***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 Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin . The US Public Health Service Study 22 compared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in the continuation phase ( the last 4 months ) of treatment for pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients . This report concerns only the HIV-seropositive part of the trial , which has ended . The HIV-seronegative part will stop follow-up in 2001 . METHODS Adults with culture-positive , drug-susceptible pulmonary tuberculosis who completed 2 months of four-drug ( isoniazid , rifampin , pyrazinamide , ethambutol ) treatment ( induction phase ) were r and omly assigned 900 mg isoniazid and 600 mg rifapentine once weekly , or 900 mg isoniazid and 600 mg rifampin twice weekly . All therapy was directly observed . Statistical analysis used univariate , Kaplan-Meier , and logistic and proportional hazards regression methods . FINDINGS 71 HIV-seropositive patients were enrolled : 61 completed therapy and were assessed for relapse . Five of 30 patients in the once-weekly isoniazid/rifapentine group relapsed , compared with three of 31 patients in the twice-weekly isoniazid/rifampin group ( log rank chi2=0.69 , p=0.41 ) . However , four of five relapses in the once-weekly isoniazid/rifapentine group had monoresistance to rifamycin , compared with none of three in the rifampin group ( p=0.05 ) . Patients who relapsed with rifamycin monoresistance were younger ( median age 29 vs 41 years ) , had lower baseline  CD4 cell counts ( median 16 vs 144 microL ) , and were more likely to have extrapulmonary involvement ( 75 % vs 18 % , p=0.03 ) and concomitant therapy with antifungal agents ( 75 % vs 9 % , p=0.006 ) . No  rifamycin monoresistant relapse has occurred among 1004 HIV-seronegative patients enrolled to date . INTERPRETATION Relapse with rifamycin monoresistant tuberculosis occurred among HIV-seropositive tuberculosis patients treated with a once-weekly isoniazid/rifapentine continuation-phase regimen . Until more effective regimens have been identified and assessed in clinical trials , HIV-seropositive people with tuberculosis should not be treated with a once-weekly isoniazid/rifapentine regimen BACKGROUND The occurrence of acquired rifamycin resistance despite use of directly observed therapy for tuberculosis is associated with advanced human immunodeficiency virus ( HIV ) disease and highly intermittent administration of antituberculosis drugs . Beyond these associations , the pathogenesis of acquired rifamycin resistance is unknown . METHODS We performed a pharmacokinetic sub study of patients in a trial of treatment with twice-weekly rifabutin and isoniazid .  RESULTS A total of 102 ( 60 % ) of 169 patients in the treatment trial participated in the pharmacokinetic sub study , including 7 of 8 patients in whom tuberculosis treatment failure or relapse occurred in association with acquired rifamycin-resistant mycobacteria ( hereafter , " ARR failure or relapse " ) . The median rifabutin area under the concentration-time curve ( AUC(0 - 24 ) ) was lower for patients with than for patients without ARR failure or relapse ( 3.3 vs. 5.2 microg*h/mL ; P = .06 , by the Mann-Whitney exact test ) . In a multivariate analysis adjusted for CD4 + T cell count , the mean rifabutin AUC(0 - 24 ) was significantly lower for patients with ARR failure or relapse than for other patients ( 3.0 microg*h/mL [ 95 % confidence interval { CI } , 1.9 - 4.5 ] vs. 5.2 microg*h/mL [ 95 % CI , 4.6 - 5.8 ] ; P = .02 , by analysis of covariance ) . The median isoniazid AUC(0 - 12 ) was not significantly associated with ARR failure or relapse ( 20.6 vs. 28.0 microg*h/mL ; P = .24 , by the Mann-Whitney exact test ) . However , in a multivariate logistic regression model that adjusted for the rifabutin AUC(0 - 24 ) , a lower isoniazid AUC(0 - 12 ) was associated with ARR failure or relapse ( OR , 10.5 ; 95 % CI , 1.1 - 100 ; P = .04 ) . CONCLUSIONS Lower plasma concentrations of rifabutin and , perhaps , isoniazid were associated with ARR failure or relapse in patients with tuberculosis and HIV infection treated with twice-weekly therapy BACKGROUND It is believed that nonadherence is the proximate cause of multidrug-resistant tuberculosis ( MDR-tuberculosis ) emergence . The level of nonadherence associated with emergence of MDR-tuberculosis is unknown . Performance of a r and omized controlled trial in which some patients are r and omized to nonadherence would be unethical ; therefore , other study design s should be utilized . METHODS We performed hollow fiber studies for both bactericidal and sterilizing effect , with inoculum spiked with 0.5 % rifampin- and isoniazid-resistant isogenic strains in some experiments . St and ard therapy was administered daily for 28 - 56 days , with extents of nonadherence varying between 0 % and 100 % . Sizes of drug-resistant population s were compared using analysis of variance . We also explored the effect of pharmacokinetic variability on MDR-tuberculosis emergence using computer-aided clinical trial simulations of 10 000 Cape Town , South Africa , tuberculosis patients . RESULTS Therapy failure was only encountered at extents of nonadherence ≥60 % . Surprisingly , isoniazid- and rifampin-resistant population s did not achieve ≥1 % proportion in any experiment and did not achieve a higher proportion with nonadherence . However , clinical trial simulations demonstrated that approximately 1 % of tuberculosis patients with perfect adherence would still develop MDR-tuberculosis due to pharmacokinetic variability alone . CONCLUSIONS These data , based on a pre clinical model , demonstrate that nonadherence alone is not a sufficient condition for MDR-tuberculosis emergence BACKGROUND