Drivers of Multi-Drug Resistance to Anti-Tuberculosis Drugs in TB/HIV Co-Infection in Tuberculosis Patients

TB/HIV co-infection is a very heavy burden, and controlling or even eliminating it is a challenge for African countries and their health services. The leading cause of mortality for those with TB/HIV co-infection is still resistance to anti-tuberculosis medications, and the factors leading to it are little known because they are less documented. The main aim of this research was to determine the drivers of multi-drug resistance to anti-tuberculosis drugs in TB/HIV co-infection in tuberculosis patients in a hospital in Kinshasa. A descriptive cross-sectional study analyzed 25 records of patients with TB/HIV co-infection undergoing antiretroviral and anti-tuberculosis treatment at the Saint-Pierre de Kabambarré Hospital in Kinshasa. The mentioned files were analyzed over a period running from October 2023 to January 2024. A descriptive analysis revealed that environmental variables, including alcohol intake, had contributed to 46.6% of patients' development of resistance to anti-tuberculosis medications, loss of sight due to relocation, compared with 40% as a result of economic factors, in particular poverty and geographical inaccessibility. Only 32% of resistance was linked to medical factors: stock-outs of anti-tuberculosis drugs, and 41% of respondents developed resistance as a result of biological factors. On the other hand, only 12% of patients developed resistant relapses due to socio-demographic factors, such as discrimination and the myth surrounding tuberculosis. Poverty combined with the global economic collapse, geographical inaccessibility, stock-outs of anti-tuberculosis drugs and antiretrovirals, increased viral load, discrimination and the myth surrounding tuberculosis are responsible for anti-tuberculosis drug resistance in patients with HIV/TB co-infection.

1. Chanda-Kapata P, Ntoumi F, Kapata N, Lungu P, Mucheleng’anga LA, Chakaya J, et al. Tuberculosis, HIV/AIDS and Malaria health services in sub-Saharan Africa – a situation analysis of the disruption and impact of the COVID-19 pandemic. Int J Infect Dis. 2022;124:541–6. doi:10.1016/j.ijid.2022.03.033
2. Moreno R, Ravasi G, Avedillo P, Lopez R. Tuberculosis and HIV coinfection and related collaborative activities in Latin America, the Caribbean. Rev Panam Salud Publica. 2020;44:e43. doi:10.26633/RPSP.2020.43
3. Sekayi W, Namyalo E, Namayanja J, Kungu JM. Prevalence and predictors of tuberculosis among HIV patients who completed isoniazid preventive therapy (IPT) at Reach out Mbuya community health initiative. Sci Rep. 2023;13(1):17602. doi:10.1038/s41598-023-44649-8
4. Ahmad SR, Yaacob NA, Jaeb MZ, Hussin Z, Wan Mohammad WMZ. Effect of diabetes mellitus on tuberculosis treatment outcomes among tuberculosis patients in Kelantan, Malaysia. Iran J Public Health. 2020;49(8):1485-93. doi:10.18502/ijph
5. Zeru MA. Prevalence and associated factors of HIV-TB co-infection among HIV patients: a retrospective study. Afr Health Sci. 2021;21(3):1003-9. doi:10.4314/ahs.v21i3.7
6. Chijioke-Akaniro OO, Ubochioma E, Omoniyi A, Fashade O, Olarewaju O, Asuke S, et al. Improving TB case notification and treatment coverage through data use. Public Health Action. 2022;12(3):128-32. doi:10.5588/pha.22.0001
7. Shrestha S, Mishra G, Hamal M, Dhital R, Shrestha S, Shrestha A, et al. Quantifying the potential epidemiological impact of a 2-year active case finding for tuberculosis in rural Nepal: a model-based analysis. BMJ Open. 2023;13(11):e062123. doi:10.1136/bmjopen-2022-062123
