Treatment of Pediatric TB€¦ · 1/5/2011 6 TB DRUGS IN CHILDREN Aminoglycosides: Mostly CNS, drug-resistant TB Amikacin preferred for CNS [more resistance to streptomycin] OtoOto--

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Pediatric TB IntensiveHouston, Texas

November 13 2009November 13, 2009

Treatment of Pediatric TBJeffrey R. Starke, M.D.y ,

November 13, 2009

MANAGEMENT OF CHILDHOOD MANAGEMENT OF CHILDHOOD TUBERCULOSISTUBERCULOSIS

Jeffrey R. Starke, M.D.Jeffrey R. Starke, M.D.Professor of PediatricsProfessor of PediatricsBaylor College of MedicineBaylor College of Medicine

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DRUG RESISTANCE IN DRUG RESISTANCE IN TUBERCULOSISTUBERCULOSIS

The development of drug The development of drug resistance in resistance in M. tuberculosisM. tuberculosis is is the result of a conspiracy the result of a conspiracy among the organism, the among the organism, the

ti t th d t d th ti t th d t d th patient, the doctor and the patient, the doctor and the healthcare system!healthcare system!

DRUG RESISTANCE IN DRUG RESISTANCE IN MYCOBACTERIUM MYCOBACTERIUM

TUBERCULOSISTUBERCULOSIS

genetic loci for resistance on genetic loci for resistance on chromosome, unlinked chromosome, unlinked

resistance of drugs independentresistance of drugs independent frequency of mutations at loci is frequency of mutations at loci is

knownknown more likely to have mutations when more likely to have mutations when

mycobacterial population is larger : mycobacterial population is larger : infection vs. diseaseinfection vs. disease

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TREATMENT OF TUBERCULOSISTREATMENT OF TUBERCULOSIS

“More bugs, more drugs!“More bugs, more drugs!

QuestionQuestion: When does tuberculosis : When does tuberculosis infection turn into tuberculosis infection turn into tuberculosis disease? When do we cross the disease? When do we cross the threshold or using more than one threshold or using more than one threshold or using more than one threshold or using more than one drug?drug?

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TB DRUGS IN CHILDRENTB DRUGS IN CHILDREN

IsoniazidIsoniazid: : [10 [10 –– 15 mg/kg/day]15 mg/kg/day] Well tolerated with few AEsWell tolerated with few AEs Well tolerated with few AEsWell tolerated with few AEs Both hepatitis and neuritis are rareBoth hepatitis and neuritis are rare Better tolerated with food in stomachBetter tolerated with food in stomach Poor tolerance of suspension > 5 kgPoor tolerance of suspension > 5 kg

RifampinRifampin: : [10 [10 –– 15 mg/kg/day]15 mg/kg/day] Well tolerated; only rare AEsWell tolerated; only rare AEs Watch for contact lensesWatch for contact lenses Can’t use OCPs for birth controlCan’t use OCPs for birth control

TB DRUGS IN CHILDRENTB DRUGS IN CHILDREN

PyrazinamidePyrazinamide: : [30 [30 –– 40 mg/kg/day]40 mg/kg/day]L ill t d d iL ill t d d i Large pill, no standard suspensionLarge pill, no standard suspension

itching > joint pain > hepatitisitching > joint pain > hepatitis

EthambutolEthambutol: : [20 mg/kg/day][20 mg/kg/day] Ocular toxicity very, very rareOcular toxicity very, very rarey y, yy y, y Watch for renal disease [elimination]Watch for renal disease [elimination] Now standard 4Now standard 4thth drug for childrendrug for children

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TB DRUGS IN CHILDRENTB DRUGS IN CHILDREN

AminoglycosidesAminoglycosides:: Mostly CNS, drugMostly CNS, drug--resistant TB resistant TB Mostly CNS, drugMostly CNS, drug resistant TB resistant TB Amikacin preferred for CNS [more Amikacin preferred for CNS [more

resistance to streptomycin]resistance to streptomycin] OtoOto-- and renal toxicity possibleand renal toxicity possible

EthionamideEthionamide: : [15 mg/kg/day][15 mg/kg/day]E ll t d f CNS TBE ll t d f CNS TB Excellent drug for CNS TBExcellent drug for CNS TB

DifficultDifficult--toto--use dosage formuse dosage form GI intolerance, but less than in adultsGI intolerance, but less than in adults

