1. Tuberculosis Treatment
Treatment Action Group
TB/HIV Advocacy Toolkit
November 2017
With thanks to Adam Almeida and Andolyn Medina

2. Topics to be covered Treatment Fundamentals How TB is Treated
Treatment in Special Groups
Treatment Research
Advocacy Priorities
Main Points

3. treatment fundamentals

4. Principles of TB treatment
The goal of treatment is to cure TB, restore health, and prevent transmission
The aim of treatment is to provide the safest and most effective therapy in the shortest period of time
Three basic principles of TB treatment:
Regimens must contain multiple drugs to which the organisms are susceptible to prevent against the development of resistance
Drug exposure (how much drug is in the body) must stay at a high enough level over time to kill bacteria – this means drugs must be taken regularly
Drug therapy must continue long enough to kill all remaining TB organisms
FUNDAMENTALS

5. Treatment Monitoring How do you know it’s working?
Bacteriologic tests: to detect live TB bacteria
Smear microscopy
Solid and liquid culture
Clinical monitoring of improvement TB symptoms (e.g., weight gain)
Radiography: the use of chest X-rays
The following should not be used to monitor treatment:
Nucleic Acid Amplification (line probe assays, Xpert MTB/RIF Ultra): dead TB bacilli can cause a false positive from these diagnostics
More information on WHO guidelines for monitoring TB treatment can be found at
FUNDAMENTALS

6. *approved for treating latent TB infection
drug discovery & development and its impact on treatment
1944
streptomycin
1920
BCG vaccine
1955
cycloserine
2000
rifapentine
1934
Gold therapy
abandoned
1951
isoniazid
1962
ethambutol
2014
rifapentine*
delamanid
1920s
1930s
1940s
1950s
1960s
1970s
1980s
1990s
2000s
2010s
1940
actinomycin
streptothricin
1957
rifampicin
1952
pyrazinamide
2012
bedaquiline
2015
WHO recommends
short course regimen
for drug-resistant TB
1924
Gold therapy
introduced
1948
PAS
thiacetazone
Duration of Treatment
24 months
6 months
FUNDAMENTALS
*approved for treating latent TB infection

7. How TB is treated

8. Knowing which drugs to use
Drug susceptibility testing (see Diagnostics module) is essential to inform treatment regimen selection to ensure the best outcome
Everyone should have Xpert MTB/RIF Ultra as a first test, and at a minimum know whether they have rifampicin-resistance or rifampicin-sensitive TB
But further testing is needed because:
People with MDR-TB need at least a 9 month regimen
People with pre-XDR-TB or XDR-TB need an individualized regimen with at least one of the newer drugs (delamanid or bedaquiline)
People with isoniazid-resistant TB (that is sensitive to rifampicin) have worse treatment outcomes if they are just given standard, drug-susceptible therapy
Source:
TREATMENT

9. drug-susceptible TB Treatment (aka first-line)
There are two phases of treatment of drug-susceptible TB:
Initial/intensive phase: to kill actively growing germs
Continuation phase: to eliminate any remaining germs and reduce failure / relapse
The WHO recommends the following regimen for those with drug-sensitive, active TB:
Two months of daily treatment with four first-line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol), followed by four months of daily isoniazid and rifampicin
This also applies to most extrapulmonary TB, with longer therapy for TB of the central nervous system, bone or joints
Adjuvant corticosteroid treatment is recommended for TB meningitis and pericarditis, in cases when there is not thought to be drug resistance
Source: WHO Treatment of Tuberculosis Guidelines, 4th Edition
TREATMENT

10. ISONIAZID-RESISTANT TB
Isoniazid is a first-line drug for TB treatment and is included in standard short-course regimen for drug-sensitive TB
Isoniazid is a powerful drug
If there is resistance to isoniazid, a different drug regimen is needed to make up for losing isoniazid:
Levofloxacin replaces isoniazid
For the first two months: levofloxacin, rifampicin, pyrazinamide, and ethambutol are given; for the next four months: only levofloxacin and rifampicin are given
TREATMENT

11. SHORTENED REGIMEN FOR DRUG RESISTANT TB
In 2016, the WHO approved a shortened drug regimen for treating TB in individuals with rifampicin-resistant TB
The shortened drug regimen is 9-12 months long (as opposed to months)
The shortened treatment is specifically for people whose TB is resistant to rifampicin and has not been treated with or show resistance to a second-line injectable or a fluoroquinolone
Source:
TREATMENT

12. Source: http://www.treatmentactiongroup.org/tb/drug-guide-2016
MDR- AND XDR-TB
Other forms of multidrug-resistant (MDR) and extensively- drug resistant TB (XDR-TB) require an month drug treatment regimen
It should include at least 5 effective drugs; if possible, pyrazinamide, one fluoroquinolone, one second-line injectable drug, and two core second-line agents including one of the newer drugs (bedaquiline or delamanid)
In cases of XDR-TB, there may not be 5 effective drugs to treat
Other add-on agents are included to reach 5 effective drugs (including p-aminosalicylic acid, imipenem-cilastatin)
TREATMENT
Source:

13. Treatment in special groups

14. TB/HIV co-infection (1 of 2)
Rifampicin, a key TB drug, reduces the amount of some antiretrovirals in the body
This requires dosing adjustments, change in HIV drugs, and/or using rifabutin instead of rifampicin
Bedaquiline interacts with some antiretrovirals
Bedaquiline should not be used with efavirenz (efavirenz reduces the amount of bedaquiline in the body) or with lopinavir/ritonavir (because both can cause side effects on the heart)
Pill burden: taking multiple drugs for TB and HIV could become overwhelming
For more information on treating TB/HIV coinfection see WHO’s 2009 Treatment of Tuberculosis: guidelines for national programme which can be found at and WHO’s 2010 ART Guidelines at
SPECIAL GROUPS