8. Wondmeneh TG, Mekonnen AT. The incidence rate of tuberculosis and its associated factors among HIV-positive persons in Sub-Saharan Africa: a systematic review and meta-analysis. BMC Infect Dis. 2023;23(1):613. doi:10.1186/s12879-023-08533-0
9. Adesanya OA, Uche-Orji CI, Adedeji YA, Joshua JI, Adesola AA, Chukwudike CJ. Bacillus Calmette-Guerin (BCG): the adroit vaccine. AIMS Microbiol. 2021;7(1):96-113. doi:10.3934/microbiol.2021007
10. Li J, Lu J, Wang G, Zhao A, Xu M. Past, present and future of bacillus Calmette-Guérin vaccine use in China. Vaccines (Basel). 2022;10(7):1157. doi:10.3390/vaccines10071157
11. Setiabudiawan TP, Reurink RK, Hill PC, Netea MG, van Crevel R, Koeken VACM. Protection against tuberculosis by Bacillus Calmette-Guérin (BCG) vaccination: a historical perspective. Med. 2022;3(1):6–24. doi:10.1016/j.medj.2021.11.006
12. Boualam A, Seghiri R, Touil D, Berrid N, Aouane EM. A cross-sectional epidemiological study of tuberculosis in the province of Sidi Kacem, Morocco. Pan Afr Med J. 2023;44(1):106. doi:10.11604/pamj.2023.44.106.25958
13. Villar-Hernández R, Ghodousi A, Konstantynovska O, Duarte R, Lange C, Raviglione M. Tuberculosis: current challenges and beyond. Breathe (Sheff). 2023;19(1):220166. doi:10.1183/20734735.0166-2022
14. World Health Organization (WHO). Global Tuberculosis Report 2022. Geneva: WHO; 2023. Available from: https://www.who.int/publications/i/item/9789240061729
15. Hamada Y, Getahun H, Tadesse BT, Ford N. HIV-associated tuberculosis. Int J STD AIDS. 2021;32(9):780–90. doi:10.1177/0956462421992257
16. Bayowa JR, Kalyango JN, Baluku JB, Katuramu R, Ssendikwanawa E, Zalwango JF, et al. Mortality rate and associated factors among patients co-infected with drug resistant tuberculosis/HIV at Mulago National Referral Hospital, Uganda, a retrospective cohort study. PLOS Glob Public Health. 2023;3(7):e0001020. doi:10.1371/journal.pgph.0001020
17. Yang N, He J, Li J, Zhong Y, Song Y, Chen C. Predictors of death among TB/HIV co-infected patients on tuberculosis treatment in Sichuan, China: a retrospective cohort study. Medicine (Baltimore). 2023;102(5):e32811. doi:10.1097/MD.0000000000032811
18. Torpey K, Agyei-Nkansah A, Ogyiri L, Forson A, Lartey M, Ampofo W, et al. Management of TB/HIV co-infection: the state of the evidence. Ghana Med J. 2020;54(3):186–96. doi:10.4314/gmj.v54i3.10
19. Pham BN, Abon N, Silas VD, Jorry R, Rao C, Okely T, et al. Tuberculosis and HIV/AIDS-attributed mortalities and associated sociodemographic factors in Papua New Guinea: evidence from the comprehensive health and epidemiological surveillance system. BMJ Open. 2022;12(6):e058962. doi:10.1136/bmjopen-2021-058962
20. Moyo E, Moyo P, Murewanhema G, Mhango M, Chitungo I, Dzinamarira T. Key populations and Sub-Saharan Africa's HIV response. Front Public Health. 2023;11:1079990. doi:10.3389/fpubh.2023.1079990
21. Kaswa M, Minga G, Nkiere N, Mingiedi B, Eloko G, Nguhiu P, et al. The economic burden of TB-affected households in DR Congo. Int J Tuberc Lung Dis. 2021;25(11):923-32. doi:10.5588/ijtld.21.0182
22. Faccin M, Rusumba O, Ushindi A, Riziki M, Habiragi T, Boutachkourt F, et al. Data-driven identification of communities with high levels of tuberculosis infection in the Democratic Republic of Congo. Sci Rep. 2022;12(1):3912. doi:10.1038/s41598-022-07633-2
23. Fari SE, Mouna M, Haja K, Jait N, Moussadik Y, Jaradat T, et al. Resistant tuberculosis in HIV-positive patients: a growing public health threat. Am J Intern Med. 2023;11(3):55–9. doi:10.11648/j.ajim.20231103.15
