Efficacy and tolerability of dolutegravir plus lamivudine as a switch simplified strategy in treatment-experienced human immunodeficiency virus/acquired immunodeficiency syndrome patients / 中华传染病杂志

Objective:To evaluate the efficacy and tolerability of the dual therapy of dolutegravir (DTG) plus lamivudine (3TC) as a switch simplified strategy in treatment-experienced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients.Methods:Treatment-experienced HIV/AIDS patients who switched to a dual therapy containing DTG (50 mg, once daily) plus 3TC (300 mg, once daily) were included in Beijing You′an Hospital, Capital Medical University from September 2016 to May 2019. HIV RNA, CD4 + T lymphocyte count, blood lipid indexes, renal function indexes were collected when patients changed the treatment regimen (baseline) and after 48 weeks of treatment. Efficacy (HIV RNA<50 copies/mL) and safety of the dual therapy were analyzed. Statistical comparisons were performed using the Wilcoxon matched-pairs signed rank test. Results:The reasons for 33 patients switching the treatment regimen were virologic failure (four cases, 12.1%), simplification of regimen (11 cases, 33.3%), and drug toxicity (18 cases, 54.5%). The patients were treated with anti-retroviral therapy (ART) for 2.13 (1.05, 4.23) years before regimens switching. Twenty-nine (87.9%) patients were virologically suppressed at baseline, and four (12.1%) patients were virological failure. After switching to DTG plus 3TC, all 33 patients showed HIV RNA<50 copies/mL after 48 weeks of treatment. The baseline CD4 + T lymphocyte count was 543 (363, 595)/μL. After switching the treatment regimens for 48 weeks, CD4 + T lymphocyte count was significantly increased to 625 (455, 651)/μL, and the difference was statistically significant ( Z=3.14, P=0.002). Compared with baseline, low-density lipoprotein-cholesterol was increased after 48 weeks of treatment (2.35(1.80, 3.08) mmol/L vs 3.12(2.74, 3.87) mmol/L), while triglyceride (2.21(1.27, 4.37) mmol/L vs 1.61(1.20, 2.22) mmol/L), the ratio of total cholesterol to high-density lipoprotein-cholesterol (5.02 (4.13, 6.40) vs 4.70 (3.55, 5.35)) and estimated glomerular filtration rate (106.4(78.2, 118.2) mL/(min·1.73 m 2) vs 88.6 (75.7, 107.9) mL/(min·1.73 m 2)) were decreased. The differences were all statistically significant ( Z=4.89, 2.37, 2.09 and 2.83, respectively, all P<0.050). No patient discontinued due to adverse events. Conclusions:The use of dual therapy containing DTG and 3TC is effective and well-tolerated in treatment-experienced HIV/AIDS patients under any prior ART without significant adverse events.

Development And Evaluation Of Lamivudine Sustained Release Matrix Tablets

Lamivudine is approved for clinical use and used widely in treatment of Hepatitis Band AIDS either alone or in combination with another antiviral drugs because of its watersolubility and shorter half-life (5-7 hrs) drug requires frequent dosing by oral route, off variousrecent techniques for controlling drug release, matrix system offer various advantages of easeof formulation better control on release profile of drug and better patient compliance. Thematrix tablets formulation by direct compression method is most acceptable in large scaleproduction. It is concluded that formulation of sustained release tablet of Lamivudinecontaining 80 mg of hydroxypropyl-methylcellulose E15 (high viscosity grade) and 80 mg ofethylcellulose i.e. formulation F7 can be taken as an ideal or optimized formulation ofsustained release tablets for 16 hours release as it fulfills all the requirements for sustainedrelease tablet and our study encourages for the further clinical trials and long term stabilitystudy on this formulation.

Drumstick Mucilage Microspheres For Controlled Release Of Lamivudine: Design, Optimization And In Vitro Evaluation

