Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

Humans Rifampin / therapeutic use HIV Infections / complications Hospitalization Tuberculosis / drug therapy Levofloxacin / therapeutic use Treatment Outcome Clinical Trials, Phase III as Topic Antitubercular Agents / therapeutic use Equivalence Trials as Topic Drug Therapy, Combination Prednisone / therapeutic use AIDS-Related Opportunistic Infections / drug therapy Time Factors

Disseminated tuberculosis HIV High dose rifampicin Levofloxacin Prednisone Randomised controlled trial

Journal

Trials

ISSN: 1745-6215

Titre abrégé: Trials

Pays: England

ID NLM: 101263253

Informations de publication

Date de publication:
08 May 2024

Historique:

received: 16 01 2024

accepted: 16 04 2024

medline: 9 5 2024

pubmed: 9 5 2024

entrez: 9 5 2024

Statut: epublish

Résumé

HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events.

DISCUSSION CONCLUSIONS

Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice.

TRIAL REGISTRATION BACKGROUND

ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Identifiants

DOI: 10.1186/s13063-024-08119-4 PMID: 38720383

pubmed: 38720383

doi: 10.1186/s13063-024-08119-4

pii: 10.1186/s13063-024-08119-4

doi:

Substances chimiques

Rifampin VJT6J7R4TR

Levofloxacin 6GNT3Y5LMF

Antitubercular Agents 0

Prednisone VB0R961HZT

Banques de données

ClinicalTrials.gov

['NCT04951986']

Types de publication

Journal Article Clinical Trial Protocol

Langues

eng

Sous-ensembles de citation

Pagination

311

Subventions

Organisme : Wellcome Trust -

ID : 214321/Z/18/Z Recipient Prof Graeme Meintjes

Informations de copyright

Références

Ford N, Matteelli A, Shubber Z, Hermans S, Meintjes G, Grinsztejn B, et al. TB as a cause of hospitalization and in-hospital mortality among people living with HIV worldwide: a systematic review and meta-analysis. J Int AIDS Soc. 2016;19(1):20714.

pubmed: 26765347 pmcid: 4712323 doi: 10.7448/IAS.19.1.20714

Bigna JJR, Noubiap JJN, Agbor AA, Plottel CS, Billong SC, Ayong APR, Koulla-Shiro S. Early mortality during initial treatment of tuberculosis in patients co-infected with HIV at the Yaoundé Central Hospital, Cameroon: an 8-year retrospective cohort study (2006-2013). PLoS One. 2015;10(7):e0132394.

pubmed: 26214516 pmcid: 4516239 doi: 10.1371/journal.pone.0132394

Subbarao S, Wilkinson KA, Van Halsema CL, Rao SS, Boyles T, Utay NS, et al. Raised venous lactate and markers of intestinal translocation are associated with mortality among in-patients with HIV-associated TB in rural South Africa. J Acquir Immune Defic Syndr. 2015;70(4):406.

pubmed: 26186506 pmcid: 4625603 doi: 10.1097/QAI.0000000000000763

Schutz C, Barr D, Andrade BB, Shey M, Ward A, Janssen S, et al. Clinical, microbiologic, and immunologic determinants of mortality in hospitalized patients with HIV-associated tuberculosis: a prospective cohort study. PLoS Med. 2019;16(7):e1002840.

pubmed: 31276515 pmcid: 6611568 doi: 10.1371/journal.pmed.1002840

Kyeyune R, den Boon S, Cattamanchi A, Davis JL, Worodria W, Yoo SD, Huang L. Causes of early mortality in HIV-infected TB suspects in an East African referral hospital. J Acquir Immune Defic Syndr. 2010;55(4):446.

pubmed: 21105258 pmcid: 3249444 doi: 10.1097/QAI.0b013e3181eb611a

Gupta-Wright A, Fielding K, Wilson D, van Oosterhout JJ, Grint D, Mwandumba HC, et al. Tuberculosis in hospitalized patients with human immunodeficiency virus: clinical characteristics, mortality, and implications from the rapid urine-based screening for tuberculosis to reduce AIDS related mortality in hospitalized patients in Africa. Clin Infect Dis. 2020;71(10):2618–26.

