***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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    Input: BACKGROUND A hypersensitivity reaction to abacavir has been known to occur in approximately 4 % of patients treated with the drug . OBJECTIVE The goal of this study was to determine risk factors associated with the development of hypersensitivity reactions to abacavir . METHODS We constructed an analysis population from all protocol s conducted by GlaxoSmithKline that involved at least 24 weeks of abacavir exposure with a quality -assured or vali date d clinical data base by June 30 , 2000 . Demographic , clinical , and laboratory characteristics of patients who developed a hypersensitivity reaction to abacavir  were compared with those of patients who did not . Univariate and multivariate logistic regression models were fit to underst and the predictive ability of each potential risk factor . Odds ratios ( ORs ) and 95 % Wald CIs were computed . RESULTS A total of 5332 patients exposed to abacavir were included in this analysis ; 197 cases of hypersensitivity reaction were reported ( 3.7 % ) . In univariate models , several associations were noted , but most subgroups produced rates within the expected range of 3 % to 6 % . The multivariate model using all demographic data available ( Model 1 ) indicated that the risk of hypersensitivity reaction among black patients ( 3 % hypersensitivity reaction ) was lower ( OR = 0.59 ; 95 % CI , 0.38 - 0.91 ) compared with other ethnic groups . In addition , a lower rate of hypersensitivity reaction was observed in patients who received previous therapy for HIV-1 infection with other antiretroviral agents ( 3 % hypersensitivity reaction ) compared with those receiving therapy for the first time ( OR = 0.58 ; 95 % CI , 0.44 - 0.78 ) . CONCLUSIONS The only characteristics identified as prognostic factors for hypersensitivity reaction to abacavir were antiretroviral treatment status ( ie , treatment experience ) and black race , each result ing in a lower rate compared with the expected incidence Thomas Campbell and colleagues report findings of a r and omized trial conducted in multiple countries regarding the efficacy of  antiretroviral regimens with simplified dosing BACKGROUND The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors ( NRTIs ) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which NRTI combination has greater efficacy and safety is not known . METHODS In a r and omized , blinded equivalence study involving 1858 eligible patients , we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection : abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir . The primary efficacy end point was the time from r and omization to virologic failure ( defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks , or > or = 200 copies per milliliter at or after 24 weeks ) . RESULTS A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy , according to the NRTI combination , among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more . At a median follow-up of 60 weeks , among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group ( hazard ratio , 2.33 ; 95 % confidence interval , 1.46 to 3.72 ; P<0.001 ) , with 57 virologic failures ( 14 % ) in the abacavir-lamivudine group versus 26 ( 7 % ) in the tenofovir DF-emtricitabine group . The time to the first adverse event was also shorter in the abacavir-lamivudine group ( P<0.001 ) . There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48 . CONCLUSIONS In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the times to virologic failure and the first adverse event were both significantly shorter in patients r and omly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine . ( Clinical Trials.gov number , NCT00118898 . Abstract : Raltegravir as initial HIV therapy was examined in a double-blind study ; 160 patients were r and omized to raltegravir  ( 400 mg bid after dose-ranging ) , 38 to efavirenz  , both with tenofovir/lamivudine . At week 240 , HIV-RNA remained < 50 copies per milliliter in 68.8 % ( raltegravir ) versus 63.2 % ( efavirenz ) , and CD4 increases were 302 versus 276 cells per microliter , respectively . Early HIV-RNA decline predicted later CD4 increases in both groups . Raltegravir resistance was observed in 3 of 10 raltegravir recipients with virologic failure . Few drug-related adverse events were reported after week 48 . Raltegravir had minimal effect on laboratory values , including lipids . Raltegravir with tenofovir/lamivudine showed durable efficacy and good tolerability over 5 years Objective : To evaluate the efficacy and safety/tolerability of dolutegravir ( DTG , S/GSK1349572 ) , a potent inhibitor of HIV integrase , through the full 96 weeks of the SPRING-1 study . Design : ING112276 ( SPRING-1 ) was a 96-week , r and omized , partially blinded , phase IIb dose-ranging study . Methods : Treatment-naive adults with HIV received DTG 10 , 25 , or 50 mg once daily or efavirenz ( EFV ) 600 mg once daily ( control arm ) combined with investigator-selected dual nucleos(t)ide reverse transcriptase inhibitor backbone regimen ( tenofovir/emtricitabine or abacavir/lamivudine ) . The primary endpoint of the study was the proportion of participants with plasma HIV-1 RNA less than 50 copies/ml , based on time to loss of virologic response at 16 weeks ( conducted for the purpose of phase III dose selection ) , with a planned analysis at 96 weeks . Safety and tolerability were also assessed . Results : Of 208 