Optimal Management of Drug-Resistant Tuberculosis and Human Immunodeficiency Virus: an Update

HIV Medicine (CJ Yoon, Section Editor)
  • 25 Downloads
Part of the following topical collections:
  1. Topical Collection on HIV Medicine

Abstract

Purpose of Review

Rifampicin-resistant tuberculosis (RR-TB) in a growing global health crisis. RR-TB and HIV co-infection is common, and this dual infection brings with it unique diagnostic and treatment challenges. Here, we review the most recent developments in the epidemiology, prevention, diagnoses, and treatment—including the use of novel antituberculosis drugs—for these diseases. We also review strategies to combat stigma and support adherence for people living with HIV and RR-TB.

Recent Findings

Advances in RR-TB diagnosis include genotypic tests, most notably Xpert MTB/RIF. Novel therapeutic advances in the treatment of RR-TB among people living with HIV include the use of new drugs (bedaquiline and delamanid), repurposed drugs (linezolid and clofazimine), and novel regimens (a shortened 9–12-month treatment). However, access to advances in diagnosis and treatment of RR-TB in people living with HIV is limited. Furthermore, there is a significant amount of stigma and discrimination against people with both HIV and RR-TB, and this could affect treatment outcomes via challenges with adherence.

Summary

We conclude that with high-quality diagnostics, treatment, and support, people living with HIV and RR-TB have good treatment outcomes; thus, access to all of these interventions is an urgent global priority.