Based on a hollow-fiber system model of tuberculosis , we hypothesize that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic variability . METHODS Clinical and pharmacokinetic data were prospect ively collected from 142 tuberculosis patients in Western Cape , South Africa . Compartmental pharmacokinetic parameters of isoniazid , rifampin , and pyrazinamide were identified for each patient . Patients were then followed for up to 2 years . Classification and regression tree analysis was used to identify and rank clinical predictors of poor long-term outcome such as microbiologic failure or death , or relapse . RESULTS Drug concentrations and pharmacokinetics varied widely between patients . Poor long-term outcomes were encountered in 35 ( 25 % ) patients . The 3 top predictors of poor long-term outcome , by rank of importance , were a pyrazinamide 24-hour area under the concentration-time curve ( AUC ) ≤ 363 mg·h/L , rifampin AUC ≤ 13 mg·h/L , and isoniazid  AUC ≤ 52 mg·h/L. Poor outcomes were encountered in 32/78 patients with the AUC of at least 1 drug below the identified threshold vs 3/64 without ( odds ratio = 14.14 ; 95 % confidence interval , 4.08 - 49.08 ) . Low rifampin and isoniazid peak and AUC concentrations preceded all cases of acquired drug resistance . CONCLUSIONS Low drug AUCs are predictive of clinical outcomes in tuberculosis patients Background Development of resistance to antituberculosis drugs during treatment ( i.e. , acquired resistance ) can lead to emergence of resistant strains and consequent poor clinical outcomes . However , it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance . Methods We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004–2011 with assigned species and lineage and both initial and final drug susceptibility test results . We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid , rifamycins , fluoroquinolones , and second-line injectables . We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins . Results M. bovis was independently associated with acquired resistance to isoniazid ( adjusted prevalence ratio = 8.46 , 95 % CI 2.96–24.14 ) adjusting for HIV status , and with acquired resistance to rifamycins ( adjusted prevalence ratio = 4.53 , 95 % CI 1.29–15.90 ) adjusting for homelessness , HIV status , initial resistance to isoniazid , site of disease , and administration of therapy . East Asian lineage was associated with acquired resistance to fluoroquinolones ( prevalence ratio = 6.10 , 95 % CI 1.56–23.83 ) . Conclusions We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data . Prospect i ve clinical studies are needed to determine the clinical significance of these findings , including whether rapid genotyping of isolates at the outset of treatment may benefit patient management OBJECTIVES To determine rates of drug resistance to Mycobacterium tuberculosis and associated risk factors , including HIV infection . DESIGN Prospect i ve cohort study of patients with pulmonary tuberculosis . SETTING The study population comprised 28,522 men working on four goldmines in Westonaria , Gauteng . Health care is provided at a 240-bed mine hospital , Gold Fields West Hospital , and its primary health care facilities . SUBJECTS All 425 patients with culture-positive pulmonary tuberculosis identified in 1995 . OUTCOME MEASURES Tuberculosis drug resistance on enrollment and after 6 months ' treatment . RESULTS There were 292 cases of new tuberculosis , 77 of recurrent disease and 56 prevalent cases in treatment failure . Two hundred and seven patients ( 48.7 % ) were HIV infected .  Primary resistance to one or more drugs ( 9 % ) was similar to the 11 % found in a previous study done on goldminers in 1989 . Primary multidrug resistance ( 0.3 % ) was also similar ( 0.8 % ) . Acquired multidrug resistance was 18.1 % : 6.5 % for recurrent disease and 33.9 % in treatment failure cases . Neither HIV infection nor the degree of immunosuppression as assessed by CD4 + lymphocyte counts was associated with drug resistance at the start or end of treatment . New patterns of drug resistance were present in 9 of 52 patients in treatment failure at 6 months , 1 of whom was HIV-infected . CONCLUSION Primary and acquired drug resistance rates are stable in this population and are not affected by the high prevalence of HIV infection RATIONALE The outcome of fully intermittent thrice-weekly antituberculosis treatment of various duration s in HIV-associated tuberculosis is unclear . OBJECTIVES To compare the efficacy of an intermittent 6-month regimen ( Reg6 M : 2EHRZ(3)/4HR(3 ) [ ethambutol , 1,200 mg ; isoniazid , 600 mg ; rifampicin , 450 or 600 mg depending on body weight < 60 or > or = 60 kg ; and pyrazinamide , 1,500 mg for 2 mo ; followed by 4 mo of isoniazid and rifampicin at the same doses ] ) versus a 9-month regimen ( Reg9 M : 2EHRZ(3)/7HR(3 ) ) in HIV/tuberculosis ( TB ) . METHODS HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were r and omly assigned to Reg6 M ( n = 167 ) or Reg9 M ( n = 160 ) and monitored by determination of clinical , immunological , and bacteriological parameters for 36 months . Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up , whereas the secondary outcome was death . Intent-to-treat and on-treatment analyses were performed . All patients were antiretroviral treatment-naive during treatment . MEASUREMENTS AND MAIN RESULTS Of the patients , 70 % had culture-positive pulmonary TB ; the median viral load was 155,000 copies/ml and the CD4(+ ) cell count was 160 cells/mm(3 ) . Favorable response to antituberculosis treatment was similar by intent to treat ( Reg 
    Output:
    
Baseline drug resistance and HIV co-infection were significant risk factors for ADR .
There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR .