Preview

Journal Infectology

Advanced search

Efficacy and safety of treatment of HIV-associated multidrug-resistant tuberculosis. Systematic review and meta-analysis

https://doi.org/10.22625/2072-6732-2025-17-1-26-35

Abstract

The aim was to conduct a systematic review and meta-analysis of published studies assessing the impact of HIV infection on treatment outcomes and the development of adverse reactions in MDR-TB patients.

Material and Methods. We searched for publications using the specified keywords in MEDLINE (PubMed), Google Scholar, and eLibrary databases. Twenty-seven publications with a total number of 13944 patients were selected for meta-analysis. Meta-analysis was performed using Review Manager software (RevMan version 5.4; Cochrane Collaboration, Oxford, UK). Statistical heterogeneity of studies was checked using a Q-test based on χ2. An effect was considered statistically significant at p<0.05.

Results. The meta-analysis revealed that the incidence of adverse outcomes in patients 6with MDR-TB/HIV coinfection was higher than in the HIV-free group and was 37%, OR=1.49 [CI: 1.15-1.93]; the incidence of fatal outcomes was 20.3%, OR=2.02 [95% CI: 1.64-2.49]. Among HIV-infected patients, there was a higher incidence of adverse adverse reactions: OSH=1.51 [95% CI: 1.01-2.26], adverse adverse reactions of severe severity: OSH=1.53 [95% DI: 1.1-2.13].

Conclusion. The results of the meta-analysis show that patients with MDR-TB/HIV coinfection are characterized by an increased incidence of adverse outcomes and risk of any adverse adverse adverse reactions, further analysis of the problem is needed to optimize treatment outcomes in this population.

About the Author

A. V. Kukurika
National Medical Research Center of Phthisiopulmonology and Infectious Diseases; Moscow Municipal Scientific Practical Center of Tuberculosis Control
Russian Federation

Moscow


Competing Interests:

None



References

1. Global tuberculosis report 2023. Geneva: World Health Organization; 2023

2. Дегтярева С.Ю., Зимина В.Н., Покровская А.В., Волченков Г.В. Безопасность и эффективность терапии туберкулеза с множественной лекарственной устойчивостью возбудителя у пациентов с различным ВИЧ-статусом // Туберкулёз и болезни лёгких. – 2022. – Т. 100, № 1. – С. 33–40. http://doi.org/10.21292/2075-1230-2022-100-1-33-40

3. Кукурика А.В., Веселова Е.И., Паролина Л. Е., Ловачева О. В. Безопасность химиотерапии у больных МЛУ/ ШЛУ-ТБ в условиях широкой распространенности ВИЧ-инфекции // Туберкулёз и болезни лёгких. – 2022. – Т. 100, № 11. – С. 56-65. http://doi.org/10.21292/2075-1230-2022-100-11-56-65

4. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., Chou R., Glanville J., Grimshaw J.M., Hróbjartsson A., Lalu M.M., Tianjing Li, Loder E.W., MayoWilson E., McDonald S., McGuinness L.A., Stewart L.A., Thomas J., Tricco A.C., Welch V.A., Whiting P., Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021. 372; 71. doi: 10.1136/bmj.n71.

5. Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res. 2014 Nov 21;14:579. doi: 10.1186/s12913-014-0579-0.

6. Bastard M, Sanchez-Padilla E, du Cros P, Khamraev AK, Parpieva N, Tillyashaykov M, Hayrapetyan A, Kimenye K, Khurkhumal S, Dlamini T, Perez SF, Telnov A, Hewison C, Varaine F, Bonnet M. Outcomes of HIV-infected versus HIV-non-infected patients treated for drug-resistance tuberculosis: Multicenter cohort study. PLoS One. 2018 Mar 8;13(3):e0193491. doi: 10.1371/journal.pone.0193491

