BACKGROUND Tenofovir alafenamide fumarate(TAF)is one of the first-line treatments used to treat chronic hepatitis B patients;TAF has strong antiviral activity and a high barrier to resistance.Although virological brea...BACKGROUND Tenofovir alafenamide fumarate(TAF)is one of the first-line treatments used to treat chronic hepatitis B patients;TAF has strong antiviral activity and a high barrier to resistance.Although virological breakthroughs in patients during TAF treatment are rare,patients with incomplete responses to TAF are occasionally observed.AIM To investigate responsible mutations in the reverse transcriptase region of hepatitis B virus(HBV)for TAF-incomplete responses.METHODS Thirteen chronic hepatitis B patients who received TAF monotherapy were included.A TAF-incomplete responder was defined as one who was continuously positive for HBV DNA over 2 years after TAF treatment initiation.The emergences of mutations in TAF-incomplete responders were evaluated before,one year after,and two years after treatment by deep sequencing of HBV DNA and RNA.RESULTS Two patients were continuously positive for HBV DNA over two years.The rtL269I mutation,one of the CYEI mutations linked to tenofovir resistance,was detected in both patients by direct sequencing.The deep sequencing analysis revealed that a combination of rtT118A and rtL220I mutations and the rtL269I mutation were predominantly detected in HBV DNA even when these mutations were barely detected in HBV RNA.This suggests a superior replication capability of the HBV variants with these mutations under TAF treatment.CONCLUSION The deep sequencing analysis of HBV DNA and RNA and comparing the detection rates of mutations were useful for estimating responsible mutations for TAF-incomplete responses.Such analysis is needed to evaluate the association between mutations that emerge during TAF treatment and incomplete responses to TAF.展开更多
BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is...BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is unclear.AIM To compare the effects of TAF and entecavir(ETV)on serum lipid levels in patients with CHB.METHODS In this retrospective cohort study,the data including the clinical features,serum lipids,and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed.We used propensity score-matched models to assess the effects on high-density lipoprotein,lowdensity lipoprotein,triglycerides,and total cholesterol(TCHO).RESULTS A total of 336 patients(75.60%male)were included;63.69%received TAF and 36.31%received ETV.Compared with the ETV group,the TAF group had significantly higher TCHO levels after treatment(4.67±0.90 vs 4.36±1.05,P=0.006).In a propensity score-matched model for body mass index,age,sex,smoking,drinking,presence of comorbidities such as NAFLD,cirrhosis,diabetes mellitus,and hypertension,TAF-treated patients had significantly increased TCHO levels compared to that at baseline(P=0.019).There was no difference for the ETV group.Body mass index,sex,hypertension,baseline TCHO,and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis.However,1-year TAF treatment did not increase the incidence of NAFLD.CONCLUSION A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV.However,TAF-induced dyslipidemia did not increase the incidence of NAFLD.展开更多
Tenofovir disoproxil fumarate(TDF)is a potent nucleotide analogue with high barrier to resistance,which is recommended for multi-drug resistant hepatitis B virus(HBV)infection.However,nephrotoxicity has been reported ...Tenofovir disoproxil fumarate(TDF)is a potent nucleotide analogue with high barrier to resistance,which is recommended for multi-drug resistant hepatitis B virus(HBV)infection.However,nephrotoxicity has been reported during TDF treatment,and tenofovir alafenamide(TAF),which has comparable efficacy to TDF and improves bone and renal safety,can be used as a replacement strategy.Herein,we describe a clinical case concerning a 60-year-old individual suffering liver cirrhosis and renal dysfunction,and being infected with multidrug-resistant HBV.When failing treatment with TDF,he received TAF as a rescue therapy.TAF effectively inhibited HBV replication without worsening renal function or serum phosphorus abnormality.Furthermore,hepatocellular carcinoma(HCC)occurred during TAF treatment despite controlling the viral load.The risk of HCC could not be eliminated and should be monitored during TAF treatment.展开更多
BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel ...BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNA<20 IU/mL,but detectable)were enrolled in the study.The patients were randomly assigned to either continue ETV(0.5 mg)daily or switch to TAF(25 mg)daily for 48 wk.The primary endpoint was the proportion of patients who achieved a virologic response(HBV DNA level<20 IU/mL)at week 48.Secondary endpoints included changes in serum alanine aminotransferase(ALT),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and anti-HBe levels,and renal and bone safety parameters.RESULTS At week 48,the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two groups.None of the patients developed genotypic resistance to ETV or TAF.Both drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse events.No significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either group.The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group(-0.8%vs-2.1%,P=0.004;-0.6%vs-1.8%,P=0.007,respectively).CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.展开更多
This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We...This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We review the related research content,topic selection,methodology,conclusions,strengths and weaknesses of this article.And evaluate it in relation to other published relevant articles.展开更多