TB DRUGS IN CHILDRENTB DRUGS IN CHILDREN

FluoroquinolonesFluoroquinolones:: Used for drugUsed for drug--resistant TB or resistant TB or

intolerance to standard drugsintolerance to standard drugs Few studies, mostly ciprofloxacinFew studies, mostly ciprofloxacin Dosages unknown for Dosages unknown for

moxafloxacin and gatifloxacinmoxafloxacin and gatifloxacinmoxafloxacin and gatifloxacinmoxafloxacin and gatifloxacin Levofloxacin: twice daily dosing Levofloxacin: twice daily dosing

for children < 5 years of agefor children < 5 years of age

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DIRECTLY OBSERVED DIRECTLY OBSERVED THERAPY FOR THERAPY FOR

TUBERCULOSISTUBERCULOSIS

means a dispassionate 3rd party is means a dispassionate 3rd party is actually present when medications actually present when medications are taken with every doseare taken with every dose

“standard of care” in U.S. for “standard of care” in U.S. for treating tuberculosis diseasetreating tuberculosis disease

desirable for high risk infections desirable for high risk infections --newborns and infants, household newborns and infants, household contacts, HIV contacts, HIV -- infected or immune infected or immune compromisedcompromised

TUBERCULOSIS IN CHILDREN TUBERCULOSIS IN CHILDREN TREATING EXPOSED TREATING EXPOSED

CHILDRENCHILDREN

Very high rate of infectionVery high rate of infection Takes up to 3 months for the skin Takes up to 3 months for the skin

test to turn positivetest to turn positive U.S. studies U.S. studies –– 10% to 20% of 10% to 20% of

childhood TB cases can be childhood TB cases can be prevented if children exposed in a prevented if children exposed in a household receive isoniazidhousehold receive isoniazid

Assume young children are Assume young children are infected until proven they are notinfected until proven they are not

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TREATING TB EXPOSED TREATING TB EXPOSED CHILDRENCHILDREN

Usually treat for 8 to 10 weeks Usually treat for 8 to 10 weeks after after h b b k h b b k b l f b l f exposure has been broken exposure has been broken by loss of by loss of

contact or treatmentcontact or treatment Must follow both the patient and the Must follow both the patient and the

source case [sputum conversion, source case [sputum conversion, drug susceptibility pattern, contact]drug susceptibility pattern, contact]drug susceptibility pattern, contact]drug susceptibility pattern, contact]

Infants: ? TST or IGRA reliable if Infants: ? TST or IGRA reliable if child < 6 months of age [little data]child < 6 months of age [little data]

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TREATMENT OF LTBI IN TREATMENT OF LTBI IN CHILDRENCHILDREN

9 months of isoniazid (daily or twice weekly 9 months of isoniazid (daily or twice weekly 9 months of isoniazid (daily or twice weekly 9 months of isoniazid (daily or twice weekly under DOT) is only accepted regimenunder DOT) is only accepted regimen

INHINH--resistance/intolerance resistance/intolerance –– rifampin for 4rifampin for 4--6 6 monthsmonths

l idl id ii ll MultidrugMultidrug--resistance resistance –– consult an expertconsult an expert

Use isoniazid unless there is documented Use isoniazid unless there is documented exposure to a specific case of drugexposure to a specific case of drug--resistant resistant TBTB

ALTERNATIVE REGIMENS FOR ALTERNATIVE REGIMENS FOR LTBILTBI

INH for 6 monthsINH for 6 months Rifampin for 4Rifampin for 4--6 months6 months INH + RIF for 3INH + RIF for 3--4 months4 months

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PEARLS OF WISDOM FOR PEARLS OF WISDOM FOR TREATING LTBITREATING LTBI

Use INH suspension only in children Use INH suspension only in children ≤ ≤ 5 kg5 kg5 kg5 kg

Use DOPT for: recent contacts, Use DOPT for: recent contacts, infants, immune compromisedinfants, immune compromised

When children aren’t tolerating INH, When children aren’t tolerating INH, the problem is more often with the the problem is more often with the parent than the childparent than the child

Routine LFTs only for: other liver Routine LFTs only for: other liver toxic drugs, liver disease, signs or toxic drugs, liver disease, signs or symptoms of hepatitissymptoms of hepatitis

Pyridoxine needed only for breastPyridoxine needed only for breast--feeding infants, pregnancy, poor dietsfeeding infants, pregnancy, poor diets

