***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 
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    ***EXAMPLES*** 
    Input: Background . Dolutegravir ( DTG ; S/GSK1349572 ) , a human immunodeficiency virus type 1 ( HIV-1 ) integrase inhibitor , has limited cross-resistance to raltegravir ( RAL ) and elvitegravir in vitro . This phase IIb study assessed the activity of DTG in HIV-1–infected subjects with genotypic evidence of RAL resistance . Methods . Subjects received DTG 50 mg once daily ( cohort I ) or 50 mg twice daily ( cohort II ) while continuing a failing regimen ( without RAL ) through day 10 , after which the background regimen was optimized , when feasible , for cohort I , and at least 1 fully active drug was m and ated for cohort II . The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log10 copies/mL from baseline or was < 400 copies/mL. Results . A rapid antiviral response was observed . More subjects achieved the primary end point in cohort II ( 23 of 24 [ 96 % ] ) , compared with cohort I ( 21 of 27 [ 78 % ] ) at day 11 . At week 24 , 41 % and 75 % of subjects had an HIV-1 RNA load of < 50 copies/mL in cohorts I and II , respectively . Further integrase genotypic evolution  was uncommon . Dolutegravir had a good , similar safety profile with each dosing regimen . Conclusion . Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen . These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL BACKGROUND Women are under-represented in HIV antiretroviral therapy ( ART ) studies . Guidelines for selection of ART as initial therapy in patients with HIV-1 infection do not contain sex-specific treatment . We aim ed to assess the safety and efficacy of the single tablet integrase inhibitor regimen containing elvitegravir , cobicistat , emtricitabine , and tenofovir disoproxil fumarate compared with a boosted protease inhibitor regimen of ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate . METHODS In this international , r and omised , controlled , double-blind , phase 3 study ( Women AntiretroViral Efficacy and Safety study [ WAVES ] ) , we recruited treatment-naive HIV-infected women with an estimated creatinine clearance of 70 mL/min or higher from 80 centres in 11 countries . Women were r and omly assigned ( 1:1 ) to receive elvitegravir , cobicistat , emtricitabine , and tenofovir disoproxil fumarate ( integrase inhibitor regimen ) or ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate ( protease inhibitor based regimen ) ; regimens were masked with matching placebos . R and omisation was done by a computer-generated allocation sequence ( block size four ) and was stratified by HIV-1 RNA viral load and race . Investigators , patients , study staff , and those assessing outcomes were masked to treatment group . All participants who received one dose of study drug were included in the primary efficacy and safety analyses . The main outcome was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by US Food and Drug Administration snapshot algorithm ( prespecified non-inferiority margin of 12 % ) . This study is registered with Clinical Trials.gov , number NCT01705574 . FINDINGS Between Nov 28 , 2012 , and March 12 , 2014 , 575 women were enrolled . 289 were r and omly assigned to receive the integrase inhibitor regimen and 286 to receive the protease inhibitor based regimen . 252 ( 87 % ) women in the integrase inhibitor group had plasma HIV-1 RNA less than 50 copies per mL at week 48 compared with 231 ( 81 % ) women in the protease inhibitor group ( adjusted difference 6·5 % ; 95 % CI 0·4 - 12·6 ) . No participant had virological failure with resistance in the integrase inhibitor group compared with three participants ( [ 1 % ] ; all Met184Val/Ile ) in the protease inhibitor group . 19 women in the protease inhibitor group discontinued because of adverse events compared with five in the integrase inhibitor group . INTERPRETATION WAVES shows that clinical trials of ART regimens in global and diverse population s of treatment-naive women are possible . The findings support guidelines recommending integrase inhibitor based regimens in first-line antiretroviral therapy . FUNDING Gilead Sciences BACKGROUND Dolutegravir ( GSK1349572 ) , a once-daily HIV integrase inhibitor , has shown potent antiviral response and a favourable safety profile . We evaluated safety , efficacy , and emergent resistance in antiretroviral-experienced , integrase-inhibitor-naive adults with HIV-1 with at least two-class drug resistance . METHODS ING111762 ( SAILING ) is a 48 week , phase 3 , r and omised , double-blind , active-controlled , non-inferiority study that began in October , 2010 . Eligible patients had two consecutive plasma HIV-1 RNA assessment s of 400 copies per mL or higher ( unless > 1000 copies per mL at screening ) , resistance to two or more classes of antiretroviral drugs , and had one to two fully active drugs for background therapy . Participants were r and omly assigned ( 1:1 ) to once-daily dolutegravir 50 mg or twice-daily raltegravir 400 mg , with investigator-selected background therapy . Matching placebo was given , and study sites were masked to treatment assignment . The primary endpoint was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 , evaluated in all participants r and omly assigned to treatment groups who received at least one dose of study drug , excluding participants at one site with violations of good clinical practice . Non-inferiority was prespecified with a 12 % margin ; if non-inferiority was established , then superiority would be tested per a prespecified sequential