Objective:To evaluate the effect of tenofovir alafenamide versus tenofovir disoproxil fumarate on antiviral efficacy in patients with hepatitis B virus infection.Methods:Randomized controlled trials were searched on C...Objective:To evaluate the effect of tenofovir alafenamide versus tenofovir disoproxil fumarate on antiviral efficacy in patients with hepatitis B virus infection.Methods:Randomized controlled trials were searched on CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Cochrane Library,Embase,ClinicalKey,Chinese Clinical Trial Registry and ClinicalTrials.gov from the date of inception to April 2020.The literature was screened according to the inclusion and exclusion criteria,and the efficacy evaluation index of the included RCT was set as the success rate of reaching the endpoint of viral suppression and achieving normalized ALT values at 48 weeks of treatment.Intentionality analysis was adopted and the analysis results were taken as the final conclusion.RevMan 5.3 software was used for this Meta-analysis.Meanwhile,VassarStats was used to evaluate the non-inferiority of TAF and calculate the difference of virus inhibition efficiency rate and 95%confidence interval between experimental group and the control group of each RCT.Results:After the literature search,411 potential articles were found,5 studies were finally included according to the criteria,and 2,120 patients were included.Intentionality analysis showed that TAF regimen and TDF regimen had similar viral suppression success rates(RR=0.97,95%CI:0.94~1.01,P=0.19).The ALT normalization rate in the TAF treatment group was higher than that in the TDF treatment group,and the difference was statistically significant(RR=1.35,95%CI:1.20-1.53,P<0.00001).The non-inferiority margin was set at 10%,and it was found that three RCT studies in the international multi-center all showed that TAF was not inferior to TDF in controlling HBV viral load,while two RCT studies in China's Mainland failed to achieve non-inferiority after calculation.Conclusions:At 48 weeks of treatment,TAF was similar to TDF in controlling HBV viral load.However,the efficacy of TAF in controlling HBV viral load may vary among different populations,which requires further confirmation by more clinical trial evidence.Based on AASLD criteria,the ALT normalization rate of the TAF group was higher than that of the TDF group at 48 weeks of treatment,showing an obvious advantage.展开更多
BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alan...BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.展开更多
Objective To compare the real-world efficacy and safety profile of tenofovir amibufenamid(TMF)and tenofovir alafenamide(TAF)tablets in the treatment of patients with chronic hepatitis B(CHB).Methods This retrospective...Objective To compare the real-world efficacy and safety profile of tenofovir amibufenamid(TMF)and tenofovir alafenamide(TAF)tablets in the treatment of patients with chronic hepatitis B(CHB).Methods This retrospective study included patientswithhchronic hepatitis B who received TMF and TAFantiviral treatment at the Infectious Disease Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023.The primary and secondary outcome was to study the patient HBV DNA conversion rate(<20 IU/ml),alanine aminotransferase(ALT)normalization rate,renal function,and lipid levels of patients at 48 weeks of treatment.TThe comparison of data between measurement data groups was differentiated using a t-test and Mann-Whitney U test.The inter-group comparison rate in count data was performed using the x?test or Fisher's exact probability.Results A total of 440 cases were enrolled,including 220 in the TMF group(63 treatment-naive and 157 treatment-experienced)and 220 cases in the TAF group(61 treatment-naive and 159 treatment-experienced).In terms of efficacy,the HBV DNA seroconversion rates in the TMF group and TAF group were 90.5%and 85.2%(P=0.372),respectively,while the ALT normalization rates were 92.1%and 88.5%(P=0.505),respectively,at 48 weeks of treatment.The HBV DNA-negative conversion rate for the newly treated patients was 99.4%and 98.7%,respectively(P=1.000),while the rates of ALT normalization were 94.9%and 92.3%,respectively(P=0.863).In terms of safety profile,the serum creatinine level was lower in the TMF group than that in the TAF group at 48 weeks of treatment[TMF group 66.5(56.3,78.3)μmol/L,TAF group 70.6(60.7,77.8)μmol/L,Z=-2.282,P=0.022].However,there was no statistically significant difference in other renal function and tubular function related indicators between the two groups of patients(P>0.05).The serum high-density lipoprotein levels were higher in the TMF group than those in the TAF group[TMF 1.4(1.1,1.6)mmol/L vs.TAF group 1.3(1.1,1.6)mmol/L,Z=-2.204,P=0.027]at 48 weeks of treatment.However,there was no statistically significant difference in other blood lipid indicators between the two groups of patients(P>0.05).Conclusion There is no statistically significant difference in efficacy and safety profiles between TMF and TAF at 48 weeks in the treatment of patients with chronic hepatitis B,and the overall safety profile is favorable.展开更多
Background and Aims:The therapeutic effect of tenofovir alafenamide fumarate(TAF),tenofovir disoproxil fumarate(TDF)and entecavir(ETV)on chronic hepatitis B(CHB)patients remains inconsistent.The aim of this study was ...Background and Aims:The therapeutic effect of tenofovir alafenamide fumarate(TAF),tenofovir disoproxil fumarate(TDF)and entecavir(ETV)on chronic hepatitis B(CHB)patients remains inconsistent.The aim of this study was to explore the differences in virological responses to TAF,TDF and ETV in patients with CHB.Methods:Literature searches were conducted of the PubMed,EMBASE,and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21,2020.Statistical comparisons of virological response between TDF,ETV,and TAF were carried out with pooled odds ratio(OR)values.Results:The virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks[OR=1.12,95%confidence interval(CI):0.89–1.41],24-weeks(OR=1.33,95%CI:1.11–1.61),48-weeks(OR=1.62,95%CI:1.16–2.25),72-weeks(OR=1.43,95%CI:0.78–2.62),and 96-weeks(OR=1.56,95%CI:0.87–2.81)treatment.No significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or TDF.The virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks,48-weeks(OR=1.54,95%CI:1.17–2.02),96-weeks,and 144-weeks.Conclusions:The virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients,but there was no significant difference between TAF and TDF.In addition,the therapeutic effect of TDF+ETV was superior to TDF alone.展开更多