Keywords

HIV Tuberculosis Rifampin-resistant Multidrug-resistant AIDS 

Notes

Compliance with Ethical Standards

Conflict of Interest

Anja Reuter declares that she has no conflict of interest. Jennifer Furin declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Dheda K, Gumbo T, Maartens G, et al. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. Lancet Respir Med. 2017;5(4):291–360. This paper is a complete and comprehensive review of the latest science of all aspects of RR-TB. There is a significant discussion of HIV co-infection.CrossRefGoogle Scholar
  2. 2.
    van Kampen SC, Susanto NH, Simon S, Astiti SD, Chandra R, Burhan E, et al. Effects of introducing Xpert MTB/RIF on diagnosis and treatment of drug-resistant tuberculosis patients in Indonesia: a pre-post intervention study. PLoS One. 2015;10(6):e0123536.  https://doi.org/10.1371/journal.pone.0123536.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Berhanu R, Schnippel K, Mohr E, Hirasen K, Evans D, Rosen S, et al. Early outcomes of decentralized care for rifampicin-resistant tuberculosis in Johannesburg, South Africa: an observational cohort study. PLoS One. 2016;11(11):e0164974.  https://doi.org/10.1371/journal.pone.0164974.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ombura IP, Onyango N, Odera S, Mutua F, Nyagol J. Prevalence of drug resistance Mycobacterium tuberculosis among patients seen in Coast Provincial General Hospital, Mombasa, Kenya. PLoS ONE. 2016;11(10):e0163994.  https://doi.org/10.1371/journal.pone.0163994.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Dessalegn M, Daniel E, Behailu S, Wagnew M, Nyagero J. Predictors of multidrug resistant tuberculosis among adult patients at Saint Peter Hospital Addis Ababa, Ethiopia. Pan Afr Med J. 2016;25(Suppl 2):5.  https://doi.org/10.11604/pamj.supp.2016.25.2.9203.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Deribwe A, Michael Y, Tesfaye M, et al. The synergy between TB and HIV co-infection on perceived stigma in Ethiopia. BMC Res Notes. 2010;3(1):249.  https://doi.org/10.1186/1756-0500-3-249.CrossRefGoogle Scholar
  7. 7.
    Dheda K, Chang KC, Guglielmetti L, Furin J, Schaaf HS, Chesov D, et al. Clinical management of adults and children with multidrug-resistant and extensively drug-resistant tuberculosis. Clin Microbiol Infect. 2017;23(3):131–40.  https://doi.org/10.1016/j.cmi.2016.10.008.CrossRefPubMedGoogle Scholar
  8. 8.
    World Health Organization. 2016 global TB report. Geneva: WHO; 2016. Available at http://www.who.int/tb/publications/global_report/en/.Google Scholar
  9. 9.
    Dean AS, Zignol M, Falzon D, Getahun H, Floyd K. HIV and multidrug-resistant tuberculosis: overlapping epidemics. Eur Respir J. 2014;44(1):251–4.  https://doi.org/10.1183/09031936.00205413.CrossRefPubMedGoogle Scholar
  10. 10.
    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 [Electronic Resource]. 2016;11(3):e0144249.  https://doi.org/10.1371/journal.pone.0144249.CrossRefGoogle Scholar
  11. 11.
    Trinh QM, Nguyen HL, Do TN, Nguyen VN, Nguyen BH, Nguyen TV, et al. Tuberculosis and HIV co-infection in Vietnam. Int J Infect Dis. 2016;46:56–60.  https://doi.org/10.1016/j.ijid.2016.03.021.CrossRefPubMedGoogle Scholar
  12. 12.
    Elmi OS, Hasan H, Abdullah S, Mat Jeab MZ, Bin Alwi Z, Naing NN. Multidrug-resistant tuberculosis and risk factors associated with its development: a retrospective study. J Infect Dev Ctries. 2015;9(10):1076–85.  https://doi.org/10.3855/jidc.6162.CrossRefPubMedGoogle Scholar
  13. 13.
    Edlin BR, Tokars JI, Grieco MH, Crawford JT, Williams J, Sordillo EM, et al. An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992;326(23):1514–21.  https://doi.org/10.1056/NEJM199206043262302.CrossRefPubMedGoogle Scholar
  14. 14.
    Mesfin YM, Hailemariam D, Biadgilign S, Kibret KT. Association between HIV/AIDS and multi-drug resistance tuberculosis: a systematic review and meta-analysis. PLoS ONE [Electronic Resource]. 2014;9(1):e82235.  https://doi.org/10.1371/journal.pone.0082235.CrossRefGoogle Scholar