24. Kandala NB, Mandungu TP, Mbela K, Nzita KPD, Kalambayi BB, Kayembe KP, et al. Child mortality in the Democratic Republic of Congo: cross-sectional evidence of the effect of geographic location and prolonged conflict from a national household survey. BMC Public Health. 2014;14:266. doi:10.1186/1471-2458-14-266
25. Bekker LG, Alleyne G, Baral S, Cepeda J, Daskalakis D, Dowdy D, et al. Advancing global health and strengthening the HIV response in the era of the sustainable development goals: the international AIDS society-lancet commission. Lancet. 2018;392(10144):312-58. doi:10.1016/S0140-6736(18)31070-5
26. Esmail A, Sabur NF, Okpechi I, Dheda K. Management of drug-resistant tuberculosis in special sub-populations including those with HIV co-infection, pregnancy, diabetes, organ-specific dysfunction, and in the critically ill. J Thorac Dis. 2018;10(5):3102-18. doi:10.21037/jtd.2018.0
27. Sossen B, Kubjane M, Meintjes G. Tuberculosis and HIV coinfection: progress and challenges towards reducing incidence and mortality. Int J Infect Dis. 2025;155:107876. doi:10.1016/j.ijid.2025.107876
28. Bongo G, Tuntufye H, Ngbolua KN, Malakalinga J, Tshiama C, Pambu A, et al. Comparative anti-mycobacterial activity on Lowenstein-Jensen slants of selected medicinal plants used in the Congolese pharmacopeia. J Dis Med Plants. 2017;3(5):88–96. doi:10.11648/j.jdmp.20170305.12
29. Bongo GN, Tuntufye HN, Malakalinga J, Ngbolua KNN, Pambu AL, Tshiama C, et al. Anti-mycobacterial activity on middlebrook 7H10 agar of selected Congolese medicinal plants. Biosci Bioeng. 2018;4(5):68–77.
30. Wilson JW, Nilsen DM, Marks SM. Multidrug-resistant tuberculosis in patients with human immunodeficiency virus. management considerations within high-resourced settings. Ann Am Thorac Soc. 2020;17(1):16–23. doi:10.1513/AnnalsATS.201902-185CME
31. Heidary M, Shirani M, Moradi M, Goudarzi M, Pouriran R, Rezaeian T, et al. Tuberculosis challenges: resistance, co-infection, diagnosis, and treatment. Eur J Microbiol Immunol (Bp). 2022;12(1):1–17. doi:10.1556/1886.2021.00021
32. Shah GH, Maluantesa L, Etheredge GD, Waterfield KC, Ikhile O, Beni R, et al. HIV Viral suppression among people living with HIV on antiretroviral therapy in Haut-Katanga and Kinshasa provinces of democratic republic of Congo. Healthcare (Basel). 2021;10(1):69. doi:10.3390/healthcare10010069
33. Mukuku O, Mutombo AM, Kakisingi CN, Musung JM, Wembonyama SO, Luboya ON. Tuberculosis and HIV co-infection in Congolese children: risk factors of death. Pan Afr Med J. 2019;33:326. doi:10.11604/pamj.2019.33.326.18911
34. The Global Fund. Results Report 2023 [Internet]. 2023 [cited 2024 Sep 26]. Available from: https://www.theglobalfund.org/media/13263/corporate_2023resultsreport_report_en.pdf
35. Seid A, Girma Y, Abebe A, Dereb E, Kassa M, Berhane N. Characteristics of TB/HIV Co-infection and patterns of multidrug-resistance tuberculosis in the Northwest Amhara, Ethiopia. Infect Drug Resist. 2023;16:3829–45. doi:10.2147/IDR.S412951
36. García JI, Allué-Guardia A, Tampi RP, Restrepo BI, Torrelles JB. New developments and insights in the improvement of mycobacterium tuberculosis vaccines and diagnostics within the end TB strategy. Curr Epidemiol Rep. 2021;8:33–45. doi:10.1007/s40471-021-00269-2
37. Palambwa AAR, Nsutier KO, Bongo GN, Nsobani LD, Amuli JJP. Risk Factors for Mortality in Patients with TB-HIV Co-Infection at the General Provincial Reference Hospital of Kinshasa. Arch Intern Med Res. 2019;2:014–24.
