THE CHALLENGES IN

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THE CHALLENGES IN DIAGNOSIS AND MANAGEMENT OF
HIV-TB COINFECTION IN CHILDREN
Dr SAM WALTERS St MARYS HOSPITAL, IMPERIAL
COLLEGE, LONDON
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HIV-TB COINFECTION
Lack paediatric data
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CHALLENGES IN DIAGNOSIS DIAGNOSIS of TB
-active disease and latent infection
Microbiological Gold Standard -low
sensitivity in children -pauci-bacillary -sput
um collection difficult Symptoms, overlap with
HIV Chest X-ray, appearances overlap
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DIAGNOSIS OF TB
-TST (Tuberculin Skin Test) limited use in young
children -worse if HIV infected
-interpretation not improved with CD4 or other
skin tests
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DIAGNOSIS OF TB -new diagnostic tests
T-CELL BASED TESTS (2 commercial assays)
-distinguish between MTB infection and BCG
exposure -expensive, laboratory
infrastructure, trained personnel -DO NOT
DISTINGUISH BETWEEN ACTIVE DISEASE AND LATENT
INFECTION -NOT ADEQUATELY VALIDATED IN
HIV-INFECTED CHILDREN
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-sensitivity ELISPOT 73 gtgt TST 36
MOPEB022 ELISPOT sensitivity 80
(Definite/Probable TB)
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• TREATMENT CHALLENGES
• Treatment of active TB cannot be delayed
• ? when to initiate ART
• -IRD (Immune Reconstitution Disease)

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IRD
Adverse consequence of restoration of
pathogen-specific immune responses during early
ART -sub-clinical infection un-masked,
partially treated infections deteriorate with ART
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IN ADULTS More likely if - ART started within
2/12 of TB treatment - extrapulmonary /
disseminated TB - advanced HIV (high viral load
/ low CD4) - good early response to ART (rapid ?
in VL, ? CD4) IN CHILDREN - case
reports/clinical series
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MANAGEMENT (lack of controlled data) -symptomat
ic treatments, steroids -delay ART for 2/12
(if possible 6/12) -significant mortality in
first 2/12
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Early Mortality if ART Delayed
Immune Reconstitution Disease with Early ART
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RIFAMPICIN

• PIs mostly incompatible
• - can use Ritonavir (taste)
• - ? ? Ritonavir boost for Kaletra

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RIFAMPICIN

• - ARV overdose ? toxicities (short-term)
• - ARV under dose ? HIV resistance (long-term)
• In resource-poor countries
• Fixed dose ARV combination tabs
• - need augmenting with individual component
  drugs

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RIFAMPICIN

• In resource-rich countries
• ? doses ? TDM ? adjust dosing
• - rifabutin (instead of rifampicin)
• (? rifabutin with PIs, ? with NNRTIs)

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TREATMENT CHALLENGES - how long, ? 6 months
treatment (no controlled trials)
-recurrence is common -1/3 due to relapse
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XDR TB

• -? transmission
• -? mortality
• -? association with HIV

- must have spread to children (no
microbiological diagnosis)
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• TREATMENT CHALLENGES
• -maintaining simultaneous treatment
• -adherence
• -overlapping side-effects
• -pill burden
• -continued drug supply
• -intact health systems
• -health of parent

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PREVENTION CHALLENGES

• -improve identification and treatment of
  infectious TB
• -improve antenatal HIV testing interruption of
  MTCT
• -INH prophylaxis

-significant ? TB and mortality, ? INH resistance
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PREVENTION CHALLENGES

• -BCG
• - not good enough
• - ? safety

-disseminated BCG gtgt in HIV infected children
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PREVENTION CHALLENGES

• -BCG

WHO Jan 07 BCG vaccine should not be used in
children known to be HIV-infected
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CHALLENGES

• WE NEED
• -new diagnostic tests
• -new drugs
• -new vaccines
• BUT
• -could do better today
• -more paediatric data
• -integrated care of TB and HIV
• -integrated family care
• MORE , MASSIVE INVESTMENT

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DIAGNOSIS OF TB
-new methods to refine old techniques -specimen
collection -induced sputum gastric aspirates