***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: Objectives We describe nevirapine and efavirenz exposure on and off tuberculosis treatment and consequences for virological efficacy and tolerance  in patients included in the ANRS 12146/12214-CARINEMO trial . Methods Participants were r and omly selected to receive either nevirapine at 200 mg twice daily ( n = 256 ) or efavirenz at 600 mg daily ( n = 270 ) , both combined with two nucleoside analogues . Blood sample s were drawn 12 h after nevirapine or efavirenz administration , while on tuberculosis treatment and after tuberculosis treatment discontinuation . In 62 participants , sample s taken 12 h after drug administration were drawn weekly for the first month of ART . Sixteen participants participated in an extensive pharmacokinetic study of nevirapine . Concentrations were compared with the therapeutic ranges of 3000–8000 ng/mL for nevirapine and 1000–4000 ng/mL for efavirenz . Results  Nevirapine concentrations at the end of the first week of treatment ( on antituberculosis drugs ) did not differ from concentrations off tuberculosis treatment , but declined thereafter . Concentrations at steady-state were 4111 ng/mL at week 12 versus 6095 ng/mL at week 48 ( P < 0.0001 ) . Nevirapine concentrations < 3000 ng/mL were found to be a risk factor for virological failure . Efavirenz concentrations were higher on than off tuberculosis treatment ( 2700 versus 2450 ng/mL , P < 0.0001 ) . Conclusions The omission of the 2 week lead-in dose of nevirapine prevented low concentrations at treatment initiation but did not prevent the risk of virological failure . Results support the WHO recommendation to use efavirenz at 600 mg daily in patients on rifampicin-based antituberculosis therapy BACKGROUND To evaluate the effect of rifampicin-based tuberculosis ( TB ) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet , and vice versa , in Tanzanian TB-HIV-coinfected patients . METHODS This was a Phase II open-label multiple dose pharmacokinetic and safety study . This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment ( rifampicin/isoniazid/pyrazinamide/ethambutol ) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks . Antiretroviral treatment ( ART ) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment . A 24-h pharmacokinetic sampling curve was recorded at week 8 ( with TB treatment ) and week 28 ( ART alone ) . For TB drugs , blood sample s at 2 and 5 h post-dose were taken at week 3 ( TB treatment alone ) and week 8 ( with ART ) . RESULTS A total of 25 patients ( 56 % male ) completed the study ; 21 had evaluable pharmacokinetic profiles . The area under the concentration-time curve 0 - 24 h post-dose of efavirenz , tenofovir and emtricitabine  were slightly higher when these drugs were coadministered with TB drugs ; geometric mean ratios ( 90 % CI ) were 1.08 ( 0.90 , 1.30 ) , 1.13 ( 0.93 , 1.38 ) and 1.05 ( 0.85 , 1.29 ) , respectively . For TB drugs , equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine .  Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported . CONCLUSIONS Coadministration of efavirenz , tenofovir and emtricitabine with a st and ard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV SETTING R and omised Phase IIB clinical trial . OBJECTIVES To assess whether increasing the dose of rifampicin ( RMP ) from 10 mg/kg to 15 or 20 mg/kg results in an increase in grade 3 or 4 hepatic adverse events and /or serious adverse events ( SAE ) . METHODS Three hundred human immunodeficiency virus negative patients with newly diagnosed microscopy-positive pulmonary tuberculosis ( TB ) were r and omly assigned to one of three regimens : 1 ) the control regimen ( R10 ) , comprising daily ethambutol ( EMB ) , isoniazid ( INH ) , RMP and pyrazinamide for 8 weeks , followed by INH and RMP daily for 18 weeks ; 2 ) Study Regimen 1 ( R15 ) , as above , with the RMP dose increased to 15 mg/kg body weight daily for the first 16 weeks ; and 3 ) Study Regimen 2 ( R20 ) , as above , with RMP increased to 20 mg/kg . Serum alanine transferase ( ALT ) levels were measured at regular intervals . RESULTS There were seven grade 3 increases in ALT levels , 1/100 ( 1 % ) among R10 arm patients , 2/100 ( 2 % ) in the R15 arm and 4/100 ( 4 % ) in the R20 arm ( trend test P = 0.15 ) . One ( R15 ) patient developed jaundice , requiring treatment modification . There were no grade 4 ALT increases . There was a non-significant increase in culture negativity at 8 weeks with increasing RMP dosage : 75 % ( 69/92 ) in R10 , 82.5 % ( 66/80 ) in R15 and 83.1 % ( 76/91 ) R20 patients ( P = 0.16 ) . CONCLUSIONS No significant increase in adverse events occurred when the RMP dose was increased from 10 mg/kg to 15 mg/kg or 20 mg/kg BACKGROUND Rifampicin induces expression of the cytochrome P450 isoenzyme 2B6 ( CYP2B6 ) , which metabolizes efavirenz . The CYP2B6 516G > T polymorphism impairs efavirenz metabolism and occurs more commonly in Africans than in Caucasians . We explored the effect of rifampicin-based antitubercular therapy and the 516G > T polymorphism on efavirenz concentrations in HIV-infected patients in South Africa . METHODS Between-patient and within-patient comparisons were made of mid-dosing interval efavirenz plasma concentrations in adults on antiretroviral therapy including efavirenz 600 mg daily , with and without antitubercular therapy . RESULTS There were 142 participants ( 40 were on antitubercular therapy and 102 were controls ) , the mean weight was 66 kg .  