Treating drug-resistant tuberculosis in an era of shorter regimens: Insights from rural South Africa


  • J-D K Lotz Department of Family Medicine and Rural Health, Walter Sisulu University, Mthatha, South Africa, Madwaleni District Hospital, Elliotdale, South Africa
  • J Porter Department of Family Medicine and Rural Health, Walter Sisulu University, Mthatha, South Africa, Division of Family Medicine, Department of Family, Community, and Emergency Care, University of Cape Town, South Africa, False Bay District Hospital, Cape Town, South Africa
  • H Conradie Department of Family Medicine and Primary Care, Stellenbosch University, Cape Town, South Africa
  • T Boyles Right to Care, Centurion, South Africa, Clinical HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa, London School of Hygiene and Tropical Medicine, London, United Kingdom
  • B Gaunt Zithulele District Hospital, Coffee Bay, South Africa
  • S Dimanda Madwaleni District Hospital, Elliotdale, South Africa
  • D Cort Department of Sociology, University of Massachusetts, Amherst, USA



tuberculosis, short regimen, rural, South Africa, drug-resistant, DR-TB, HIV


Background. Progressive interventions have recently improved programmatic outcomes in drug-resistant tuberculosis (DR-TB) care in South Africa (SA). Amidst these, a shorter regimen was introduced in 2017 with weak evidence, and has shown mixed results. Outcomes still fall short of national targets, and the coronavirus disease 2019 pandemic has undermined progress to date.

Objectives. To describe the outcomes of participants treated for DR-TB using a shorter, compared with a longer, regimen in a deeply rural SA setting, and to explore other factors affecting these outcomes.

Methods. This retrospective cohort study describes outcomes in short and long DR-TB treatment regimens, over 5 years, at two rural treatment sites in SA. Characteristics were analysed for outcome correlates using multivariable logistic regression models.

Results. Of 282 treatment episodes, 62% were successful, with higher success in shorter (69%) compared with longer regimens (58%). Mortality was approximately 21% in both groups. Characteristics included high proportions of HIV co-infection (61%). Injectables (adjusted odds ratio (aOR) 3.00, 95% confidence interval (CI) 1.48 - 6.09), bedaquiline (aOR 3.16, 95% CI 1.36 - 7.35), increasing age (aOR 0.97, 95% CI 0.95 - 0.99) and HIV viraemia defined as final HIV-RNA viral load >1 000 copies/mL (aOR 0.16, 95% CI 0.07 - 0.37) were all significantly and independently associated with treatment success. Injectables (aOR 0.22, 95% CI 0.08 - 0.57), bedaquiline (aOR 0.05, 95% CI 0.01 - 0.19), increasing age (aOR 1.09, 95% CI 1.05 - 1.13), extra-pulmonary TB (aOR 8.15, 95% CI 1.62 - 41.03) and HIV viraemia (aOR 9.20, 95% CI 3.22 - 26.24) were all significantly and independently associated with mortality.

Conclusion. In a rural context, treating DR-TB amid limited resources and a high burden of HIV co-infection, we found that after considering controls, a short regimen was no different to a longer regimen in terms of success or mortality. Therefore, by alleviating burdens on multiple stakeholders, a short regimen is likely to be favourable for rural patients, clinicians, and healthcare systems. Besides other previously described correlates of outcomes, HIV viraemia emerged as a novel marker for reliably predicting poor outcomes in DR-TB with HIV co-infection, and a pragmatic target for intervention.


World Health Organization. Global tuberculosis report 2022. Geneva: WHO, 2022. https://www.who. int/teams/global-tuberculosis-programme/tb-reports (accessed 10 October 2022).

World Health Organization. Global tuberculosis report 2020. Geneva: WHO, 2020. https://www.who. int/publications/i/item/9789240013131 (accessed 15 November 2020).

Lange C, Dheda K, Chesov D, Mandalakas AM, Udwadia Z, Horsburgh CR. Management of drug- resistant tuberculosis. Lancet 2019;394:953-966.

World Health Organization. Rapid communication: Key changes to the treatment of drug- resistant tuberculosis. Geneva: WHO, 2022. item/WHO-UCN-TB-2022-2#:~:text=These%20updates%20include%20shorter%20novel,of%20 MDR%2FRR%2DTB (accessed 15 July 2022).

World Health Organisation. Global tuberculosis report 2019. Geneva: WHO, 2019. https://www.who. int/teams/global-tuberculosis-programme/tb-reports/global-report-2019 (accessed 15 November 2020).

The World Bank. Inequality in Southern Africa: An assessment of the Southern African Customs Union. Washington, DC: World Bank, 2022. en/099125303072236903/pdf/P1649270c02a1f06b0a3ae02e57eadd7a82.pdf (accessed 10 October 2022).

World Bank. Rural population – South Africa. World Bank, 2019. indicator/SP.RUR.TOTL.ZS?locations=ZA (accessed 24 October 2020).

Eagar D, Versteeg-Mojanaga M, Cooke R. Defining rurality within the context of health policy, planning, resourcing and service delivery: complexities, typologies and recommendations. Johannesburg: Rural Health Advocacy Project, 2014. RHAP-Submission-NHI-Bill_291119.pdf (accessed 10 October 2020).

Cox H, Dickson-Hall L, Jassat W, et al. Drug-resistant tuberculosis in South Africa: History, progress and opportunities for achieving universal access to diagnosis and effective treatment. In: Padarath A, Barron P, eds. South African Health Review 2017. 20th ed. Durban: Health Systems Trust, 2017:157-168.

National Department of Health, South Africa. Multi-drug resistant tuberculosis: A policy framework on decentralised and deinstitutionalised management for South Africa. Pretoria: NDoH, 2011. http:// (accessed 8 October 2020).

