***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: CONTEXT Abacavir , a nucleoside analogue , has demonstrated suppression of human immunodeficiency virus ( HIV ) replication alone and in combination therapy . However , the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a st and ard protease inhibitor-containing regimen for initial antiretroviral treatment . OBJECTIVE To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen . DESIGN AND SETTING A multicenter , phase 3 , r and omized , double-blind trial with an enrollment period from August 1997 to June 1998 , with follow-up through 48 weeks at 73 clinical research units in the United States , Canada , Australia , and Europe . PATIENTS Five hundred sixty-two antiretroviral-naive , HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. INTERVENTIONS Patients were stratified by baseline HIV RNA level and r and omly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo . After 16 weeks , patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving r and omized treatment or receive open-label therapy . MAIN OUTCOME MEASURE Virologic suppression , defined as HIV RNA concentration of 400 copies/mL or less at week 48 . RESULTS The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group ( 51 % [ 133/262 ] ) and in the indinavir group ( 51 % [ 136/265 ] ) with a treatment difference of -0.6 % ( 95 % confidence interval [ CI ] , -9 % to 8 % ) . In patients with baseline HIV RNA levels greater than 100 000 copies/mL , the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45 % ( 45/100 ) vs 31 % ( 30/96 ) and a treatment diference of -14 % ( 95 % CI , -27 % to 0 % ) . The 2 treatments were comparable with respect to their effects on CD4 cell count . There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities . One death in the abacavir group was attributed to hypersensitivity reaction , which occurred following rechallenge with abacavir , approximately 3 weeks after initiating study treatment . CONCLUSIONS In this study of antiretroviral-naive HIV-infected adults , the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks Patients with sustained virological suppression on protease inhibitor (PI)-based therapy were r and omly assigned to switch the PI to nevirapine ( n = 155 ) , efavirenz ( n = 156 ) , or abacavir ( n = 149 ) and were followed for at least 3 years regardless of the discontinuation of assigned therapy . There was a higher probability of maintaining virological suppression after 3 years of follow-up with nevirapine or efavirenz than with abacavir . In contrast , abacavir showed a lower incidence of adverse effects leading to drug discontinuation BACKGROUND Evidence from r and omized controlled trials supports the use of triple therapy . Research is required on the effectiveness of quadruple therapy in comparison to this and the relative effectiveness of specific highly active antiretroviral therapy ( HAART ) combinations . METHODS Antiretroviral-naive individuals ( n = 53 ) with an HIV-1 viral load > 100 000 copies/mL were r and omized to receive  three-drug HAART with zidovudine/lamivudine ( Combivir ) and efavirenz or quadruple therapy with zidovudine/lamivudine/abacavir ( Trizivir ) and efavirenz ( quad regimen ) . Patients continued on HAART for 48 weeks with regular clinical and immunological assessment . St and ard and ultrasensitive ( < 5 copies/mL ) viral load testing was carried out . RESULTS A DAVG ( difference in averages ) analysis of the fall in viral load and increase in CD4 count showed no significant differences between regimens . Triple therapy result ed in a -4.17 log change ( 95 % CI , -4.48 to -3.85 ) and quadruple therapy in a -4.36 log change ( 95 % CI , -4.68 to -4.03 ) in viral load . For CD4 counts , the triple therapy arm increased by 164 cells/mm(3 ) ( 95 % CI 112 - 217 ) and the quadruple arm by 185 ( 95 % CI , 133 - 237 ) . In an intent-to-treat analysis , 77 % of patients in the triple therapy group reached an undetectable viral load ( < 50 copies/mL ) compared with 84.2 % of the quadruple therapy group . For ultrasensitive viral load testing , 23 % and 18 % of each group , respectively , reached undetectable viral loads . The hazard ratio for attaining a viral load of < 5 copies/mL was 0.59 ( 95 % CI , 0.26 - 1.33 ) for quadruple versus triple therapy . Three individuals in the triple therapy arm and nine in the quadruple therapy arm discontinued treatment . CONCLUSIONS No differences in any analyses were observed between a st and ard of care regimen ( zidovudine/lamivudine and efavirenz ) and the quad regimen ( zidovudine/lamivudine/abacavir and efavirenz ) Background : The OK04 trial has shown that 48 weeks of lopinavir-ritonavir monotherapy with re introduction of nucleosides as needed was noninferior to continuation of triple therapy with 2 nucleosides and lopinavir-ritonavir in patients with prior stable suppression . However , it is still uncertain if this experimental strategy can maintain suppression in the long term . Methods : Patients entered this noninferiority trial ( upper limit 95 % confidence interval : + 12 % ) with no history of virological failure while receiving a protease inhibitor and receiving 2 nucleosides plus lopinavir/ritonavir , with HIV RNA < 50 copies per milliliter for more than 6 months . Primary end point was percent of patients without therapeutic failure , defined as confirmed HIV RNA > 500 copies per milliliter with exclusion of monotherapy