  15. 15.
    Suchindran S, Brouwer ES, Van Rie A. Is HIV infection a risk factor for multi-drug resistant tuberculosis? A Systematic Review. PLoS ONE. 2009;4(5):e5561.  https://doi.org/10.1371/journal.pone.0005561.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    •• Podlekareva DN, Efsen AM, Schultze A, Post FA, Skrahina AM, Panteleev A, et al. Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study. Lancet HIV. 2016;3(3):e120–31.  https://doi.org/10.1016/S2352-3018(15)00252-0. This paper discusses the significant impact of HIV and drug resistance on TB outcomes in three settings. They find an exceptionally high rate of mortality among persons living with HIV, which is further compounded by drug resistance.CrossRefPubMedGoogle Scholar
  17. 17.
    Furin J, Isaakidis P. The tuberculosis emergency in eastern Europe. Lancet HIV. 2016;3(3):e107–8.  https://doi.org/10.1016/S2352-3018(16)00002-3.CrossRefPubMedGoogle Scholar
  18. 18.
    Farmer PE, Nizeye B, Stulac S, Keshavjee S. Structural violence and clinical medicine. PLoS Med. 2016;3(10):e449.  https://doi.org/10.1371/journal.pmed.0030449.CrossRefGoogle Scholar
  19. 19.
    Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368(9547):1575–80.  https://doi.org/10.1016/S0140-6736(06)69573-1.CrossRefPubMedGoogle Scholar
  20. 20.
    Moodley P, Shah NS, Tayob N, Connolly C, Zetola N, Gandhi N, et al. Spread of extensively drug-resistant tuberculosis in KwaZulu-Natal Province, South Africa. PLoS One. 2011;6(5):e17513.  https://doi.org/10.1371/journal.pone.0017513.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Umanah T, Ncayiyana J, Padanilam X, Nyasulu PS. Treatment outcomes in multidrug resistant tuberculosis-human immunodeficiency virus co-infected patients on anti-retroviral therapy at Sizwe Tropical Disease Hospital Johannesburg, South Africa. BMC Infect Dis. 2015;15(1):478.  https://doi.org/10.1186/s12879-015-1214-3.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363(11):1005–15.  https://doi.org/10.1056/NEJMoa0907847.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    World Health Organization. WHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MT. Accessed 29/09/2017. Available at: http://who.int/tb/publications/2017/XpertUltra/en/
  24. 24.
    Tomasicchio M, Theron G, Pietersen E, Streicher E, Stanley-Josephs D, van Helden P, et al. The diagnostic accuracy of the MTBDRplus and MTBDRsl assays for drug-resistant TB detection when performed on sputum and culture isolates. Sci Rep. 2016;6(1):17850.  https://doi.org/10.1038/srep17850.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Walker TM, Kohl TA, Omar SV, Hedge J, del Ojo Elias C, Bradley P, et al. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort. Lancet Infect Dis. 2015;15(10):1193–202.  https://doi.org/10.1016/S1473-3099(15)00062-6.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Leeds IL, Magee MJ, Kurbatova EV, del Rio C, Blumberg HM, Leonard MK, et al. Site of extrapulmonary tuberculosis is associated with HIV infection. Clin Infect Dis. 2012;55(1):75–81.  https://doi.org/10.1093/cid/cis303.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Pontali E, Sotgiu G, Centis R, D'Ambrosio L, Spanevello A, Migliori GB. Management of drug resistant TB in patients with HIV co-infection. Expert Opin Pharmacother. 2015;16(18):2737–50.  https://doi.org/10.1517/14656566.2015.1100169.CrossRefPubMedGoogle Scholar
  28. 28.
    •• Peter JG, Zijenah LS, Chanda D, Clowes P, Lesosky M, Gina P, et al. Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial. Lancet. 2016;387(10024):1187–97.  https://doi.org/10.1016/S0140-6736(15)01092-2. This paper presents data on the urinary LAM antigen as a diagnostic test for TB in persons living with HIV. The findings show that LAM has a mortality benefit.CrossRefPubMedGoogle Scholar
  29. 29.
