{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:16:29Z","timestamp":1785525389400,"version":"3.56.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Recent tuberculosis treatment trials failed to show that some 4-month (4m) regimens were noninferior to conventional 6-month (6m) regimens for a composite clinical outcome. Novel shortened regimens may still have important clinical and economic benefits in populations with high loss to follow-up (LTFU) and in subgroups such as people with human immunodeficiency virus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify scenarios in which a novel 4m regimen would be preferred to a conventional 6m regimen for treatment of drug-susceptible tuberculosis in people with human immunodeficiency virus in South Africa, in terms of short-term and long-term clinical and economic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used the Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to project outcomes modeled on participants in the OFLOTUB trial. For calibration purposes, we did a base case analysis by applying trial-informed parameters for the 4m\/6m regimens, including monthly LTFU during treatment (0.68%\/0.83%), average monthly tuberculosis recurrence (0.65%\/0.31%), and monthly drug costs (U.S. dollars [USD]25.90\/3.70). We then evaluated different scenarios and 4m regimen characteristics, varying key parameters, including LTFU (informed by observational cohort data), recurrence, and cost. We projected outcomes, including 2-year mortality and life expectancy. We conducted a cost-effectiveness analysis, evaluating the incremental cost-effectiveness ratio of a 4m versus 6m regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the base case model analysis, risk of the composite unfavorable outcome in the 4m\/6m groups was 19.8%\/15.9%, similar to the trial; projected life expectancies were 22.1\/22.3 years. In analyses of alternative scenarios and 4m regimen characteristics, a 4m regimen yielded lower risk of the composite unfavorable outcome than the conventional 6m regimen if LTFU increased to greater than 3.5%\/mo or if average recurrence after a 4m regimen decreased to less than 0.45%\/mo, and it yielded higher life expectancy if LTFU was greater than 3.5%\/mo or if recurrence was less than 0.5%\/mo. A 4m regimen was not cost-effective in the base case but became cost-effective (incremental cost-effectiveness ratio &amp;lt;USD940\/yr of life saved) in two-way sensitivity analysis; for example, if LTFU was greater than or equal to 5.3%\/mo and either average recurrence was less than or equal to 0.5%\/mo or drug cost was less than or equal to USD15\/mo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A novel shortened tuberculosis treatment regimen could improve outcomes such as survival despite conferring a higher recurrence risk, particularly in settings where LTFU is higher than that seen in recent trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.201905-418oc","type":"journal-article","created":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T15:34:56Z","timestamp":1572968096000},"page":"202-211","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":8,"title":["Shortened Tuberculosis Treatment for People with HIV in South Africa. A Model-based Evaluation and Cost-effectiveness Analysis"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1832-2193","authenticated-orcid":false,"given":"Krishna P.","family":"Reddy","sequence":"first","affiliation":[{"name":"Medical Practice Evaluation Center"},{"name":"Division of Pulmonary and Critical Care Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Robert","family":"Horsburgh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts"},{"name":"Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Wood","sequence":"additional","affiliation":[{"name":"Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi F.","family":"Fields","sequence":"additional","affiliation":[{"name":"Medical Practice Evaluation Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Girouard","sequence":"additional","affiliation":[{"name":"Medical Practice Evaluation Center"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Costantini","sequence":"additional","affiliation":[{"name":"Medical Practice Evaluation Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taige","family":"Hou","sequence":"additional","affiliation":[{"name":"Medical Practice Evaluation Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth A.","family":"Freedberg","sequence":"additional","affiliation":[{"name":"Medical Practice Evaluation Center"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of General Internal Medicine, and"},{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Department of Health Policy and Management, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle P.","family":"Walensky","sequence":"additional","affiliation":[{"name":"Medical Practice Evaluation Center"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of General Internal Medicine, and"},{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,1]]},"reference":[{"key":"2026012203420635300_bib1","author":"UNAIDS"},{"key":"2026012203420635300_bib2","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1093\/cid\/ciw376","article-title":"Official American Thoracic Society\/Centers for Disease Control and