanga, Colombia.
Hepatitis B virus (HBV) antiviral Resistance-Associated Mutations (RAMs) in human immunodeficiency virus (HIV) coinfected patients undergoing highly active antiretroviral therapy (HAART) are complex and incompletely understood. We aimed to determine the prevalence of HBV coinfection, HBV genotypes, and RAMs in a cohort of people living with HIV (PLWH) in the northeastern region of Colombia. This cross-sectional study was carried out between February 2013 and February 2014. Virological, immunological and HAART data were collected from clinical records. In-house nested PCR and Sanger sequencing of the HBV gene were used to identify coinfections, genotypes, RAMs and HBV s antigen (HBsAg) escape mutants. Among 275 PLWH, HBV coinfection was confirmed in 32 patients (11.6%), of whom nine (28.2%) were HBsAg positive (active hepatitis B), and 23 (71.8%) were occult hepatitis B infections (OBI). All HBV sequences (n = 23) belonged to the genotype F3. Among HIV/HBV coinfections, 71.9% had CD4+ T cell counts above 200 cells/mm and 37.5% had undetectable HIV viral loads. The RAMs rtL80I, rtL180M, and rtM204V, which confer resistance to Lamivudine/Telbivudine and partially resistant to Entecavir, were found in all HBV isolates. An unknown rt236Y mutation to Tenofovir was also identified. Most patients under HAART received first-generation HBV antiviral therapy with a low genetic barrier to resistance. Antiviral Drug-associated Potential Vaccine-escape Mutations (ADAPVEMs) in the gene were observed in all isolates ranging from 1-20 amino acid substitutions. However, no vaccine escape mutants were detected. In Conclusion, these findings highlight the importance of HBV molecular screening, antiviral resistance monitoring and new guidelines for PLWH to overcome RAMs and prevent HBV-related liver disease.
PubMed: 37555061
DOI: 10.3389/fmicb.2023.1202342 -
Water Research Jun 2023Wastewater-based epidemiology (WBE) is a promising technique for monitoring the rapidly increasing use of antiviral drugs during the COVID-19 pandemic. It is essential...
Wastewater-based epidemiology (WBE) is a promising technique for monitoring the rapidly increasing use of antiviral drugs during the COVID-19 pandemic. It is essential to evaluate the in-sewer stability of antiviral drugs in order to determine appropriate biomarkers. This study developed an analytical method for quantification of 17 typical antiviral drugs, and investigated the stability of target compounds in sewer through 4 laboratory-scale gravity sewer reactors. Nine antiviral drugs (lamivudine, acyclovir, amantadine, favipiravir, nevirapine, oseltamivir, ganciclovir, emtricitabine and telbivudine) were observed to be stable and recommended as appropriate biomarkers for WBE. As for the other 8 unstable drugs (abacavir, arbidol, ribavirin, zidovudine, ritonavir, lopinavir, remdesivir and efavirenz), their attenuation was driven by adsorption, biodegradation and diffusion. Moreover, reaction kinetics revealed that the effects of sediments and biofilms were regarded to be independent in gravity sewers, and the rate constants of removal by biofilms was directly proportional to the ratio of surface area against wastewater volume. The study highlighted the potential importance of flow velocity for compound stability, since an increased flow velocity significantly accelerated the removal of unstable biomarkers. In addition, a framework for graded evaluation of biomarker stability was proposed to provide reference for researchers to select suitable WBE biomarkers. Compared with current classification method, this framework considered the influences of residence time and different removal mechanisms, which additionally screened four antiviral drugs as viable WBE biomarkers. This is the first study to report the stability of antiviral drugs in gravity sewers.
Topics: Humans; Sewage; Wastewater-Based Epidemiological Monitoring; Antiviral Agents; Pandemics; Water Pollutants, Chemical; COVID-19; Biomarkers
PubMed: 37150064
DOI: 10.1016/j.watres.2023.120023 -
Scientific Reports Apr 2024Chronic hepatitis B remains a worldwide health concern. Presently, many drugs, such as Clevudine and Telbivudine, are recommended for the treatment of chronic hepatitis...
Chronic hepatitis B remains a worldwide health concern. Presently, many drugs, such as Clevudine and Telbivudine, are recommended for the treatment of chronic hepatitis B disease. For this purpose, the quantum chemical analysis of E (E), ionization potential (IP), electron affinity (EA), electronegativity (EN), chemical hardness (η), chemical potential (μ), chemical softness (S), electrophilicity index (ω), electron accepting capability (ω), electron-donating capability (ω), Nucleophilicity index (N), additional electronic charge (∆N), Optical softness (σ) and Dipole Moment, IR and UV-Vis spectra, molecular electrostatic potential (MEP) profile, Mulliken charge analysis, natural bond orbital (NBO) were examined in this study. The dipole moment of the compounds suggests their binding pose and predicted binding affinity. The electrophilic and nucleophilic regions were identified, and techniques such as NBO, UV-Vis, and IR were used to gain insights into the molecular structure, electronic transitions, and potential drug design for Hepatitis B treatment. Calculations for this study were carried out using the Gaussian 09 program package coupled with the DFT/TDDFT technique. The hybrid B3LYP functional method and the 6-311++G(d, p) basis set were used for the calculations.