Background:Central nervous system(CNS)symptoms after efavirenz(EFV)treatment in people living with human immunodeficiency virus(HIV)could persist and impact their quality of life.We assessed the impact of EFV-based re...Background:Central nervous system(CNS)symptoms after efavirenz(EFV)treatment in people living with human immunodeficiency virus(HIV)could persist and impact their quality of life.We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide(E/C/F/TAF),which is considered an alternative option for subjects who do not tolerate EFV.Most specifically,we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants’neuropsychiatric toxicity symptoms in a real-life setting.Methods:A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity≥grade 2.The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks.The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire,as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index.The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12,24,and 48.Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.Results:One hundred ninety-six participants(96.9%men,median age:37.5 years,median:3.7 years on prior EFV-containing regimens)were included in the study.Significant improvements in anxiety and sleep disturbance symptoms were observed at 12,24,and 48 weeks after switching to E/C/F/TAF(P<0.05).No significant change in depression symptom scores was observed.At 48 weeks after switch,HIV viral load<50 copies/mL was maintained in all of the participants,median fasting lipid levels were moderately increased(total cholesterol[TC]:8.2 mg/dL,low-density lipoprotein cholesterol[LDL-C]:8.5 mg/dL,high-density lipoprotein cholesterol[HDL-C]:2.9 mg/dL,and triglyceride(TG):1.6 mg/dL,and the TC:HDL-C ratio remained stable.Conclusions:The single-pill combination regimens E/C/F/TAF is safe and well tolerated.This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.展开更多
Background and Aims:With an increasing understanding of hepatitis B,the antiviral indications have been broadening gradually.To evaluate the effectiveness of tenofovir alafena-mide(TAF)in chronic hepatitis B(CHB)patie...Background and Aims:With an increasing understanding of hepatitis B,the antiviral indications have been broadening gradually.To evaluate the effectiveness of tenofovir alafena-mide(TAF)in chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and detectable hepatitis B virus(HBV)DNA,those who are ineligible for broader anti-viral criteria from the Chinese CHB prevention guide(2019).Methods:A total of 117 patients were recruited and their data were collected from paper or electronic medical records.HBV DNA and liver function were measured at baseline and throughout the 24-week follow-up.The effectiveness end-point was complete virological response.The safety endpoint was the first occurrence of any clinical adverse event during the treatment.Results:Among the 117 patients,45 had normal ALT as well as detectable HBV DNA and they were not recommended for antiviral therapy according to Chinese Guidelines(2019).After TAF antiviral therapy,the rates of patients who achieved HBV DNA<20 IU/mL at 4,12 and 24 weeks were 77.1%,96.7%and 96.8%respectively.Among them,the undetectable rates of HBV DNA in patients with low baseline viral load at 4,12 and 24 weeks were 92.3%,100%and 100%,while the rates of those with high baseline viral load were 68.2%,94.1%and 94.4%.Compared with 71.4%,94.4%and 94.7%in the high baseline group,the undetectable rates of HBV DNA at 4,12 and 24 weeks in the low baseline liver stiffness group were 85.7%,100%and 100%.There was no statistical significance among the above groups.Conclusions:CHB patients who had normal ALT and detectable HBV DNA and did not meet“CHB prevention guide(2019)”,could achieve complete virological response in 24 weeks after antiviral treatment by TAF.展开更多
Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fum...Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.展开更多
Background: Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bi...Background: Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals.Methods: This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24.Results: Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant’s decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1).Conclusions: A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP.展开更多
Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumara...Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log_(10) IU/mL),Middle-G(7 log_(10) IU/mL≤titer<8 log_(10) IU/mL)and Low-G(titer<7 log_(10) IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log_(10) IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log_(10) IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log_(10) IU/mL.展开更多
Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofo...Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofovir disoproxil fumarate(TDF),or entecavir(ETV)in treating HBV-ACLF globally.This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.Methods:In this prospective,real-world cohort study,patients with HBV-ACLF were assigned to the TAF,TDF,and ETV groups.A total of 199 patients completed the 144-week follow-up.After propensity score matching(PSM),44 patients remained in each group for further analysis of survival status,incidence of hepatocellular carcinoma(HCC),virological response,and liver and renal function indicators.Results:In the original cohort,HCC developed in one patient in each group.No serious drug-related adverse events were observed.In the PSM cohort,the 144-week survival rates were 56.82%,75.00%,and 59.09%in the TAF,TDF,and ETV groups,respectively(P=0.118).When stratified into noncirrhosis and cirrhosis subgroups at baseline,the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients(P=0.338),and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients(P=0.052),but the differences were not statistically significant.The long-term overall survival rates in the TAF,TDF,and ETV groups were comparable.After 144 weeks,no significant difference in the virological response rate or liver or renal function indicators was found among the three groups,except for the level of aspartate aminotransferase,which was significantly higher in the TDF group than in the ETV group at week 144(P=0.001).Conclusions:There were no significant differences in the survival rate,incidence of HCC,efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.展开更多
Tenofovir amibufenamide(TMF)is a novel prodrug of tenofovir that demonstrates a promising safety and efficacy profile.A recent study by Peng et al compared TMF with tenofovir alafenamide in the treatment of chronic he...Tenofovir amibufenamide(TMF)is a novel prodrug of tenofovir that demonstrates a promising safety and efficacy profile.A recent study by Peng et al compared TMF with tenofovir alafenamide in the treatment of chronic hepatitis B.The findings indicated that both medications offer similar efficacy in terms of viral response and alanine aminotransferase normalization.Notably,TMF showed potential advantages in lipid management,as it did not significantly affect cholesterol levels,unlike tenofovir alafenamide.This correspondence highlights the need for further research to evaluate the long-term safety and efficacy of TMF,its impact on cardiovascular risk,and its use in specific patient populations.展开更多
Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Ve...Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.展开更多
Background:Antiretroviral therapy(ART)was often associated with dyslipidemia among human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.This study aimed to assess treatment-naïve adu...Background:Antiretroviral therapy(ART)was often associated with dyslipidemia among human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir,emtricitabine,and tenofovir alafenamide(BIC/FTC/TAF)or lamivudine,efavirenz,and tenofovir disoproxil fumarate(3TC+EFV+TDF),monitoring at weeks 4,12,24,and 48.Methods:A case-control retrospective study was conducted.The newly diagnosed HIV-infected individuals attending the sexual transmission disease(STD)/AIDS clinic of Beijing Youan Hospital,Capital Medical University,from January to December 2021.The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group.High-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),and total cholesterol(TC)at different time points over 48 weeks between two groups were compared.A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results:A total of 870 participants,with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group.There were no statistically significant differences in median age,baseline CD4/CD8 ratio,median body mass index(BMI)between the two groups.In both two groups,levels of TG,TC,and LDL-C were higher at 4 weeks,12 weeks,and 24 weeks of treatment(all P<0.05),and there were no statistically significant differences at 48 weeks compared to those at baseline(all P>0.05).In addition,the differences in average changes of the level of TG,TC,HDL-C,and LDL-C from weeks 4,12,24,and 48 to baseline between two groups were not statistically significant(all P>0.05).Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA≥10^(5)copies/mL(compared with<10^(5)copies/mL)was associated with an increased risk of elevated LDL-C(hazard ratio=1.26,95%confidence interval:1.07-1.48,P=0.005).Conclusions:Transient elevations in blood lipid levels(TC,TG,HDL-C,and LDL-C)were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks,12 weeks,and 24 weeks of treatment.However,these levels did not differ significantly from baseline after 48 weeks of treatment,regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.展开更多
I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of M...I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of Medicine.When I graduated展开更多
Aim:In long-term nucleos(t)ide analog(NA)suppressed patients with chronic hepatitis B(CHB),hepatocellular carcinoma(HCC)can still develop.Few data exist on the incidence and the predictors of HCC development beyond th...Aim:In long-term nucleos(t)ide analog(NA)suppressed patients with chronic hepatitis B(CHB),hepatocellular carcinoma(HCC)can still develop.Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients.To assess the prevalence,incidence,and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years.Methods:All CHB patients under NAs for≥60 months with stable virologic response were enrolled.HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients.The baseline PAGE-B score was calculated for each patient.Results:343 patients(76%male,86%HBeAg-negative,30%cirrhotic)were enrolled.During a median(IQR)follow-up of 144(105-182)months,21 patients(6%)developed HCC despite virologic suppression(incidence rate 40 cases/1000 person-years follow-up).In multivariate analysis,higher PAGE B score[adjusted Hazard Ratio,aHR 1.26(95%CI:1.13-1.54),P=.022]and cirrhosis[aHR 9.71(95%CI:2.02-46.48),P=.005]were predictors of HCC development.PAGE B score showed a significant association with HCC(R20.225,P<.001)and good prognostic capacity(AUC 0.863)of HCC.Conclusions:Our results confirm that in successfully NA-treated CHB patients,sustained viral replication suppression does not abolish the risk of HCC.The PAGE-B score could be a useful tool for identifying high-risk subjects.展开更多
基金Supported by the Japan Agency for Medical Research and Development(AMED),No.JP22fk0310503.
