Chakaya J'M

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Confronting HIV Associated TB in the era of
increasing anti-TB drug resistance

• Chakaya J.M
• Kenya Medical Research Institute

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Disease Burden
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TB and HIV Infection
11 million (TB and HIV co-infected)
HIV infection
TB infection
33 Million
2 Billion
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Latest global TB Estimates - 2006
Estimated number of cases
Estimated number of deaths
1.65 million (25 per 100,000)
9.15 million (139 per 100,000)
All forms of TB
Multidrug-resistant TB (MDR-TB)
130,000
489,000
Extensively drug-resistant TB (XDR-TB)
20,000
35,000
HIV-associated TB
709,000 (8)
231,000
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Global TB incidence





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Geographical distribution of estimated
HIV-positive TB cases, 2006
WHO Report 2008. WHO/HTM/TB/2008.293
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HIV and Tuberculosis

• Reactivation of latent TB infection
• Rapid progression of new TB infection to disease
• TB recurrence
• smear negative PTB and EP
• Risk of death
• Risk of drug adverse effects
• Risk of paradoxical reactions

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HIV testing for TB patients in selected
countries, 2006
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The Three Is

• Isoniazid Preventive Therapy
• Intensified TB Case Finding
• Infection Control for TB

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TB Preventive Therapy
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Comparison of Isoniazid versus Placebo
Cochrane Database Syst Rev 2004(1)CD000171.DOI1
0.1002/14651858.CD000171.pub2
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IPT and Survival of HIV Infected Children
Heather J Zar et al BMJ 2007 334 136
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Impact of IPT and ART
Golub et al. AIDS 2007 21 1441-1448
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All progress is precarious and the solution of
one problem brings us face to face with another
problem Martin Luther King Jr.
IPT Under Programme Conditions
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IPT in People Living with HIV

• Unacceptable low uptake
• FEAR Side effects, low adherence, resistance
• Unclear policy (Personal vs public health
  intervention)
• Left to NTPs and friends of NTPs
• Non involvement of HIV control programmes
• Little community engagement

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Intensified TB Case Finding(TB screening in
people living with HIV)
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Rationale for TB ICF

• In people living with HIV
• Prevalent (25) and incident (11) TB are common
• Associated with increased mortality (15-20) in
  PLHIV on ART
• Improve safety of ART initiation
• Improve uptake of IPT

Lawn et al AIDS 2006, 2016051612)
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Methods for TB Screening

• Symptom and signs screening
• Sputum examination
• Chest x-ray
• Tuberculin skin testing
• Interferon gamma release assays

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Observations from country practice

• Screening tools vary from country to country
• More and more non-specific constitutional
  symptoms and signs included in tools
• Children and extrapulmonary TB mostly are not
  addressed
• Presence of nationally recommended screening tool
  does not always guarantee implementation

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Percentage of PLHIV screened for TB in countries
with 80 of the global burden, 2006.
WHO Report 2008. WHO/HTM/TB/2008.293
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Intensified TB case finding, diagnosis of TB and
IPT provision among HIV-positive people, 2006
0.96
12
0.08
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Preventing Transmission of TB in Health Care
Settings(TB Infection Control)
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Hospital Transmission of TB
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Clinic Congestion
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Ward Congestion
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TB Infection Control 10 Essential Actions

• Involve community
• Develop IC plan
• Safe sputum collection
• Cough hygiene
• Triage TB suspects
• Rapid diagnosis and treatment
• Improve room ventilation
• Protect health care workers
• Capacity building
• Monitor IC practices

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TB Infection Control at country level

• Hierarchical Confusion
• Health care worker demands for isolation, masks ,
  complex ventilation systems, exchange, UV
  germicidal irradiation
• Administrative , common sense approaches are
  often ignored
• Measuring outcomes of Infection Control

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What is needed for nationwide scale up of TB/HIV
Collaborative Activities

• National policies and Guidelines
• Recording and reporting tools
• Collaboration and communication
• Leadership and commitment
• Target setting
• Human resources including health Care worker
  recruitment, training, support and task shifting
• Financing
• National partnerships for results
• Providing services under one roof

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Challenges to HIV/TB Care
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Treatment challenges

• Optimal time to initiate ART
• Co administration of ART and TB treatment
• Pill burden
• Overlapping toxicities peripheral neuropathy,
  hepatitis, cutaneous reactions
• Pharmacokinetic drug interactions
• Organization and delivery of services

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Optimal time to initiate ART in TB patients

• Aim
• Decrease mortality and morbidity
• Maintain or improve quality of Life
• What is the best strategy to achieve this?

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Zachariah R, et al Int J Tuberc Lung Dis 2007
11 848 -853
Of 983 TB patients
855 (87) were tested for HIV
82 (31)of 658 HIV died before ART
658(77) were HIV
36/396(9) not started on ART
14/180 (7) started on ART died
ART in TB Patients Impact on Mortality during
TB Treatment
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TB Immune Reconstitution Inflammatory Syndrome
(IRIS)

• Characteristics
• High Fever
• Increased size and inflammation of involved lymph
  nodes
• Appearance of new lymph nodes
• Expanding CNS lesions
• Worsening pulmonary parenchymal lesions
• Increased pleural effusions

• Diagnostic Criteria
• Worsening TB at original site or appearance of TB
  at a new site
• Occurrence of TB associated with initiating ART
• No alternative explanation
• Evidence of immune restoration
• Evidence of a virological response to ART

IRIS could significantly complicate the delivery
of ART
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Risk Factors for TB-IRIS
AIDS 2007 21 335-341
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HIV and anti TB Drug Induced Hepatitis

• High risk for hepatitis B and or C infection in
  HIV endemic settings
• HIV a risk factor for anti-TB Drug Induced
  Hepatitis (DIH)
• No increased risk with Hepatitis B Carriage
  (HBsAg)
• Hepatitis C an independent and additive risk
  factor for anti-TB DIH

• Am J Respir Crit Care Med 1988 1571871-1876
• PLoS ONE3(3) e1809.doi10.1371/journal.pone.00018
  09
• J Postgrad Med 20065292-6

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Emerging threats to TB/HIV care
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XDR TB documented in all the regions of the
world
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MDRTB outbreaks linked with HIV
Well CD et al, JID 2007 196(Suppl 1) S86-S107
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Survival of XDR TB among people living with HIV

• 221 of 1539 had MDR-TB
• 53(24) of MDRTB had XDR-TB
• 44 of XDR-TB tested for HIV, all HIV
• 55 of XDR-TB no previous TB treatment
• 67 of XDR-TB admitted in the last two years
• 52(98) died in a median of 16 days

Lancet 2006368 1575-80
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MDR and XDR TB for HIV the lessons

• A consequence of sub optimal TB control
• HIV infected persons, at risk of acquiring TB
  including MDR and XDR TB in health care settings
• When HIV infected persons acquire XDRTB the
  outcomes are very poor
• Inadequate Infection Control Practices encourage
  the transmission of TB including MDR and XDRTB

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Conclusion

• HIV Associated TB - a public health concern
• Good progress being made with decreasing the
  burden of HIV in TB patients ( testing, CPT and
  ART)
• Slow progress with decreasing the burden of TB in
  PLHIV (3Is)- HIV Control programmes play a
  critical role
• Greater collaboration between TB and HIV
  communities is needed
• The HIV community needs to take greater
  role/responsibility in the implementation of the
  TB/HIV collaborative activities especially the
  3Is

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Collaboration Between the TB and HIV Communities
is not optional it is mandatory
Knowing is not enough we must apply. Willing is
not enough we must do. Johann Wofgang von Goethe
Thank You