Objective: The objective of this study was to design and evaluate controlled release mucoadhesive microspheres of lamivudine using mucoadhesive polymers and mucilage. Methods: Mucoadhesive microspheres of lamivudine were formulated by ionic gelation method. The response surface methodology was adapted for optimization of formulation using central composite design (CCD) for two factors at three levels each was employed to study the effect of independent variables, Sodium alginate-drumstick mucilage (X1) and calcium chloride (CaCl2) concentration (X2) on dependent variables, namely drug encapsulation efficiency (DEE) and particle size (PS). Optimized drumstick mucilage mucoadhesive microspheres of lamivudine were obtained by using numerical optimization of desirability approach. The observed microspheres were coincided well with the predicted values by the experimental design. Results: The microspheres formed were spherical in shape, and Particle size (PS) ranged between 681.63-941.57μm. Drug encapsulation efficiency (DEE) was ranged between 69.63-94.56 %. The drug release for an optimized formulation was 96.58 %. The mechanism of drug release from microspheres followed Korsemeyer’s-Peppas and exponential ‘n’ value was greater than 0.45, indicating the drug release was non-fickian i.e., swelling followed by erosion mechanism. Conclusion: This work suggests that mucoadhesive microspheres, an effective drug delivery system for lamivudine, can be prepared using drumstick mucilage in improving the bioavailability of the drug.

Comparison of the efficacy of lamivudine and enticavir in preventing hepatitis B virus reactivation in patients with B-cell non-Hodgkin lymphoma / 中国基层医药

Objective@#To investigate the efficacy of enticavir and lamivudine in preventing rituximab-associated hepatitis B virus(HBV) reactivation in patients with B-cell non-Hodgkin lymphoma complicated with resolved hepatitis B during chemotherapy.@*Methods@#This retrospective study included 216 B-cell non-Hodgkin lymphoma patients with complete data from January 2012 to January 2018 treated in 3 hospitals.Of 78 patients with resolved hepatitis B, they were divided into lamivudine prophylactic group(17 cases), entecavir prophylactic group(11 cases) and control group(50 cases). The changes of HBVM, HBV DNA and liver function before or after rituximab combination chemotherapy were analyzed.The incidence of HBV reactivation, liver function injury and chemotherapy delay were compared.@*Results@#Compared to the other 71 patients, 7 cases experienced HBV reactivation in 78 patients with resolved hepatitis B. There were no statistically significant differences between the two groups in patient demographics, pathological pattern, chemotherapy regimen.Six patients in the control group developed HBV reactivation(12%) and 1 patient in lamivudine prophylactic group(5.88%), none had HBV reactivation in enticavir prophylactic group.There was statistically significant difference among three groups(Fisher P=0.016). A total of 7 cases experienced HBV reactivation in 78 patients with resolved hepatitis B respectively, 2 cases in the first chemotherapy period, 2 cases in the third chemotherapy period, 1 case in the fifth chemotherapy period, the last one occurred after the completion of chemotherapy.Four patients had HBsAg reverse seroconversion, occurred in the 1, 3, 5 cycles during and after the completion of chemotherapy.Twenty patients (40.0%) experienced liver function parameters abnormal in the control group, 4 cases(23.5%) in lamivudine prophylaxis group, 2 cases (18.2%) in enticavir prophylaxis group during chemotherapy.@*Conclusion@#Antiviral prophylaxic therapy can potentially prevent rituximab associated HBV reactivation in patients with resolved hepatitis B. Entecavir can more reduce the risk of rituximab associated HBV reactivation than lamivudine.

The inhibition mechanism of the uptake of lamivudine via human organic anion transporter 1 by Stellera chamaejasme L. extracts / 中国天然药物

Stellera chamaejasme L. is a traditional Chinese medicine with a long history to treat stubborn skin ulcer, and it also has antiviral and antitumor effects. Neochamaejasmine B (NCB), Neochamaejasmine A (NCA) and Chamaechromone (CMC) are the major components in dried roots of Stellera chamaejasme L.. Our studies suggested that NCB, NCA and CMC are inhibitors of Organic anion transporter 1 (OAT1). OAT1 is encoded by solute carrier family 22 member 6 gene (SLC22A6) in humans and plays a critical role in the organic anion drug uptake and excretion in the kidney. Lamivudine is the typical substrate of OAT1 and is frequently used in combination with other antiviral drugs in clinical antiviral treatments. The aim of this study is to investigate the interaction and its mechanism between these bi-flavone components in Stellera chamaejasme L. and lamivudine via OAT1 both in vitro and in vivo. In vitro, the uptake studies in Madin-Darby canine kidney (MDCK) cells overexpressing OAT1 suggested that NCB inhibited the uptake of 6-CFL and lamivudine.Similar results were obtained for NCA and CMC. NCB was a noncompetitive and competitive inhibitor interaction with OAT1. IC values of NCB, NCA and CMC for inhibiting OAT1-mediated lamivudine transport were 2.46, 8.35 and 0.61 μmol·L, respectively. In vivo, the pharmacokinetic results of lamivudine in rats showed that the mean area under the plasma concentration-time curve (AUC) and maximal plasma concentration (C) of lamivudine after co-administration is increased 2.94-fold and 1.87-fold, respectively, compared to lamivudine administration alone. The results of interactions between lamivudine and these bi-flavone components in Stellera chamaejasme L. extracts via OAT1 in vivo are consistent with studies in vitro. The inhibition of OAT1-mediated uptake of lamivudine by NCB, NCA and CMC is the possible mechanism for Stellera chamaejasme L. extracts improving the oral bioavailability of lamivudine in rats.