testing procedure . A key prespecified secondary endpoint was the proportion of patients with treatment-emergent integrase-inhibitor resistance . The trial is registered at Clinical Trials.gov , NCT01231516 . FINDINGS Analysis included 715 patients ( 354 dolutegravir ; 361 raltegravir ) . At week 48 , 251 ( 71 % ) patients on dolutegravir had HIV-1 RNA less than 50 copies per mL versus 230 ( 64 % ) patients on raltegravir ( adjusted difference 7·4 % , 95 % CI 0·7 to 14·2 ) ; superiority of dolutegravir versus raltegravir was then concluded ( p=0·03 ) . Significantly fewer patients had virological failure with treatment-emergent integrase-inhibitor resistance on dolutegravir ( four vs 17 patients ; adjusted difference -3·7 % , 95 % CI -6·1 to -1·2 ; p=0·003 ) . Adverse event frequencies were similar across groups ; the most commonly reported events for dolutegravir versus raltegravir were diarrhoea ( 71 [ 20 % ] vs 64 [ 18 % ] patients ) , upper respiratory tract infection ( 38 [ 11 % ] vs 29 [ 8 % ] ) , and headache ( 33 [ 9 % ] vs 31 [ 9 % ] ) . Safety events leading to discontinuation were infrequent in both groups ( nine [ 3 % ] dolutegravir , 14 [ 4 % ] raltegravir ) . INTERPRETATION Once-daily dolutegravir , in combination with up to two other antiretroviral drugs , is well tolerated with greater virological effect compared with twice-daily raltegravir in this treatment-experienced patient group . FUNDING ViiV Healthcare BACKGROUND Dolutegravir ( S/GSK1349572 ) is a new HIV-1 integrase inhibitor that has antiviral activity with once daily , unboosted dosing . SPRING-1 is an ongoing study design ed to select a dose for phase 3 assessment . We present data from preplanned primary and interim analyses . METHODS In a phase 2b , multicentre , dose-ranging study , treatment-naive adults were r and omly assigned ( 1:1:1:1 ) to receive 10 mg , 25 mg , or 50 mg dolutegravir or 600 mg efavirenz . Dose but not drug allocation was masked . R and omisation was by a central integrated voice-response system according to a computer-generated code . Study drugs were given with either tenofovir plus emtricitabine or abacavir plus lamivudine . Our study was done at 34 sites in France , Germany , Italy , Russia , Spain , and the USA beginning on July 9 , 2009 . Eligible participants were seropositive for HIV-1 , aged 18 years or older , and had plasma HIV RNA viral loads of at least 1000 copies per mL and CD4 counts of at least 200 cells per μL. Our primary endpoint was the proportion of participants with viral load of less than 50 copies per mL at week 16 and we present data to week 48 . Analyses were done on the basis of allocation group and included all participants who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00951015 . FINDINGS 205 patients were r and omly allocated and received at least one dose of study drug : 53 , 51 , and 51 to receive 10 mg , 25 mg , and 50 mg dolutegravir , respectively , and 50 to receive efavirenz . Week 16 response rates to viral loads of at most 50 copies per mL were 93 % ( 144 of 155 participants ) for all doses of dolutegravir ( with little difference between dose groups ) and 60 % ( 30 of 50 ) for efavirenz ; week 48 response rates were 87 % ( 139 of 155 ) for all doses of dolutegravir and 82 % ( 41 of 50 ) for efavirenz . Response rates between nucleoside reverse transcriptase inhibitor subgroups were similar . We identified three virological failures in the dolutegravir groups and one in the efavirenz group-we did not identify any integrase inhibitor mutations . We did not identify any dose-related clinical or laboratory toxic effects , with more drug-related adverse events of moderate-or-higher intensity in the efavirenz group ( 20 % ) than the dolutegravir group ( 8 % ) . We did not judge that any serious adverse events were related to dolutegravir . INTERPRETATION Dolutegravir was effective when given once daily without a pharmacokinetic booster and was well tolerated at all assessed doses . Our findings support the assessment of once daily 50 mg dolutegravir in phase 3 trials Objectives The objective of this analysis is to perform an indirect comparison of elvitegravir , cobicistat , emtricitabine and tenofovir DF ( E/C/F/TDF ) to abacavir/lamivudine and dolutegravir ( ABC/3TC + DTG ) by using 2 trials evaluating each of these regimens in comparison to efavirenz , emtricitabine and tenofovir DF ( EFV/FTC/TDF ) . Methods An indirect comparison was performed by using a generalization of Bucher 's methodology to calculate risk differences . Two phase III clinical trials ( GS-US-236 - 0102 and SINGLE — described above ) were used . Results Results of the indirect comparison showed no statistically significant risk difference of the efficacy endpoint of achieving HIV RNA < 50 copies/mL between E/C/F/TDF and ABC/3TC + DTG for the ITT population at weeks 48 , 96 and 144 : respectively -3.7 % ( CI95 % = [ -10.8 % ; 3.4 % ] ) , -5.2 % ( CI95 % = [ -13.2 % ; 2.8 % ] ) and -3.1 % ( CI95 % = [ -12.0 % ; 5.7 % ] ) . There was no statistically significant differences in the risk difference for serious adverse events ( 5.7 % ( CI95 % = [ -2.2 % ; 12.3 % ] ) ) , drug related adverse event ( 2.7 % ( CI95 % = [ -7.0%;12.4 % ] ) ) , drug related serious adverse event ( 0.8 % ( CI95 % = [ -1.6%;3.2 % ] ) ) and death ( 0.5 % ( CI95 % = [ 
    Output:
    
Starting treatment in naive patients with dolutegravir containing ART has an increased likelihood of achieving viral suppression in the comparison with non-dolutegravir containing ART .
The average benefit is particularly evident in those with high baseline viral load