HIV and Tuberculosis – the deadly combination

8/2/2019 HIV and Tuberculosis the deadly combination

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HIV and Tuberculosis the

deadly combinationPanel discussion

Moderator : Dr.Govindaraju MPanelists: Dr Shivananda

Dr BalasubramaniamDr.Atul Agarwal

Dr. Sharad Thora


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Question - Why is this

combination so deadly?


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Impact of HIV on TB

Palme et al found that TB childrenwho were HIV + were:

- Younger

- Underweight

- 6 fold increase in mortality

- only 58% cure rate

- More severe manifestations

- Progression to death more rapid

Palme et al . Impact of HIV-1 infection on clinical presentation,treatment outcome and survival in a cohort of Ethiopian children withTB. Pediatr Infect Dis J 2002; 21:1053-61


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Question : What are the

possibilities

Dr.Sharad Thora


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Question : What are the

possibilities Fever, Altered sensorium andconvulsions a triad of CNS Infection:

Pyogenic meningitis

TB meningitis

Viral encephalitis

Cerebral malaria

Rickettsial encephalitis


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Case scenario

Family history:

- Father died of tuberculosis 2 yearsback and was being treated for thesame.

- Mother is alive and well, with nocomplaints

Past history:

- He has never been hospitalized


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Case scenario

On examination:

- Grade III PEM

- Cervical lymphadenopathy multiplematted lymph nodes

- Pallor +

- Right sided Facial nerve palsy + withright sided hemiparesis

- Chest clear


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Diagnosis: Right sidedhemiplegia with facial nerve

palsy probably due to

Tuberculous meningitis


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Case scenario

CT scan of the brain showed:

- Hypo dense lesions in left parietallobe and internal capsule

-Two ring enhancing lesions in the leftparietal lobe

- Diffuse cerebral edema +


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A diagnosis ofNeurotuberculosis

meningitis made!


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Question Do yourecommend HIV testing in

all children with TBM?

Dr.Balasubramaniam


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Prevalence

What is the prevalence of TB inHIV +?

What is the HIV seroprevalencein children with TB?


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Prevalence of TB in HIVinfected children

Author N Tuberculosis %

Shah I 2005 317 43.4%

Shah SR 2005 50 38%

Madhivanan P 2004 58 35%

Verghese VP 2002 88 12%

Merchant RH 2001 285 29.47%

Dhurat 2000 55 67.5%

Lodha 2000 27 13%

Tuberculosis is reported in 14 to 54% ofIndian children with HIV/AIDS


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HIV seroprevalence in childrenwith TB

Author Seroprevalence

South African study group 42%

Merchant and Shroff et al 18%

Karande et al 16.2%

Shahab et al 2%

Greater probability of detecting HIVinfection in children with disseminated

TB


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Question What are theclinical signs that suggest

HIV infection in a child?Dr.Atul Agarwal


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Clinical signs suggestive ofHIV

Failure to thrive < 6 months or history ofweight loss > 6 months

Recurrent bacterial infections

Generalized symmetricallymphadenopathy

Extensive oropharyngeal candidiasis

Generalised rash

Bilateral non tender parotid glandenlargement


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Case scenario

As recommended HIV testing wasdone:

- All three samples were found to bepositive

Hence, child is diagnosed to have HIVwith tuberculosis


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What tests do yourecommend for diagnosis of

TB in this child?

Dr.Balasubramaniam


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Pulmonary TB

Mantoux test

Gastric lavage isolation / sputum forculture and smear

Radio logical Chest X-ray


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Extra-Pulmonary TB

Culture of affected body fluid ortissue obtained by fine needleaspiration or biopsy


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Mantoux test/Tuberculintest

Can be done using 5TU intradermally

Induration > 5 mm is consideredpositive

Negative test seen in 50% childrenwith HIV

Hence negative test does not ruleout tuberculosis


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Gastric Lavage/Sputumexamination

50-70% of adults - + ve

Children with TB disease rarely

produce sputum voluntarily and havea low bacterial load.

Three consecutive morning gastric

aspirates have a better yield than asingle sample.

Better diagnostic yield is seen on

culture.


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Chest X-ray

Localized pulmonary infiltrates withhilar adenopathy

Middle lobe collapse andconsolidation

Pleural effusion

In older children cavitatorytuberculosis.


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Culture

Specimens should be cultured for 2-6weeks by radiometric culturemethods (Bactec).

Culture on L-J medium for 8 weeks.

Antimycobacterial drug sensitivityshould be done on the initial positiveculture if treatment fails or relapseoccurs.