Novel fluoronucleoside analog NCC inhibits lamivudine-resistant hepatitis B virus in a hepatocyte model

ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.

Lamivudine plus tenofovir versus lamivudine plus adefovir for the treatment of hepatitis B virus in HIV-coinfected patients, starting antiretroviral therapy

Background: Combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and efavirenz (EFV) is preferred in the treatment of HIV/hepatitis B virus (HBV) coinfection. We postulated that a HBV active nucleoside reverse transcriptase (RT) inhibitor/nucleotide RT inhibitor backbone of adefovir dipivoxil (ADV) +3TC would be as effective as TDF +3TC for the Indian population. Objective: ADV + 3TC could be an alternative option for these HIV/HBV coinfected individuals, preserving the dually active TDF + 3TC as second-line nucleoside backbone following failure of the first-line ART. Materials and Methods: This randomised control trial (CTRI/2012/03/002471) was carried out at the ART Centre of Calcutta School of Tropical Medicine, India. Seventy-eight (39 on each arm) treatment-naïve HIV/HBV coinfected patients were randomised to receive either the combination of lamivudine + tenofovir + EFV or lamivudine + adefovir + zidovudine + EFV and followed up for 120 weeks. Results: Median age of the study participants was 36 years (21–62), majority were male (61/78; 78.2%) and heterosexually (39/78; 50%) infected. Baseline characteristics were identical in both arms. There was no statistically significant difference in median aspartate aminotransferase (37 vs. 29.5 U/L), alanine aminotransferase (ALT) (36 vs. 34.5 U/L), ALT normalisation rate (80 vs. 70%), AST to platelet ratio index (0.45 vs. 0.33), CD4 count (508 vs. 427 cells/mm3), HBV DNA suppression (81.8 vs. 70%), hepatitis B e antigen loss (9 vs. 5%), hepatitis B surface antigen seroclearance rate (6.06 vs. 18.75%) and death (3 vs. 3) at 120 weeks between TDF (n = 33) and ADV (n = 32), respectively. Conclusions: Adefovir plus lamivudine is an effective alternative of tenofovir plus lamivudine in long-term HBV treatment outcome in HIV/HBV coinfected patients.

Preventive effects of lamivudine combined with chemotherapy drugs on HBV reactivation in patients with HBV infection and tumor / 中国综合临床

Objective To investigate the preventive effects of lamivudine combined with chemotherapy drugs on hepatitis B virus reactivation in patients with HBV infection and tumor. Methods From July 2014 to February 2017,a total of one hundred and twenty patients with HBV infection and tumor in Nanchong Central Hospital were selected and were divided into the observation group and control group with 60 cases in each group. The control group received conventional chemotherapy and liver protection treatment,the observation group was given lamivudine prophylaxis treatment(100 mg/d,1 time/d) based on the treatment in the control group, two groups were treated for 8 weeks. Results The rates of hepatitis B virus reactivation in the observation group and the control group were 5. 0％(3/60) and 33. 3％(20/60),respectively,and the difference between the two groups was statistically significant (χ2=15. 692,P<0. 05) . There was no significant difference in serum glutamic acid transferase and aspartic transferase in the patients before and after treatment ( P>0. 05 ) , and the control group showed an upward trend ( P<0. 05) . After treatment,the serum ALT and AST in the observation group ((31. 98±6. 33)U/L,(26. 38±4. 98)U/L) were lower than those in the control group((43. 89±6. 73)U/L, (51. 78±5. 99)U/L)(t=8. 294,11. 842,P<0. 05). After treatment,the HBV DNA in the observation group and the control group((0. 16±0. 04) ×103copies/ml,(5. 02±1. 72) ×103copies/ml) were lower than those before treatment ((14. 55±2. 14)×103copies/ml,(14. 09±1. 98 copies/ml )(t=25. 498,8. 142,P<0. 05),and the HBV DNA in the observation group after treatment was also lower than that of the control group. The difference between the two groups was statistically significant ( t=24. 292,P<0. 05) . Conclusion Lamivudine combined with chemotherapy drugs used in patients with HBV infection and tumor can prevent hepatitis B virus reactivation,it does not affect the patient′s liver function,it can inhibit the replication of hepatitis B virus,so it has good application values.