    Hermans S, Babirye J, Mbabazi, et al. Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert® MTB/RIF era: a cohort study. BMC Infect Dis. 2017;17(1):433.  https://doi.org/10.1186/s12879-017-2534-2.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    UNAIDS. Fact sheet—the latest on the status of the AIDS epidemic. 2016. Accessed 29/09/2017. Availbale at: http://www.unaids.org/en/resources/fact-sheet.
  31. 31.
    Gupta S, Abimbola T, Date A, Suthar AB, Bennett R, Sangrujee N, et al. Cost-effectiveness of the three I’s for HIV/TB and ART to prevent TB among people living with HIV. Int J Tuberc Lung Dis. 2014;18(10):1159–65.  https://doi.org/10.5588/ijtld.13.0571.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Swindells S, Komarow L, Tripathy S, Cain KP, MacGregor RR, Achkar JM, et al. Screening for pulmonary tuberculosis in HIV-infected individuals: AIDS Clinical Trials Group Protocol A5253. Int J Tuberc Lung Dis. 2013 Apr;17(4):532–9.  https://doi.org/10.5588/ijtld.12.0737.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    van’t Hoog AH, Onozaki I, Lonnroth K. Choosing algorithms for TB screening: a modelling study to compare yield, predictive value and diagnostic burden. BMC Infect Dis. 2014;14(1):532.  https://doi.org/10.1186/1471-2334-14-532.CrossRefGoogle Scholar
  34. 34.
    Gómez-Gómez A, Magaña-Aquino M, López-Meza S, Aranda-Álvarez M, Díaz-Ornelas DE, Hernández-Segura MG, et al. Diabetes and other risk factors for multi-drug resistant tuberculosis in a Mexican population with pulmonary tuberculosis: case control study. Arch Med Res. 2015;46(2):142–8.  https://doi.org/10.1016/j.arcmed.2015.01.006.CrossRefPubMedGoogle Scholar
  35. 35.
    Isaakidis P, Rangan S, Pradhan A, Ladomirska J, Reid T, Kielmann K. ‘I cry every day’: experiences of patients co-infected with HIV and multidrug-resistant tuberculosis. Tropical Med Int Health. 2013;18(9):1128–33.  https://doi.org/10.1111/tmi.12146.CrossRefGoogle Scholar
  36. 36.
    Andrews JR, Shah NS, Weissman D, Moll AP, Friedland G, Gandhi NR. Predictors of multidrug- and extensively drug-resistant tuberculosis in a high HIV prevalence community. PLoS One. 2010;5(12):e15735.  https://doi.org/10.1371/journal.pone.0015735.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Umanah TA, Ncayiyana JR, Nyasulu PS. Predictors of cure among HIV co-infected multidrug-resistant TB patients at Sizwe Tropical Disease Hospital Johannesburg, South Africa. Trans R Soc Trop Med Hyg. 2015;109(5):340–8.  https://doi.org/10.1093/trstmh/trv025.CrossRefPubMedGoogle Scholar
  38. 38.
    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. Int J Tuberc Lung Dis. 2015;19(2):163–71.  https://doi.org/10.5588/ijtld.14.0369.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Heysell SK, Ogarkov OB, Zhdanova S, Zorkaltseva E, Shugaeva S, Gratz J, et al. Undertreated HIV and drug-resistant tuberculosis at a referral hospital in Irkutsk, Siberia. Int J Tuberc Lung Dis. 2016;20(2):187–92.  https://doi.org/10.5588/ijtld.14.0961.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Falzon D, Schunemann H, Harausz E, et al. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update. Eur Respir J. 2017;49(3):1602308.  https://doi.org/10.1183/13993003.02308-2016.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis 2016 update. Accessed 18/10/17. Available at: http://apps.who.int/iris/bitstream/10665/250125/1/9789241549639-eng.pdf.
  42. 42.
    World Health Organization (WHO). WHO treatment guidelines for drug resistant tuberculosis: 2016 update. Geneva: World Health Organization; 2016. WHO/HTM/TB/2016.04Google Scholar
  43. 43.
    Reuter A, Tisile P, von Delft D, Cox H, Cox V, Ditiu L, et al. The devil we know: is the use of injectable agents for the treatment of MDR-TB justified? Int J Tuberc Lung Dis. 2017;21(11):1114–26.  https://doi.org/10.5588/ijtld.17.0468.CrossRefPubMedGoogle Scholar
  44. 44.