pubmed: 31781758 doi: 10.1093/cid/ciz1133

Gupta RK, Lucas SB, Fielding KL, Lawn SD. Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS. 2015;29(15):1987–2002.

pubmed: 26266773 doi: 10.1097/QAD.0000000000000802

Boloko L, Schutz C, Sibiya N, Balfour A, Ward A, Shey M, et al. Xpert Ultra testing of blood in severe HIV-associated tuberculosis to detect and measure Mycobacterium tuberculosis blood stream infection: a diagnostic and disease biomarker cohort study. Lancet Microbe. 2022;3(7):e521-ee32.

pubmed: 35644157 pmcid: 9242865 doi: 10.1016/S2666-5247(22)00062-3

Barr DA, Schutz C, Balfour A, Shey M, Kamariza M, Bertozzi CR, et al. Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis. EBioMedicine. 2022;78:103949.

pubmed: 35325781 pmcid: 8938880 doi: 10.1016/j.ebiom.2022.103949

Jacob ST, Pavlinac PB, Nakiyingi L, Banura P, Baeten JM, Morgan K, et al. Mycobacterium tuberculosis bacteremia in a cohort of HIV-infected patients hospitalized with severe sepsis in Uganda–high frequency, low clinical sand derivation of a clinical prediction score. PloS One. 2013;8(8):e70305.

pubmed: 23940557 pmcid: 3734073 doi: 10.1371/journal.pone.0070305

Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. Jama. 2017;318(13):1233–40.

pubmed: 28973227 pmcid: 5710318 doi: 10.1001/jama.2017.10913

Acocella G. Clinical pharmacokinetics of rifampicin. Clin Pharmacokinet. 1978;3(2):108–27.

pubmed: 346286 doi: 10.2165/00003088-197803020-00002

Boeree MJ, Heinrich N, Aarnoutse R, Diacon AH, Dawson R, Rehal S, et al. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis. 2017;17(1):39–49.

pubmed: 28100438 pmcid: 5159618 doi: 10.1016/S1473-3099(16)30274-2

Dian S, Yunivita V, Ganiem AR, Pramaesya T, Chaidir L, Wahyudi K, et al. Double-blind, randomized, placebo-controlled phase II dose-finding study to evaluate high-dose rifampin for tuberculous meningitis. Antimicrob Agents Chemother. 2018;62(12):e01014–8.

pubmed: 30224533 pmcid: 6256787 doi: 10.1128/AAC.01014-18

Te Brake LH, de Jager V, Narunsky K, Vanker N, Svensson EM, Phillips PP, et al. Increased bactericidal activity but dose-limiting intolerability at 50 mg· kg− 1 rifampicin. Eur Respir J. 2021;58(1).

Svensson RJ, Aarnoutse RE, Diacon AH, Dawson R, Gillespie SH, Boeree MJ, Simonsson USH. A population pharmacokinetic model incorporating saturable pharmacokinetics and autoinduction for high rifampicin doses. Clin Pharmacol Ther. 2018;103(4):674–83.

pubmed: 28653479 doi: 10.1002/cpt.778

Chirehwa MT, Rustomjee R, Mthiyane T, Onyebujoh P, Smith P, McIlleron H, Denti P. Model-based evaluation of higher doses of rifampin using a semimechanistic model incorporating autoinduction and saturation of hepatic extraction. Antimicrob Agents Chemother. 2016;60(1):487–94.

pubmed: 26552972 doi: 10.1128/AAC.01830-15

Jayaram R, Gaonkar S, Kaur P, Suresh BL, Mahesh BN, Jayashree R, et al. Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis. Antimicrob Agents Chemother. 2003;47(7):2118–24.

