{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:50:11Z","timestamp":1792191011439,"version":"4.4.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,6,21]],"date-time":"2020-06-21T00:00:00Z","timestamp":1592697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100005627","name":"Thrasher Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005627","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH\/NIAID K23AI120793"],"award-info":[{"award-number":["NIH\/NIAID K23AI120793"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH\/NIAID 2K24AI137310"],"award-info":[{"award-number":["NIH\/NIAID 2K24AI137310"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R25TW009345"],"award-info":[{"award-number":["R25TW009345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH UL1TR000423"],"award-info":[{"award-number":["NIH UL1TR000423"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human immunodeficiency virus (HIV)\u2013exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg\/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-\u03b3 release assay (QuantiFERON-TB Gold Plus) and\/or tuberculin skin test (TST, added 6 months after first participant exit).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287\/298), and 88.9% (265\/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28\/265); 7.6% (10\/132) in the INH arm and 13.5% (18\/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24\u20131.14]; P\u2005=\u2005.11]), and driven primarily by TST positivity (8.6% [8\/93] in INH and 18.1% [17\/94] in no INH; relative risk, 0.48 [95% CI, .22\u20131.05]; P\u2005=\u2005.07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21\/150] vs no INH, 10.7% [16\/150]; P\u2005=\u2005.38), with no INH-related adverse events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT02613169.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa827","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T19:11:19Z","timestamp":1592248279000},"page":"e337-e344","source":"Crossref","is-referenced-by-count":8,"title":["A Randomized Controlled Trial of Isoniazid to Prevent <i>Mycobacterium tuberculosis<\/i> Infection in Kenyan Human Immunodeficiency Virus\u2013Exposed Uninfected Infants"],"prefix":"10.1093","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-5997","authenticated-orcid":false,"given":"Sylvia M","family":"LaCourse","sequence":"first","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA"},{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbra A","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA"},{"name":"Department of Biostatistics, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kinuthia","sequence":"additional","affiliation":[{"name":"Research and Programs, Kenyatta National Hospital, Nairobi, Kenya"},{"name":"Department of Obstetrics and Gynaecology, Kenyatta National Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Warr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Maleche-Obimbo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Matemo","sequence":"additional","affiliation":[{"name":"Research and Programs, Kenyatta National Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Cranmer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Diseases, Emory University, Atlanta, Georgia, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerphason","family":"Mecha","sequence":"additional","affiliation":[{"name":"Research and Programs, Kenyatta National Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-774X","authenticated-orcid":false,"given":"Jaclyn N","family":"Escudero","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R","family":"Hawn","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"John-Stewart","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA"},{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA"},{"name":"Department of Epidemiology, University of Washington, Seattle, Washington, USA"},{"name":"Department of Pediatrics, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,21]]},"reference":[{"key":"2021071520001455800_CIT0001","doi-asserted-by":"crossref","first-page":"e898","DOI":"10.1016\/S2214-109X(17)30289-9","article-title":"The global burden of tuberculosis mortality in children: a mathematical modelling study","volume":"5","author":"Dodd","year":"2017","journal-title":"Lancet Glob 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