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Tuberculosis – Treatment Overview

Treatment Overview

For treatment of latent TB infection in PLWHIV, see the Risk Factors and Prevention Section

The World Health Organization (WHO) states that the first priority for HIV-positive TB patients is to initiate TB treatment, followed by co-trimoxazole and antiretroviral therapy (ART).1

  • The WHO clinical protocol for the management of TB and HIV co-infection in the European region states that:
    • TB treatment in HIV-infected patients is a priority and should be started as soon as active TB has been diagnosed
    • treating TB promptly will reduce TB-related mortality and the risk of transmission2
  • The US Department of Health and Human Services also recommend that all HIV-infected patients with diagnosed active TB should be:
    • started on TB treatment immediately
    • treated with ART
  • In PLWHIV who require an ART regimen containing a boosted protease inhibitor, substitution of rifampicin with rifabutin is recommended to avoid drug-drug interactions1,3,4

For a discussion of directly observed therapy for treating TB, see Volmink J, Garner P. (2007) Directly observed therapy for treating tuberculosis (Review).6 Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003343.

 

Download TB Treatment Guidelines:

Co-Trimoxazole Preventive Therapy (CPT)

CPT substantially reduces mortality in HIV-positive TB patients.1,7,8

  • CPT should be initiated as soon as possible, and given throughout TB treatment in all HIV-positive TB patients.1

– continuation of CPT after TB treatment is completed should be considered in accordance with national guidelines.1

ART (antiretroviral therapy)

ART improves survival in PLWHIV, reduces TB rates at the individual and population level, and reduces TB recurrence rates.1

  • The WHO recommends that ART should be initiated for all PLWHIV with active TB irrespective of CD4 cell count1,9
  • The recommended first-line ARV regimens for TB patients currently include efavirenz to minimise interactions with anti-TB therapy1,10

– visit the drug-drug interactions section for more information

  • The optimal time to initiate ART with respect to the start of TB therapy is not clear.11–13

– starting ART early during the course of TB therapy increases pill burden and the risk of poor adherence, and is accompanied by an increased risk of TB associated immune reconstitution inflammatory syndrome (IRIS)11–13
– however, delaying ART therapy increases morbidity and mortality associated with AIDS11–13

  • In 2009, the WHO recommended that TB therapy should be initiated first, followed by ART as soon as possible, and within the first 8 weeks of starting TB treatment1,9
  • In 2011, the European AIDS Clinical Society (EACS) provided the following recommendations for initiating ART in TB/HIV coinfection:10

– rifabutin may be unavailable or expensive in some countries with high rates of HIV-related tuberculosis5

  • See the drug-drug interactions section for more information on interactions between TB therapies and ART
  • Extension of the continuation phase to 7 months may be necessary for patients with:4

– drug-sensitive TB whose initiation phase did not include pyrazinamide
– cavitating pulmonary disease who remain sputum culture positive after 2 months of treatment
– CNS involvement, such as meningitis or tuberculoma (continuation phase should be extended to 7–10 months)

– the analyses demonstrated that TB risk was reduced by half among PLWHIV when ART was initiated at CD4 counts > 350 cells/mm3
– the Policy Updating Group agreed on the role of earlier access to and initiation of ART (eg CD4 counts >350 cells/mm3) for the prevention of TB and other clinical conditions for PLWHIV

  • the next revision of WHO guidelines on ART will address this issue specifically in light of its implication on TB risk reduction

– WHO recommends that ART is initiated in all PLWHIV with CD4 counts ≤350 cells/mm314

For more information, download WHO Treatment of Tuberculosis Guidelines1, Rapid advice Antiretroviral therapy for HIV infection in adults and adolescents9, and EACS Guidelines.10 

  • Three separate clinical trials investigating the timing of ART and TB therapy published in October 2011 demonstrated that:

– early initiation of ART (within 212,13, or 411 weeks of initiation of TB therapy) in patients with CD4+ counts <50/mm3 was associated with increased AIDS-free survival and a lower rate of new AIDS-defining illness and death11–13

– in two of the three studies, deferral of ART initiation for between 8–12 weeks after the initiation of TB therapy for patients with CD4+ counts >50/mm3 reduced the risk of IRIS and other adverse events related to ART without increasing the risk of AIDS or death11,13

– in the third study, initiation of ART within 2 weeks of starting TB therapy was associated with significantly improved survival for patients with CD4+ counts <200/mm3 12

  • Updated information and guidance on this rapidly evolving field will be provided by the WHO (access WHO HIV Guidelines).
  • For more information on IRIS and adverse events associated with concomitant TB and HIV therapy, see the Possible Complications section.