TREATMENT OF TREATMENT OF TUBERCULOSIS DISEASE TUBERCULOSIS DISEASE

IN CHILDRENIN CHILDRENPulmonaryPulmonary

INH RIF f 6 th + PZA f fi t 2 INH RIF f 6 th + PZA f fi t 2 INH, RIF for 6 months + PZA for first 2 INH, RIF for 6 months + PZA for first 2 monthsmonths

Add EMB initially if risk of INH resistanceAdd EMB initially if risk of INH resistance Can be q.day or twice weeklyCan be q.day or twice weekly INHINH--resistant: RIF+PZA+EMB for 9 monthsresistant: RIF+PZA+EMB for 9 months MDR MDR -- depends on susceptibility depends on susceptibility -- at least at least

18 months18 months18 months18 monthsCNS, DisseminatedCNS, Disseminated usually start with 4 drugs (INH, RIF, PZA + usually start with 4 drugs (INH, RIF, PZA +

EMB)EMB) usual lengthusual length: 9: 9--12 months12 months q.day initially, may use twice weekly laterq.day initially, may use twice weekly later

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TREATMENT RULE OF THUMB TREATMENT RULE OF THUMB FOR CNS TUBERCULOSISFOR CNS TUBERCULOSIS

Treatment for tuberculous meningitis Treatment for tuberculous meningitis should be started while the workshould be started while the work up up should be started, while the workshould be started, while the work--up up is being undertaken, for any child is being undertaken, for any child with meningitis, no obvious cause with meningitis, no obvious cause [such as a positive Gram stain] and [such as a positive Gram stain] and any of: basilar enhancement, any of: basilar enhancement, hydrocephalus, cranial nerve hydrocephalus, cranial nerve y p ,y p ,abnormality, infarction, possible abnormality, infarction, possible tuberculomatuberculoma

TREATMENT OF TUBERCULOUS TREATMENT OF TUBERCULOUS MENINGITISMENINGITIS

MedicationsMedications

Always start at least 4 antiAlways start at least 4 anti--TB drugsTB drugs1.1. IsoniazidIsoniazid2.2. RifampinRifampin3.3. PyrazinamidePyrazinamide4.4. Ethionamide or an aminoglycosideEthionamide or an aminoglycoside

Always start corticosteroids [4Always start corticosteroids [4--6 6 weeks]weeks]

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TREATMENT OF TUBERCULOUS TREATMENT OF TUBERCULOUS MENINGITISMENINGITIS

Other MeasuresOther Measures

Fluid/electrolyte managementFluid/electrolyte management Airway managementAirway management Seizure controlSeizure control Ventriculostomy or VP shuntVentriculostomy or VP shunt Physical therapyPhysical therapy

TREATMENT OF LYMPHATIC TUBERCULOSIS

Biggest problem is differentiating TB gg p gfrom NTM adenitis and Bartonella

Surgical Approach1. Fine needle aspiratep2. Incision and drainage [Not!]3. Excisional biopsy

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TREATMENT OF LYMPHATIC TUBERCULOSIS

Can use standard anti-TB regimens Can use standard anti TB regimens Relapse/recrudescence rates are

fairly high Empiric regimen for “mycobacterial”

lymphadenitis:y pINH+RIF+EMB+Clarithromycin[covers TB, M. bovis, many NTM]

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TUBERCULOSIS IN CHILDREN TUBERCULOSIS IN CHILDREN IMPACT OF DRUGIMPACT OF DRUG--RESISTANCERESISTANCE

Usually must link the child with an adult case Usually must link the child with an adult case to identify itto identify itto identify itto identify it

Adults with drugAdults with drug--resistant TB are as resistant TB are as contagious as those with susceptible diseasecontagious as those with susceptible disease

Disease expression in children the same as Disease expression in children the same as sease e p ess o c d e t e sa e assease e p ess o c d e t e sa e aswith susceptible strainswith susceptible strains

Children tolerate and respond well to secondChildren tolerate and respond well to second--line drugsline drugs

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PRINCIPLES OF TREATING MDR PRINCIPLES OF TREATING MDR TUBERCULOSIS IN CHILDRENTUBERCULOSIS IN CHILDREN

ff ExposureExposure: often don’t treat: often don’t treat InfectionInfection: two best available : two best available

drugsdrugs DiseaseDisease: usually 4 to 6 drugs, : usually 4 to 6 drugs, y g ,y g ,

best availablebest available

PRINCIPLES OF TREATING DRUGPRINCIPLES OF TREATING DRUG--RESISTANT TB IN CHILDRENRESISTANT TB IN CHILDREN

1.1. Get susceptibility patternGet susceptibility pattern2.2. LTBILTBI: RIF if susceptible; if resistant to both : RIF if susceptible; if resistant to both

INH and RIF, use two best drugs INH and RIF, use two best drugs PZA+EMB or PZA+quinolone; PZA+EMB or PZA+quinolone; 99--12 mos.12 mos.

3.3. DiseaseDisease: Need 2 cidal drugs, if possible, : Need 2 cidal drugs, if possible, plus at least 2 other drugsplus at least 2 other drugsp gp g

daily therapy onlydaily therapy only INHINH--RR: 9 months of therapy: 9 months of therapy MDRMDR: at least 12 months of therapy: at least 12 months of therapy XDRXDR: ???: ???

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25 YEAR EXPERIENCE WITH DRUG 25 YEAR EXPERIENCE WITH DRUG RESISTANT TB IN CHILDRENRESISTANT TB IN CHILDREN

Jeffrey Starke, MD Lydia Ong, PAJeffrey Starke, MD Lydia Ong, PA--C and Andrea Cruz, MDC and Andrea Cruz, MD

158 patients: 65 exposure, 55 infection, 38 disease158 patients: 65 exposure, 55 infection, 38 diseasep p , ,p p , ,

79 MDR79 MDR--TB: 41 exposure, 28 infection, 10 diseaseTB: 41 exposure, 28 infection, 10 disease

Resistance: INHResistance: INH––150, RIF150, RIF––103, PZA103, PZA––33, EMB33, EMB--2727

No child with exposure or infection progressed to No child with exposure or infection progressed to diseasediseasediseasedisease

All children with disease had resolution All children with disease had resolution For 76% of patients, drug resistance known at For 76% of patients, drug resistance known at

onset of treatment [contact investigation]onset of treatment [contact investigation] Adverse reactions very infrequentAdverse reactions very infrequent

CORTICOSTEROIDS IN CORTICOSTEROIDS IN PEDIATRIC PEDIATRIC

TUBERCULOSISTUBERCULOSIS Useful when host inflammatory Useful when host inflammatory Useful when host inflammatory Useful when host inflammatory

response is contributing to tissue response is contributing to tissue damage or dysfunctiondamage or dysfunction•• meningitismeningitis•• endobronchialendobronchial

milia ith al eola blockmilia ith al eola block•• miliary with alveolar blockmiliary with alveolar block•• pericardial with constrictionpericardial with constriction•• vertebral with spinal root irritationvertebral with spinal root irritation

Can use prednisone or Can use prednisone or dexamethasonedexamethasone

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TREATMENT OF TB IN HIVTREATMENT OF TB IN HIV--INFECTED CHILDRENINFECTED CHILDREN

Respond well to standard regimensRespond well to standard regimens Use 4 drugs initially for TB diseaseUse 4 drugs initially for TB disease Length of therapy 9Length of therapy 9--12 months12 months Rifampin drug interactions a problemRifampin drug interactions a problem*can give rifampin for 1*can give rifampin for 1--2 months, 2 months, then change to other TB drugsthen change to other TB drugsthen change to other TB drugsthen change to other TB drugs*can use rifabutin [though few data *can use rifabutin [though few data for children, esp. infants]for children, esp. infants]

TREATING TB IN IATROGENICALLY TREATING TB IN IATROGENICALLY IMMUNE SUPPRESSED CHILDRENIMMUNE SUPPRESSED CHILDREN

Corticosteroids, antiCorticosteroids, anti--TNF antibodies, TNF antibodies, ,, ,,cancer chemotherapy, anticancer chemotherapy, anti--rejection rejection drugsdrugs

Need to stop the immunosuppression Need to stop the immunosuppression as much as possible for at least 4as much as possible for at least 4--6 6

k l f tik l f ti TNF tib diTNF tib diweeks, longer for antiweeks, longer for anti--TNF antibodiesTNF antibodies CaseCase--byby--case basiscase basis

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MOST COMMON REPORTED MOST COMMON REPORTED ADVERSE REACTIONS TO ANTIADVERSE REACTIONS TO ANTI--TB TB

DRUGS IN CHILDRENDRUGS IN CHILDREN

Upset stomach [all]Upset stomach [all] Upset stomach [all]Upset stomach [all] Loose stools [INH suspension]Loose stools [INH suspension] Decreased appetite [? all]Decreased appetite [? all] Change in behavior [? not related]Change in behavior [? not related] Headaches [esp. INH; ? Not related]Headaches [esp. INH; ? Not related] Headaches [esp. INH; ? Not related]Headaches [esp. INH; ? Not related] Itching [PZA]Itching [PZA] Sore joints and muscles [PZA]Sore joints and muscles [PZA] Signs of peripheral neuritis [INH]Signs of peripheral neuritis [INH]

DEALING WITH LIVER TOXICITY DEALING WITH LIVER TOXICITY IN CHILDRENIN CHILDREN

More common with severe TB More common with severe TB disease especially early ondisease especially early ondisease, especially early ondisease, especially early on

More common with underlying liver More common with underlying liver abnormality or coabnormality or co--administration of administration of hepatotoxic drugs [anticonvulsants]hepatotoxic drugs [anticonvulsants]

Most common in first two months, Most common in first two months, b t t tib t t tibut can occur at any timebut can occur at any time

**Warn parentsWarn parents: “Stop drugs first, call : “Stop drugs first, call me second” [child on INH alone]me second” [child on INH alone]

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DEALING WITH LIVER TOXICITY DEALING WITH LIVER TOXICITY IN CHILDRENIN CHILDREN

Check liver enzymes for vomiting, Check liver enzymes for vomiting, y g,y g,abdominal pain and/or jaundiceabdominal pain and/or jaundice

Liver “sparing” regimen: ethambutol, Liver “sparing” regimen: ethambutol, aminoglycoside, fluoroquinoloneaminoglycoside, fluoroquinolone

Restart drugs one at a time; check Restart drugs one at a time; check liver enzymes after 3liver enzymes after 3--5 days for each5 days for each

PZA is most expendable drugPZA is most expendable drug

FOLLOWFOLLOW--UP EVALUATIONS UP EVALUATIONS FOR CHILDREN WITH FOR CHILDREN WITH

TUBERCULOSISTUBERCULOSIS skin test stays positive “forever”skin test stays positive “forever” frequent chest xfrequent chest x--rays unnecessary: rays unnecessary:

at diagnosis, 1at diagnosis, 1--2 months, end of 2 months, end of therapy therapy

follow growth & development closelyfollow growth & development closely adequate nutritionadequate nutritionqq routine liver enzyme monitoring not routine liver enzyme monitoring not

necessarynecessary routine vitamin Broutine vitamin B66 not necessary not necessary

except breastexcept breast--feeding, pregnant feeding, pregnant adolescents, poor dietadolescents, poor diet

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IMMUNE RECONSTITUTION IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME [IRIS]INFLAMMATORY SYNDROME [IRIS] happens in a variety of situations when happens in a variety of situations when

severely immunocompromised patients have severely immunocompromised patients have y p py p prapid restoration of immune functionrapid restoration of immune function

e.g.: neutropenic cancer patients with e.g.: neutropenic cancer patients with CandidemiaCandidemia

in HIV, a/w a variety of organisms, in HIV, a/w a variety of organisms, including mycobacteria, CMV, hepatitis B including mycobacteria, CMV, hepatitis B

d C i HSV JC i ( i d C i HSV JC i ( i and C viruses, HSV, JC virus (progressive and C viruses, HSV, JC virus (progressive multifocal leucoencephalopathy), multifocal leucoencephalopathy), Pneumocystis, Cryptococcus, Pneumocystis, Cryptococcus, leishmaniasis, leishmaniasis, cerebral toxoplasmosiscerebral toxoplasmosis

Mycobacteria account for 40% of the casesMycobacteria account for 40% of the cases

IRIS AND MYCOBACTERIAIRIS AND MYCOBACTERIA SoSo--called “paradoxical reactions” occur in called “paradoxical reactions” occur in

2% to 23% of HIV2% to 23% of HIV--negative adult patients negative adult patients receiving treatment for tuberculosisreceiving treatment for tuberculosisreceiving treatment for tuberculosisreceiving treatment for tuberculosis