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Others

PCR assays are not useful as primarydiagnostic tool

Negative PCR does not rule out TBand

Positive result does not absolutelyconfirm M.Tuberculosis infection.

False positive rates are high withsensitivity ranging from 45-83%.

Serological tests for TB are not verys ecific


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Question What other differentials

would you consider in viewof this child being HIV+ ?

Do you recommend any

other investigationsDr.Shivananda


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Cryptococcal meningitis

< 1% in children

Patients present with fever,headache and altered mental status.

HIV infected children between 6-12years of age with severeimmunosuppression are prone.

Neck stiffness and focal neurologicaldeficit is rare.


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Cryptococcal meningitis

CSF opening pressure should bemeasured.

CSF analysis with INDIA INK a must

Cryptococcal antigen (SF antigen)titres to be obtained.

Fungal cultures from CSF or blood


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Toxoplasmosis

Acquired primary toxoplasmosis israre.

CNS toxoplasmosis may present asheadache, fever, changes in mentalstatus, seizures, psychosis and focalneurological deficits.

Toxoplasma specific IgG +


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Toxoplasmosis

Space occupying lesion on imagingstudies of the brain ring-enhancinglesions in the basal ganglia and

cerebral corticomedullary junction.

Definitive diagnosis requires

histologic or cytologic confirmationby brain biopsy


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Viral encephalitis

HSV encephalitis

CMV encephalitis

Disseminated Varicella infection


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Case scenario

Other tests done:

- CSF IgM Toxoplasma Negative

- CSF AMA Negative

CD4 count - 440/cu.mm

CD4 % - 22%


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Question At what CD4count in HIV does TBM

occur?Dr.Balasubramaniam


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TB an AIDS defining illness

Diagnosing extrapulmonary TBin HIVis important as it is an AIDS definingillness.

Tuberculosis can occur at any CD4count.

The more atypical the clinicalfeatures, the more likely is the CD4count to be low.


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Case scenario

Chest X ray showed bilateral nonhomogenous opacities, diffuselyinvolving all the lobes of the lung.

ABG :

pH 7.52

pCO2 22

pO2 48

HCO3 - 16


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Question - What is yourdifferential diagnosis for non-

homogenous opacities in a HIV +child?

Dr.Shivananda


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Differential Diagnosis

Miliary tuberculosis

Lymphocytic interstitial pneumonia(LIP)

Pneumocystis jiroveci pneumonia(PCP)

Bacterial pneumonia

Rarely:

- Fungal pneumonia


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Miliary tuberculosis


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PCP pneumonia


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Lymphocytic interstitialpneumonia (LIP)


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Fungal pneumonia


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Question Do you treatwith ATT first or with ART

first?Dr.Atul Agarwal

P i i l f t ti TB


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Principles of treating TBwith HIV

1) Treatment of TB takes precedenceover HIV treatment

2) In patients already on HAART,continue the same withmodifications

3) In those not receiving HAART,initiation depends on CD4 countsand t e of TB

P i i l f t ti TB


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Principles of treating TBwith HIV

If CD4 counts > 15% and nosignificant HIV related illness treat for TB first

Monitor carefully for worsening ofimmune status

If CD4 counts < 15% or significantHIV related illness Treat with ATTand HAART


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Initiation of ART

Starting ARV therapy for theindividual child is rarely anemergency!

Management of life-threateningopportunistic infections can be anemergency.

Treat opportunistic infections beforestarting ART

Any child less than 2 years,

irrespective of CD4 count ART is

R d ti f i iti ti


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Recommendations for initiatingART in infants and children

WHOPaediatric

Stage

Availability ofCD4 cell

measurements

Age-specific treatment recommendation

< 2 years 2 years

4 CD4 Treat all

3 CD4 Treat all Treat all, CD4 guided inthose children with TB,

LIP, OHL,thrombocytopenia

2 CD4 Treat all CD4 guided

1 CD4 Treat all CD4-guided


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CD4 criteria of severe HIVimmunodeficiency

Immunological marker

Age-specific recommendation to initiate ART

11 months 12 months-35 months

36 months-59 months

5 years

CD4 % 25% 20% 15% 15%

CD4 count 1500cells/mm3

750cells/mm3

350cells/mm3

200cells/mm3

ART should be initiated by these cut-off levels, regardless of clinical

stage; a drop of CD4 below these levels significantly increases the

risk of disease progression and mortality

% CD4 is preferred for children


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Case scenario

Child was started on RNTCP Category1 treatment:

- 2HRZES + 4HR for 9 months


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Question Is thistreatment sufficient? How

long do we treat?Dr. Sharad Thora


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ATT in HIV + children

American Thoracic society Minimum duration of 6 months andmay be extended if response is

suboptimal

American Academy of Pediatrics 9

months

Indian Academy of Pediatrics 9months


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Treatment

Treatment of TB in HIV infected childis the same as that for an HIVuninfected child.

