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Xpert MTB\/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>At 22 clinics, ART enrollees &gt;\u200912\u2009years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184\/\u03bcL in SOC, 246\/\u03bcL in EC, and 241\/\u03bcL in EC+X). By 6\u2009months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61\u20130.97,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      Retrospectively registered: ClinicalTrials.gov (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02538952\">NCT02538952<\/jats:ext-link>\n                      )\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-019-1489-0","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T19:05:21Z","timestamp":1581361521000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of tuberculosis screening and retention interventions on early antiretroviral therapy mortality in Botswana: a stepped-wedge cluster randomized trial"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5089-9163","authenticated-orcid":false,"given":"Andrew F.","family":"Auld","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tefera","family":"Agizew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anikie","family":"Mathoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Boyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Date","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri L.","family":"Pals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Serumola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unami","family":"Mathebula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tedd V.","family":"Ellerbrock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goabaone","family":"Rankgoane-Pono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontsho","family":"Pono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Shepherd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Fielding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison D.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Finlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"issue":"15","key":"1489_CR1","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1097\/QAD.0000000000000802","volume":"29","author":"RK Gupta","year":"2015","unstructured":"Gupta RK, Lucas SB, Fielding KL, Lawn SD. 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All consent procedures were approved by the ethical review committees. For the SOC cohort, a waiver of informed consent for chart abstraction was granted in accordance with 45CFR 46.116 (d). Written informed consent was obtained from all EC and EC+X enrollees. XPRES is registered at ClinicalTrials.gov (trial registration no. NCT02538952). Oversight of study initiation and quarterly review of implementation was conducted by the Office of the Associate Director of Science at CDC Atlanta. Per guidance from oversight bodies, XPRES was registered at ClinicalTrials.gov following the change in the US Health and Human Services (HHS) and National Institutes of Health (NIH) accepted definition of a clinical trial on January 25, 2015 [\n                      \n                      ]. At the time of study initiation on August 1, 2012, investigators and oversight bodies did not consider XPRES met the pre-2015 HHS and NIH definition of a clinical trial that was testing the \u201csafety and effectiveness\u201d of an intervention, because the XPRES interventions were already considered safe and were recommended by the Ministry of Health and World Health Organization.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}