Gregory P Bisson1, Mayara Bastos2, Jonathon R Campbell3, Didi Bang4, James C Brust5, Petros Isaakidis6, Christoph Lange7, Dick Menzies3, Giovanni B Migliori8, Jean W Pape9, Domingo Palmero10, Parvaneh Baghaei11, Payam Tabarsi11, Piret Viiklepp12, Stalz Vilbrun13, Jonathan Walsh14, Suzanne M Marks15. 1. Department of Medicine and Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: bisson@pennmedicine.upenn.edu. 2. Social Medicine Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. 3. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. 4. Virus & Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark. 5. Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA. 6. Médecins Sans Frontières, Cape Town, South Africa. 7. Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany. 8. WHO Collaborating Centre for TB and Lung Diseases, Maugeri Care and Research Institute, Tradate, Italy. 9. Weill Cornell Medicine, New York, NY, USA. 10. División Neumotisiología, Hospital Muñiz, Buenos Aires, Argentina. 11. Clinical Tuberculosis and Epidemiology Research Center National Research Institute for Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 12. National Institute of Health Development, Tallinn, Estonia. 13. Groupe Haitien d'Étude du Sarcome de Kaposi et des infections Opportunistes, Port-au-Prince, Haiti. 14. Department of Medicine and Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 15. Centers for Disease Control and Prevention, Atlanta, GA, USA.
Abstract
BACKGROUND: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. METHODS: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. FINDINGS: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. INTERPRETATION: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.
BACKGROUND:HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. METHODS: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. FINDINGS: We included 11 920 multidrug-resistant tuberculosispatients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. INTERPRETATION: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.
Authors: K F Laserson; L E Thorpe; V Leimane; K Weyer; C D Mitnick; V Riekstina; E Zarovska; M L Rich; H S F Fraser; E Alarcón; J P Cegielski; M Grzemska; R Gupta; M Espinal Journal: Int J Tuberc Lung Dis Date: 2005-06 Impact factor: 2.373
Authors: Nafees Ahmad; Shama D Ahuja; Onno W Akkerman; Jan-Willem C Alffenaar; Laura F Anderson; Parvaneh Baghaei; Didi Bang; Pennan M Barry; Mayara L Bastos; Digamber Behera; Andrea Benedetti; Gregory P Bisson; Martin J Boeree; Maryline Bonnet; Sarah K Brode; James C M Brust; Ying Cai; Eric Caumes; J Peter Cegielski; Rosella Centis; Pei-Chun Chan; Edward D Chan; Kwok-Chiu Chang; Macarthur Charles; Andra Cirule; Margareth Pretti Dalcolmo; Lia D'Ambrosio; Gerard de Vries; Keertan Dheda; Aliasgar Esmail; Jennifer Flood; Gregory J Fox; Mathilde Fréchet-Jachym; Geisa Fregona; Regina Gayoso; Medea Gegia; Maria Tarcela Gler; Sue Gu; Lorenzo Guglielmetti; Timothy H Holtz; Jennifer Hughes; Petros Isaakidis; Leah Jarlsberg; Russell R Kempker; Salmaan Keshavjee; Faiz Ahmad Khan; Maia Kipiani; Serena P Koenig; Won-Jung Koh; Afranio Kritski; Liga Kuksa; Charlotte L Kvasnovsky; Nakwon Kwak; Zhiyi Lan; Christoph Lange; Rafael Laniado-Laborín; Myungsun Lee; Vaira Leimane; Chi-Chiu Leung; Eric Chung-Ching Leung; Pei Zhi Li; Phil Lowenthal; Ethel L Maciel; Suzanne M Marks; Sundari Mase; Lawrence Mbuagbaw; Giovanni B Migliori; Vladimir