pubmed: 12821456 pmcid: 161844 doi: 10.1128/AAC.47.7.2118-2124.2003

Tsukamura M, Nakamura E, Yoshii S, Amano H. Therapeutic effect of a new antibacterial substance ofloxacin (DL8280) on pulmonary tuberculosis. Am Rev Respir Dis. 1985;131(3):352–6.

pubmed: 3856412

Ji B, Lounis N, Truffot-Pernot C, Grosset J. In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1995;39(6):1341–4.

pubmed: 7574527 pmcid: 162738 doi: 10.1128/AAC.39.6.1341

Yew WW, Kwan SY-L, Ma WK, Khin MA, Chan PY. In-vitro activity of ofloxacin against Mycobacterium tuberculosis and its clinical efficacy in multiply resistant pulmonary tuberculosis. J Antimicrob Chemother. 1990;26(2):227–36.

pubmed: 2120177 doi: 10.1093/jac/26.2.227

Yew W, Piddock L, Li M, Lyon D, Chan C, Cheng A. In-vitro activity of quinolones and macrolides against mycobacteria. J Antimicrob Chemother. 1994;34(3):343–51.

pubmed: 7829409 doi: 10.1093/jac/34.3.343

Gosling RD, Uiso LO, Sam NE, Bongard E, Kanduma EG, Nyindo M, et al. The bactericidal activity of moxifloxacin in patients with pulmonary tuberculosis. Am J Respir Crit Care Med. 2003;168(11):1342–5.

pubmed: 12917230 doi: 10.1164/rccm.200305-682OC

Merle CS, Fielding K, Sow OB, Gninafon M, Lo MB, Mthiyane T, et al. A four-month gatifloxacin-containing regimen for treating tuberculosis. N Engl J Med. 2014;371(17):1588–98.

pubmed: 25337748 doi: 10.1056/NEJMoa1315817

Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014;371(17):1577–87.

pubmed: 25196020 pmcid: 4277680 doi: 10.1056/NEJMoa1407426

Jindani A, Harrison TS, Nunn AJ, Phillips PP, Churchyard GJ, Charalambous S, et al. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014;371(17):1599–608.

pubmed: 25337749 pmcid: 4233406 doi: 10.1056/NEJMoa1314210

Jindani A, Borgulya G, de Patino IW, Gonzales T, de Fernandes RA, Shrestha B, et al. A randomised phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis. Int J Tuberc Lung Dis. 2016;20(6):832–8.

pubmed: 27155189 doi: 10.5588/ijtld.15.0577

Gillespie S, Billington O. Activity of moxifloxacin against mycobacteria. J Antimicrob Chemother. 1999;44(3):393–5.

pubmed: 10511409 doi: 10.1093/jac/44.3.393

Cremades R, Rodríguez JC, García-Pachón E, Galiana A, Ruiz-García M, López P, Royo G. Comparison of the bactericidal activity of various fluoroquinolones against Mycobacterium tuberculosis in an in vitro experimental model. J Antimicrob Chemother. 2011;66(10):2281–3.

pubmed: 21733966 doi: 10.1093/jac/dkr281

Dorman SE, Nahid P, Kurbatova EV, Phillips PP, Bryant K, Dooley KE, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384(18):1705–18.

pubmed: 33951360 pmcid: 8282329 doi: 10.1056/NEJMoa2033400

Nijland H, Ruslami R, Suroto AJ, Burger D, Alisjahbana B, Van Crevel R, Aarnoutse RJ. Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis. Clin Infect Dis. 2007;45(8):1001–7.

pubmed: 17879915 doi: 10.1086/521894

Naidoo A, Chirehwa M, McIlleron H, Naidoo K, Essack S, Yende-Zuma N, et al. Effect of rifampicin and efavirenz on moxifloxacin concentrations when co-administered in patients with drug-susceptible TB. J Antimicrob Chemother. 2017;72(5):1441–9.

pubmed: 28175315 pmcid: 5890691 doi: 10.1093/jac/dkx004

Noel GJ, Goodman DB, Chien S, Solanki B, Padmanabhan M, Natarajan J. Measuring the effects of supratherapeutic doses of levofloxacin on healthy volunteers using four methods of QT correction and periodic and continuous ECG recordings. J Clin Pharmacol. 2004;44(5):464–73.

pubmed: 15102866 doi: 10.1177/0091270004264643

FDA U. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. FDA Drug Safety Communication; 2018. p. 2020.

Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: a systematic review. Neurology. 2015;85(15):1332–41.

pubmed: 26400582 doi: 10.1212/WNL.0000000000002023

Mayosi BM, Ntsekhe M, Bosch J, Pandie S, Jung H, Gumedze F, et al. Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis. N Engl J Med. 2014;371(12):1121–30.

pubmed: 25178809 pmcid: 4912834 doi: 10.1056/NEJMoa1407380

Meintjes G, Wilkinson RJ, Morroni C, Pepper DJ, Rebe K, Rangaka MX, et al. Randomized placebo-controlled trial of prednisone for paradoxical TB-associated immune reconstitution inflammatory syndrome. AIDS (London, England). 2010;24(15):2381.

pubmed: 20808204 pmcid: 2940061 doi: 10.1097/QAD.0b013e32833dfc68

Prasad K, Singh MB, Ryan H. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 2016;4.

Wiysonge CS, Ntsekhe M, Thabane L, Volmink J, Majombozi D, Gumedze F, et al. Interventions for treating tuberculous pericarditis. Cochrane Database Syst Rev. 2017;9.

Meintjes G, Stek C, Blumenthal L, Thienemann F, Schutz C, Buyze J, et al. Prednisone for the prevention of paradoxical tuberculosis-associated IRIS. N Engl J Med. 2018;379(20):1915–25.

pubmed: 30428290 doi: 10.1056/NEJMoa1800762

Stern A, Skalsky K, Avni T, Carrara E, Leibovici L, Paul M. Corticosteroids for pneumonia. In: Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2017.

Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for treating sepsis. Cochrane Database Syst Rev. 2015;12.

Dequin P-F, Meziani F, Quenot J-P, Kamel T, Ricard J-D, Badie J, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931–41.

pubmed: 36942789 doi: 10.1056/NEJMoa2215145

Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol. 2001;33(4):289–94.

pubmed: 11588541 doi: 10.1097/00004836-200110000-00006

Roth P, Wick W, Weller M. Steroids in neurooncology: actions, indications, side-effects. Curr Opin Neurol. 2010;23(6):597–602.

pubmed: 20962642 doi: 10.1097/WCO.0b013e32833e5a5d

Ewald H, Raatz H, Boscacci R, Furrer H, Bucher HC, Briel M. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015;4.

Bozzette SA, Sattler FR, Chiu J, Wu AW, Gluckstein D, Kemper C, et al. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. N Engl J Med. 1990;323(21):1451–7.

pubmed: 2233917 doi: 10.1056/NEJM199011223232104

Costiniuk CT, Fergusson DA, Doucette S, Angel JB. Discontinuation of Pneumocystis jirovecii pneumonia prophylaxis with CD4 count< 200 cells/μL and virologic suppression: a systematic review. PloS one. 2011;6(12):e28570.

pubmed: 22194853 pmcid: 3241626 doi: 10.1371/journal.pone.0028570

Schutz C, Davis AG, Sossen B, Lai RP, Ntsekhe M, Harley YX, Wilkinson RJ. Corticosteroids as an adjunct to tuberculosis therapy. Expert Rev Respir Med. 2018;12(10):881–91.

pubmed: 30138039 pmcid: 6293474 doi: 10.1080/17476348.2018.1515628

Dooley DP, Carpenter JL, Rademacher S. Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature. Clin Infect Dis. 1997;25(4):872–87.

pubmed: 9356803 doi: 10.1086/515543

Pletz MW, De Roux A, Roth A, Neumann K-H, Mauch H, Lode H. Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study. Antimicrob Agents Chemother. 2004;48(3):780–2.

pubmed: 14982764 pmcid: 353154 doi: 10.1128/AAC.48.3.780-782.2004

Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968–81 e7.