Dheda K, Cox H, Esmail A, Wasserman S, Chang KC, Lange C. Recent controversies about MDR and XDR-TB: Global implementation of the WHO shorter MDR-TB regimen and bedaquiline for all with MDR-TB? Respirology 2018;23(1):36-45.

National Department of Health, South Africa. Introduction of new drugs and drug regimens for the management of drug-resistant tuberculosis in South Africa: Policy framework. Pretoria: NDoH; 2015.

Ndjeka N, Conradie F, Schnippel K, et al. Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: An interim cohort analysis. Int J Tuberc Lung Dis 2015;19(8):979-985.

World Health Organisation. WHO treatment guidelines for drug-resistant tuberculosis: 2016 update. Geneva: WHO, 2016. (accessed 5 October 2020).

National Department of Health, South Africa. Management of rifampicin-resistant tuberculosis: A clinical reference guide. Pretoria: NDoH, 2019.

NdjekaN,HughesJ,ReuterA,etal.Implementingnovelregimensfordrug-resistantTBinSouthAfrica: What can the world learn? Int J Tuberc Lung Dis 2020;24(10):1073-1080. ijtld.20.0174

Massyn N, Barron P, Day C, Ndlovu N, Padarath A. District Health Barometer 2018/19. Vol. 53. Durban: Health Systems Trust, 2020.

Van Deun A, Maug AKJ, Salim MAH, et al. Short, highly effective, and inexpensive standardised treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 2010;182(5):684-692.

Nunn AJ, Phillips PPJ, Meredith SK, et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med 2019;380(13):1201-1213.

World Health Organisation. WHO consolidated guidelines on drug-resistant tuberculosis treatment. Geneva: WHO, 2019.

Directorate Drug-Resistant TB TB & HIV, National Department of Health, South Africa. Management of drug-resistant TB: Policy guidelines. Pretoria: NDoH, 2013. uploads/2014/06/MDR-TB-Clinical-Guidelines-Updated-Jan-2013.pdf (accessed 12 October 2020).

National Department of Health, South Africa. Interim clinical guidance for the implementation of injectable-free regimens for rifampicin-resistant tuberculosis in adults, adolescents and children. Pretoria: NDoH, 2018.

World Health Organization. Global Tuberculosis Report 2021. Geneva: WHO, 2021. publications/i/item/9789240037021 (accessed 18 October 2022).

World Health Organization. Definitions and reporting framework for tuberculosis – 2013 revision. Vol. 18, Eurosurveillance. Geneva: WHO, 2013.

Bursac Z, Gauss CH, Williams DK, Hosmer DW. Source code for biology and purposeful selection of variables in logistic regression. Source Code Biol Med 2008;3(17):1-8.

Ahmad N, Ahuja SD, Akkerman OW, et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet 2018;392(10150):821- 834.

Ndjeka N, Campbell J, Meintjes G, et al. Treatment outcomes 24 months after initiating short, all-oral bedaquiline-containing or injectable-containing rifampicin-resistant tuberculosis treatment regimens in South Africa: A retrospective cohort study. Lancet Infect Dis 2022;22(7):1042-1051. https://doi. org/10.1016/S1473-3099(21)00811-2

Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. PLoS Med 2010;7(3):1-7. 29. Foster N, Vassall A, Cleary S, Cunnama L, Churchyard G, Sinanovic E. The economic burden of

TB diagnosis and treatment in South Africa. Soc Sci Med 2015;130:42-50.


Sweeney S, Vassall A, Guinness L, et al. Examining approaches to estimate the prevalence of catastrophic costs due to tuberculosis from small-scale studies in South Africa. Pharmacoeconomics 2020;38(6):619-631.

Verguet S, Riumallo-Herl C, Gomez GB, et al. Catastrophic costs potentially averted by tuberculosis control in India and South Africa: A modelling study. Lancet Glob Heal 2017;5(11):e1123-1132.

Madan JJ, Rosu L, Tefera MG, et al. Economic evaluation of short treatment for multidrug-resistant tuberculosis, Ethiopia and South Africa: The stream trial. Bull World Health Organ 2020;98(5):306- 314.

Masuku SD, Berhanu R, Van Rensburg C, et al. Managing multidrug-resistant tuberculosis in South Africa: A budget impact analysis. Int J Tuberc Lung Dis 2020;24(4):376-382. ijtld.19.0409

Bastos ML, Cosme LB, Fregona G, et al. Treatment outcomes of MDR-tuberculosis patients in Brazil: A retrospective cohort analysis. BMC Infect Dis 2017;17(718):1-12. 017-2810-1

Edessa D, Sisay M, Dessie Y. Unfavorable outcomes to second-line tuberculosis therapy among HIV-infected versus HIV-uninfected patients in sub-Saharan Africa: A systematic review and meta- analysis. PLoS One 2020;15(8): e0237534.

World Health Organization. The End TB Strategy. Vol. 53. Geneva: WHO, 2015.

South African National AIDS Council. South Africa’s National Strategic Plan for HIV, TB and STIs 2017-2022. Pretoria: SANAC, 2017.

FullDocument_FINAL.pdf (accessed 14 October 2020).







How to Cite

Lotz J-DK, Porter J, Conradie H, Boyles T, Gaunt B, Dimanda S, et al. Treating drug-resistant tuberculosis in an era of shorter regimens: Insights from rural South Africa. S Afr Med J [Internet]. 2023 Nov. 6 [cited 2023 Dec. 2];113(11):47-56. Available from:

Similar Articles

1-10 of 207

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)

1 2 3 4 5 6 7 8 9 10 > >>