Prevention\/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis","volume":"63","author":"Nahid","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2026012203420635300_bib3","doi-asserted-by":"crossref","first-page":"e1002595","DOI":"10.1371\/journal.pmed.1002595","article-title":"Adherence interventions and outcomes of tuberculosis treatment: a systematic review and meta-analysis of trials and observational studies","volume":"15","author":"Alipanah","year":"2018","journal-title":"PLoS Med"},{"key":"2026012203420635300_bib4","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1038\/s41591-018-0224-2","article-title":"A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis","volume":"24","author":"Imperial","year":"2018","journal-title":"Nat Med"},{"issue":"Suppl_7","key":"2026012203420635300_bib5","doi-asserted-by":"crossref","first-page":"S702","DOI":"10.1093\/infdis\/jix335","article-title":"The South African tuberculosis care cascade: estimated losses and methodological challenges","volume":"216","author":"Naidoo","year":"2017","journal-title":"J Infect Dis"},{"key":"2026012203420635300_bib6","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1056\/NEJMoa1315817","article-title":"A four-month gatifloxacin-containing regimen for treating tuberculosis","volume":"371","author":"Merle","year":"2014","journal-title":"N Engl J Med"},{"key":"2026012203420635300_bib7","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1056\/NEJMoa1407426","article-title":"Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis","volume":"371","author":"Gillespie","year":"2014","journal-title":"N Engl J Med"},{"key":"2026012203420635300_bib8","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1056\/NEJMoa1314210","article-title":"High-dose rifapentine with moxifloxacin for pulmonary tuberculosis","volume":"371","author":"Jindani","year":"2014","journal-title":"N Engl J Med"},{"key":"2026012203420635300_bib9","doi-asserted-by":"crossref","first-page":"603","DOI":"10.5588\/ijtld.12.0505","article-title":"Tuberculosis patients in primary care do not start treatment: what role do health system delays play?","volume":"17","author":"Claassens","year":"2013","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026012203420635300_bib10","doi-asserted-by":"crossref","first-page":"e37634","DOI":"10.1371\/journal.pone.0037634","article-title":"Assessment at antiretroviral clinics during TB treatment reduces loss to follow-up among HIV-infected patients","volume":"7","author":"Pepper","year":"2012","journal-title":"PLoS One"},{"key":"2026012203420635300_bib11","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1056\/NEJMsa1214720","article-title":"Cost-effectiveness of HIV treatment as prevention in serodiscordant couples","volume":"369","author":"Walensky","year":"2013","journal-title":"N Engl J Med"},{"key":"2026012203420635300_bib12","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1097\/QAD.0b013e3283522d47","article-title":"The cost-effectiveness of routine tuberculosis screening with Xpert MTB\/RIF prior to initiation of antiretroviral therapy: a model-based analysis","volume":"26","author":"Andrews","year":"2012","journal-title":"AIDS"},{"key":"2026012203420635300_bib13","doi-asserted-by":"crossref","first-page":"e200","DOI":"10.1016\/S2214-109X(18)30436-4","article-title":"Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling study","volume":"7","author":"Reddy","year":"2019","journal-title":"Lancet Glob Health"},{"key":"2026012203420635300_bib14","doi-asserted-by":"crossref","first-page":"776","DOI":"10.4102\/sajhivmed.v18i1.776","article-title":"Adult antiretroviral therapy guidelines 2017","volume":"18","author":"Meintjes","year":"2017","journal-title":"South Afr J HIV Med"},{"key":"2026012203420635300_bib15","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1001\/jama.2016.12195","article-title":"Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: Second Panel on Cost-Effectiveness in Health and Medicine","volume":"316","author":"Sanders","year":"2016","journal-title":"JAMA"},{"key":"2026012203420635300_bib16","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1093\/cid\/ciu186","article-title":"The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study","volume":"58","author":"Marx","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2026012203420635300_bib17","doi-asserted-by":"crossref","first-page":"e1001718","DOI":"10.1371\/journal.pmed.1001718","article-title":"Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies","volume":"11","author":"Boulle","year":"2014","journal-title":"PLoS Med"},{"key":"2026012203420635300_bib18","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.7196\/SAMJ.2016.v106i10.10745","article-title":"Outcomes of treatment of drug-susceptible tuberculosis at public sector primary healthcare clinics in Johannesburg, South Africa: a retrospective cohort study","volume":"106","author":"Budgell","year":"2016","journal-title":"S Afr Med J"},{"key":"2026012203420635300_bib19","doi-asserted-by":"crossref","first-page":"e1002850","DOI":"10.1371\/journal.pmed.1002850","article-title":"Designing noninferiority tuberculosis treatment trials: identifying practical advantages for drug regimens with acceptable effectiveness","volume":"16","author":"Olliaro","year":"2019","journal-title":"PLoS Med"},{"key":"2026012203420635300_bib20","doi-asserted-by":"crossref","first-page":"e0145796","DOI":"10.1371\/journal.pone.0145796","article-title":"The