{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:43:16Z","timestamp":1773812596874,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["2D43TW009771-06"],"award-info":[{"award-number":["2D43TW009771-06"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB\/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB\/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A subset of 138 PLHIV from the \u2018SOUTH\u2019 study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 81 patients (58.7%) were males, median age 34 (IQR 29\u00a0 \u0336 40) years, median CD4 cell count of 180 (IQR 68\u00a0 \u0336 345) cells\/\u03bcL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0\u00a0 \u0336 30.1). A unit Increase in the ct value was associated with a 5% (IRR\u2009=\u20091.05 95% CI 1.04\u00a0 \u0336 1.06) and 3% (IRR\u2009=\u20091.03 95% CI 1.03\u00a0 \u0336 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient\u2019s colony grade was reduced by 0.86 times (0R\u2009=\u20090.86 95% CI 0.74\u00a0 \u0336 0.97) at week 2 and 0.84 times (OR\u2009=\u20090.84 95% CI 0.79\u00a0 \u0336 0.95 <jats:italic>P<\/jats:italic>\u2009=\u20090.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point \u226528 best predicted culture negativity at week 4 with a sensitivity of 91. 7% &amp; specificity 53.7% while a cut point \u226523 best predicted culture negativity at week 8.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Baseline Xpert MTB\/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-021-06220-6","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T15:34:29Z","timestamp":1622561669000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Baseline Xpert MTB\/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study"],"prefix":"10.1186","volume":"21","author":[{"given":"Juliet","family":"Namugenyi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Musaazi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achilles","family":"Katamba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Kalyango","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Sendaula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Kambugu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Fehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Castelnouvo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukari C.","family":"Manabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willy","family":"Ssengooba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Sekaggya-Wiltshire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"6220_CR1","first-page":"2020","volume-title":"Global Tuberculosis Report","author":"WHO","year":"2020","unstructured":"WHO. Global Tuberculosis Report; 2020. p. 2020."},{"key":"6220_CR2","unstructured":"World Health Organisation 2018. WHO global TB report [internet]. Geneva; 2019. Available from: https:\/\/apps.who.int\/iris\/handle\/10665\/274453. Accessed 10 Mar\u00a02020."},{"issue":"5","key":"6220_CR3","first-page":"560","volume":"14","author":"A Hesseling","year":"2010","unstructured":"Hesseling A, Walzl G, Enarson D, Carroll N, Duncan K, Lukey P, et al. Baseline sputum time to detection predicts month two culture conversion and relapse in non-HIV-infected patients. Int J Tuberculosis Lung Dis. 2010;14(5):560\u201370.","journal-title":"Int J Tuberculosis Lung Dis."},{"issue":"22","key":"6220_CR4","first-page":"6","volume":"60","author":"R Parikh","year":"2012","unstructured":"Parikh R, Nataraj G, Kanade S, Khatri V, Mehta P. Time to sputum conversion in smear positive pulmonary TB patients on category I DOTS and factors delaying it. J Assoc Physicians India. 2012;60(22):6.","journal-title":"J Assoc Physicians India"},{"issue":"8","key":"6220_CR5","doi-asserted-by":"publisher","first-page":"e0160062","DOI":"10.1371\/journal.pone.0160062","volume":"11","author":"S Shenai","year":"2016","unstructured":"Shenai S, Ronacher K, Malherbe S, Stanley K, Kriel M, Winter J, et al. Bacterial Loads Measured by the Xpert MTB\/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB. PLoS One. 2016;11(8):e0160062 Available from: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27508390.","journal-title":"PLoS One"},{"key":"6220_CR6","doi-asserted-by":"publisher","unstructured":"Lombardi G, Di Gregori V, Girometti N, Tadolini M, Bisognin F, Dal MP. Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB\/RIF. PLoS one. 2017;12(4):e0176186. https:\/\/doi.org\/10.1371\/journal.pone.0176186.","DOI":"10.1371\/journal.pone.0176186"},{"issue":"1","key":"6220_CR7","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1186\/s12879-016-2009-x","volume":"16","author":"JCS Ngabonziza","year":"2016","unstructured":"Ngabonziza JCS, Ssengooba W, Mutua F, Torrea G, Dushime A, Gasana M, et al. Diagnostic performance of smear microscopy and incremental yield of Xpert in detection of pulmonary tuberculosis in Rwanda. BMC Infect Dis. 2016;16(1):660. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/27825314. https:\/\/doi.org\/10.1186\/s12879-016-2009-x.","journal-title":"BMC Infect Dis"},{"issue":"3","key":"6220_CR8","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S1473-3099(09)70043-X","volume":"9","author":"MJ Reid","year":"2009","unstructured":"Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis. 2009;9(3):173\u201384. https:\/\/doi.org\/10.1016\/S1473-3099(09)70043-X.","journal-title":"Lancet Infect Dis"},{"key":"6220_CR9","first-page":"2013","volume-title":"Tuberculosis diagnostics: Xpert MTB\/RIF test. Updated WHO recommendations as of October","author":"World Health Organization","year":"2013","unstructured":"World Health Organization. Tuberculosis diagnostics: Xpert MTB\/RIF test. Updated WHO recommendations as of October; 2013. p. 2013."},{"issue":"4","key":"6220_CR10","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/S1473-3099(13)70008-2","volume":"13","author":"SD Lawn","year":"2013","unstructured":"Lawn SD, Mwaba P, Bates M, Piatek A, Alexander H, Marais BJ, et al. Advances in tuberculosis diagnostics: the Xpert MTB\/RIF assay and future prospects for a point-of-care test. Lancet Infect Dis. 2013;13(4):349\u201361. https:\/\/doi.org\/10.1016\/S1473-3099(13)70008-2.","journal-title":"Lancet Infect Dis"},{"key":"6220_CR11","doi-asserted-by":"publisher","unstructured":"Rachow A, Zumla A, Heinrich N, Rojas-Ponce G, Mtafya B, Reither K, et al. Rapid and accurate detection of Mycobacterium tuberculosis in sputum samples by Cepheid Xpert MTB\/RIF assay--a clinical validation study. PLoS One. 2011;6(6):e20458. https:\/\/doi.org\/10.1371\/journal.pone.0020458.\u00a0\u00a0","DOI":"10.1371\/journal.pone.0020458"},{"issue":"9","key":"6220_CR12","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1164\/rccm.201103-0536OC","volume":"184","author":"R Blakemore","year":"2011","unstructured":"Blakemore R, Nabeta P, Davidow AL, Vadwai V, Tahirli R, Munsamy V, et al. A multisite assessment of the quantitative capabilities of the Xpert MTB\/RIF assay. Am J Respir Crit Care Med. 2011;184(9):1076\u201384 Available from: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21836139.","journal-title":"Am J Respir Crit Care Med"},{"key":"6220_CR13","doi-asserted-by":"publisher","unstructured":"Bodmer T, Str\u00f6hle A. Diagnosing pulmonary tuberculosis with the Xpert MTB\/RIF. J Vis Exp. 2012;(62):e3547. https:\/\/doi.org\/10.3791\/3547.\u00a0 \u00a0","DOI":"10.3791\/3547"},{"issue":"6","key":"6220_CR14","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1128\/JCM.03290-12","volume":"51","author":"XA Kayigire","year":"2013","unstructured":"Kayigire XA, Friedrich SO, Venter A, Dawson R, Gillespie SH, Boeree MJ, et al. Direct comparison of Xpert MTB\/RIF assay with liquid and solid mycobacterial culture for quantification of early bactericidal activity. J Clin Microbiol. 2013;51(6):1894\u20138 Available from: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23596237.","journal-title":"J Clin Microbiol"},{"key":"6220_CR15","doi-asserted-by":"publisher","unstructured":"Agbor AA, Bigna JJR, Billong SC, Tejiokem MC, Ekali GL, Plottel CS, et al. Factors associated with death during tuberculosis treatment of patients co-infected with HIV at the Yaound\u00e9 Central Hospital, Cameroon: an 8-year hospital-based retrospective cohort study (2006\u20132013). PLoS one. 2014;9(12):e115211. https:\/\/doi.org\/10.1371\/journal.pone.0115211.\u00a0 \u00a0","DOI":"10.1371\/journal.pone.0115211"},{"key":"6220_CR16","doi-asserted-by":"publisher","unstructured":"Ismawati Ismail AB. Predictors of death during tuberculosis treatment in TB\/HIV co-infected patients in Malaysia. PLoS one. 2013;8(8):e73250. https:\/\/doi.org\/10.1371\/journal.pone.0073250.","DOI":"10.1371\/journal.pone.0073250"},{"issue":"8","key":"6220_CR17","first-page":"672","volume":"6","author":"P Jeena","year":"2002","unstructured":"Jeena P, Pillay P, Pillay T, Coovadia H. Impact of HIV-1 co-infection on presentation and hospital-related mortality in children with culture proven pulmonary tuberculosis in Durban, South Africa. Int J Tuberculosis Lung Dis. 2002;6(8):672\u20138.","journal-title":"Int J Tuberculosis Lung Dis"},{"issue":"7","key":"6220_CR18","first-page":"829","volume":"8","author":"C Kang\u2019Ombe","year":"2004","unstructured":"Kang\u2019Ombe C, Harries AD, Ito K, Clark T, Nyirenda T, Aldis W, et al. Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB. Int J Tuberculosis Lung Dis. 2004;8(7):829\u201336.","journal-title":"Int J Tuberculosis Lung Dis"},{"key":"6220_CR19","doi-asserted-by":"publisher","unstructured":"Hermans SM, Kiragga AN, Schaefer P, Kambugu A, Hoepelman AI, Manabe YC. Incident tuberculosis during antiretroviral therapy contributes to suboptimal immune reconstitution in a large urban HIV clinic in sub-Saharan Africa. PLoS one. 2010;5(5):e10527. https:\/\/doi.org\/10.1371\/journal.pone.0010527.","DOI":"10.1371\/journal.pone.0010527"},{"key":"6220_CR20","volume-title":"Mycobacterium, p 400\u2013437. Manual of clinical microbiology, 6th ed","author":"F Nolte","year":"1995","unstructured":"Nolte F, Metchock B. Mycobacterium, p 400\u2013437. Manual of clinical microbiology, 6th ed. Washington, DC: ASM Press; 1995."