文摘BACKGROUND Tenofovir alafenamide fumarate(TAF)is one of the first-line treatments used to treat chronic hepatitis B patients;TAF has strong antiviral activity and a high barrier to resistance.Although virological breakthroughs in patients during TAF treatment are rare,patients with incomplete responses to TAF are occasionally observed.AIM To investigate responsible mutations in the reverse transcriptase region of hepatitis B virus(HBV)for TAF-incomplete responses.METHODS Thirteen chronic hepatitis B patients who received TAF monotherapy were included.A TAF-incomplete responder was defined as one who was continuously positive for HBV DNA over 2 years after TAF treatment initiation.The emergences of mutations in TAF-incomplete responders were evaluated before,one year after,and two years after treatment by deep sequencing of HBV DNA and RNA.RESULTS Two patients were continuously positive for HBV DNA over two years.The rtL269I mutation,one of the CYEI mutations linked to tenofovir resistance,was detected in both patients by direct sequencing.The deep sequencing analysis revealed that a combination of rtT118A and rtL220I mutations and the rtL269I mutation were predominantly detected in HBV DNA even when these mutations were barely detected in HBV RNA.This suggests a superior replication capability of the HBV variants with these mutations under TAF treatment.CONCLUSION The deep sequencing analysis of HBV DNA and RNA and comparing the detection rates of mutations were useful for estimating responsible mutations for TAF-incomplete responses.Such analysis is needed to evaluate the association between mutations that emerge during TAF treatment and incomplete responses to TAF.
基金Supported by Natural Science Foundation of Fujian Province,No.2021J01123300.
文摘BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is unclear.AIM To compare the effects of TAF and entecavir(ETV)on serum lipid levels in patients with CHB.METHODS In this retrospective cohort study,the data including the clinical features,serum lipids,and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed.We used propensity score-matched models to assess the effects on high-density lipoprotein,lowdensity lipoprotein,triglycerides,and total cholesterol(TCHO).RESULTS A total of 336 patients(75.60%male)were included;63.69%received TAF and 36.31%received ETV.Compared with the ETV group,the TAF group had significantly higher TCHO levels after treatment(4.67±0.90 vs 4.36±1.05,P=0.006).In a propensity score-matched model for body mass index,age,sex,smoking,drinking,presence of comorbidities such as NAFLD,cirrhosis,diabetes mellitus,and hypertension,TAF-treated patients had significantly increased TCHO levels compared to that at baseline(P=0.019).There was no difference for the ETV group.Body mass index,sex,hypertension,baseline TCHO,and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis.However,1-year TAF treatment did not increase the incidence of NAFLD.CONCLUSION A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV.However,TAF-induced dyslipidemia did not increase the incidence of NAFLD.
基金Supported by the Chinese Foundation for Hepatitis Prevention and Control-WBE Liver Fibrosis Foundation,No.WBE20161013the Science and Technology project of Changzhou,No.CJ20160024 and No.CJ20179030
文摘Tenofovir disoproxil fumarate(TDF)is a potent nucleotide analogue with high barrier to resistance,which is recommended for multi-drug resistant hepatitis B virus(HBV)infection.However,nephrotoxicity has been reported during TDF treatment,and tenofovir alafenamide(TAF),which has comparable efficacy to TDF and improves bone and renal safety,can be used as a replacement strategy.Herein,we describe a clinical case concerning a 60-year-old individual suffering liver cirrhosis and renal dysfunction,and being infected with multidrug-resistant HBV.When failing treatment with TDF,he received TAF as a rescue therapy.TAF effectively inhibited HBV replication without worsening renal function or serum phosphorus abnormality.Furthermore,hepatocellular carcinoma(HCC)occurred during TAF treatment despite controlling the viral load.The risk of HCC could not be eliminated and should be monitored during TAF treatment.
基金Study on the efficacy and safety of tenofovir alafenamide in treating chronic hepatitis B patients with poor entecavir response,No.SKJP22020201008.
文摘BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNA<20 IU/mL,but detectable)were enrolled in the study.The patients were randomly assigned to either continue ETV(0.5 mg)daily or switch to TAF(25 mg)daily for 48 wk.The primary endpoint was the proportion of patients who achieved a virologic response(HBV DNA level<20 IU/mL)at week 48.Secondary endpoints included changes in serum alanine aminotransferase(ALT),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and anti-HBe levels,and renal and bone safety parameters.RESULTS At week 48,the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two groups.None of the patients developed genotypic resistance to ETV or TAF.Both drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse events.No significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either group.The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group(-0.8%vs-2.1%,P=0.004;-0.6%vs-1.8%,P=0.007,respectively).CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.
文摘This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We review the related research content,topic selection,methodology,conclusions,strengths and weaknesses of this article.And evaluate it in relation to other published relevant articles.