However, modified treatmentduration schedule and medications

are recommended for specificinstances.

Treatment of TB should be initiated


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Treatment

For HIV infected children with activepulmonary disease, the minimumrecommended duration ofATT is 9

months.

For children with extrapulmonary

disease involving the bones or joints,CNS or miliary disease, the minimumrecommended duration of treatment

is 12 months.


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Question Should steroids

be started? For how long?Dr. Atul Agarwal


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Role of steroids

Adjunctive use of steroids isindicated in patients with:

- TBM

- Serosal TB

- Miliary TB and

- Endobronchial tuberculosis.

Duration: 6 8


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Case scenario

Child was treated with short coursechemotherapy and monitored withCD4 counts.

After 2 months CD4 counts droppedto 128/cu mm (CD% - 8%)


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Question If you arestarting HAART, whatprecautions to take with

ATT?Dr. Shivananda


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Monitoring

In children with HIV and TB coinfection,periodic monitoring of liver enzymes isadvised.

Mild elevations in serum transaminases(e.g., 2-3 times upper limit of normal) doesnot require discontinuation of the drugs.

All patients should be monitored monthlyfor clinical and bacteriological response.


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Monitoring

For patients with pulmonary TB,Chest X-rays should be obtainedafter 2-3 months of therapy to

evaluate response.

Hilar adenopathy might persist for as

long as 2-3 years despite successfulATT and is not a criteria forcontinuation of ATT.

Adverse drug reactions of


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Adverse drug reactions ofATT in HIV

ADRs increase with advancedimmuno suppression and in the first2 months.

Thiacetazone rashes,hepatotoxicity and fatal ADR contraindicated in HIV

INH more prone to develop INH

Adverse drug reactions of


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Adverse drug reactions ofATT in HIV

Rifampicin with Protease Inhibitorscontraindicated due to interactionwith cytochrome p450 enzymes.

Efavirenz can be used withrifampicin.

Malabsorption of ATT is known in

HIV hence monitor response


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What regimen to use if

the child is on rifampicin?Dr. Sharad Thora

What 1st line regimen to


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guse if the child is on

rifampicin?If starting ART after rifampicin-based anti-TB treatment

Preferred regimen Alternative regimen

AZT or d4T + 3TC + ABC 2NRTI + NVP (in children < 3 years old or weigh < 10 kg)2 NRTI + EFV (in children >= 3 years old)

After completing rifampicin-based anti-TBtreatment, consider switching treatment tostandard first line regimen with 2NRTI+NVPor EFV for better efficacy

Continue treatment after completingrifampicin-based anti-TB treatment.

What 1st line regimen to


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guse if the child is on

rifampicin?If already on first-line ART when starting rifampicin-based ATT

Current first line

regimen

Preferred regimen

2NRTI + EFV Continue the same regimen

2NRTI + NVP Switch to either 2NRTI +ABC or 2NRTI +EFV (if age > 3 years and weigh > 10 kg)

2NRTI + ABC Continue the same regimen


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Is there a role forprophylactic ATT in HIV ?

Dr.Shivananda


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Prophylaxis

All HIV infected children with positiveMantoux test and no evidence ofactive TB or no history of previous

treatment for TB should be treatedfor latent TB.

Regimen 6 months of INH +Rifampicin.

There is no role of sin le dru INH


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Prophylaxis

HIV infected children in close contactwith person with Open TB shouldbe treated for latent TB.

Treat regardless of their MT test andprevious treatment for TB after

excluding active TB.

Regimen 6 months of INH +

Rifam icin


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Case scenario

Child was started on HAART usingefavirenz and zidovudine, along withATT

After 1 month of treatment, he wasbrought with complaints of:

- Spiking fever

- Increasing headache and vomiting

- Increase in size of lymph nodes


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Question What are the

possibilities?Dr. Balasubramaniam

IRIS Immune


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Reconstitution Inflammatory

Syndrome It is a paradoxical reaction that occurs in

the course of ATT when HAART restores

the immune function.