Drug-Resistant TB

  • The WHO recommends that drug susceptibility testing (DST) be carried out prior to starting TB therapy in all HIV-positive TB patients1

– rapid DST is strongly encouraged in sputum smear-positive PLWHIV

  • The Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America recommend:15

– testing for susceptibility to first-line agents (isoniazid, rifampin, ethambutol, and pyrazinamide) should be performed for all PLWHIV with TB disease, regardless of the source of the specimen15
– second-line DST should be performed only in reference laboratories and should be limited to specimens from patients who

• have had previous therapy
• are contacts of patients with drug-resistant TB disease
• have demonstrated resistance to rifampin or to other first-line drugs
• have positive cultures after 3 months of treatment
• are from regions with a high prevalence of MDR or XDR TB15

  • DST for isoniazid, rifampicin, fluoroquinolones and injectable agents is reasonably reliable. For other agents it is less reliable, and basing individualized treatments on DST for such agents should be avoided

– the clinical effectiveness or ineffectiveness of a drug cannot be predicted by DST with 100% certainty1

  • Treatment regimens should consist of at least four drugs with either certain, or almost certain, effectiveness.

– where evidence about the effectiveness of a drug is unclear, the drug can be part of the regimen but it should not be depended upon for success
– often, more than four drugs may be started if the susceptibility pattern is unknown or the effectiveness of one or more agents is questionable1

Extrapulmonary TB

  • Additional information on, and considerations for treating extrapulmonary TB can be found in these reviews:

– Sharma SK, Mohan A. (2004) Extrapulmonary tuberculosis.18 
– Fuentes ZM, Caminero JA. (2006) Controversies in the treatment of extrapulmonary tuberculosis.19

References

  1. World Health Organization. Treatment of Tuberculosis Guidelines Fourth Edition (2010). Accessed 30 November 2011.
  2. World Health Organization. Management of TB and HIV coinfection: clinical protocol for the WHO European region. Update to page 140, Table 1: World Health Organization Management of TB and HIV coinfection: clinical protocol for the WHO European region update 18 July 2008.  Accessed 17 February 2012.
  3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents. Department of Health and Human Services. October 14 2011;1–167.] Accessed 17 February 2012.
  4. British HIV Association. Guidelines for the Treatment of TB/HIV Coinfection 2011. Accessed 25 November 2011.
  5. Department of Health and Human Services Centers for Disease Control and Prevention. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis. Accessed 26 November 2011.
  6. Volmink J, Garner P. Directly observed therapy for treating tuberculosis (Review). Cochrane Database Syst Rev 2007;(4):CD003343.
  7. Harries AD, Zachariah R, Lawn SD. Providing HIV care for co-infected tuberculosis patients: a perspective from sub-Saharan Africa. Int J Tuberc Lung Dis 2009;13:6–16. 
  8. World Health Organization. Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults in resource-limited settings: recommendations for a public health approach (2006). Accessed 1 December 2011.
  9. World Health Organization. Rapid advice antiretroviral therapy for HIV infection in adults and adolescents (November 2009). Accessed 1 December 2011.
  10. European AIDS Clinical Society. Guidelines Version 6.0. Accessed 17 April 2012.
  11. Abdool Karim SS, Naidoo K, Grobler A, et al. Integration of Antiretroviral Therapy with Tuberculosis Treatment. N Engl J Med 2011;365:1492–1501.
  12. Blanc FX, Thim S, Laureillard D, et al. Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis. N Engl J Med 2011;365:1741–1781. 
  13. Havlir DV, Kendall MA, Ive P, et al. Timing of Antiretroviral Therapy for HIV-1 Infection and Tuberculosis. N Engl J Med 2011;365:1482–1491.
  14. World Health Organization. Policy on collaborative TB/HIV activities (2012). Accessed 13 April 2012.
  15. Centers for Disease Control and Prevention. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR 2009;58(No. RR-4):1–217. Accessed 17 February 2012.
  16. World Health Organization. Guidelines for the Programmatic Management of Drug-resistant Tuberculosis 2011 Update.  Accessed 1 December 2011.
  17. Johnston JC, Shahidi NC, Sadatsafavi M, et al. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS One 2009;4:e6914.
  18. Sharma SK, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res 2004;120:316–353.
  19. Fuentes ZM, Caminero JA. Controversies in the treatment of extrapulmonary tuberculosis. Arch Bronconeumol. 2006;42:194–201.
  20. Cherian A, Thomas SV. Central nervous system tuberculosis. Afr Health Sci. 2011;11:116–127.