Milanov; Ann C Miller; Carole D Mitnick; Chawangwa Modongo; Erika Mohr; Ignacio Monedero; Payam Nahid; Norbert Ndjeka; Max R O'Donnell; Nesri Padayatchi; Domingo Palmero; Jean William Pape; Laura J Podewils; Ian Reynolds; Vija Riekstina; Jérôme Robert; Maria Rodriguez; Barbara Seaworth; Kwonjune J Seung; Kathryn Schnippel; Tae Sun Shim; Rupak Singla; Sarah E Smith; Giovanni Sotgiu; Ganzaya Sukhbaatar; Payam Tabarsi; Simon Tiberi; Anete Trajman; Lisa Trieu; Zarir F Udwadia; Tjip S van der Werf; Nicolas Veziris; Piret Viiklepp; Stalz Charles Vilbrun; Kathleen Walsh; Janice Westenhouse; Wing-Wai Yew; Jae-Joon Yim; Nicola M Zetola; Matteo Zignol; Dick Menzies Journal: Lancet Date: 2018-09-08 Impact factor: 79.321
Authors: Diane V Havlir; Michelle A Kendall; Prudence Ive; Johnstone Kumwenda; Susan Swindells; Sarojini S Qasba; Anne F Luetkemeyer; Evelyn Hogg; James F Rooney; Xingye Wu; Mina C Hosseinipour; Umesh Lalloo; Valdilea G Veloso; Fatuma F Some; N Kumarasamy; Nesri Padayatchi; Breno R Santos; Stewart Reid; James Hakim; Lerato Mohapi; Peter Mugyenyi; Jorge Sanchez; Javier R Lama; Jean W Pape; Alejandro Sanchez; Aida Asmelash; Evans Moko; Fred Sawe; Janet Andersen; Ian Sanne Journal: N Engl J Med Date: 2011-10-20 Impact factor: 91.245
Authors: Emily B Wong; Tanvier Omar; Gosetsemang J Setlhako; Regina Osih; Charles Feldman; David M Murdoch; Neil A Martinson; David R Bangsberg; W D F Venter Journal: PLoS One Date: 2012-10-16 Impact factor: 3.240
Authors: Hind Satti; Megan M McLaughlin; Bethany Hedt-Gauthier; Sidney S Atwood; David B Omotayo; Likhapha Ntlamelle; Kwonjune J Seung Journal: PLoS One Date: 2012-10-24 Impact factor: 3.240
Authors: D M Kokebu; S Ahmed; R Moodliar; C-Y Chiang; G Torrea; A Van Deun; R L Goodall; I D Rusen; S K Meredith; A J Nunn Journal: Int J Tuberc Lung Dis Date: 2022-08-01 Impact factor: 3.427
Authors: Afsatou Ndama Traoré; Mpumelelo Casper Rikhotso; Ntshuxeko Thelma Banda; Maphepele Sara Mashilo; Jean Pierre Kabue Ngandu; Vuyo Mavumengwana; Andre G Loxton; Craig Kinnear; Natasha Potgieter; Scott Heysell; Rob Warren Journal: Pathogens Date: 2022-06-01
Authors: Khasan Safaev; Nargiza Parpieva; Irina Liverko; Sharofiddin Yuldashev; Kostyantyn Dumchev; Jamshid Gadoev; Oleksandr Korotych; Anthony D Harries Journal: Int J Environ Res Public Health Date: 2021-04-27 Impact factor: 3.390
Authors: Joseph Baruch Baluku; Bridget Nakazibwe; Joshua Naloka; Martin Nabwana; Sarah Mwanja; Rose Mulwana; Mike Sempiira; Sylvia Nassozi; Febronius Babirye; Carol Namugenyi; Samuel Ntambi; Sharon Namiiro; Felix Bongomin; Richard Katuramu; Irene Andia-Biraro; William Worodria Journal: J Clin Tuberc Other Mycobact Dis Date: 2021-01-27
Authors: E Mohr-Holland; J Daniels; A Reuter; C A Rodriguez; C Mitnick; Y Kock; V Cox; J Furin; H Cox Journal: Int J Tuberc Lung Dis Date: 2022-02-01 Impact factor: 2.373
Authors: Nabila Ismail; Emmanuel Rivière; Jason Limberis; Stella Huo; John Z Metcalfe; Rob M Warren; Annelies Van Rie Journal: Lancet Microbe Date: 2021-08-31
Authors: James C M Brust; Neel R Gandhi; Sean Wasserman; Gary Maartens; Shaheed V Omar; Nazir A Ismail; Angela Campbell; Lindsay Joseph; Alexandria Hahn; Salim Allana; Alfonso C Hernandez-Romieu; Chenshu Zhang; Koleka Mlisana; Charle A Viljoen; Benjamin Zalta; Ismaeel Ebrahim; Meghan Franczek; Iqbal Master; Limpho Ramangoaela; Julian Te Riele; Graeme Meintjes Journal: Clin Infect Dis Date: 2021-12-06 Impact factor: 9.079