基金General Project of the National Natural Science Foundation of China(No.81572007)。
文摘Objective:To evaluate the effect of tenofovir alafenamide versus tenofovir disoproxil fumarate on antiviral efficacy in patients with hepatitis B virus infection.Methods:Randomized controlled trials were searched on CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Cochrane Library,Embase,ClinicalKey,Chinese Clinical Trial Registry and ClinicalTrials.gov from the date of inception to April 2020.The literature was screened according to the inclusion and exclusion criteria,and the efficacy evaluation index of the included RCT was set as the success rate of reaching the endpoint of viral suppression and achieving normalized ALT values at 48 weeks of treatment.Intentionality analysis was adopted and the analysis results were taken as the final conclusion.RevMan 5.3 software was used for this Meta-analysis.Meanwhile,VassarStats was used to evaluate the non-inferiority of TAF and calculate the difference of virus inhibition efficiency rate and 95%confidence interval between experimental group and the control group of each RCT.Results:After the literature search,411 potential articles were found,5 studies were finally included according to the criteria,and 2,120 patients were included.Intentionality analysis showed that TAF regimen and TDF regimen had similar viral suppression success rates(RR=0.97,95%CI:0.94~1.01,P=0.19).The ALT normalization rate in the TAF treatment group was higher than that in the TDF treatment group,and the difference was statistically significant(RR=1.35,95%CI:1.20-1.53,P<0.00001).The non-inferiority margin was set at 10%,and it was found that three RCT studies in the international multi-center all showed that TAF was not inferior to TDF in controlling HBV viral load,while two RCT studies in China's Mainland failed to achieve non-inferiority after calculation.Conclusions:At 48 weeks of treatment,TAF was similar to TDF in controlling HBV viral load.However,the efficacy of TAF in controlling HBV viral load may vary among different populations,which requires further confirmation by more clinical trial evidence.Based on AASLD criteria,the ALT normalization rate of the TAF group was higher than that of the TDF group at 48 weeks of treatment,showing an obvious advantage.
文摘BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.
文摘Objective To compare the real-world efficacy and safety profile of tenofovir amibufenamid(TMF)and tenofovir alafenamide(TAF)tablets in the treatment of patients with chronic hepatitis B(CHB).Methods This retrospective study included patientswithhchronic hepatitis B who received TMF and TAFantiviral treatment at the Infectious Disease Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023.The primary and secondary outcome was to study the patient HBV DNA conversion rate(<20 IU/ml),alanine aminotransferase(ALT)normalization rate,renal function,and lipid levels of patients at 48 weeks of treatment.TThe comparison of data between measurement data groups was differentiated using a t-test and Mann-Whitney U test.The inter-group comparison rate in count data was performed using the x?test or Fisher's exact probability.Results A total of 440 cases were enrolled,including 220 in the TMF group(63 treatment-naive and 157 treatment-experienced)and 220 cases in the TAF group(61 treatment-naive and 159 treatment-experienced).In terms of efficacy,the HBV DNA seroconversion rates in the TMF group and TAF group were 90.5%and 85.2%(P=0.372),respectively,while the ALT normalization rates were 92.1%and 88.5%(P=0.505),respectively,at 48 weeks of treatment.The HBV DNA-negative conversion rate for the newly treated patients was 99.4%and 98.7%,respectively(P=1.000),while the rates of ALT normalization were 94.9%and 92.3%,respectively(P=0.863).In terms of safety profile,the serum creatinine level was lower in the TMF group than that in the TAF group at 48 weeks of treatment[TMF group 66.5(56.3,78.3)μmol/L,TAF group 70.6(60.7,77.8)μmol/L,Z=-2.282,P=0.022].However,there was no statistically significant difference in other renal function and tubular function related indicators between the two groups of patients(P>0.05).The serum high-density lipoprotein levels were higher in the TMF group than those in the TAF group[TMF 1.4(1.1,1.6)mmol/L vs.TAF group 1.3(1.1,1.6)mmol/L,Z=-2.204,P=0.027]at 48 weeks of treatment.However,there was no statistically significant difference in other blood lipid indicators between the two groups of patients(P>0.05).Conclusion There is no statistically significant difference in efficacy and safety profiles between TMF and TAF at 48 weeks in the treatment of patients with chronic hepatitis B,and the overall safety profile is favorable.
基金This study was supported by a grant from the National Natural Science Foundation of China(No.31770837)。
文摘Background and Aims:The therapeutic effect of tenofovir alafenamide fumarate(TAF),tenofovir disoproxil fumarate(TDF)and entecavir(ETV)on chronic hepatitis B(CHB)patients remains inconsistent.The aim of this study was to explore the differences in virological responses to TAF,TDF and ETV in patients with CHB.Methods:Literature searches were conducted of the PubMed,EMBASE,and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21,2020.Statistical comparisons of virological response between TDF,ETV,and TAF were carried out with pooled odds ratio(OR)values.Results:The virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks[OR=1.12,95%confidence interval(CI):0.89–1.41],24-weeks(OR=1.33,95%CI:1.11–1.61),48-weeks(OR=1.62,95%CI:1.16–2.25),72-weeks(OR=1.43,95%CI:0.78–2.62),and 96-weeks(OR=1.56,95%CI:0.87–2.81)treatment.No significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or TDF.The virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks,48-weeks(OR=1.54,95%CI:1.17–2.02),96-weeks,and 144-weeks.Conclusions:The virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients,but there was no significant difference between TAF and TDF.In addition,the therapeutic effect of TDF+ETV was superior to TDF alone.
