***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A major hurdle in the long-term treatment of chronic hepatitis B ( CHB ) patients is to maintain viral suppression in the absence of drug resistance . To date , no evidence of resistance to tenofovir disoproxil fumarate ( TDF ) has been observed . A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted . Patients in studies GS-US-174 - 0102 ( HBeAg- ) and GS-US-174 - 0103 ( HBeAg+ ) were r and omized 2:1 to receive TDF or adefovir dipivoxil ( ADV ) for 48 weeks followed by open-label TDF through year 8 . Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and , annually if viremic , at discontinuation , or with addition of emtricitabine . Overall , 88/641 ( 13.7 % ) patients qualified for sequence analysis at one or more time points . The percentage of patients qualifying for sequence analysis declined over time , from 9 to 11 % in years 1 - 2 to < 4 % over years 3 - 8 . Forty-one episodes of virologic breakthrough ( VB ) occurred throughout the study , with most ( n=29 , 70 % ) associated with nonadherence to study medication . Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression . A minority of patients who qualified for sequencing had polymorphic ( 41/165 , 24.8 % ) or conserved ( 17/165 , 10.3 % ) site changes in pol/RT , with six patients developing lamivudine and /or ADV resistance-associated mutations . No accumulation of conserved site changes was detected . The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years , with no evidence of TDF resistance or accumulation of conserved site changes BACKGROUND Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue  to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) BACKGROUND The proposed definition of a partial virological response ( PVR ) to nucleos(t)ide analogue therapy in the 2009 European Association for the Study of the Liver ( EASL ) guidelines is based on limited evidence , especially in terms of the cutoff HBV DNA level and the time point at which to judge it . This study assessed optimal PVR criteria for predicting virological response ( VR ) at week 96 in treatment-naive patients with chronic hepatitis B ( CHB ) receiving entecavir ( ETV ) .  METHODS A total of 175 patients ( 126 men , 49 women ) who completed 96 weeks of first-line ETV therapy were prospect ively recruited . For predicting VR at week 96 , the area under the receiver operating characteristic curve ( AUC ) was used to find the optimal time point and the Youden index was used to calculate the optimal cutoff HBV DNA level . RESULTS After 96 weeks of ETV therapy , 139 ( 79.4 % ) patients achieved VR . The AUC at week 48 was significantly better than that at week 24 for predicting VR at week 96 ( P=0.023 ) . The optimal cutoff HBV DNA level at week 48 was 35 IU/ml . Forty-one ( 23.4 % ) patients met this PVR criteria of ETV ( HBV DNA level > 35 IU/ml at week 48 ) . CONCLUSIONS An HBV DNA level > 35 IU/ml at week 48 is the optimal PVR criteria for predicting non-VR at week 96 in treatment-naive patients with CHB who are receiving ETV . This study supports the proposed EASL PVR for ETV based on scientific evidence Background and aims In patients with chronic hepatitis B ( CHB ) who have failed on other nucleos(t)ide analogs ( NUCs ) , the combination of entecavir ( ETV ) plus tenofovir disoproxil fumarate ( TDF ) , two potent agents with non-overlapping resistance profiles , may provide a single rescue regimen . Methods In this single-arm , open-label study , 92 CHB patients with a primary non-response , partial response , or virologic breakthrough on their current NUC were switched to ETV ( 1 mg ) plus TDF ( 300 mg ) and treated for 96 weeks . Results At baseline , 62 % of patients were HBeAg(+ ) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy , with the latest regimen consisting of monotherapy with ETV ( 53 % ) , lamivudine ( LVD 22 % ) , TDF ( 12 % ) , adefovir ( ADV 4 % ) , or telbivudine ( 2 % ) , or combinations of these agents ( 7 % ) ; 58 % had evidence of single- or multidrug resistance mutations ( LVD 52 % , ETV 26 % ; ADV 7 % ) . Response rates for HBV DNA < 50 IU/mL were 76 % ( 70/92 ) at week 48 ( primary endpoint ) , and 85 % ( 78/92 ) at week 96 , including 80 % ( 16/20 ) in prior LVD failures , 100 % ( 4/4 ) in ADV failures , 82 % ( 9/11 ) in TDF failures , and 88 % ( 42/48 ) in ETV failures . No treatment-emergent resistance to ETV