Most common features are fever and lymph Most common features are fever and lymph node enlargement, though respiratory node enlargement, though respiratory failure and neurologic deterioration also failure and neurologic deterioration also occuroccur

Median time is 40Median time is 40--90 days after TB 90 days after TB treatment is startedtreatment is startedtreatment is startedtreatment is started

Abnormality is at the original site of Abnormality is at the original site of infection in 75% of cases, at a new location infection in 75% of cases, at a new location in 25%in 25%

Mechanism: increased tumor necrosis factorMechanism: increased tumor necrosis factor

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IRIS AND MYCOBACTERIAIRIS AND MYCOBACTERIA

In HIVIn HIV--uninfected children treated for uninfected children treated for tuberculosis, paradoxical reactions are tuberculosis, paradoxical reactions are commoncommon

Enlarged hilar/mediastinal lymph nodes, Enlarged hilar/mediastinal lymph nodes, tuberculomas are most commontuberculomas are most common

Changes may be only radiographic or clinical Changes may be only radiographic or clinical Changes may be only radiographic or clinical Changes may be only radiographic or clinical -- stridor, respiratory distress, seizures stridor, respiratory distress, seizures (tuberculoma)(tuberculoma)

Natural history vs. immune reconstitutionNatural history vs. immune reconstitution

IRIS AND MYCOBACTERIAIRIS AND MYCOBACTERIA

Definition: “presentation or clinical deterioration of an Definition: “presentation or clinical deterioration of an opportunistic infection in HIVopportunistic infection in HIV--infected patients as a infected patients as a direct result of the enhancement of immune direct result of the enhancement of immune direct result of the enhancement of immune direct result of the enhancement of immune responses to those pathogens during HAART”responses to those pathogens during HAART”

Strongest clue is usually a temporal association (30Strongest clue is usually a temporal association (30--90 days)90 days)

No specific laboratory test availableNo specific laboratory test available

Clinical judgment is important (but may be Clinical judgment is important (but may be Clinical judgment is important (but may be Clinical judgment is important (but may be nonspecific)nonspecific)

Can also be a worsening of the opportunistic Can also be a worsening of the opportunistic infection due to poor compliance, poor absorption or infection due to poor compliance, poor absorption or drug resistancedrug resistance

Can also be a new infection or conditionCan also be a new infection or condition

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IRIS IN CHILDRENIRIS IN CHILDREN

Puthanakit et al. Pediatr Infect Dis J 2006; 25:53Puthanakit et al. Pediatr Infect Dis J 2006; 25:53

32/153 (21%) HIV32/153 (21%) HIV i f t d Th i hild d l d i f t d Th i hild d l d 32/153 (21%) HIV32/153 (21%) HIV--infected Thai children developed infected Thai children developed IRIS after starting HAARTIRIS after starting HAART

14/32 (44%) episodes associated with mycobacteria 14/32 (44%) episodes associated with mycobacteria [3[3--TB, 2TB, 2--BCG, 7BCG, 7--MAC Complex, 2MAC Complex, 2--other]other]

In 11 of 14 patients, the mycobacterial infections had In 11 of 14 patients, the mycobacterial infections had not been diagnosed prior to starting HAARTnot been diagnosed prior to starting HAART

7 varicella7 varicella--zoster, 7HSV, 3 zoster, 7HSV, 3 Cryptococcus, Cryptococcus, 1 Guillain1 Guillain--BarreBarre

Children who developed IRIS had significantly lower Children who developed IRIS had significantly lower baseline CD4 lymphocyte countsbaseline CD4 lymphocyte counts

PREVENTION AND TREATMENT OF IRISPREVENTION AND TREATMENT OF IRIS

Watch out! CD4 lymphocyte count Watch out! CD4 lymphocyte count < 100 cells < 100 cells viral load > 10viral load > 105 5 copies/mlcopies/ml

? if HAART should be delayed in patients ? if HAART should be delayed in patients with TBwith TB

Must balance risk of IRIS with risk of other Must balance risk of IRIS with risk of other opportunistic infection if CD4 count stays opportunistic infection if CD4 count stays low and viral load stays highlow and viral load stays high

Adjunctive treatment Adjunctive treatment -- only anecdotal only anecdotal evidence at presentevidence at present

Oral corticosteroids can help when severe Oral corticosteroids can help when severe manifestations occur ( same as TB in HIVmanifestations occur ( same as TB in HIV--uninfected children!)uninfected children!)