    Seddon JA, Godfrey-Faussett P, Jacobs K, Ebrahim A, Hesseling AC, Schaaf HS. Hearing loss in patients on treatment for drug-resistant tuberculosis. Eur Respir J. 2012;40(5):1277–86.  https://doi.org/10.1183/09031936.00044812.CrossRefPubMedGoogle Scholar
  45. 45.
    Modongo C, Sobota RS, Kesenogile B, Ncube R, Sirugo G, Williams SM, et al. Successful MDR-TB treatment regimens including amikacin are associated with high rates of hearing loss. BMC Infect Dis. 2014;14(1):542.  https://doi.org/10.1186/1471-2334-14-542.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Tang S, Yao L, Hao X, Zhang X, Liu G, Liu X, et al. Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China. Eur Respir J. 2015;45(1):161–70.  https://doi.org/10.1183/09031936.00035114.CrossRefPubMedGoogle Scholar
  47. 47.
    Ndjeka, N. Incorporation of bedaquiline in the South African National TB Program. Poster presentation at the 2016 Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA. February 22–25, 2016, Abstract number 754.Google Scholar
  48. 48.
    Guglielmetti L, Hewison C, Avaliani Z, Hughes J, Kiria N, Lomtadze N, et al. Examples of bedaquiline introduction for the management of multidrug-resistant tuberculosis in five countries. Int J Tuberc Lung Dis. 2017;21(2):167–74.  https://doi.org/10.5588/ijtld.16.0493.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    World Health Organization. The use of delamanid in the treatment of multidrug-resistant tuberculosis: interim policy guidance. Geneva: World Health Organization; 2014.Google Scholar
  50. 50.
    World Health Organization. A 2016 review of available evidence on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis. Geneva, Switzerland, 2017. WHO/HTM/TB/2017.01. Available at http://www.who.int/tb/publications/2017/GDGreport_Bedaquiline/en/. Accessed April 20, 2017.
  51. 51.
    Furin, J, Brigden, G, Lessem, E, Rich M, Vaughan L, Lynch S. Global progress and challenges in the implementation of new medications for the treatment of multidrug-resistant tuberculosis. Emerg Infect Dis. 2016;22(3):e151430.  https://doi.org/10.3201/eid2203.151430
  52. 52.
    World Health Organization. A 2016 review of available evidence on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis. Available at http://www.who.int/tb/publications/2017/Appendix_GDGReport_Bedaquiline.pdf. Accessed July 7, 2017.
  53. 53.
    • Diacon A, Pym A, Grobusch M, et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014;371(8):723–32.  https://doi.org/10.1056/NEJMoa1313865. This paper presents the phase IIB data from bedaquiline, the first novel TB treatment to be developed in almost 50 years.CrossRefPubMedGoogle Scholar
  54. 54.
    Gler MT, Skripconoka V, Sanchez-Garavito E, Xiao H, Cabrera-Rivero JL, Vargas-Vasquez DE, et al. Delamanid for multidrug resistant pulmonary tuberculosis. New Engl J Med. 2012;366(23):2151–60.  https://doi.org/10.1056/NEJMoa1112433.CrossRefPubMedGoogle Scholar
  55. 55.
    • Ndjeka N, Conradie F, Schnippel K, Hughes J, Bantubani N, Ferreira H, 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):979–85.  https://doi.org/10.5588/ijtld.14.0944. This paper presents the largest global experience using bedaquiline in persons living with HIV.CrossRefPubMedGoogle Scholar
  56. 56.
    Zumla A, Chakaya J, Centis R, D'Ambrosio L, Mwaba P, Bates M, et al. Tuberculosis treatment and management—an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med. 2015;3(3):220–34.  https://doi.org/10.1016/S2213-2600(15)00063-6.CrossRefPubMedGoogle Scholar
  57. 57.
    RESIST-TB. DR-TB clinical trials progress report. http://www.resisttb.org/?page_id=1602.
  58. 58.
    Daniels JF, Khogali M, Mohr E, Cox V, Moyo S, Edginton M, et al. Time to ART initiation among patients treated for rifampicin-resistant tuberculosis in Khayelitsha. PLoS One. 2015;10(11):e0142873.  https://doi.org/10.1371/journal.pone.0142873.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Palacios E, Franke M, Munoz M, Hurtado R, Dallman R, Chalco K, et al. HIV-positive patients treated for multidrug-resistant tuberculosis: clinical outcomes in the HAART era. Int J Tuberc Lung Dis. 2012;16(3):348–54.  https://doi.org/10.5588/ijtld.11.0473.CrossRefPubMedGoogle Scholar
