OBJECTIVETo observe the distribution of HBV variants resistant to lamivudine and their relation to clinical manifestations of chronic hepatitis.

METHODSUsing direct sequencing, YMDD (tyrosine-methionine-aspartate-aspartate) variants in patients with chronic HBV were detected before and during treatment with lamivudine. A statistical analysis of the distribution of HBV strains resistant to lamivudine was performed.

RESULTFour variant strains existed in patients before lamivudine treatment, 128 variant resistant strains were noted after 6 mouths of lamivudine treatment including 42 YVDD (valine) variants, 20 YIDD (isoleusine) variants and 66 non-YMDD variants. According to the hepatitis severity, 8 patients were mild, 108 moderate and 12 severe. Viral loading was higher and clinical types were more severe in no-YMDD variants.

CONCLUSIONVariant strains including strains resistant to lamivudine exist naturally before lamivudine treatment, but lamivudine-resistant ones become more dominant after treatment. Liver inflammation is more severe in non-YMDD group.

Antiviral Agents ; pharmacology ; Drug Resistance, Viral ; Genetic Variation ; Hepatitis B virus ; drug effects ; genetics ; Lamivudine ; pharmacology

The study is aimed to investigate the effect of lamivudine on growth and metabolism of three intestinal characteristic bacteria (namely, Bifidobacterium adolescentis, Escherichia coli and Shigella dysenteriae). The growth condition of the three bacteria was quantitatively evaluated by microcalorimetry with four characteristic parameters of the thermal power-time curves, including the growth rate constant (k), thermal power (p), time to peak (t) and calorific value (Q). The results showed that the IC50 value of lamivudine on B. adolescentis was 200 microg x mL(-1), and the IC50 values of lamivudine on S. dysenteriae and E. coli were higher than 3 000 microg x mL(-1) and 6 000 microg x mL(1), respectively. Therefore, lamivudine made different inhibitory effects on the three bacteria, in which the B. adolescentis was most susceptible to lamivudine. This work showed that taking lamivudine chronically is likely to affect the balance of good flora in the intestinal tract, and might increase endotoxin release, leading to inflammation and disease progression in hepatopathy.
Anti-Bacterial Agents ; pharmacology ; Bifidobacterium ; growth & development ; Calorimetry ; Escherichia coli ; growth & development ; Lamivudine ; pharmacology ; Shigella dysenteriae ; growth & development

BACKGROUNDTo evaluate the inhibitive effect of combination of 3TC with Ara-AMP against HBV in vitro.

METHODSUsed 2.2.15 cell as target cell. With radioimmunological technique and blot slot, the inhibitive effect of 3TC, Ara-AMP and the combination of both against the HBsAg, HBeAg and intracellular HBV DNA were investigated.

RESULTSThe inhibitive ratio of Ara-AMP against HBsAg, HBeAg was 45.48% and 41.46% respectively when its concentration was 400.0 microgram/ml. Although 3TC also has inhibitive effect in its experimental concentration, its effect is weaker. When Ara-AMP 50.0 microgram/ml was combined with 3TC 1.25 and 5.00 microgram/ml respectively, the inhibitive ratio against HBsAg were 19.92% and 17.32% respectively. Compared with using same concentration 3TC alone, the difference of results was significant (P<0.05). But when compared with using the same concentration Ara-AMP alone, the difference of results had no statistical significance (P <0.05). Remarkable inhibitive effects of combination of 3TC with Ara-AMP against HBeAg were n ot found. When 3TC 5.00 microgram/ml was combined with Ara-AMP 12.5 and 50.0 microgram/ml respectively, the inhibitive ratio against HBV DNA was 45.90% and 50.36% respectively. Comparing the content of HBV DNA in these groups with that of control group and the groups using the same concentration 3TC and Ara-AMP alone, the differences were significant (P <0.05).

CONCLUSIONSCombination of 3TC with Ara-AMP could enhance the inhibitive effects against HBV DNA.

Antiviral Agents ; pharmacology ; DNA, Viral ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Drug Synergism ; Hepatitis B virus ; drug effects ; Humans ; In Vitro Techniques ; Lamivudine ; pharmacology ; Vidarabine Phosphate ; pharmacology

OBJECTIVETo construct a lamivudine-resistant plasmid containing 1.2 unit genome of duck hepatitis B virus and identify its replication and drug-resistance in avian LMH hepatica cells.

METHODSThe recombinant plasmid PBS-DHBV1.2 was constructed using the 1.2-genome length DHBV DNA sequence from a dimer DHBV genome with pcDNA3.1 as the template. With site-directed mutagenesis, we obtained PBS-DHBV1.2-M512V plasmids with polymerase gene mutation from PBS-DHBV1.2. Two constructed plasmids were transiently transfected into LMH cells using FuGENETM6 transfection reagent and cultured in the medium containing different concentrations of lamivudine. Southern blot hybridization was performed to detect DHBV replication intermediates.

RESULTSPCR amplification, restriction digestion and plasmid sequencing all confirmed successful construction of PBS-DHBV1.2-M512V recombinant plasmid. Southern blot analysis identified the presence of all the expected DHBV replication intermediates in LMH cells. The replication capacity of the mutant plasmid was decreased by 2.7 times compared with that of the wild plasmid. The IC(50) of lamivudine was 37.12∓8.81 ng/ml for the mutant, greater than that of the wild plasmid (10.90∓4.80 ng/ml).