patients who resuppressed to < 50 copies per milliliter after resuming baseline nucleosides , or loss to follow-up , or change of r and omized therapy other than reinduction . Results : Through 96 weeks , percentage of patient without therapeutic failure was 87 % ( monotherapy , n = 100 ) vs. 78 % ( triple therapy , n = 98 ; 95 % confidence interval : −20 % to + 1.2 % ) . Percentage with HIV RNA < 50 copies per milliliter ( intention to treat , missing = failure , reinduction = failure ) : 77 % ( monotherapy ) vs. 78 % ( triple therapy ) . Low-level viral rebound was more frequent in the monotherapy group . Twelve patients in the monotherapy group ( 12 % ) needed reinduction with nucleosides . Discontinuations due to adverse events were significantly more frequent in the triple therapy group ( 8 % ) than in the monotherapy group ( 0 % ) ; P = 0.003 . Conclusions : At 96-week lopinavir/ritonavir monotherapy with re introduction of nucleosides as needed was noninferior to continuation of triple therapy . Incidence of adverse events leading to treatment discontinuation was significantly lower with monotherapy . ( Clinical Trials.gov number , NCT00114933 ) Background : The NEFA Study was a r and omized study comparing nevirapine ( NVP ) , efavirenz ( EFV ) or abacavir ( ABC ) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors . Objective : To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms . Methods : Patients with virological failure , defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml , were analysed for phenotypic susceptibility and HIV-1 mutations . Results : Of the 460 patients included in the study , 51 ( 11 % ) experienced virological failure after 24 months of follow-up while on assigned study medication . A higher proportion of patients in the ABC [ 25 ( 17 % ) ] than in the NVP [ 14 ( 9 % ) ] or EFV [ 12 ( 8 % ) ] arms selected resistance to the study drug ( P = 0.04 ) . Moreover , a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms . In general , there was a good concordance among genotype and phenotype resistance testing , except for ABC , stavudine and didanosine , where phenotypic resistance testing added valuable information ( fold change in the median inhibitory concentration ) . Conclusions : Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy . Phenotypic resistance testing may be helpful in interpreting unclear genotypic results BACKGROUND Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele . This study was design ed to establish the effectiveness of prospect i ve HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir . METHODS This double-blind , prospect i ve , r and omized study involved 1956 patients from 19 countries , who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir .  We r and omly assigned patients to undergo prospect i ve HLA-B*5701 screening , with exclusion of HLA-B*5701-positive  patients from abacavir treatment ( prospect ive-screening group ) , or to undergo a st and ard-of-care approach of abacavir use without prospect i ve HLA-B*5701 screening ( control group ) .  All patients who started abacavir were observed for 6 weeks . To immunologically confirm , and enhance the specificity of , the clinical diagnosis of hypersensitivity reaction to abacavir , we performed epicutaneous patch testing with the use of abacavir . RESULTS The prevalence of HLA-B*5701 was 5.6 % ( 109 of 1956 patients ) . Of the patients receiving abacavir , 72 % were men , 84 % were white , and 18 % had not previously received antiretroviral therapy . Screening eliminated immunologically confirmed hypersensitivity reaction ( 0 % in the prospect ive-screening group vs. 2.7 % in the control group , P<0.001 ) , with a negative predictive value of 100 % and a positive predictive value of 47.9 % . Hypersensitivity reaction was clinical ly diagnosed in 93 patients , with a significantly lower incidence in the prospect ive-screening group ( 3.4 % ) than in the control group ( 7.8 % ) ( P<0.001 ) . CONCLUSIONS HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir . In predominantly white population s , similar to the one in this study , 94 % of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir . Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug . ( Clinical Trials.gov number , NCT00340080 . Background : Darunavir/ritonavir ( darunavir/r ) maintenance strategy , in patients with suppressed HIV RNA viremia , is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs . Methods : MONOtherapy Inhibitor protease is a prospect i ve , open-label , noninferiority , 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were r and omized to a darunavir/r triple drug regimen or darunavir/r monotherapy .  The primary endpoint was the proportion of patients with HIV 
    Output:
    
For the outcomes discontinuation for adverse events and virologic failures , the RRs were not significant , albeit being not far from the alpha level of 0.05 , thus suggesting a weak evidence of lower incidence of side effects and an higher incidence of virologic failure in the 3NRTI group compared to controls .
The strategy of switching to triple nucleoside regimens shows weak evidence of lower incidence of side effects and a higher incidence of virologic failure in the 3NRTI group compared to controls .
Simplification with 3NRTI holds the advantages of preserving other classes of antiretroviral drugs , to lower blood lipids , and to be cost effective and simple to administer .