  60. 60.
    Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365(16):1482–91.  https://doi.org/10.1056/NEJMoa1013607.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray AL, et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med. 2011;365(16):1492–501.  https://doi.org/10.1056/NEJMoa1014181.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Blanc FX, Sok T, Laureillard D, Borand L, Rekacewicz C, Nerrienet E, et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med. 2011;365(16):1471–81.  https://doi.org/10.1056/NEJMoa1013911.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Lawn SD, Török ME, Wood R. Optimum time to start antiretroviral therapy during HIV-associated opportunistic infections. Curr Opin Infect Dis. 2011;24(1):34–42.  https://doi.org/10.1097/QCO.0b013e3283420f76.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Freidland G. Tuberculosis immune reconstitution inflammatory syndrome: drug resistance and the critical need for better diagnostics. Clin Infect Dis. 2009;48(5):677–9.  https://doi.org/10.1086/596765.CrossRefGoogle Scholar
  65. 65.
    Lanzafame M, Vento S. Tuberculosis immune reconstitution inflammatory syndrome. J Clinical Tuberc Other Mycobact Dis. 2016;3:6–9.  https://doi.org/10.1016/j.jctube.2016.03.002.CrossRefGoogle Scholar
  66. 66.
    Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007;4(1):9.  https://doi.org/10.1186/1742-6405-4-9.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Van Heeswijk RP, Dannemann B, Hoetelmans RM. Bedaquiline: a review of human pharmacokinetics and drug–drug interactions. J Antimicrob Chemother. 2014;69(9):2310–8.  https://doi.org/10.1093/jac/dku171.CrossRefPubMedGoogle Scholar
  68. 68.
    Pandie M, Wiesner L, McIlleron H, Hughes J, Siwendu S, Conradie F, et al. Drug–drug interactions between bedaquiline and the antiretrovirals lopinavir/ritonavir and nevirapine in HIV-infected patients with drug-resistant TB. J Antimicrob Chemother. 2016;71(4):1037–40. Svensson AAC 2013.  https://doi.org/10.1093/jac/dkv447.CrossRefPubMedGoogle Scholar
  69. 69.
    Sasahara K, Shimokawa Y, Hirao Y, Koyama N, Kitano K, Shibata M, et al. Pharmacokinetics and metabolism of delamanid, a novel anti-tuberculosis drug, in animals and humans: importance of albumin metabolism in vivo. Drug Metab Dispos. 2015;43(8):1267–76.  https://doi.org/10.1124/dmd.115.064527.CrossRefPubMedGoogle Scholar
  70. 70.
    Mallikaarjun S, Wells C, Petersen C, Paccaly A, Shoaf SE, Patil S, et al. Delamanid coadministered with antiretroviral drugs or antituberculosis drugs shows no clinically relevant drug-drug interactions in healthy subjects. Antimicrob Agents Chemother. 2016;60(10):5976–85.  https://doi.org/10.1128/AAC.00509-16.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Cox H, Ford N. Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2012;16(4):447–54.  https://doi.org/10.5588/ijtld.11.0451.CrossRefPubMedGoogle Scholar
  72. 72.
    Shah NS, Auld SC, Brust JC, Mathema B, Ismail N, Moodley P, et al. Transmission of extensively drug-resistant tuberculosis in South Africa. N Engl J Med. 2017;376(3):243–53.  https://doi.org/10.1056/NEJMoa1604544.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Trieu L, Proops DC, Ahuja SD. Moxifloxacin prophylaxis against MDR TB, New York, New York, USA. Emerg Infect Dis. 2015;21(3):500–3.  https://doi.org/10.3201/eid2103.141313.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Marks SM, Mase SR, Bamrah Morris S. Systematic review, meta-analysis, and cost effectiveness of treatment of latent tuberculosis infection to reduce progression to multidrug-resistant tuberculosis. Clin Infect Dis. 2017;64(12):1670–7.  https://doi.org/10.1093/cid/cix208.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Seddon JA, Schaaf HS. Drug-resistant tuberculosis and advances in the treatment of childhood tuberculosis. Pneumonia. 2016;8(1):20.  https://doi.org/10.1186/s41479-016-0019-5.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    O'Donnell MR, Wolf A, Werner L, Horsburgh CR, Padayatchi N. Adherence in the treatment of patients with extensively drug-resistant tuberculosis and HIV in South Africa: a prospective cohort study. Journal of Acquired Immune Deficiency Syndromes. JAIDS. 2014 Sep 01;67(1):22–9.  https://doi.org/10.1097/QAI.0000000000000221.PubMedPubMedCentralGoogle Scholar