基金the 13th Five-year National Major Project for HIV/AIDS and Hepatitis B Control and Prevention and the Chinese Ministry of Science and Technology(No.2017ZX10202102005004).
文摘Background:Central nervous system(CNS)symptoms after efavirenz(EFV)treatment in people living with human immunodeficiency virus(HIV)could persist and impact their quality of life.We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide(E/C/F/TAF),which is considered an alternative option for subjects who do not tolerate EFV.Most specifically,we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants’neuropsychiatric toxicity symptoms in a real-life setting.Methods:A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity≥grade 2.The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks.The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire,as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index.The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12,24,and 48.Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.Results:One hundred ninety-six participants(96.9%men,median age:37.5 years,median:3.7 years on prior EFV-containing regimens)were included in the study.Significant improvements in anxiety and sleep disturbance symptoms were observed at 12,24,and 48 weeks after switching to E/C/F/TAF(P<0.05).No significant change in depression symptom scores was observed.At 48 weeks after switch,HIV viral load<50 copies/mL was maintained in all of the participants,median fasting lipid levels were moderately increased(total cholesterol[TC]:8.2 mg/dL,low-density lipoprotein cholesterol[LDL-C]:8.5 mg/dL,high-density lipoprotein cholesterol[HDL-C]:2.9 mg/dL,and triglyceride(TG):1.6 mg/dL,and the TC:HDL-C ratio remained stable.Conclusions:The single-pill combination regimens E/C/F/TAF is safe and well tolerated.This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
基金This work was supported by the National Nature Science Foundation of China(grant number 81770582).
文摘Background and Aims:With an increasing understanding of hepatitis B,the antiviral indications have been broadening gradually.To evaluate the effectiveness of tenofovir alafena-mide(TAF)in chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and detectable hepatitis B virus(HBV)DNA,those who are ineligible for broader anti-viral criteria from the Chinese CHB prevention guide(2019).Methods:A total of 117 patients were recruited and their data were collected from paper or electronic medical records.HBV DNA and liver function were measured at baseline and throughout the 24-week follow-up.The effectiveness end-point was complete virological response.The safety endpoint was the first occurrence of any clinical adverse event during the treatment.Results:Among the 117 patients,45 had normal ALT as well as detectable HBV DNA and they were not recommended for antiviral therapy according to Chinese Guidelines(2019).After TAF antiviral therapy,the rates of patients who achieved HBV DNA<20 IU/mL at 4,12 and 24 weeks were 77.1%,96.7%and 96.8%respectively.Among them,the undetectable rates of HBV DNA in patients with low baseline viral load at 4,12 and 24 weeks were 92.3%,100%and 100%,while the rates of those with high baseline viral load were 68.2%,94.1%and 94.4%.Compared with 71.4%,94.4%and 94.7%in the high baseline group,the undetectable rates of HBV DNA at 4,12 and 24 weeks in the low baseline liver stiffness group were 85.7%,100%and 100%.There was no statistical significance among the above groups.Conclusions:CHB patients who had normal ALT and detectable HBV DNA and did not meet“CHB prevention guide(2019)”,could achieve complete virological response in 24 weeks after antiviral treatment by TAF.
文摘Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.
基金Gilead Sciences, including provision of the study drug, and the Capital Health Research and Development of Special Fund(No. 2022-1G-3015)。
文摘Background: Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals.Methods: This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24.Results: Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant’s decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1).Conclusions: A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP.
基金supported by the Key Project of Hangzhou Science and Technology Bureau of Agriculture and Social Development Scientific Research(2022A04A02)Zhejiang Province Medical and Health Research Project(2018KY628)Hangzhou City Social Development Scientific Research Active Design Project(20172016A03).
文摘Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log_(10) IU/mL),Middle-G(7 log_(10) IU/mL≤titer<8 log_(10) IU/mL)and Low-G(titer<7 log_(10) IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log_(10) IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log_(10) IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log_(10) IU/mL.
基金supported by grants from Key-Area Research and Development Program of Guangdong Province(No.2020B0101130015)Guangdong Medical Science and Technology Research Fund(No.A2021304)+5 种基金the Natural Science Foundation of China(No.82070611)Guangzhou Science and Technology Plan Projects(No.2023B03J1287)Guangzhou Science and Technology Program Key Projects(No.2023B01J1007)Sun Yat-Sen University Clinical Research 5010 Program(No.2020007)the Five-Year Plan of Third Affiliated Hospital of Sun Yat-sen University(No.2023W106)Clinical trial number:ClinicalTrials.gov ID:NCT03920618.