participants r and omized to treatment , 205 received study drug . At week 96 , the proportion of participants achieving plasma HIV-1 RNA less than 50 copies/ml was 79 , 78 , and 88 % for DTG 10 , 25 , and 50 mg , respectively , compared with 72 % for EFV . The median increase from baseline in CD4 + cells was 338 cells/&mgr;l with DTG ( all treatment groups combined ) compared with 301 cells/&mgr;l with EFV ( P = 0.155 ) . No clinical ly significant dose-related trends in adverse events were observed , and fewer participants who received DTG withdrew because of adverse events ( 3 % ) compared with EFV ( 10 % ) . Conclusion : Throughout the 96 weeks of the SPRING-1 study , DTG demonstrated sustained efficacy and favorable safety/tolerability in treatment-naive individuals with HIV-1 Background : Atazanavir , an azapeptide protease inhibitor ( PI ) , has pharmacokinetics that allow once-daily dosing , and it is not associated with significant PI-associated dyslipidemia . Methods : A r and omized , double-blind , double-dummy , active-controlled , 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily . The 810 treatment-naive patients were stratified by HIV RNA level . The primary efficacy end point was the proportion of treated patients with HIV RNA levels < 400 copies/mL through week 48 . Results : At week 48 , HIV RNA levels were < 400 copies/mL in 70 % of patients receiving atazanavir and 64 % of patients receiving efavirenz ( intent-to-treat , difference ; 95 % confidence interval : 5.2 % ; −1.2 % , 11.7 % ) . Median CD4 + cell counts increased at comparable magnitudes and rates in the 2 treatment arms ( mean change at week 48 : 176 cells/mm3 with atazanavir , 160 cells/mm3 with efavirenz ) . Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol , fasting low-density lipoprotein cholesterol , or fasting triglycerides over 48 weeks of therapy . Atazanavir-linked bilirubin elevations infrequently result ed in treatment discontinuation ( < 1 % ) . Atazanavir treatment did not increase fasting glucose or insulin levels . Conclusions : For initial HIV treatment , a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine ABSTRACT Once-daily administration of 300 mg of lamivudine in combination with other antiretroviral agents has been proposed as a possible way to optimize anti-human immunodeficiency virus ( HIV ) treatment and to facilitate adherence . A single-center , r and omized , two-way , crossover study was conducted in 60 healthy subjects to compare the steady-state pharmacokinetics of lamivudine in plasma and its putative active anabolite , lamivudine 5′-triphosphate ( lamivudine-TP ) , in peripheral blood mononuclear cells ( P BMC s ) following 7 days of treatment with lamivudine at 300 mg once daily and 7 days of the st and ard regimen of 150 mg twice daily . Serial blood sample s were collected over 24 h for determination of plasma lamivudine concentrations by liquid chromatography-mass spectrometry and intracellular lamivudine-TP concentrations in peripheral blood mononuclear cells by high-performance liquid chromatography/radioimmunoassay methods . Pharmacokinetic parameters were calculated based on lamivudine and lamivudine-TP concentration-time data . Regimens were considered bioequivalent if 90 % confidence intervals ( CI ) for the ratio ( once daily/twice daily ) of geometric least-squares ( GLS ) means for lamivudine and lamivudine-TP pharmacokinetic values fell within the acceptance range of 0.8 to 1.25 . Steady-state plasma lamivudine pharmacokinetics following the once- and twice-daily regimens were bioequivalent with respect to the area under the drug concentration-time curve from 0 to 24 h at steady state ( AUC24,ss ) ( GLS mean ratio , 0.94 ; 90 % CI , 0.92 , 0.97 ) and average plasma lamivudine concentration over the dosing interval ( Cave , ss ) ( GLS mean ratio , 0.94 ; 90 % CI , 0.92 , 0.97 ) . Steady-state intracellular lamivudine-TP pharmacokinetics after the once- and twice-daily regimens were bioequivalent with respect to AUC24,ss ( GLS mean ratio , 0.99 ; 90 % CI , 0.88 , 1.11 ) , Cave , ss ( GLS mean ratio , 0.99 ; 90 % CI , 0.88 , 1.11 ) , and maximum lamivudine concentration ( Cmax , ss ) ( GLS mean ratio , 0.93 ; 90 % CI , 0.81 , 1.07 ) . Lamivudine-TP trough concentrations were modestly lower ( by 18 to 24 % ) during the once-daily regimen ; the clinical importance of this is unclear , given the large intersubject variability in values that was observed ( coefficient of variation , 48 to 124 % ) . Once-daily lamivudine was as well tolerated as the twice-daily regimen . Overall , the results of this study suggest that for key AUC-related parameters , lamivudine at 300 mg once daily is pharmacokinetically equivalent to lamivudine at 150 mg twice daily Emtricitabine ( FTC ) is a potent deoxycytidine nucleoside analogue that was recently approved for the treatment of HIV infection .  Emtricitabine is activated by intracellular phosphorylation to its 5'-triphosphate ( FTC5'-TP ) , a competitive inhibitor of the HIV 
    Output:
    
Greatest efficacy was associated with use of tenofovir-emtricitabine ( vs. other nucleoside analogue backbones ) and integrase str and transfer inhibitors ( vs. other third drug classes ) .
CONCLUSION Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy , but are more effective when commenced at plasma viral loads < 100,000 copies/mL. Rising viral load should be considered an indication for starting treatment .
Integrase inhibitors offer a treatment advantage ( vs. other third drug classes )