Clinical observation of continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B / 中华肝脏病杂志

Objective@#To observe continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B.@*Methods@#Data of patients with active stage of chronic hepatitis B over the past 6 years were collected and analyzed retrospectively. The incidence of drug resistance mutation and related factors between patients taking LAM or ETV continuously and intermittently were compared with those taking LAM or ETV. Data comparison was performed using χ2 test.@*Results@#Patients with HBV DNA≥105 copies / ml at the time of initial treatment had higher resistance mutation rates than those with HBV DNA < 105 copies / ml at either continuous or intermittent treatment, and patients with intermittent treatment had higher resistance mutation rates than those with continuous treatment. Simultaneously, the incidence of drug resistance mutation in LAM and ETV in the first, second and third years were significantly higher in intermittent treatment than that of continuous treatment (P < 0.05). There was a positive correlation between the frequency of drug withdrawal and the rate of drug resistance mutation. There were no individual difference and drug difference between LAM and ETV.@*Conclusion@#In the treatment of chronic hepatitis B with oral nucleoside analogues, drug resistance may occur in either continuous or intermittent treatment. When comparing continuous with intermittent treatment, it suggests that intermittent is more likely to cause viral resistance mutation.

Compare the effect of combined therapy between telbivudine plus adefovir dipivoxil and lamivudine plus adefovir dipivoxil corresponding to renal function in patients with hepatitis B virus infection / 中华肝脏病杂志

Objective@#To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients.@*Methods@#A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ 2 test.@*Results@#There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min-1 ·(1.73 m2)-1] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal.@*Conclusion@#For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.

Efficacy and safety of Entecavir monotherapy switched from Lamivudine combined Adefovir Dipivoxil for chronic hepatitis B virus-related compensated liver cirrhosis / 中华肝脏病杂志

Objective@#To observe the efficacy and safety of de novo combination of Lamivudine(LAM) and Adefovir Dipivoxil (ADV) therapy counter to Entecavir (ETV) monotherapy in patients with chronic hepatitis B (CHB)- related compensated liver cirrhosis.@*Methods@#Patients with chronic hepatitis B-related compensated cirrhosis who were initially treated with LAM and ADV for more than 1 year were randomly assigned to two groups, one half replaced with ETV monotherapy, and the other half continued LAM and ADV co-therapy. Liver biochemistry, renal biochemistry, estimated glomerular filtration rate, alpha-fetoprotein, HBV serology markers and serum HBV DNA were measured every 3 months. Urine β2-microglobulin was measured every 6 months And retinol binding protein, followed up for 3 years. The mean values of the two groups were compared with t-test, and the rate of comparison was analyzed by x2 test.@*Results@#A total of 580 cases were collected, 290 cases were replaced with ETV monotherapy, the other 290 patients continued to LAM and ADV combination therapy. In the ETV group, the rates of HBV DNA negative conversion at 1 year, 2 years and 3 years were 77.6%, 84.5% and 94.5% respectively, while the HBV DNA negative conversion rates at 1, 2 and 3 years in the LAM and ADV combination groups were 69.3%, 73.4% and 80.3% respectively. Among them, the negative rates of HBV DNA in the second year and the third year were P < 0.05, the difference was statistically significant. The 3-year cumulative gene-resistant rate in the ETV group was 1.4%, while the combined treatment was as high as 8.6%, and the difference was statistically significant in the two groups. The estimated value of serum creatinine and glomerular filtration rate in ETV group was followed by 3 years, and the baseline level was maintained, in the same group, the serum creatinine was higher than baseline, and the estimated value of glomerular filtration rate decreased. The results showed that there were 6.2%, 12.1%, 22.1% and 0, 0.3%, 1%, respectively, in 1, 2 and 3 years for the group of consecutive treatment and the replacement of ETV Group. The estimated glomerular filtration rate decreased by more than 30% compared with the baseline. The difference was statistically significant; the proportion of serum creatinine in the 1 year, 2 years and 3 years of the combined treatment group was 1.7%, 4.5% and 6.6%, compared with the baseline rise of > 50 μmol/l, and the ETV group was replaced in the 1 year, The values of 2 and 3 years were 0,0,0.7%, of which the 2nd and 3rd years were statistically significant; the proportion of microalbuminuria and retinol-binding protein in patients with combined treatment group was also significantly higher than that of Β2-m ETV Group.@*Conclusion@#The initial combination of LAM and ADV therapy is inferior in terms of ETV monotherapy. Single therapy with ETV increase the rate of viral response, reduce the incidence of drug resistance, and also reduce the incidence of renal impairment in patients with chronic hepatitis B -related compensated liver cirrhosis.

