Impact of HIV infection on outcome of treatment for TB

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HIV AND Tuberculosis

• Dr Farida Amod
• Infectious Disease Unit,
• Department of Medicine
• Nelson R Mandela school of Medicine
• University of Natal, Durban
• Acknowledgements
• Prof UG Lalloo
• Dr P Jeena

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HIV/TB A Crippling Duet

• Epidemiology of TB and HIV in Africa
• Interrelationship between TB and HIV
• How does TB affect HIV infection
• How does HIV affect TB
• (presentation,
  treatment,outcome)
• How does the HIV epidemic affect TB control
  programs and hospitals
• The way forward

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Burden of Tuberculosis

• Annual incidence of TB in sub-Saharan Africa
  229 per 100 000 (highest TB incidence in the
  world).
• Unenviable position of having 2 epidemics that
  fuel each other occurring in tandem
• 68 of all people co-infected with TB and HIV
  live in sub-Saharan Africa.

WHO report 2000 UNAIDS report 2000
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The Unenviable African Position
Highest incidence of TB in the world
Largest number of HIV-infected persons in the
world
Large pool of people susceptible to TB
Large infectious pool
Both living side by side
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Size of the Problem

• 18.8 million AIDS deaths worldwide so far and
  overall, about 1/3 attributed to TB (UNAIDS
  report 2000).
• Of the 500 000 HIV-infected TB deaths for the
  year 2000, 239 000 (47.8) will occur in Africa
  (projected estimates in 1994)
• How did it turn out?

Bull WHO 1994,72213-220
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Aetiology of TB

• Organism- M.tuberculosis
• Infection spread by inhaling small droplets of
  cough aerosol (5? in diameter)
• 2 forms of TB
• Primary TB
• Post-primary
  (reactivation TB)

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TuberculosisInteractions
MTB
Increased reactivation of latent disease
Increased virus replication Increased
acquisition
Acceleration to AIDS Progression to Disease
HIV
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HIV and Clinical TB

• TB commonest OI in HIV-infected persons in
  Africa. Leading cause of death worldwide
• TB can occur at any CD4 count
• HIV epidemic responsible for
• Dramatic increase in number of TB cases
• Increase in smear negative and extra-pulm TB
• Increase in mortality in patients with TB and HIV

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How does HIV affect the clinical presentation of
TB ?

• Some presentations have remained unchanged (TBM,
  Tb osteitis)
• Certain peculiar TB syndromes
• - Pulmonary Syndrome
• - Lymphadenopathy Syndrome
• - Serositis Syndrome
• - Constitutional Syndrome
• Increased incidence of extra-pulmonary TB

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PULMONARY COMPLICATIONS IN HIV INFECTED PERSONS
TB commonest pulm complication in HIV patients
in Africa
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Pulmonary syndrome

• Relatively high CD4 ? apical, cavitatory TB
• sputum
  smear positive
• low CD4 ? no cavitation smear negative
• non-specific infiltrates
• lower lobe involvement
• Extra-pulmonary TB
• Why the difference in presentation?

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TB PLEURAL EFFUSIONHILAR ADENOPATHY
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DIFFUSE PULMONARY INFILTRATE
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PCP
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How does HIV affect the clinical presentation of
TB

• Certain peculiar TB syndromes
• Pulmonary Syndrome
• Lymphadenopathy Syndrome
• Serositis Syndrome
• Constitutional Syndrome
• Increased incidence of extra-pulmonary TB
• (abd TB, liver, bone, lymph node, pericardium)

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INTRATHORACIC ADENOPATHY
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Diagnosis of TB

• Diagnosis can be difficult.
• Cornerstone sputum microscopy ( culture)
• Other modalities
• Induced sputum
• Fine needle aspiration of lymph nodes
• Biopsy (lymph node, liver, bone marrow, lung)
  histology and culture

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AFB HIV
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Treatment

• WHO/ National guidelines 6 month therapy (rif/
  INH/ PZA/etham for 2 months, then rif/INH for 2
  months). DOT essential
• No difference in response and relapse rate
  between HIV and HIV- patients.
• Increased mortality in HIV patients during and
  after therapy due to other HIV-related
  complications.