CONCLUSIONCompared with the wild plasmid, the mutant plasmid has a lower replication capacity and sensitivity to lamivudine in vitro.

Antiviral Agents ; pharmacology ; Drug Resistance, Viral ; drug effects ; genetics ; Hepatitis B Virus, Duck ; drug effects ; genetics ; Lamivudine ; pharmacology ; Mutagenesis, Site-Directed ; Plasmids

Antiviral Agents ; pharmacology ; Gene Frequency ; Genes, Viral ; drug effects ; Hepatitis B virus ; drug effects ; genetics ; Humans ; Lamivudine ; pharmacology ; Mutation ; drug effects

OBJECTIVETo investigate the influence of SEN virus infection on their response to lamivudine in patients with chronic hepatitis B (CHB).

METHODSSEN virus-D and -H DNA were detected in 45 CHB patients who received lamivudine 12 months with nested-PCR, and YMDD motif mutations in HBV DNA were investigated with gene chip.

RESULTSThe positive rate of SEN virus DNA was 11.1% (5/45), and there were four out of the five SEN virus DNA positive patients whose HBV DNA was positive, among them, two patients existed YMDD motif mutation. While ten out of the forty SEN virus DNA negative patients appeared HBV DNA positive. The response rate was significant lower in SEN virus-infected patients than that in uninfected patients (chi 2=3.97, P<0.05).

CONCLUSIONCoinfection with SEN virus in chronic hepatitis B patients may adversely affect the outcome of treatment with lamivudine

Anti-HIV Agents ; pharmacology ; DNA, Viral ; analysis ; drug effects ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; complications ; virology ; Humans ; Lamivudine ; pharmacology ; Respirovirus Infections ; complications ; Sendai virus

Antiviral Agents ; pharmacology ; DNA, Viral ; analysis ; Drug Resistance, Viral ; genetics ; Hepatitis B virus ; drug effects ; genetics ; Humans ; Lamivudine ; pharmacology ; Mutation ; Oligonucleotide Array Sequence Analysis

Anti-HIV Agents ; pharmacology ; DNA Mutational Analysis ; methods ; DNA, Viral ; genetics ; Drug Resistance, Viral ; genetics ; Hepatitis B virus ; drug effects ; genetics ; Lamivudine ; pharmacology ; Mutation

BACKGROUND: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. METHODS: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). RESULTS: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. CONCLUSIONS In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Adult ; Humans ; Anti-HIV Agents/therapeutic use* ; China ; Emtricitabine/pharmacology* ; HIV Infections/drug therapy* ; HIV-1 ; Lamivudine/pharmacology* ; Lipids ; Retrospective Studies

OBJECTIVETo study the factors influencing the long-term usage of lamivudine (LAM) in chronic hepatitis B (CHB) patients and the management after drug-resistance.

METHODS383 cases of naive CHB patients in our outpatient clinic were treated with lamivudine (100 mg/d) and followed up for at least over 1 year from 2001 to 2010. 129 cases encountered lamivudine-resistance and were then divided into two groups: patients in group A were switched to adefovir dipivoxil (ADV) alternative treatment and those patients in group B were added with ADV for continuous treatment. Efficacy assessment factors included serum HBV markers, HBV DNA, ALT, AFP and other biochemical indicators.

RESULTSAmong the 383 cases, patients with HBV DNA negative conversion (PCR below test line) at 3 months, 6 months, 1 year, 2 years, 3 years and > 3 years after initial treatment were respectively 156 cases (40.7%), 213 cases (55.6%), 228 cases (59.5% ), 217cases (56.7%), 214 cases (55.9%) and 213 cases (55.6%). HBeAg/HBeAb seroconversion occurred in 62 cases (22.6%). 12 cases were found with primary LAM resistance, 129 cases with HBV breakthrough and rebound, the cumulative resistance rate was 36.8% and the cumulative rebound rate was 34.8%. High baseline viral load, baseline ALT levels < 2 ULN, Lower virologic response rate at week 24 were associated with a higher rebound rate (chi2 is 35.716, 8.728, 43.534, respectively, all with P < 0.01).Viral breakthrough and rebound occurred in 112 patients (86.8%) within 1 year and a half, 123 patients (95.3%) occurred at the end of 2 years and no patient with viral breakthrough and rebound after 5 years. For the patients with viral rebound in group A and group B, the rates of HBV DNA loss were 22.7% (15/66) and 58.7% (37/63) respectively, and the viral response rates were 59.1% (39/66) and 87.3% (52/63) respectively, with chi2 values equaled 17.364 and 12.975 respectively (P < 0.01).

CONCLUSIONFor the chronic hepatitis B patients on initial treatment with lamivudine, the viral rebound occurred mainly within 2 years. LAM combined with ADV is more effective than ADV alone for lamivudine-resistant patients.

Adenine ; analogs & derivatives ; pharmacology ; therapeutic use ; Adolescent ; Adult ; Aged ; Antiviral Agents ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; Female ; Follow-Up Studies ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; pharmacology ; therapeutic use ; Young Adult