***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: Background Tuberculosis ( TB ) is a major cause of morbidity and mortality among children infected with HIV . Strategies to prevent TB in children include isoniazid preventive therapy ( IPT ) and antiretroviral therapy ( ART ) . IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children . Objective To investigate the combined effect of IPT and ART on TB risk in children infected with HIV . Methods A cohort analysis was done within a prospect i ve , double-blinded , placebo-controlled trial of isoniazid ( INH ) compared with placebo in children infected with HIV in Cape Town , South Africa , a high TB incidence setting . In May 2004 the placebo arm was terminated and all children were switched to INH . ART was not widely available at the start of the study , but children were started on ART following the establishment of the national ART program in 2004 . Data were analysed using Cox proportional hazard regression . Results After adjusting for age , nutritional status and immunodeficiency at enrolment , INH alone , ART alone and INH combined with ART reduced the risk of TB disease by 0.22 ( 95 % CI 0.09 to 0.53 ) , 0.32 ( 95 % CI 0.07 to 1.55 ) and 0.11 ( 95 % CI 0.04 to 0.32 ) respectively . INH reduced the risk of TB disease in children on ART by 0.23 ( 95 % CI 0.05 to 1.00 ) . Conclusions The finding that IPT may offer additional protection in children on ART has significant public health implication s because this offers a possible strategy for reducing TB in children infected with HIV . Widespread use of this strategy will however require screening of children for active TB disease . Trial registration Trial registration — Clinical Trials NCT00330304 BACKGROUND The dual epidemic of human immunodeficiency virus ( HIV ) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa . We conducted a double-blind , r and omized , placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period . METHODS We r and omly assigned 548 HIV-infected and 804 HIV-uninfected infants ( 91 to 120 days of age ) to isoniazid ( 10 to 20 mg per kilogram of body weight per day ) or matching placebo for 96 weeks . All patients received bacille Calmette-Guérin ( BCG ) vaccination against tuberculosis within 30 days after birth . HIV-infected children had access to antiretroviral therapy . The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection , tuberculosis disease , and death in HIV-uninfected children within 96 to 108 weeks after r and omization . RESULTS Antiretroviral therapy was initiated in 98.9 % of HIV-infected children during the study . Among HIV-infected children , protocol -defined tuberculosis or death occurred in 52 children ( 19.0 % ) in the isoniazid group and 53 ( 19.3 % ) in the placebo group ( P=0.93 ) . Among HIV-uninfected children , there was no significant difference in the combined incidence of tuberculosis infection , tuberculosis disease , or death between the isoniazid group ( 39 children , 10 % ) and the placebo group ( 45 children , 11 % ; P=0.44 ) . The rate of tuberculosis was 121 cases per 1000 child-years ( 95 % confidence interval [ CI ] , 95 to 153 ) among HIV-infected children as compared with 41 per 1000 child-years ( 95 % CI , 31 to 52 ) among HIV-uninfected children . There were no significant differences in clinical or severe laboratory toxic effects between treatment groups . CONCLUSIONS Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine . Despite access to antiretroviral therapy , the burden of tuberculosis remained high among HIV-infected children . ( Funded by the National Institutes of Health and Secure the Future ; Clinical Trials.gov number , NCT00080119 . ) Background Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa .  Isoniazid prophylaxis can reduce tuberculosis incidence in this population . However , for the treatment to be effective , adherence to the medication must be optimized . We investigated adherence to isoniazid prophylaxis administered daily , compared to three times a week , and predictors of adherence amongst HIV-infected children . Methods We investigated adherence to study medication in a two centre , r and omized trial comparing daily to three times a week dosing of isoniazid . The study was conducted at two tertiary paediatric care centres in Cape Town , South Africa . Over a 5 year period , we followed 324 HIV-infected children aged ≥ 8 weeks . Adherence information based on pill counts was available for 276 children .  Percentage adherence was calculated by counting the number of pills returned . Adherence ≥ 90 % was considered to be optimal . Analysis was done using summary and repeated measures , comparing adherence to the two dosing schedules . Mean percentage adherence ( per child during follow-up time ) was used to compare the mean of each group as well as the proportion of children achieving an adherence of ≥ 90 % in each group . For repeated measures , percentage adherence ( per child per visit ) was dichotomized at 90 % . A logistic regression model with generalized estimating equations , to account for within-individual correlation , was used to evaluate the impact of the dosing schedule . Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants . Results The overall adherence to  isoniazid  was excellent , with a mean adherence of 94.7 % ( 95 % confidence interval [ CI ] 93.5 - 95.9 ) ; similar mean adherence was achieved by the group taking daily medication ( 93.8 % ; 95 % CI 92.1 - 95.6 ) and by the three times a week group ( 95.5 % ; 95 % CI 93.8 - 97.2 ) . Two-hundred and seventeen ( 78.6 % ) children achieved a mean adherence of ≥ 90 % . Adherence was similar for daily and three times a week dosing schedules in univariate ( odds ratio [ OR ] 0.88 ; 95 % CI 0.66 - 1.17 ; P = 0.38 ) and multivariate ( adjusted OR 0.85 ; 95 % CI 0.64 - 1.11 ; P = 0.23 ) models . Children from overcrowded homes were less adherent ( adjusted OR 0.71 ; 95 % CI 0.54 - 0.95 ; P = 0.02 ) . Age at study visit was predictive of adherence , with better adherence achieved in children older than 4 years ( adjusted OR 1.96 ; 95 % CI 1.16 - 3.32 ; P = 0.01 ) . Conclusion Adherence to isoniazid was excellent regardless of the dosing schedule used . Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing , without compromising adherence or efficacy . Trial registration Clinical Trials BACKGROUND Antiretroviral therapy reduces the risk of tuberculosis , but tuberculosis is more common in people with HIV than in people without HIV . We aim ed to assess the effect of isoniazid preventive therapy on the risk of tuberculosis in people infected with HIV-1 concurrently receiving antiretroviral therapy . METHODS For this pragmatic r and omised double-blind , placebo-controlled trial in Khayelitsha , South Africa , we r and omly assigned ( 1:1 ) patients to receive either isoniazid preventive therapy or a placebo for 12 months ( could be completed during 15 months ) . R and omisation was done with r and om number generator software . Participants , physicians , and pharmacy staff were masked to group assignment . The primary endpoint was time to development of incident tuberculosis ( definite , probable , or possible ) . We excluded tuberculosis at screening by sputum culture . We did a modified intention-to-treat analysis and excluded all patients r and omly assigned to groups who withdrew before receiving study drug or whose baseline sputum culture results suggested prevalent tuberculosis . This study is registered with Clinical Trials.gov , number NCT00463086 . FINDINGS 1329 participants were r and omly assigned to receive isoniazid preventive therapy ( n=662 ) or placebo ( n=667 ) between Jan 31 , 2008 , and Sept 31 , 2011 , and contributed 3227 person-years of follow-up to the analysis . We recorded 95 incident cases of tuberculosis ; 37 were in the isoniazid preventive therapy group ( 2·3 per 100 person-years , 95 % CI 1·6 - 3·1 ) , and 58 in the placebo group ( 3·6 per 100 person-years , 2·8 - 4·7 ; hazard ratio [ HR ] 0·63 , 95 % CI 0·41 - 0·94 ) . Study drug was discontinued because of grade 3 or 4 raised alanine transaminase concentrations in 19 of 662 individuals in the isoniazid preventive therapy group and ten of the 667 individuals in the placebo group ( risk ratio 1·9 , 95 % CI 0·90 - 4·09 ) . We noted no evidence that the effect of isoniazid preventive therapy was restricted to patients who were positive on tuberculin skin test or interferon gamma release assay ( adjusted HR for patients with negative tests 0·43 [ 0·21 - 0·86 ] and 0·43 [ 0·20 - 0·96 ] ; for positive tests 0·86 [ 0·37 - 2·00 ] and 0·55 [ 0·26 - 1·24 ] , respectively ) . INTERPRETATION Without a more predictive test or a multivariate algorithm that predicts benefit , isoniazid preventive therapy should be recommended to all patients receiving antiretroviral therapy in moderate or high incidence areas irrespective of tuberculin skin test or interferon gamma release assay status . FUNDING Department of Health of South Africa , the Wellcome Trust , Médecins Sans Frontières , European and Developing Countries Clinical Trials Partnership , Foundation for Innovation and New Diagnostics , the European Union , and Hasso Plattner ( Institute of Infectious Diseases and Molecular Medicine , University of Cape Town ) BACKGROUND There are limited population -based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged < or = 12 months . We aim ed to estimate the population -based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province , South Africa . METHODS The incidences of pulmonary , extrapulmonary , and disseminated tuberculosis were estimated over a 3-year period ( 2004 - 2006 ) with use of prospect i ve representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants . The total number of HIV-infected and HIV-uninfected infants was calculated using population -based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates . RESULTS There were 245 infants with culture-confirmed tuberculosis . The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants ( 95 % confidence interval [ CI ] , 1151 - 2132 cases per 100,000 population ) and 65.9 cases per 100,000 population among HIV-uninfected infants ( 95 % CI , 56 - 75 cases per 100,000 population ) . The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 ( 95 % CI , 17 - 34 ) . The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population ( 95 % CI , 89 - 433 cases per 100,000 population ) among HIV-infected infants and 14.1 cases per 100,000 population ( 95 % CI , 10 - 18 cases per 100,000 population ) among HIV-uninfected infants ( relative risk , 17.1 ; 95 % CI , 6 - 
    Output:
    
Authors ' conclusions Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV‐positive children not on ART in studies from Africa .
For children on ART , no clear benefit was detected . .