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Areas of Intervention

• Transmission?Primary inf ?latent infection
• 
  
• 
  Reactivation Disease
• (Treatment of
  Reactivation TB)

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Preventive therapy for TB

• TB can be prevented by giving TB preventive
  therapy.
• INH prophylaxis for 9 months or
• rifampicin and pyrizinamide for 2 months.
• USA/ Europe INH given to all HIV-infected
  persons with a positive tuberculin test (gt5mm) or
  a history of recent TB contact.
• S.A situation is more complex.

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Preventive therapy for TB in S.A

• Current national guidelines for HIV persons
• Offer INH prophylaxis if
• Active TB excluded (no symptoms normal CXR)
• Patients can be followed monthly (adherence /
  exclude active disease)
• Local AIDS program takes responsibility
• No need to do tuberculin testing in S.A
• Duration of therapy controversial in view of
  repeated exposures.

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What is the mortality outcome of tuberculosis in
HIV-infected persons?
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Correlation between TB CFR and HIV prevalence in
adults in selected African countries
Trans Roy soc Trop Med 1998,92343-347 Int J
Tuberc Lung Dis 1998,2919-925
Malawi
S.A (Hlabisa)
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Impact of HIV infection on outcome of treatment
for TB

• Mortality higher in HIV than in HIV negative
  patients with TB
• 0.5 vs 13.7 in a South african mineworkers
  cohort
• 13.5 vs 9 in a Hlabisa study (May93)
• Similar results in other studies in Africa
  (Malawi,
• Cote D Ivoire)

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Outcome at 6 months follow-up
Am J Respir Crit Care Med 1999159733-740
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Epidemiology of HIV and TB

• TB- leading cause of morbidity and mortality
  amongst HIV-infected people
• HIV epidemic has resulted in
• Dramatic increase in incidence of TB cases.
• Dramatic increase in TB CFR.

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When do deaths occur?

• Bimodal distribution
• 1st peak - within first 3 months
• 2nd peak - around 21st month
• Timing differs among HIV and HIV- patients
• Early mortality due to TB.
• Late deaths due to opportunistic infections e.g
  cryptococcal pneumonia.
• Highlights the need for vigilance for concurrent
  infections in HIV-infected patients with TB

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Outcome of HIV-infected persons with TB on
treatment

• Dramatic increase in TB case fatality rates in
  high HIV prevalence areas.
• TB CFR increases with declining CD4 counts
• In S.A mineworkers with TB and HIV
• CD4 counts lt200/ul? CFR of 22.1
• CD4 counts bet 200-500/ul ? CFR of 7.7
• Higher case fatality rates in smear-negative and
  extra-pulmonary disease

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Factors relating to mortality in HIV-infected
patients on TB treatment

• Early mortality (within 1 month of diagnosis) ?
  due to TB
• Late mortality (between 1-6 months) ? due to
  nontuberculous AIDS-related conditions.
• Excess mortality in HIV-infected TB patients
  appear to be due to HIV-related conditions other
  than TB

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Effect of HIV epidemic on National TB Programs
(NTP)

• Increased mortality may threaten the reputation
  of NTP
• NTP may find it difficult to ensure that TB
  patients complete treatment.
• Increasing patient-load may overwhelm the
  services
• Despondency and negative attitude of staff
• Staff also affected by HIV epidemic

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Impact of HIV/TB on Hospitals

• Increased risk of nosocomial TB amongst patients
  and staff.
• Need to devise practical ways to diminish this
  risk
• - cohort nursing
• - use of masks (patients and staff)
• - open windows/ sunlight
• High index of suspicion early recognition and
  treatment

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Measures to Tackle High TB Mortality in
HIV-Infected Persons

• Strengthening of TB control programs
• Revision of current guidelines on screening
• Collaboration between TB programs and HIV/AIDS
  prevention and treatment programs
• Preventive therapy and treatment of HIV-related
  diseases
• Increased vigilance to detect concomitant
  opportunistic infections
• The increased use of anti-retroviral therapy in
  Africa

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Impact of ARV on TB Epidemic
SAMJ Vol 91, 8 650-1Aug 2001
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Conclusion

• HIV pandemic has had a devastating effect on TB
  in sub-Saharan Africa.
• 30 of the 2.4 million AIDS related deaths in
  2000 due to TB.
• Whilst health care systems seem overwhelmed,
  important to remember that TB can be prevented
  and effectively treated in HIV-infected persons.
• Important to prevent and treat concomitant
  opportunistic infections to decrease mortality.
• Our aim should be to do all this optimally whilst
  we wait for the introd of ARVs in the public
  sector.