38. Sultana ZZ, Hoque FU, Beyene J, Akhlak-Ul-Islam MD, Khan HR, Ahmed S, et al. HIV infection and multidrug resistant tuberculosis: a systematic review and meta-analysis. BMC Infect Dis. 2021;21:51. doi:10.1186/s12879-020-05749-2
39. Jackson S, Kabir Z, Corniskey C. Effects of migration on tuberculosis epidemiological indicators in low and medium tuberculosis incidence countries: a systematic review. J Clin Tuberc Other Mycobact Dis. 2021;23:100225. doi:10.1016/j.jctube.2021.100225
40. Pareek M, Greenaway C, Noori T, Munoz J, Zenner D. The impact of migration on tuberculosis epidemiology and control in high-income countries: a review. BMC Med. 2016;14:48. doi:10.1186/s12916-016-0595-5
41. Cerrone M, Bracchi M, Wasserman S, Pozniak A, Meintjes G, Cohen K, et al. Safety implications of combined antiretroviral and anti-tuberculosis drugs. Expert Opin Drug Saf. 2020;19(1):23-41. doi:10.1080/14740338.2020.1694901
42. Feldman C, Theron AJ, Cholo MC, Anderson R. Cigarette smoking as a risk factor for tuberculosis in adults: epidemiology and aspects of disease pathogenesis. Pathogens. 2024;13(2):151. doi:10.3390/pathogens13020151
43. Quan DH, Kwong AJ, Hansbro PM, Britton WJ. No smoke without fire: the impact of cigarette smoking on the immune control of tuberculosis. Eur Respir Rev. 2022;31(164):210252. doi:10.1183/16000617.0252-2021
44. Todd H, Hudson M, Grolmusova N, Kazibwe J, Pearman J, Skender K, et al. Social protection interventions for TB-affected households: a scoping review. Am J Trop Med Hyg. 2023;108(4):650–9. doi:10.4269/ajtmh.22-0470
45. Smith JP, Oeltmann JE, Hill AN, Tobias JL, Boyd R, Click ES, et al. Characterizing tuberculosis transmission dynamics in high-burden urban and rural settings. Sci Rep. 2022;12:6780. doi:10.1038/s41598-022-10488-2
46. Hunter RL. The Pathogenesis of tuberculosis-the Koch phenomenon reinstated. Pathogens. 2020;9(10):813. doi:10.3390/pathogens9100813
47. Tiwari D, Martineau AR. Inflammation-mediated tissue damage in pulmonary tuberculosis and host-directed therapeutic strategies. Semin Immunol. 2023;65:101672. doi:10.1016/j.smim.2022.101672
48. Kaushik G, Vashishtha R, Verma C, Sharma S, Kumar V. Genetic variation in Toll-Like Receptors (TLRs) 2, 4, and 9 influences HIV disease progression toward active TB and AIDS. J Inflamm Res. 2024;17:3283–91. doi:10.2147/JIR.S451431
49. McLaren PJ, Fellay J. HIV-1 and human genetic variation. Nat Rev Genet. 2021;22(10):645-57. doi:10.1038/s41576-021-00378-0
50. Izudi J, Okello G, Bajunirwe F. Low treatment success rate among previously treated persons with drug-susceptible pulmonary tuberculosis in Kampala, Uganda. J Clin Tuberc Other Mycobact Dis. 2023;32:100375. doi:10.1016/j.jctube.2023.100375