15. TB/HIV co-infection (2 of 2)
In people diagnosed with TB and HIV at the same time, timing of antiretroviral therapy (ART) is important:
A serious reaction called immune reconstitution inflammatory syndrome (IRIS) can occur in people simultaneously starting TB treatment and ART
IRIS is avoided by starting TB therapy before ART and timing is dependent on the CD4 count
For people with CD4 lymphocyte <50 cells/mm3, start ART after 2 weeks
For people with CD4 lymphocyte cells/mm3, start ART after 8-12 weeks to prevent death and AIDS-related conditions
For people with TB meningitis, start ART after at least 8-12 weeks to prevent IRIS in the central nervous system
For more information on treating TB/HIV coinfection see WHO’s 2009 Treatment of Tuberculosis: guidelines for national programme which can be found at and WHO’s 2010 ART Guidelines at
SPECIAL GROUPS

16. Adolescent and childhood TB
Adolescents have very similar TB and metabolism to adults
Adolescents should be treated for TB as adults are
Children are at increased risk for disease progression, but also tend to have fewer bacteria and may not need as long treatment
New pediatric-friendly, appropriately dosed formulations of standard TB treatment are available
Lack of pediatric formulations of most second-line drugs
delamanid is WHO-recommended for children age 6 and up
Difficulty diagnosing, monitoring, and assessing treatment
Lack of inclusion in research of either adolescents or children, despite consensus of how to include them
For more information on treating Childhood TB see WHO’s 2010 Rapid Advice: treatment of tuberculosis in children at
Source:
SPECIAL GROUPS

17. TB treatment and opioid substitution therapy (OST)
Some people who have used heroin or other opiates take OST to help them stop
Methadone and buprenorphine are the most commonly used forms of OST
Rifampicin reduces methadone and buprenorphine levels in the body
People with TB on OST may need rifabutin (similar to rifampicin, but does not interact with methadone in this way) or a higher dose of OST
Bedaquiline likely also reduces the amount of methadone and buprenorphine in the body
*for more information on opiod substitution therapy go to
*for more information on TB drug interactions go to
for more information on opiod substitution therapy go to
SPECIAL GROUPS

18. treatment research

19. drug development process
Preclinical (conducted in laboratories)
In vitro (in test tubes)
Animal models
Clinical trials (conducted in humans)
Phase I evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics of a drug; usually in healthy participants for a very short amount of time
Phase IIa evaluates early bactericidal activity and dosing in participants with TB (usually two weeks)
Phase IIb evaluates anti-TB activity and early safety in slightly larger group of participants with TB (usually for 2-6 months)
Phase IIc is small like a Phase IIb but follows patients for longer like phase III to give more info about final outcome
Phase III evaluates the efficacy of the drug in a larger group of participants at multiple locations and follows patients through to final outcome (relapse-free cure, treatment failure, or death)
Phase IV collects information on the postmarketing use of the drug
RESEARCH

20. New drugs in clinical trials
RESEARCH

21. Source: http://www.treatmentactiongroup.org/tbrd2017
TB treatment RESEARCH FUNDING, 2016
For more information on TB R&D funding trends check out TAG’s TB R&D Resource Tracking Report at
RESEARCH
Source: 21

22. Source: http://www.treatmentactiongroup.org/tbrd2016
TB RESEARCH FUNDING, 2015
RESEARCH
Source:

23. Advocacy PRIORITIES

24. THE PUSH FOR BETTER DRUGS
Drugs used in TB treatment are far from perfect. The following are a few of the reasons why activists are advocating for better drugs:
Adherence issues
Duration of treatment
Potentially toxic side effects
Hard to tolerate (e.g., painful injections)
Drug availability and quality
Drug interactions
Poor cure rates for MDR-TB and XDR-TB
No appropriate child-friendly formulations for most second-line drugs
Very little information on treating MDR-TB in pregnant/lactating women
Note to facilitator: This list is by no means exhaustive and facilitators are encouraged to ask group to explore more gaps and challenges of TB treatment
ADVOCACY

25. Advocacy Priorities
Representation of people living HIV, children and pregnant women in operational and clinical studies
Clear information about optimal use of new drugs, which must be given in combination
Increased funding of basic science, later stage clinical trials, and operational research
A standardized regulatory pathway across countries and regions to accelerate the approval of promising treatments
Drugs, once developed, need to be priced affordably and registered widely
Countries must budget for both research and buying newer drugs
Expanded access and compassionate use to promising treatments preapproval to those in desperate need while ensuring appropriate use of the drugs
Uptake of the new treatment options available: delamanid (including for children), bedaquiline, and shortened regimen
Note to facilitator: This list of advocacy issues is based on the content of this presentation and is not meant to be an exhaustive list of TB treatment advocacy issues. This list should be considered and modified as appropriate to the audience and the facilitator.
ADVOCACY

26. Main points

27. TB treatment takeaways
TB is curable
Treatment must be guided by drug susceptibility testing
New treatment options (shortened regimen, bedaquiline, delamanid, linezolid, clofazimine) must be available
Much more research is needed
MAIN POINTS

28. ADDITIONAL RESOURCES
The Treatment Action Group has created ‘An Activist’s Guide to Tuberculosis Drugs’, which expands upon what has been outlined in these slide decks To access: guide-2016
MAIN POINTS