or ADV was observed . ETV/TDF was well tolerated , with no significant renal or additive toxicities observed . Conclusions In NUC-experienced patients who have failed prior NUC therapy , ETV/TDF was well tolerated and effective , achieving virologic suppression through 96 weeks in the majority ( 85 % ) , irrespective of prior NUC exposure , without occurrence of treatment-emergent resistance to either agent Background / Aims Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance . We aim ed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response , including quantitative hepatitis B surface antigen ( qHBsAg ) levels . Methods One thous and and nine treatment-naïve chronic hepatitis B ( CHB ) patients were evaluated for cumulative rates of virologic response , biochemical response , and entecavir mutations .  The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment . Results The median duration of entecavir treatment was 26.5 months . The cumulative rate of virologic response at years 1 , 3 , and 5 were 79.0 % , 95.6 % , and 99.4 % , respectively . The cumulative rate of entecavir resistance was 1.0 % and 2.1 % in years 3 and 5 . Multivariate analysis identified baseline hepatitis B e antigen ( HBeAg ) negative status ( p < 0.001 ) and lower hepatitis B virus ( HBV ) DNA ( p < 0.001 ) as predictors of virologic response . Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg . There were no serious adverse events during treatment . Conclusions Long-term entecavir treatment of nucleos(t)ide-naïve CHB patients was associated with an excellent virologic response and a low rate of  entecavir-resistant mutations at 5 years . Baseline HBV DNA load , qHBsAg levels , and HBeAg status were predictors of virologic response during entecavir treatment We previously demonstrated superior efficacy and safety advantages in HIV-infected , virologically suppressed adults switched to a regimen containing tenofovir alafenamide ( TAF ) as compared with those remaining on a tenofovir disoproxil fumarate ( TDF ) regimen through week 48 . We now report long-term data through week 96 . In this r and omized , active-controlled , multicenter , open-label , noninferiority trial ( Clinical Trials.gov No. NCT01815736 ) , we r and omized virologically suppressed ( HIV-1 RNA < 50 copies/ml ) adults ( 2:1 ) to receive a once-daily , single-tablet regimen containing elvitegravir ( EVG ) , cobicistat ( COBI ) , emtricitabine ( FTC ) , and TAF group or to continue one of four TDF-containing regimens ( TDF group ) for 96 weeks . We evaluated efficacy ( HIV-1 RNA < 50 copies/ml using the FDA snapshot algorithm ) and prespecified bone and renal endpoints at week 96 . We r and omized and treated 1,436 participants in this study ( TAF n = 959 , TDF n = 477 ) . At week 96 , TAF was superior to TDF in virologic efficacy , with 93 % on TAF and 89 % on TDF having HIV-1 RNA < 50 copies/ml ( difference 3.7 % , 95 % confidence interval : 0.4%-7.0 % ) . Improvements in hip and spine bone mineral density for those assigned to TAF versus TDF continued through week 96 ( p < .001 ) . Significant improvements in urine protein or albumin to creatinine ratios were also seen among those in the TAF group versus TDF through week 96 ( p < .001 ) . There were no cases of investigator-reported proximal renal tubulopathy in the TAF group as compared with one case in the TDF group . Switching to EVG/COBI/FTC/TAF ( E/C/F/TAF ) was associated with statistically significant efficacy and safety advantages over remaining on a st and ard-of-care TDF-based regimen BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS In this phase 3 , double-blind trial , we r and omly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) . RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated ( 70 percent ) , as compared with 174 of 287 such patients in the lamivudine group ( 61 percent , P=0.01 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus ( HBV ) DNA levels according to a polymerase-chain-reaction assay ( 90 percent vs. 72 
    Output:
    
Telbivudine and TAF were the best for ALT norm .
Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes .
Conclusions Our results are consonant with current clinical guidelines and other evidence review s. For both HBeAg-positive and HBeAg-negative population s , TDF and TAF are the most effective agents for virologic suppression , and TAF is effective across all outcomes