pubmed: 32966765 pmcid: 7474869 doi: 10.1016/j.cell.2020.09.016

Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383(23):2255–73.

pubmed: 33264547 pmcid: 7727315 doi: 10.1056/NEJMra2026131

Group RC. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704.

doi: 10.1056/NEJMoa2021436

Western Cape Government, Provincial TB dashboard. Number of tuberculosis (TB) cases in the Western Cape 2023 [cited 2023 05/07/2023]. Available from: https://www.westerncape.gov.za/site-page/provincial-tb-dashboard .

Mnguni AT, Schietekat D, Ebrahim N, Sonday N, Boliter N, Schrueder N, Gabriels S, Sigwadhi LN, Zemlin AE, Chapanduka ZC, Ngah V. The clinical and epidemiological characteristics of a series of patients living with HIV admitted for COVID-19 in a district hospital. BMC Infect Dis. 2023;23(1):123.

Organization WH, Initiative ST. Treatment of tuberculosis: guidelines. World Health Organization; 2010.

Africa DoHS. National Tuberculosis Management Guidelines: National Department of Health; 2013 [Guideline]. [cited 2023 1/10/2023]. Available from: https://knowledgehub.health.gov.za/system/files/elibdownloads/2023-04/National%252520TB%252520management%252520guidelines%2525202014.pdf .

Wasserman S, Davis A, Stek C, Chirehwa M, Botha S, Daroowala R, et al. Plasma pharmacokinetics of high-dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial. Antimicrob Agents Chemother. 2021;65(8):e00140–e00121.

pubmed: 33972248 pmcid: 7611291 doi: 10.1128/AAC.00140-21

Chigutsa E, Visser ME, Swart EC, Denti P, Pushpakom S, Egan D, et al. The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications. Antimicrob Agents Chemother. 2011;55(9):4122–7.

pubmed: 21709081 pmcid: 3165308 doi: 10.1128/AAC.01833-10

Lawn SD, Wilkinson RJ, Lipman MC, Wood R. Immune reconstitution and “unmasking” of tuberculosis during antiretroviral therapy. Am J Respir Crit Care Med. 2008;177(7):680–5.

pubmed: 18202347 pmcid: 2277208 doi: 10.1164/rccm.200709-1311PP

Diacon A, Patientia R, Venter A, Van Helden P, Smith P, McIlleron H, et al. Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears. Antimicrob Agents Chemother. 2007;51(8):2994–6.

pubmed: 17517849 pmcid: 1932511 doi: 10.1128/AAC.01474-06

McIlleron H, Rustomjee R, Vahedi M, Mthiyane T, Denti P, Connolly C, et al. Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines. Antimicrob Agents Chemother. 2012;56(6):3232–8.

pubmed: 22411614 pmcid: 3370773 doi: 10.1128/AAC.05526-11

Court R, Chirehwa MT, Wiesner L, Wright B, Smythe W, Kramer N, McIlleron H. Quality assurance of rifampicin-containing fixed-drug combinations in South Africa: dosing implications. Int J Tuberc Lung Dis. 2018;22(5):537–43.

pubmed: 29663959 pmcid: 5905389 doi: 10.5588/ijtld.17.0697

Health NDo. 2023 ART Clinical Guidelines for the Management of HIV in Adults, Pregnancy, Breastfeeding, Adolescents, Children, Infants and Neonates. 2023. [cited 2023 1/10/2023]. Available from: https://knowledgehub.health.gov.za/system/files/elibdownloads/2023-07/National%20ART%20Clinical%20Guideline%20AR%204.5%2020230713%20Version%204%20WEB.pdf .