7. Brust JCM, Shah NS, Mlisana K, Moodley P, Allana S, Campbell A, Johnson BA, Master I, Mthiyane T, Lachman S, Larkan LM, Ning Y, Malik A, Smith JP, Gandhi NR. Improved Survival and Cure Rates With Concurrent Treatment for Multidrug-Resistant Tuberculosis-Human Immunodeficiency Virus Coinfection in South Africa. Clin Infect Dis. 2018;66(8):1246-1253. doi: 10.1093/cid/cix1125

8. Oladimeji O, Isaakidis P, Obasanya OJ, Eltayeb O, Khogali M, Van den Bergh R, Kumar AM, Hinderaker SG, Abdurrahman ST, Lawson L, Cuevas LE. Intensive-phase treatment outcomes among hospitalized multidrug-resistant tuberculosis patients: results from a nationwide cohort in Nigeria. PLoS One. 2014 Apr 10;9(4):e94393. doi: 10.1371/journal.pone.0094393

9. Ndjeka N, Schnippel K, Master I, Meintjes G, Maartens G, Romero R, Padanilam X, Enwerem M, Chotoo S, Singh N, Hughes J, Variava E, Ferreira H, Te Riele J, Ismail N, Mohr E, Bantubani N, Conradie F. High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen. Eur Respir J. 2018 Dec 20;52(6):1801528. doi: 10.1183/13993003.01528-2018

10. Satti H, McLaughlin MM, Hedt-Gauthier B, Atwood SS, Omotayo DB, Ntlamelle L, Seung KJ. Outcomes of multidrug-resistant tuberculosis treatment with early initiation of antiretroviral therapy for HIV co-infected patients in Lesotho. PLoS One. 2012;7(10):e46943. doi: 10.1371/journal.pone.0046943

11. Meressa D, Hurtado RM, Andrews JR, Diro E, Abato K, Daniel T, Prasad P, Prasad R, Fekade B, Tedla Y, Yusuf H, Tadesse M, Tefera D, Ashenafi A, Desta G, Aderaye G, Olson K, Thim S, Goldfeld AE. Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia--an observational cohort study. Thorax. 2015 Dec;70(12):1181-8. doi: 10.1136/thoraxjnl-2015-207374

12. van der Walt M, Lancaster J, Shean K. Tuberculosis Case Fatality and Other Causes of Death among Multidrug-Resistant Tuberculosis Patients in a High HIV Prevalence Setting, 2000-2008, South Africa. PLoS One. 2016 Mar 7;11(3):e0144249. doi: 10.1371/journal.pone.0144249

13. Mugabo P, Adewumi AO, Theron D, Burger A, Van ZL. Do HIV infection and antiretroviral therapy influence multidrug-resistant tuberculosis treatment outcomes? Afr J Pharm Pharmacol. 2015;9(35):875–80.

14. Shin SS, Modongo C, Boyd R, Caiphus C, Kuate L, Kgwaadira B, Zetola NM. High treatment success rates among HIV-infected Multidrugresistant tuberculosis patients after expansion of antiretroviral therapy in Botswana, 2006–2013. J Acquir Immune Defic Syndr. 2017;74(1):65–71.

15. Mohr E, Cox V, Wilkinson L, Moyo S, Hughes J, Daniels J, Muller O, Cox H. Programmatic treatment outcomes in HIV-infected and uninfected drug-resistant TB patients in Khayelitsha, South Africa. Trans R Soc Trop Med Hyg. 2015;109(7):425-32. doi: 10.1093/trstmh/trv037

16. Wakjira MK, Sandy PT, Mavhandu-Mudzusi AH. Treatment outcomes of patients with MDR-TB and its determinants at referral hospitals in Ethiopia. PLoS One. 2022;17(2):e0262318. doi: 10.1371/journal.pone.0262318.