impact and cost-effectiveness of a four-month regimen for first-line treatment of active tuberculosis in South Africa","volume":"10","author":"Knight","year":"2015","journal-title":"PLoS One"},{"key":"2026012203420635300_bib21","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1186\/s12879-016-2064-3","article-title":"Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis","volume":"16","author":"Gomez","year":"2016","journal-title":"BMC Infect Dis"},{"key":"2026012203420635300_bib22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1473-3099(16)30274-2","article-title":"High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial","volume":"17","author":"Boeree","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2026012203420635300_bib23","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1164\/rccm.201712-2524OC","article-title":"Efficacy and safety of high-dose rifampin in pulmonary tuberculosis: a randomized controlled trial","volume":"198","author":"Vel\u00e1squez","year":"2018","journal-title":"J Respir Crit Care Med"},{"key":"2026012203420635300_bib24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/cid\/ciy026","article-title":"The potential for treatment shortening with higher rifampicin doses: relating drug exposure to treatment response in patients with pulmonary tuberculosis","volume":"67","author":"Svensson","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2026012203420635300_bib25","first-page":"329","article-title":"Changes in tuberculosis in human immunodeficiency virus infected patients in a Spanish tertiary hospital (1995-2013)","volume":"31","author":"Gonz\u00e1lez-Garc\u00eda","year":"2018","journal-title":"Rev Esp Quimioter"},{"key":"2026012203420635300_bib26","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12916-018-1169-5","article-title":"Gender differences in tuberculosis treatment outcomes: a post hoc analysis of the REMoxTB study","volume":"16","author":"Murphy","year":"2018","journal-title":"BMC Med"},{"key":"2026012203420635300_bib27","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/hec.853","article-title":"When does quality-adjusting life-years matter in cost-effectiveness analysis?","volume":"13","author":"Chapman","year":"2004","journal-title":"Health Econ"},{"key":"2026012203420635300_bib28","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0140-6736(16)31012-1","article-title":"Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"GBD 2015 Mortality and Causes of Death Collaborators","year":"2016","journal-title":"Lancet"},{"key":"2026012203420635300_bib29","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(16)31678-6","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"GBD 2015 Disease and Injury Incidence and Prevalence Collaborators","year":"2016","journal-title":"Lancet"},{"key":"2026012203420635300_bib30","doi-asserted-by":"crossref","first-page":"e816","DOI":"10.1016\/S2214-109X(16)30265-0","article-title":"Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models","volume":"4","author":"Menzies","year":"2016","journal-title":"Lancet Glob Health"},{"key":"2026012203420635300_bib31","first-page":"156","article-title":"Age- and sex-specific social contact patterns and incidence of Mycobacterium tuberculosis infection","volume":"183","author":"Dodd","year":"2016","journal-title":"Am J Epidemiol"},{"key":"2026012203420635300_bib32","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1093\/aje\/kwt246","article-title":"Estimated rate of reactivation of latent tuberculosis infection in the United States, overall and by population subgroup","volume":"179","author":"Shea","year":"2014","journal-title":"Am J Epidemiol"},{"key":"2026012203420635300_bib33","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/QAI.0b013e318293ae48","article-title":"Community viral load and CD4 count distribution among people living with HIV in a South African township: implications for treatment as prevention","volume":"63","author":"Kranzer","year":"2013","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026012203420635300_bib34","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1473-3099(09)70328-7","article-title":"Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review","volume":"10","author":"Barth","year":"2010","journal-title":"Lancet Infect Dis"},{"key":"2026012203420635300_bib35","author":"Management Sciences for Health"},{"key":"2026012203420635300_bib36","author":"Clinton Health Access Initiative"}],"container-title":["Annals of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/17\/2\/202\/66347946\/annalsats_17_2_202.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/17\/2\/202\/66347946\/annalsats_17_2_202.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:46:55Z","timestamp":1769071615000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/article\/17\/2\/202\/8419155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,1]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2,1]]},"published-print":{"date-parts":[[2020,2,1]]}},"URL":"https:\/\/doi.org\/10.1513\/annalsats.201905-418oc","relation":{},"ISSN":["2329-6933","2325-6621"],"issn-type":[{"value":"2329-6933","type":"print"},{"value":"2325-6621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,2]]},"published":{"date-parts":[[2020,2,1]]},"assertion":[{"value":"2019-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}