Median efavirenz concentration was 2.4 mg/l ( interquartile range [ IQR ] 1.3 - 3.1 ) and 1.8 mg/l ( IQR 1.4 - 4.4 ) in participants on antitubercular therapy and controls , respectively ( P=0.734 ) . Paired efavirenz concentrations during and after antitubercular therapy in 17 participants were also similar ( P=0.113 ) . Genotyping results were 60 ( 49 % ) G/G homozygotes , 46 ( 38 % ) G/T heterozygotes and 16 ( 13 % ) T/T homozygotes . In a multivariate logistic regression model adjusted for sex , weight and concomitant antitubercular therapy , the 516G > T polymorphism was strongly associated with high ( > 4 mg/l ) efavirenz concentrations : odds ratio ( OR ) 4.4 ( 95 % confidence interval [ CI ] 1.3 - 14.9 ) for G/T versus G/G and 31.1 ( 95 % CI 6.6 - 146.6 ) for T/T versus G/G. High efavirenz concentrations were associated with severe sleep disturbance ( P=0.048 ) . Low ( < 1 mg/l ) efavirenz concentrations were associated with virological failure ( OR 12.5 , 95 % CI 2.7 - 57.3 ) . CONCLUSIONS Efavirenz can be used together with rifampicin-based antitubercular therapy without dose adjustment in this population . The 516G > T polymorphism occurred commonly and was associated with high efavirenz concentrations Purpose Drug interactions are of concern when treating patients co-infected with human immunodeficiency virus ( HIV ) and tuberculosis . Concomitant use of efavirenz ( EFV ) with the enzyme inducer rifampicin might be expected to increase EFV clearance . We investigated the influence of concomitant tuberculosis treatment on the plasma clearance of EFV . Methods Fifty-eight patients were r and omized to receive their EFV-containing antiretroviral therapy either during or after tuberculosis treatment .  Steady-state EFV plasma concentrations ( n = 209 sample s ) were measured , 83 in the presence of rifampicin . Data were analyzed using a non-linear mixed effects model , and the model was evaluated using non-parametric bootstrap and visual predictive checks . Results The patients had a median age of 32 ( range 19–55 ) years and 43.1 % were women . There was a bimodal distribution of apparent clearance , with slow EFV metabolizers accounting for 23.6 % of the population and having a metabolic capacity 36.4 % of that of the faster metabolizers . Apparent EFV clearance after oral administration in fast metabolizers was 12.9 L/h/70 kg whilst off tuberculosis treatment and 9.1 L/h/70 kg when on tuberculosis treatment . In slow metabolizers , the clearance estimates were 3.3 and 4.7 L/h/70 kg in the presence and absence of TB treatment , respectively . Overall there was a 29.5 % reduction in EFV clearance during tuberculosis treatment . Conclusion Unexpectedly , concomitant rifampicin-containing tuberculosis treatment reduced apparent EFV clearance with a corresponding increase in EFV exposure . While the reasons for this interaction require further investigation , cytochrome P450 2B6 polymorphisms in the population studied may provide some explanation Objectives : Efavirenz is an effective antiretroviral agent , but central nervous system side effects occur commonly , and population ( racial ) differences in pharmacokinetics and response have been reported . Efavirenz is metabolized by cytochrome P4502B6 ( CYP2B6 ) . We investigated whether polymorphisms in CYP2B6 , CYP3A4 , CYP3A5 , and MDR1 were associated with efavirenz central nervous system side effects and pharmacokinetics . Design : Twenty-four week cohort from a r and omized study . Methods : Adult AIDS Clinical Trials Group study A5097s examined relationships between central nervous system side effects and efavirenz  plasma concentration – time profiles in HIV-infected subjects .  Efavirenz plasma pharmacokinetics were estimated by a population -based method . Central nervous system symptoms were assessed by question naires and neuropsychological testing . Results : Study subjects included 89 ( 57 % ) European-Americans , 50 ( 32 % ) African-Americans , and 15 ( 10 % ) Hispanics . The CYP2B6 T/T genotype at position 516 ( Gln172His ) was more common in African-Americans ( 20 % ) than in European-Americans ( 3 % ) , and was associated with greater efavirenz plasma exposure ( P < 0.0001 ) . The median efavirenz [ area-under-the-curve ] ( 0–24 h ) according to G/G , G/T , and T/T genotype was 44 ( n = 78 ) , 60 ( n = 60 ) , and 130 ( n = 14 ) μg.h/ml , respectively ( P < 0.0001 ) . The CYP2B6 G516 T genotype was also associated with central nervous system symptoms at week 1 ( P = 0.036 ) . Analysis of DNA from other subjects confirmed population differences in frequency of the G516 T variant . No associations were apparent with the other polymorphisms studied . Conclusions : A CYP2B6 allelic variant that is more common in African-Americans than in Europeans-Americans was associated with significantly greater efavirenz plasma exposure during HIV therapy . Inter-individual differences in metabolism may , in part , explain susceptibility to efavirenz central nervous system side effects Background & objectives : Among patients with HIV-associated tuberculosis ( TB ) , reduced plasma non-n 
    Output:
    
Anti-TB drug coadministration minimally affect the  EFV exposure , efficacy and safety among TB-HIV coinfected African and Asian patients .