17. Loveday M, Wallengren K, Brust J, Roberts J, Voce A, Margot B, et al.: Community-based care vs. centralised hospitalisation for MDR-TB patients, KwaZulu-Natal, South Africa. The International Journal of Tuberculosis and Lung Disease 2015, 19(2):163–171. https://doi.org/10.5588/ijtld.14.0369

18. Leveri TH, Lekule I, Mollel E, Lyamuya F, Kilonzo K. Predictors of Treatment Outcomes among Multidrug Resistant Tuberculosis Patients in Tanzania. Tuberc Res Treat. 2019 Feb 12;2019:3569018. doi: 10.1155/2019/3569018.

19. Huerga H, Bastard M, Kamene M, Wanjala S, Arnold A, Oucho N, Chikwanha I, Varaine F. Outcomes from the first multidrug-resistant tuberculosis programme in Kenya. Int J Tuberc Lung Dis. 2017 Mar 1;21(3):314-319. doi: 10.5588/ijtld.16.0661.

20. Alene KA, Viney K, McBryde ES, Tsegaye AT, Clements AC. Treatment outcomes in patients with multidrug-resistant tuberculosis in north-west Ethiopia. Trop Med Int Health. 2017 Mar;22(3):351-362. doi: 10.1111/tmi.12826.

21. Sam S, Shapiro AE, Sok T, Khann S, So R, Khem S, Chhun S, Noun S, Koy B, Sayouen PC, Im Sin C, Bunsieth H, Mao TE, Goldfeld AE. Initiation, scale-up and outcomes of the Cambodian National MDR-TB programme 2006-2016: hospital and community-based treatment through an NGO-NTP partnership. BMJ Open Respir Res. 2018 Jun 4;5(1):e000256. doi: 10.1136/bmjresp-2017-000256.

22. Van LH, Phu PT, Vinh DN, Son VT, Hanh NT, Nhat LTH, Lan NH, Vinh TV, Trang NTM, Ha DTM, Thwaites GE, Thuong NTT. Risk factors for poor treatment outcomes of 2266 multidrug-resistant tuberculosis cases in Ho Chi Minh City: a retrospective study. BMC Infect Dis. 2020 Feb 22;20(1):164. doi: 10.1186/s12879-020-4887-1.

23. Limenh LW, Kasahun AE, Sendekie AK, Seid AM, Mitku ML, Fenta ET, Melese M, Workye M, Simegn W, Ayenew W. Tuberculosis treatment outcomes and associated factors among tuberculosis patients treated at healthcare facilities of Motta Town, Northwest Ethiopia: a five-year retrospective study. Sci Rep. 2024 Apr 2;14(1):7695. doi: 10.1038/s41598-024-58080-0

24. Smith JP, Gandhi NR, Shah NS, Mlisana K, Moodley P, Johnson BA, Allana S, Campbell A, Nelson KN, Master I, Brust JCM. The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events. J Acquir Immune Defic Syndr. 2020 Jan 1;83(1):47-55. doi: 10.1097/QAI.0000000000002190

25. Jacobs T. Q., Ross A. Adverse effects profile of multidrugresistant tuberculosis treatment in a South African outpatient clinic, South African Family Practice. 2012; 54:6, 531-539, DOI: 10.1080/20786204.2012.10874288

26. Brust JC, Shah NS, van der Merwe TL, Bamber S, Ning Y, Heo M, Moll AP, Loveday M, Lalloo UG, Friedland GH, Gandhi NR. Adverse events in an integrated home-based treatment program for MDR-TB and HIV in KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr. 2013 Apr 1;62(4):436-40. doi: 10.1097/QAI.0b013e31828175ed.

27. Hughes J, Reuter A, Chabalala B, Isaakidis P, Cox H, Mohr E. Adverse events among people on delamanid for rifampicin-resistant tuberculosis in a high HIV prevalence setting. Int J Tuberc Lung Dis. 2019 Sep 1;23(9):1017-1023. doi: 10.5588/ijtld.18.0651

28. Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, Mendel CM, Egizi E, Moreira J, Timm J, McHugh TD, Wills GH, Bateson A, Hunt R, Van Niekerk C, Li M, Olugbosi M, Spigelman M; Nix-TB Trial Team. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. N Engl J Med. 2020 Mar 5;382(10):893-902. doi: 10.1056/NEJMoa1901814.