},{"key":"6220_CR21","volume-title":"Stata statistical software: Release 13","author":"StataCorp L","year":"2013","unstructured":"StataCorp L. Stata statistical software: Release 13. College Station, TX: StataCorp LP; 2013."},{"issue":"1","key":"6220_CR22","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s13104-017-2497-9","volume":"10","author":"G Diriba","year":"2017","unstructured":"Diriba G, Kebede A, Yaregal Z, Getahun M, Tadesse M, Meaza A, et al. Performance of Mycobacterium growth Indicator tube BACTEC 960 with Lowenstein\u2013Jensen method for diagnosis of Mycobacterium tuberculosis at Ethiopian National Tuberculosis Reference Laboratory, Addis Ababa, Ethiopia. BMC Res Notes. 2017;10(1):181. https:\/\/doi.org\/10.1186\/s13104-017-2497-9.","journal-title":"BMC Res Notes"},{"issue":"2","key":"6220_CR23","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1128\/JCM.35.2.364-368.1997","volume":"35","author":"GE Pfyffer","year":"1997","unstructured":"Pfyffer GE, Welscher H-M, Kissling P, Cieslak C, Casal MJ, Gutierrez J, et al. Comparison of the mycobacteria growth Indicator tube (MGIT) with radiometric and solid culture for recovery of acid-fast bacilli. J Clin Microbiol. 1997;35(2):364\u20138. https:\/\/doi.org\/10.1128\/JCM.35.2.364-368.1997.","journal-title":"J Clin Microbiol"},{"issue":"5","key":"6220_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216901","volume":"14","author":"I Najjingo","year":"2019","unstructured":"Najjingo I, Muttamba W, Kirenga BJ, Nalunjogi J, Bakesiima R, Olweny F, et al. Comparison of GeneXpert cycle threshold values with smear microscopy and culture as a measure of mycobacterial burden in five regional referral hospitals of Uganda-a cross-sectional study. PLoS One. 2019;14(5):e0216901. https:\/\/doi.org\/10.1371\/journal.pone.0216901.","journal-title":"PLoS One"},{"issue":"2","key":"6220_CR25","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.jmii.2019.10.008","volume":"53","author":"W-C Chao","year":"2020","unstructured":"Chao W-C, Yen C-L, Wu C-H, Shieh C-C. How mycobacteria take advantage of the weakness in human immune system in the modern world. J Microbiol Immunol Infect. 2020;53(2):209\u201315. https:\/\/doi.org\/10.1016\/j.jmii.2019.10.008.","journal-title":"J Microbiol Immunol Infect"},{"issue":"1","key":"6220_CR26","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1164\/rccm.201311-2106PP","volume":"190","author":"CW Ong","year":"2014","unstructured":"Ong CW, Elkington PT, Friedland JS. Tuberculosis, pulmonary cavitation, and matrix metalloproteinases. Am J Respir Crit Care Med. 2014;190(1):9\u201318. https:\/\/doi.org\/10.1164\/rccm.201311-2106PP.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"6220_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12916-018-1053-3","volume":"16","author":"S Murthy","year":"2018","unstructured":"Murthy S, Chatterjee F, Crook A, Dawson R, Mendel C, Murphy M, et al. Pretreatment chest x-ray severity and its relation to bacterial burden in smear positive pulmonary tuberculosis. BMC Med. 2018;16(1):1\u201311.","journal-title":"BMC Med"},{"issue":"12","key":"6220_CR28","doi-asserted-by":"publisher","first-page":"4064","DOI":"10.1128\/JCM.01780-07","volume":"45","author":"M Palaci","year":"2007","unstructured":"Palaci M, Dietze R, Hadad DJ, Ribeiro FKC, Peres RL, Vinhas SA, et al. Cavitary disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J Clin Microbiol. 2007;45(12):4064\u20136. https:\/\/doi.org\/10.1128\/JCM.01780-07.","journal-title":"J Clin Microbiol"},{"issue":"5","key":"6220_CR29","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1590\/S0036-46652003000500007","volume":"45","author":"M Gomes","year":"2003","unstructured":"Gomes M, Saad R Jr, Stirbulov R. Pulmonary tuberculosis: relationship between sputum bacilloscopy and radiological lesions. Rev Inst Med Trop Sao Paulo. 2003;45(5):275\u201381. https:\/\/doi.org\/10.1590\/S0036-46652003000500007.","journal-title":"Rev Inst Med Trop Sao Paulo"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06220-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-021-06220-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06220-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T15:35:58Z","timestamp":1622561758000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-021-06220-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["6220"],"URL":"https:\/\/doi.org\/10.1186\/s12879-021-06220-6","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,1]]},"assertion":[{"value":"30 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The SOUTH study obtained ethical approval from the Joint Clinical Research Centre Ethics Committee, from Uganda National Council of Science and technology (UNCST) and from the National Drug Authority (NDA).\u2019 Written informed consent was obtained from every patient prior to enrollment.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"513"}}