A Multicenter Study of the Antiviral Efficacy of Entecavir Monotherapy Compared to Lamivudine Monotherapy in Children with Nucleos(t)ide-naïve Chronic Hepatitis B

BACKGROUND: The aim of this study was to compare the long-term efficacy of entecavir (ETV) and lamivudine (LAM) therapy in children with chronic hepatitis B (CHB) who had not received nucleoside analogue treatment. METHODS: In this multicenter, retrospective study, we included pediatric CHB patients younger than 20 years who received ETV or LAM treatment for at least 12 months and had no concomitant diseases. All of the patients were followed up every 1 to 3 months. At each visit, the patients underwent clinical evaluation and biochemical testing. RESULTS: Eight (53.3%), 14 (93.3%), and 2 (15.4%) of the ETV-treated patients achieved virologic suppression, alanine aminotransferase (ALT) normalization and hepatitis B e antigen (HBeAg) seroconversion, respectively, at 1 year. In the ETV group, the cumulative rate of virologic suppression at 3 years was 91.7%, which was significantly higher than that in the LAM group (P < 0.001). The mean duration of treatment before virologic suppression was shorter in the ETV group than in the LAM group (P = 0.040). The cumulative rate of seroconversion in the ETV group at 3 years was 39.4%, which was not significantly different from that in the LAM group (P = 0.439). The ETV group showed lower cumulate rates of virologic breakthrough (33.3% at 6 years) and genotypic mutation than the LAM group (P = 0.033 and P = 0.011, respectively). CONCLUSION: ETV is superior to LAM in pediatric CHB treatment because of its higher virologic suppression rate and lower cumulative rates of virologic breakthrough and genotypic mutation.

Antiviral Efficacy of Tenofovir Monotherapy in Children with Nucleos(t)ide-naive Chronic Hepatitis B

BACKGROUND: The purpose was to compare the efficacy between tenofovir disoproxil fumarate (TDF) and lamivudine (LMV) in children with nucleos(t)ide-naive chronic hepatitis B (CHB) infection. Patients with CHB were treated with TDF in the immune-reactive phase and compared with a historical control group of patients treated with LMV before the TDF era. METHODS: Hepatitis B virus (HBV) DNA titer decrements (> 3 log₁₀ IU/mL) were monitored after treatment initiation. The treatment duration for HBV DNA clearance ( 3 log₁₀ IU/mL) was achieved in 100% (16/16) of the TDF group but in only 62.5% (15/24) of the LMV group (P = 0.005) at 48 weeks. The HBV DNA clearance (< 357 IU/mL) in the TDF and LMV groups was, respectively, as follows: 62.5% (10/16) and 25.0% (6/24) at 12 weeks (P = 0.018), 81.3% (13/16) and 37.5% (9/24) at 24 weeks (P = 0.006), 93.8% (15/16) and 50.0% (12/24) at 48 weeks (P = 0.004), and 100% (16/16) and 54.2% (13/24) at 96 weeks (P = 0.001). Complete response occurred in 41.7% (5/12) of HBeAg-positive patients in the TDF group and 28.6% (6/21) of the LMV group at 96 weeks (P = 0.443). CONCLUSION: TDF monotherapy for 96 weeks produced a significantly more effective virologic response than LMV monotherapy in children with nucleos(t)ide-naive CHB.