文摘Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofovir disoproxil fumarate(TDF),or entecavir(ETV)in treating HBV-ACLF globally.This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.Methods:In this prospective,real-world cohort study,patients with HBV-ACLF were assigned to the TAF,TDF,and ETV groups.A total of 199 patients completed the 144-week follow-up.After propensity score matching(PSM),44 patients remained in each group for further analysis of survival status,incidence of hepatocellular carcinoma(HCC),virological response,and liver and renal function indicators.Results:In the original cohort,HCC developed in one patient in each group.No serious drug-related adverse events were observed.In the PSM cohort,the 144-week survival rates were 56.82%,75.00%,and 59.09%in the TAF,TDF,and ETV groups,respectively(P=0.118).When stratified into noncirrhosis and cirrhosis subgroups at baseline,the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients(P=0.338),and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients(P=0.052),but the differences were not statistically significant.The long-term overall survival rates in the TAF,TDF,and ETV groups were comparable.After 144 weeks,no significant difference in the virological response rate or liver or renal function indicators was found among the three groups,except for the level of aspartate aminotransferase,which was significantly higher in the TDF group than in the ETV group at week 144(P=0.001).Conclusions:There were no significant differences in the survival rate,incidence of HCC,efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.
文摘Tenofovir amibufenamide(TMF)is a novel prodrug of tenofovir that demonstrates a promising safety and efficacy profile.A recent study by Peng et al compared TMF with tenofovir alafenamide in the treatment of chronic hepatitis B.The findings indicated that both medications offer similar efficacy in terms of viral response and alanine aminotransferase normalization.Notably,TMF showed potential advantages in lipid management,as it did not significantly affect cholesterol levels,unlike tenofovir alafenamide.This correspondence highlights the need for further research to evaluate the long-term safety and efficacy of TMF,its impact on cardiovascular risk,and its use in specific patient populations.
文摘Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.
基金supported by the Gilead Sciences and the Capital Health Research and Development of Special Fund(No.2022-1G-3015)
文摘Background:Antiretroviral therapy(ART)was often associated with dyslipidemia among human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir,emtricitabine,and tenofovir alafenamide(BIC/FTC/TAF)or lamivudine,efavirenz,and tenofovir disoproxil fumarate(3TC+EFV+TDF),monitoring at weeks 4,12,24,and 48.Methods:A case-control retrospective study was conducted.The newly diagnosed HIV-infected individuals attending the sexual transmission disease(STD)/AIDS clinic of Beijing Youan Hospital,Capital Medical University,from January to December 2021.The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group.High-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),and total cholesterol(TC)at different time points over 48 weeks between two groups were compared.A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results:A total of 870 participants,with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group.There were no statistically significant differences in median age,baseline CD4/CD8 ratio,median body mass index(BMI)between the two groups.In both two groups,levels of TG,TC,and LDL-C were higher at 4 weeks,12 weeks,and 24 weeks of treatment(all P<0.05),and there were no statistically significant differences at 48 weeks compared to those at baseline(all P>0.05).In addition,the differences in average changes of the level of TG,TC,HDL-C,and LDL-C from weeks 4,12,24,and 48 to baseline between two groups were not statistically significant(all P>0.05).Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA≥10^(5)copies/mL(compared with<10^(5)copies/mL)was associated with an increased risk of elevated LDL-C(hazard ratio=1.26,95%confidence interval:1.07-1.48,P=0.005).Conclusions:Transient elevations in blood lipid levels(TC,TG,HDL-C,and LDL-C)were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks,12 weeks,and 24 weeks of treatment.However,these levels did not differ significantly from baseline after 48 weeks of treatment,regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.
文摘I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of Medicine.When I graduated
文摘Aim:In long-term nucleos(t)ide analog(NA)suppressed patients with chronic hepatitis B(CHB),hepatocellular carcinoma(HCC)can still develop.Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients.To assess the prevalence,incidence,and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years.Methods:All CHB patients under NAs for≥60 months with stable virologic response were enrolled.HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients.The baseline PAGE-B score was calculated for each patient.Results:343 patients(76%male,86%HBeAg-negative,30%cirrhotic)were enrolled.During a median(IQR)follow-up of 144(105-182)months,21 patients(6%)developed HCC despite virologic suppression(incidence rate 40 cases/1000 person-years follow-up).In multivariate analysis,higher PAGE B score[adjusted Hazard Ratio,aHR 1.26(95%CI:1.13-1.54),P=.022]and cirrhosis[aHR 9.71(95%CI:2.02-46.48),P=.005]were predictors of HCC development.PAGE B score showed a significant association with HCC(R20.225,P<.001)and good prognostic capacity(AUC 0.863)of HCC.Conclusions:Our results confirm that in successfully NA-treated CHB patients,sustained viral replication suppression does not abolish the risk of HCC.The PAGE-B score could be a useful tool for identifying high-risk subjects.