Features include hectic fevers,lymphadenopathy and worsening of TB

Treatment patients generally feel well.Can treat with short term steroids rarely


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How do you treat drugresistant tuberculosis in

this child?Dr.Shivananda


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Drug resistant TB

Minimum of three drugs should begiven, including at least 2bactericidal drugs to which the

organism is susceptible.

Multidrug resistant tuberculosis (i.e.

resistant to INH and RIF) aggressive treatment with a regimean amino glycoside or capreomycin

and a fluoroquinolone

Suggested Regimens


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Suggested RegimensPattern of

drugresistance

suggest

regimen

Minimum

duration oftreatment

comments

H (+/- S) R , Z and E 6 - 9 A fluroquinolonecan be added forpts with extensivedisease

H and Z R ,E and

fluroquinolones

9 - 12 A longer durationfor those with

extensivedisease.

H and E R ,E and

fluroquinol

9 - 12 A longer durationfor those withextensive

disease.

Suggested Regimens


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drugresistance

suggest

regimen

Minimum


comments

R H , E

fluroquinolones plusatleast2 monthsof Z

12 - 18 An injectableagent maystrengthen theregimen for ptswith extensivedisease.

R andE(+/- S)

H , Zfluroquinolones plus aninjectable agent

for at least the

18 A longer course( 6 months) of theinjectable agentmay strengthenthe regimen forpts with extensive

disease.

Suggested Regimens


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drugresistance

suggest

regimen

Minimum


comments

R and Z

(+/- S)

H , E

fluroquinolones plus aninjectable agentfor at least thefirst 2-3months.

18 A longer course( 6 months) of theinjectable agentmay strengthenthe regimen forpts with extensivedisease.

H , E , Z

(+/- S)

R,Fluroquinolones , plusan oral secondline plus an

18 A longer course( 6 months) of theinjectable agentmay strengthen

the regimen for


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When will you suspectatypical mycobacterial

infectionDr. Atul Agarwal

Mycobacterium avium


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Mycobacterium aviumcomplex (MAC)

MAC - M. avium, M. intracellulare,and M. paratuberculosis.

MAC can appear as isolated

lymphadenitis among HIV infectedchildren.

CD4 count < 50 cells/cumm is an

important risk factor for developmentof MAC.

Lungs, liver, spleen, GI tract, bone

marrow and l m h nodes are

Cli i l F


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Clinical Features

Isolated pulmonary disease is rare.

Patients present with recurrent fever, weight

loss or failure to thrive, night sweats, fatigue,chronic diarrhea and recurrent abdominalpain.

Patients have lymphadenopathy,hepatomegaly and splenomegaly.

Associated laboratory findings of neutropenia,anemia and leuko enia are seen


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What investigations willyou consider in MAC with

HIV?Dr.Balasubramanium

Di i


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Diagnosis

Is accomplished by isolation oforganism from blood or biopsy sites(bone marrow, lymph node or other

tissues).

Culture can yield the organisms in 2

weeks.

Culture is necessary for species

identification.

Di i


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Diagnosis

Anemia out of proportion to thestage of the HIV disease

Elevated serum alkaline phosphatasemay be seen.


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What is the treatment of

MAC with HIV?Dr.Shivananda

T t t


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Treatment

Combination therapy with aminimum of 2 drugs isrecommended.

Clarithromycin or Azithromycin plusEthambutol is recommended.

Additional drugs such asCiprofloxacin, Amikacin or

Stre tom cin ma be considered

T t t


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Treatment

For disseminated disease, 3 or 4drugs are essential.

Most patients show improvementwithin 4-6 weeks.

Treatment should then be continuedwith 2 drugs.

P h l i


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Prophylaxis

Age CD4 count(cells/cumm)

WHO Stage CDC Class

< 12 months < 750 - -

1-2 years < 500 - -

2-6 years < 75 - -

> 6 years < 50 - -

Any Age - IV C

After initial treatment, secondary prophylaxis isrecommended for life time


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Prophylaxis may be stopped if CD4

percent is more than 15% for 6months and ART has been continuedfor more than 12 months and child isasymptomatic

Drugs Dosage

Clarithromycin 15 mg/kg/day PO BD (max 500 mg/day)

Azithromycin 20 mg/kg/day weekly (max 1.25 gm/day

Ethambutol 15-20 mg/kg/day PO OD (max 1.5gm/day)

Ciprofloxacin 20-30 mg/kg/day PO/IV OD/BD (max 1.5gm/day)


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THANK YOU !!! to all the

panelists!

HIV and Tuberculosis – the deadly combination

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