Therapeutic Efficacy of Lamivudine in Children and Adolescents with Chronic Hepatitis B

PURPOSE: This prospective study aimed to investigate the therapeutic efficacy of lamivudine in children with chronic hepatitis B virus (HBV) infection. METHODS: During July 2003 through October 2015, children with chronic hepatitis B who visited our institution were included in this study. Fifty-five patients, who received first-line treatment of lamivudine (3 mg/kg, 100 mg maximum) for over three months, were enrolled. After initiating lamivudine, alanine aminotransferase (ALT), HBV-DNA, and HBV markers were followed up at 1 month, 3 months, and every 3 months, thereafter. The treatment endpoint was determined as 1) normalization of ALT, 2) HBeAg seroconversion, and 3) anti-HBe positivity for twelve consecutive months. RESULTS: Thirty-one male (56.4%) and 24 female (43.6%) patients were included. The mean age at treatment initiation was 8.1 years. The mean duration of treatment was 23.4 months. ALT normalization was found in 98.2% (54 of 55). Anti-HBe seroconversion was found in 70.6% (36/51). Loss of HBsAg was found in 10.9% (6/55). All biochemical responses occurred under age seven. The rate of virologic response (defined as HBV-DNA <2,000 IU/mL) at six months after treatment initiation was 78.7% (37/47). At twelve months after reaching treatment endpoint, 87.2% (34/39) maintained their virologic response. Resistance to lamivudine was found in 16.4% (9/55). CONCLUSIONS: Lamivudine treatment in Korean pediatric patients with chronic hepatitis B showed better outcomes compared with other studies that implemented similar protocols in foreign populations. Further studies are needed to investigate the efficacy of newly recommended antiviral drugs on the Korean pediatric population.

Zidovudine/Lamivudine vs. Abacavir/Lamivudine vs. Tenofovir/Emtricitabine in fixed-dose combinations as initial treatment for HIV patients: a systematic review and network meta-analysis / Zidovudina/Lamivudina vs Abacavir/Lamivudina vs Tenofovir/Emtricitabina en combinaciones de dosis fija como tratamiento inicial en pacientes con VIH: revisión sistemática y metanálisis en red

Abstract Introduction: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. Objective: To compare the efficacy and safety of these three combinations. Methods: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Results: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC Conclusions: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.

Resumen Introducción: El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad. Objetivo: Comparar la eficacia y seguridad de las 3 combinaciones Métodos: Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC). Resultados: Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC. Conclusión: Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.

Hipersensibilidade a lamivudina em paciente infectada pelo HIV: relato de caso / Lamivudine's hypersensitivity in an HIV infected patient: case report

Importância do problema: Relatar um caso de hipersensibilidade à lamivudina, droga considerada segura e antirretroviral indicado como de primeira linha para início de tratamento para pacientes infectados pelo HIV. Comentários: É relatado o caso de paciente infectada pelo HIV que evoluiu com farmacodermia associada à terapia antirretroviral (TARV) utilizando tenofovir, lamivudina e efavirenz. Inicialmente, a hipersensibilidade foi atribuída ao efavirenz, pela maior incidência de eventos desta natureza com este medicamento e este foi substituído por fosamprenavir/ ritonavir. Apesar da substituição, paciente desenvolveu síndrome de Stevens-Johnson. Foi hospitalizada e iniciou novo esquema, com introdução de droga a droga, com atazanavir/ritonavir, seguido de zidovudina e lamivudina, desenvolvendo manifestação de eritema multiforme após a última droga, sendo esta considerada a responsá- vel pela hipersensibilidade. (AU)

Relevance: To report a case of hypersensitivity to lamivudine, a medicine that is considered safe and is indicated as part of the initial therapy for HIV infected patients. Comments: It is reported the evolution of an HIV patient who developed a drug eruption due to the following antirretroviral therapy: tenofovir, lamivudine and efavirenz. It initially was attributed to efavirenz, due to its higher incidence in these adverse reactions and it was replaced by fosamprenavir/ritonavir. In spite of the replacement, the patient developed Stevens-Johnson's Syndrome. She was hospitalized and began a new therapy with atazanavir/ritonavir, followed by zidovudine and lamivudine and presented a drug reaction with the last one, which was considered to be the responsible for the hypersensitivity. (AU)

Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV. METHODS: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV. RESULTS: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001). CONCLUSIONS: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.

Is it possible to predict the development of an entecavir resistance mutation in patients with chronic hepatitis B in clinical practice?

No abstract available.

Lamivudine: fading into the mists of time

No abstract available.

Efficacy and safety of entecavir versus lamivudine over 5 years of treatment: A randomized controlled trial in Korean patients with hepatitis B e antigen-negative chronic hepatitis B

BACKGROUND/AIMS: Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. METHODS: Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P < 0.0001), and week 240 (95.0% vs. 47.6%, P < 0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P < 0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P < 0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. CONCLUSIONS: Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.