29. Merid MW, Gezie LD, Kassa GM, Muluneh AG, Akalu TY, Yenit MK. Incidence and predictors of major adverse drug events among drug-resistant tuberculosis patients on second-line anti-tuberculosis treatment in Amhara regional state public hospitals; Ethiopia: a retrospective cohort study. BMC Infect Dis. 2019 Mar 27;19(1):286. doi: 10.1186/s12879-019-3919-1.

30. Harris T, Bardien S, Schaaf HS, Petersen L, De Jong G, Fagan JJ. Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients. S Afr Med J. 2012 May 8;102(6 Pt 2):363-6. doi: 10.7196/samj.4964.

31. Van der Walt M, Lancaster J, Odendaal R, Davis JG, Shean K, Farley J. Serious treatment related adverse drug reactions amongst anti-retroviral na ve MDR-TB patients. PLoS One. 2013;8(4):e58817. doi: 10.1371/journal.pone.0058817.

32. Shean K, Streicher E, Pieterson E, Symons G, van Zyl Smit R, Theron G, Lehloenya R, Padanilam X, Wilcox P, Victor TC, van Helden P, Grobusch MP, Warren R, Badri M, Dheda K. Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa. PLoS One. 2013 May 7;8(5):e63057. doi: 10.1371/journal.pone.0063057

33. Modongo C, Sobota RS, Kesenogile B, Ncube R, Sirugo G, Williams SM, Zetola NM. Successful MDR-TB treatment regimens including amikacin are associated with high rates of hearing loss. BMC Infect Dis. 2014 Oct 9;14:542. doi: 10.1186/1471-2334-14-542

34. Isaakidis P, Casas EC, Das M, Tseretopoulou X, Ntzani EE, Ford N. Treatment outcomes for HIV and MDR-TB co-infected adults and children: systematic review and meta-analysis. Int J Tuberc Lung Dis. 2015 Aug;19(8):969-78. doi: 10.5588/ijtld.15.0123

35. 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 Aug 14;15(8):e0237534. doi: 10.1371/journal.pone.0237534.

36. Kajogoo VD, Lalashowi J, Olomi W, Atim MG, Assefa DG, Sabi I. Treatment outcomes of multi-drug resistant tuberculosis patients with or without human immunodeficiency virus co-infection in Africa and Asia: Systematic review and meta-analysis. Ann Med Surg (Lond). 2022 May 11;78:103753. doi: 10.1016/j.amsu.2022.103753

37. Chem ED, Van Hout MC, Hope V. Treatment outcomes and antiretroviral uptake in multidrug-resistant tuberculosis and HIV co-infected patients in Sub Saharan Africa: a systematic review and meta-analysis. BMC Infect Dis. 2019 Aug 16;19(1):723. doi: 10.1186/s12879-019-4317-4.

38. Lazarus G, Tjoa K, Iskandar AWB, Louisa M, Sagwa EL, Padayatchi N, Soetikno V. The effect of human immunodeficiency virus infection on adverse events during treatment of drug-resistant tuberculosis: A systematic review and meta-analysis. PLoS One. 2021 Mar 4;16(3):e0248017. doi: 10.1371/journal.pone.0248017.

39. Schnippel K, Firnhaber C, Berhanu R, Page-Shipp L, Sinanovic E. Adverse drug reactions during drug-resistant TB treatment in high HIV prevalence settings: a systematic review and meta-analysis. J Antimicrob Chemother. 2017 Jul 1;72(7):1871-1879. doi: 10.1093/jac/dkx107.


Review

For citations:


Kukurika A.V. Efficacy and safety of treatment of HIV-associated multidrug-resistant tuberculosis. Systematic review and meta-analysis. Journal Infectology. 2025;17(1):26-35. (In Russ.) https://doi.org/10.22625/2072-6732-2025-17-1-26-35

Views: 203


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2072-6732 (Print)