  77. 77.
    • Daftary A, Padayatchi N, O'Donnell M. Preferential adherence to antiretroviral therapy over tuberculosis treatment: a qualitative study of drug-resistant TB/HIV co-infected patients in South Africa. Glob Public Health. 2014;9(9):1107–16.  https://doi.org/10.1080/17441692.2014.934266. A groundbreaking paper looking at persons with HIV and RR-TB and the factors associated with adherence. The study showed that patients were significantly more likely to be adherent to HIV treatment and that, paradoxically, the use of DOT may have worsened adherenceCrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Acha J, Sweetland A, Guerra D, Chalco K, Castillo H, Palacios E. Psychosocial support groups for patients with multidrug-resistant tuberculosis: five years of experience. Glob Public Health. 2007;2(4):404–17.  https://doi.org/10.1080/17441690701191610.CrossRefPubMedGoogle Scholar
  79. 79.
    Benbaba S, Isaakidis P, Das M, Jadhav S, Reid T, Furin J. Direct observation (DO) for drug-resistant tuberculosis: DO we really DO? PLoS One. 2015;10(12):e0144936.  https://doi.org/10.1371/journal.pone.0144936.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Thomas BE, Shanmugam P, Malaisamy M, Ovung S, Suresh C, Subbaraman R, et al. Psycho-socio-economic issues challenging multidrug resistant tuberculosis patients: a systematic review. PLoS One. 2016;11(1):e0147397.  https://doi.org/10.1371/journal.pone.0147397.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Das M, Isaakidis P, Van den Bergh R, Kumar AM, Nagaraja SB, Valikayath A, et al. HIV, multidrug-resistant TB and depressive symptoms: when three conditions collide. Glob Health Action. 2014;7(1):24912.  https://doi.org/10.3402/gha.v7.24912.CrossRefPubMedGoogle Scholar
  82. 82.
    Shringarpure KS, Isaakidis P, Sagili KD, Baxi RK, Das M, Daftary A. “When treatment is more challenging than the disease”: a qualitative study of MDR-TB patient retention. PLoS One. 2016;11(3):e0150849.  https://doi.org/10.1371/journal.pone.0150849.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Lessem E, Cox H, Daniels C, Furin J, McKenna L, Mitnick CD, et al. Access to new medications for the treatment of drug-resistant tuberculosis: patient, provider and community perspectives. Int J Infect Dis. 2015;32:56–60.  https://doi.org/10.1016/j.ijid.2014.12.012.CrossRefPubMedGoogle Scholar
  84. 84.
    Cremers AL, de Laat MM, Kapata N, Gerrets R, Klipstein-Grobusch K, Grobusch MP. Assessing the consequences of stigma for tuberculosis patients in urban Zambia. PLoS One. 2015;10(3):e0119861.  https://doi.org/10.1371/journal.pone.0119861.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Daftary A. HIV and tuberculosis: the construction and management of double stigma. Soc Sci Med. 2012;74(10):1512–9.  https://doi.org/10.1016/j.socscimed.2012.01.027.CrossRefPubMedGoogle Scholar
  86. 86.
    Mohr E, Cox V, Wilkinson L, Moyo S, Hughes J, Daniels J, et al. 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.  https://doi.org/10.1093/trstmh/trv037.CrossRefPubMedGoogle Scholar
  87. 87.
    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;19(8):969–78.  https://doi.org/10.5588/ijtld.15.0123.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Medicins Sans FrontieresKhayeltishaSouth Africa
  2. 2.Department of Global Health and Social MedicineHarvard Medical SchoolBostonUSA

Personalised recommendations