IPT and ICF Guidelines Update

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IPT and ICF Guidelines Update
Reuben GranichHIV/AIDS DepartmentWorld Health
Organization
Haileyesus GetahunSTOP TB DepartmentWorld
Health Organization
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TB related questions

• Background
• Guidelines Review Committee (GRC)
• Timeline
• GRC process
• Committee
• PICOT Questions
• Criteria
• Other considerations

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CD4 level is associated with TB incidence

• Havlir, Getahun et al. 2008 JAMA 300(4)423-430

"TB death zone"
Courtesy Abhishek Sharma_adapted from Havlir et al
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WHO 2004 policy on collaborative TB/HIV activities

• A. Establish NTP-NACP collaborative mechanisms
• Set up coordinating bodies for effective TB/HIV
  activities
• at all levels
• Conduct surveillance of HIV prevalence among TB
  cases
• Carry out joint TB/HIV planning
• Monitor and evaluate collaborative TB/HIV
  activities
• B. Decrease burden of TB among PLHIV (the "Three
  I's")
• Establish intensified TB case finding
• Introduce INH preventive therapy
• Ensure TB infection control in health care and
  congregate
• settings
• C. Decrease burden of HIV among TB patients
• Provide HIV testing and counselling
• Introduce HIV prevention methods
• Introduce co-trimoxazole preventive therapy
• Ensure HIV/AIDS care and support
• Introduce ARVs

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WHO/UNAIDS 1998 IPT Policy
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WHO TB/HIV Clinical Manual
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WHO Guidelines for National TB Programmes on the
management of children
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WHO HIV/AIDS Department Priority Interventions
(IAS Mexico 2008)
IPT is recommended for PLHIV
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Implementation progress
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Call for rigor and transparency

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Guidelines Review Committee rationale

• For principle and/or controversial
  recommendations
• Synthesis of ALL available evidence
• Evidence summaries for group meetings using
  standard template
• Formal assessment of quality of evidence
• Consideration of resource use and costs
• Link evidence to recommendations, explaining
  reasons for judgements

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IPT/ICF guideline revision process HIV/AIDS and
STOP TB Departments (Getahun and Granich)
1. Scoping the document reasons for choosing the
topic, problems with existing guidelines,
variations and gaps,
2. Group composition
3. Conflict of interest
4. Formulations of the questions and choice of
the relevant outcomes
5. Evidence retrieval, evaluation and synthesis
(balance sheet, evidence table)
6. Benefit/risk profile integrating evidence
with values and preferences, equity and costs
Benefit/risk profile affected community
7. Formulation of the recommendations
8. Committee review/finalization (January 25th
2010)
Reporting standard and process
9. Submission to GRC for approval
10. Dissemination
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IPT/ICF guideline revision process

• Ideal recommendations
• Screening algorithm for IPT and further TB
  evaluation
• Recommendations regarding diagnostic methods for
  ruling out TB
• Preferred regimen for adults and children
• Answer questions regarding duration, toxicity,
  cost, and resistance
• Populations being considered
• HIV adults, adolescents and children
• HIV pregnant women
• Relevant outcomes
• Mortality
• Disease progression (morbidity)
• Severe or regimen limiting adverse events
• Adherence and retention on IPT
• Durability of IPT regimen effect
• Cost effectiveness

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Expected functions of the guideline group

• Review scope and questions for guideline
• Identify outcomes critical for decision making
• Provide end user input
• Assist in evidence retrieval, evaluation and
  synthesis (balance sheet, evidence table)
• Formulate recommendations
• Review drafts of guideline document
• Review and approve final recommendations

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PICOT framework
P opulation of interest I ntervention to be
assessed C omparison with current standard of
care Outcomes for patients and community T
imeline in which each outcome needs to be assessed

1. What is the best combination of signs, symptoms
   and diagnostic procedures (e.g., smear
   microscopy, radiography, serum-based tests such
   as IGRA, etc.) as a screening tool to determine
   eligibility for LTBI treatment and to diagnose TB
   among PLHIV?
2. What is the optimal duration and drug regimen
   (e.g., INH, RIF, etc.) for treatment of LTBI to
   reduce the risk of developing Tuberculosis among
   PLHIV?
3. What is the optimal time to start considering
   IPT? (i.e., should immune status be considered
   and should IPT be started with ART)?
4. Does treatment for LTBI among PLHIV lead to
   significant development of mono-resistance
   against the drugs used for LTBI treatment?
5. Should PLHIV who had received TB treatment in the
   past be provided secondary treatment of LTBI to
   prevent re-infection or recurrence of
   Tuberculosis?
6. Will low adherence rates to LTBI treatment be a
   barrier to implementation of LTBI treatment among
   PLHIV?
7. Is provision of treatment for LTBI
   cost-effective?