Topics: Humans; Models, Molecular; Telbivudine; Spectroscopy, Fourier Transform Infrared; Hepatitis B, Chronic; Quantum Theory; Spectrum Analysis, Raman; Spectrophotometry, Ultraviolet; Arabinofuranosyluracil
PubMed: 38584189
DOI: 10.1038/s41598-024-58599-2 -
Journal of Global Antimicrobial... Jun 2023We conducted this study to describe whether mutations in the gene coding for the enzyme reverse transcriptase (RT) were related to drugs used in the treatment of...
OBJECTIVES
We conducted this study to describe whether mutations in the gene coding for the enzyme reverse transcriptase (RT) were related to drugs used in the treatment of hepatitis B in Vietnam.
METHODS
Patients receiving antiretroviral therapy with evidence of treatment failure were included in the study. The RT fragment was cloned using the polymerase chain reaction technique after being extracted from patients' blood samples. The nucleotide sequences were analysed using Sanger method. The HBV drug resistance database contains mutations associated to resistance to existing HBV therapies. Medical records were accessed to collect information on patient parameters, such as treatment, viral load, biochemistry, and blood count.
RESULTS
Resistance mutations to lamivudine, telbivudine, and entecavir were found in the highest proportion (75-91.7%) of HBV samples from patients who had failed antiretroviral therapy. Only 20.8% of HBV strains had mutations exhibiting adefovir resistance, while none had mutations conferring tenofovir resistance. M204I/V, L180M, and L80I are frequent variants linked with resistance to lamivudine, telbivudine, and entecavir. In contrast, the A181L/T/V mutation was detected predominantly in tenofovir-resistant HBV strains. Following the drug resistance mutation test, patients achieved the greatest virological response after 24 weeks of therapy with tenofovir and entecavir at a daily dose of one tablet.
CONCLUSION
Lamivudine, telbivudine, and entecavir were all highly resistant to the RT enzyme modifications in 24 treatment failure patients, with M204I/V, L180M, and L80I being the most prevalent mutations. Tenofovir resistance mutations have not been found in Vietnam.
Topics: Humans; Hepatitis B virus; Lamivudine; Antiviral Agents; RNA-Directed DNA Polymerase; Telbivudine; Hepatitis B, Chronic; Vietnam; Drug Resistance, Viral; Tenofovir; Mutation; HIV Infections; Treatment Failure
PubMed: 36849052
DOI: 10.1016/j.jgar.2023.02.013 -
Journal of Clinical and Translational... Oct 2023Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific...
BACKGROUND AND AIMS
Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.
METHODS
This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger's sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool.
RESULTS
Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (=2) and rt180M+rt204V+rt202G (=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18).
CONCLUSIONS
The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.
PubMed: 37577226
DOI: 10.14218/JCTH.2022.00135S -
Immunity, Inflammation and Disease Feb 2024To compare the efficacy and safety of telbivudine (LdT), tenofovir alafenamide fumarate (TAF), and tenofovir disoproxil fumarate (TDF) for preventing hepatitis B...
OBJECTIVE
To compare the efficacy and safety of telbivudine (LdT), tenofovir alafenamide fumarate (TAF), and tenofovir disoproxil fumarate (TDF) for preventing hepatitis B transmission in immune-tolerant pregnant women with HBV infection.
METHODS
We conducted a retrospective cohort study involving women who had hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 2 × 10 IU/mL and initiated LdT, TDF, or TAF to prevent mother-to-child transmission (MTCT). The primary endpoint was the safety of mothers and infants. The secondary endpoints were maternal HBV DNA reduction at delivery and MTCT rate.
RESULTS
A total of 96 patients were enrolled in the study (LdT group, n = 36; TDF group, n = 35; TAF group, n = 25). All infants received hepatitis B virus immunoprophylaxis. The MTCT rate was 0%([0 of 25] vs. [0 of 35] vs. [0 of 36], p > .05). No severe liver function damage occurred in any of the mothers. Babies delivered in all groups had prenatal ultrasound screening abnormalities, but abnormality rates were not statistically significant between groups.
CONCLUSION
The application of TDF, TAF, or LdT to immune-tolerant HBV-infected pregnant women in middle-late pregnancy can successfully interrupt MTCT of the HBV virus. However, for all three groups of pregnant women who delivered babies with abnormal prenatal ultrasound screening, an expanded sample size may be needed for further observation.
Topics: Infant; Female; Humans; Pregnancy; Tenofovir; Telbivudine; Retrospective Studies; Antiviral Agents; Pregnant Women; DNA, Viral; Pregnancy Complications, Infectious; Infectious Disease Transmission, Vertical; Hepatitis B e Antigens; Hepatitis B; Adenine
PubMed: 38414328
DOI: 10.1002/iid3.1204