Manosuthi W, Chottanapand S, Thongyen S, Chaovavanich A, Sungkanuparph S. Survival rate and risk factors of mortality among HIV/tuberculosis-coinfected patients with and without antiretroviral therapy. JAIDS J Acquir Immune Defic Syndr. 2006;43(1):42–6.

pubmed: 16885778 doi: 10.1097/01.qai.0000230521.86964.86

Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008;8(8):516–23.

pubmed: 18652998 pmcid: 2804035 doi: 10.1016/S1473-3099(08)70184-1

Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174(8):935–52.

pubmed: 17021358 doi: 10.1164/rccm.200510-1666ST

Rizvi I, Malhotra HS, Garg RK, Kumar N, Uniyal R, Pandey S. Fluoroquinolones in the management of tuberculous meningitis: systematic review and meta-analysis. J Infect. 2018;77(4):261–75.

pubmed: 30017610 doi: 10.1016/j.jinf.2018.06.009

Niemi M, Backman JT, Fromm MF, Neuvonen PJ, Kivistö KT. Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet. 2003;42:819–50.

pubmed: 12882588 doi: 10.2165/00003088-200342090-00003

Waitt C, Squire S. A systematic review of risk factors for death in adults during and after tuberculosis treatment. Int J Tuberc Lung Dis. 2011;15(7):871–85.

pubmed: 21496360 doi: 10.5588/ijtld.10.0352

Straetemans M, Bierrenbach AL, Nagelkerke N, Glaziou P, van der Werf MJ. The effect of tuberculosis on mortality in HIV positive people: a meta-analysis. PLoS One. 2010;5(12):e15241.

pubmed: 21209936 pmcid: 3012688 doi: 10.1371/journal.pone.0015241

Cresswell FV, Ellis J, Kagimu E, Bangdiwala AS, Okirwoth M, Mugumya G, et al. Standardized urine-based tuberculosis (TB) screening with TB-lipoarabinomannan and Xpert MTB/RIF Ultra in Ugandan adults with advanced human immunodeficiency virus disease and suspected meningitis. In: Open forum infectious diseases. Oxford University Press US; 2020.

Atherton RR, Cresswell FV, Ellis J, Skipper C, Tadeo KK, Mugumya G, et al. Detection of Mycobacterium tuberculosis in urine by Xpert MTB/RIF Ultra: a useful adjunctive diagnostic tool in HIV-associated tuberculosis. Int J Infect Dis. 2018;75:92–4.

pubmed: 30031800 pmcid: 6170999 doi: 10.1016/j.ijid.2018.07.007

Boyles TH, Griesel R, Stewart A, Mendelson M, Maartens G. Incremental yield and cost of urine Determine TB-LAM and sputum induction in seriously ill adults with HIV. Int J Infect Dis. 2018;75:67–73.

pubmed: 30125689 pmcid: 6202059 doi: 10.1016/j.ijid.2018.08.005

Fiorentino M, Nishimwe M, Protopopescu C, Iwuji C, Okesola N, Spire B, et al. Early ART initiation improves HIV status disclosure and social support in people living with HIV, linked to care within a universal test and treat program in rural South Africa (ANRS 12249 TasP Trial). AIDS Behavior. 2021;25:1306–22.

pubmed: 33206263 doi: 10.1007/s10461-020-03101-y

Girum T, Yasin F, Wasie A, Shumbej T, Bekele F, Zeleke B. The effect of “universal test and treat” program on HIV treatment outcomes and patient survival among a cohort of adults taking antiretroviral treatment (ART) in low income settings of Gurage zone, South Ethiopia. AIDS Res Ther. 2020;17(1):1–9.

doi: 10.1186/s12981-020-00274-3

Lanoix J-P, Chaisson RE, Nuermberger EL. Shortening tuberculosis treatment with fluoroquinolones: lost in translation? Clin Infect Dis. 2016;62(4):484–90.

pubmed: 26527614

Williams KJ, Duncan K. Current strategies for identifying and validating targets for new treatment-shortening drugs for TB. Curr Mol Med. 2007;7(3):297–307.

pubmed: 17504114 doi: 10.2174/156652407780598575

Johnson J, Hadad D, Boom W, Daley C, Peloquin C, Eisenach K, et al. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2006;10(6):605–12.

pubmed: 16776446