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Judgments about the strength of a recommendation
criteria to consider for WHO
Factors Comments
Quality of the evidence Higher the quality of the evidence the more likely a strong recommendation can be made
Balance between desirable and undesirable effects Larger the gap or gradient between these then more likely a strong recommendation will be made
Values and preferences If there is a great deal of variability or strong reasons that the recommended course of action is unlikely to be accepted then it is more likely a weak recommendation will be made.
Costs/financial implications (resource use) Higher the cost both financial and in terms of infrastructure, equipment or requirements, and more resource intensive requirements, then less likely to make a strong recommendation
Feasibility Is the intervention possible and practical in the settings where greatest impact is likely to be attained or is being sought
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GRADE profile
Population group PLWHA children Population group PLWHA children Population group PLWHA children Population group PLWHA children Population group PLWHA children Population group PLWHA children Population group PLWHA children Population group PLWHA children
Intervention IPT (Any regimen) Intervention IPT (Any regimen) Intervention IPT (Any regimen) Intervention IPT (Any regimen) Intervention IPT (Any regimen) Intervention IPT (Any regimen) Intervention IPT (Any regimen) Intervention IPT (Any regimen)
Comparison IPT vs Placebo Comparison IPT vs Placebo Comparison IPT vs Placebo Comparison IPT vs Placebo Comparison IPT vs Placebo Comparison IPT vs Placebo Comparison IPT vs Placebo Comparison IPT vs Placebo
Outcome Incidence of active TB Outcome Incidence of active TB Outcome Incidence of active TB Outcome Incidence of active TB Outcome Incidence of active TB Outcome Incidence of active TB Outcome Incidence of active TB Outcome Incidence of active TB
Timeframe Lifetime Timeframe Lifetime Timeframe Lifetime Timeframe Lifetime Timeframe Lifetime Timeframe Lifetime Timeframe Lifetime Timeframe Lifetime
No of studies Design Limitations Consistency Directness or generalisability Imprecise or sparse data Other factors QUALITY RANK
2 RCT 4 Serious limitations -1 Serious inconsitency -1 No serious Undirectness No serious imprecision Low Quality of evidence
Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY
2 RCT 4 Serious limitations -1 Serious inconsitency -1 No serious Undirectness No serious imprecision Low Quality of evidence
Outcome INTERVAL to TB Outcome INTERVAL to TB Outcome INTERVAL to TB Outcome INTERVAL to TB Outcome INTERVAL to TB Outcome INTERVAL to TB Outcome INTERVAL to TB Outcome INTERVAL to TB
1 RCT Serious limitations -1 No serious inconsistency No serious Undirectness No serious imprecision Moderate Quality of evidence
Outcome INTERVAL to DEATH Outcome INTERVAL to DEATH Outcome INTERVAL to DEATH Outcome INTERVAL to DEATH Outcome INTERVAL to DEATH Outcome INTERVAL to DEATH Outcome INTERVAL to DEATH Outcome INTERVAL to DEATH
1 RCT Serious limitations -1 No serious inconsistency No serious Undirectness No serious imprecision Moderate Quality of evidence
Outcome ADVERSE EVENTS Outcome ADVERSE EVENTS Outcome ADVERSE EVENTS Outcome ADVERSE EVENTS Outcome ADVERSE EVENTS Outcome ADVERSE EVENTS Outcome ADVERSE EVENTS Outcome ADVERSE EVENTS
2 RCT Serious limitations -1 ? No serious Undirectness No serious imprecision Moderate Quality of evidence
No of studies Design Limitations Consistency Directness or generalisability Imprecise or sparse data Other factors QUALITY RANK
2 RCT 4 Serious limitations -1 Serious inconsitency -1 No serious Undirectness No serious imprecision Low Quality of evidence
Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY Outcome MORTALITY
2 RCT 4 Serious limitations -1 Serious inconsitency -1 No serious Undirectness No serious imprecision Low Quality of evidence
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Considering cost

• Resource implications, including health system
  changes, for each recommendation in a WHO
  guideline should be explored. At the minimum, a
  qualitative description that can serve as a gross
  indicator of the amount of resources needed,
  relative to current practice, should be provided.
• A scenario approach can be used, and will also
  need to include health system implications of the
  recommendations, from training, changes in
  supervision, monitoring and evaluation, advocacy,
  etc.
• Ideally models should be made available and
  designed to allow for analysts to make changes in
  key parameters and reapply results in their own
  country.
• Users of the guidelines need to work out the cost
  implications for their own service

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End of the dayRecommendation(s)
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Other WHO guidelines

• WHO normative guidelines
• 2009 IPT/ICF Guidelines
• 2009 ART Guidelines
• 2009 PMTCT
• 2010 MDR TB Guidelines
• 2010 WHO HIV/TB research
• 2010 Opportunististic Infections
• Ongoing WHO IMAI

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• Laws, like sausages, cease to inspire respect
  in proportion as we know how they are made.

Otto von Bismarck 1930
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Thank you
Review Team Georgina Russell (NHS) Date, Anand
(CDC/CCID/NCHHSTP) Abhishek Sharma Martina
Penazatto Chair (TBD) Writer (TBD)

WHO Committee Haileyesus Getahun (STOP TB
Co-lead) Andrew Doupe (HIV/AIDS) Christian
Gunneberg (STOP TB) Lulu Mussa Muhe (HIV/AIDS and
CAH) Malgorzata Grzemska (STOP TB) Reuben Granich
(HIV/AIDS) Siobhan Crowley (HIV/AIDS)