Molebogeng X Rangaka|Robert J. Wilkinson|Andrew Boulle|Judith R. Glynn|Katherine Fielding|Gilles Van Cutsem|Katalin A. Wilkinson|René Goliath|Shaheed Mathee|Eric Goemaere|Gary Maartens
Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial
London School of Hygiene & Tropical Medicine|University of Cape Town|Wellcome Centre for Infectious Diseases Research in Africa|Imperial College London|Wellcome Centre for Infectious Diseases Research in Africa|University of Cape Town|University of Cape Town|London School of Hygiene & Tropical Medicine|London School of Hygiene & Tropical Medicine|Médecins Sans Frontières|University of Cape Town|Wellcome Centre for Infectious Diseases Research in Africa|University of Cape Town|Wellcome Centre for Infectious Diseases Research in Africa|University of Cape Town|Government of South Africa|Médecins Sans Frontières|University of Cape Town
backgroundantiretroviral therapy reduces risk tuberculosis tuberculosis common people hiv people without hiv aimed assess effect isoniazid preventive therapy risk tuberculosis people infected hiv1 concurrently receiving antiretroviral therapymethodsfor pragmatic randomised doubleblind placebocontrolled trial khayelitsha south africa randomly assigned 11 patients receive either isoniazid preventive therapy placebo 12 months could completed 15 months randomisation done random number generator software participants physicians pharmacy staff masked group assignment primary endpoint time development incident tuberculosis definite probable possible excluded tuberculosis screening sputum culture modified intentiontotreat analysis excluded patients randomly assigned groups withdrew receiving study drug whose baseline sputum culture results suggested prevalent tuberculosis study registered clinicaltrialsgov number nct00463086findings1329 participants randomly assigned receive isoniazid preventive therapy n662 placebo n667 jan 31 2008 sept 31 2011 contributed 3227 personyears followup analysis recorded 95 incident cases tuberculosis 37 isoniazid preventive therapy group 23 per 100 personyears 95 ci 1631 58 placebo group 36 per 100 personyears 2847 hazard ratio hr 063 95 ci 041094 study drug discontinued grade 3 4 raised alanine transaminase concentrations 19 662 individuals isoniazid preventive therapy group ten 667 individuals placebo group risk ratio 19 95 ci 090409 noted evidence effect isoniazid preventive therapy restricted patients positive tuberculin skin test interferon gamma release assay adjusted hr patients negative tests 043 021086 043 020096 positive tests 086 037200 055 026124 respectivelyinterpretationwithout predictive test multivariate algorithm predicts benefit isoniazid preventive therapy recommended patients receiving antiretroviral therapy moderate high incidence areas irrespective tuberculin skin test interferon gamma release assay statusfundingdepartment health south africa wellcome trust mdecins sans frontires european developing countries clinical trials partnership foundation innovation new diagnostics european union hasso plattner institute infectious diseases molecular medicine university cape town