Pediatric HIV
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Transcript of Pediatric HIV
Pediatric HIV
Dr.Bujji Babu
M.D.
EPIDEMIOLOGY
• >5 million infected• India is second to South Africa in total cases• Average adult prevalence is 0.8-1%• 25%women are infected• Andhra pradesh is 3rd in order of infected cases• 16% of all new cases occur in children<15yr
PEDIATRIC vs ADULT HIV
• Acquisition of infection –PERINATAL• In utero exposure to antiretrovirals• HIV virologic tests to diagnose infants• Age specific differences in immunological
markers• Differences in drug pharmacokinetics• Morbidity profile and natural history is different• Children with HIV have lower survival• Adherence to antiretroviral needs special care
PEDIATRIC vs ADULT HIV
• Increased incidence of PCP(12%)• HIV encephalopathy is more common• CNS lymphoma,toxoplasmosis and cryptococcosis
are infrequent• Incidence of TBM is lower• Parotitis,LIP are more common• Kaposis sarcoma is rare• HIV nephropathy and cardiomyopathy may occur
TRANSMISSION
• Transfusion related 30%
• Vertical 70%
• In utero 30-40%
• Intrapartum 50-70%
• Breast feeding 14-29%
Clinical features
• Failure to thrive 100%
• Fever 95%
• Recurrent/persistent LRT 86%
• Recurrent diarrhea 45%
• Lymphadenopathy 40%
• Hepatosplenomegaly 75%
• CNS involvement 13%
Clinical manifestations
• INFECTIONS:bacterial
• viral
• fungal
• parasitic
• Organ specific:CNS, GIT, Pulmonary, renal, hematology,CVS, Skin,Malignancy
• Ophthalmology
CDC Pediatric HIV Classification
Immune Category
N-No sign/sym
A-Mild sign/sym
B-Mod sign/sym
C-Severe
Sign/sym
Suppression No
N1 A1 B1 C1
Moderate N2 A2 B2 C2
Severe N3 A3 B3 C3
CDC Revised Pediatric HIV Classification:Immune categoriesImmune categories
<12 months 1-5years >6years
No suppression
>1500cell/l
>25%
>1000
>25%
>500
>25%
Moderate suppression
750-1499c/l
15-24%
500-999
15-24%
200-499
15-24%
Severe suppression
<750
<15%
<500
<15%
<200
<15%
CLINICAL MANIFESTATIONS
• Infections:recurrent bacterial infections
persistent pneumonias
Opportunistic infections:
PCP
MAC
Oral Candidiasis,Cryptosporidiosis
Disseminated CMV,Herpes,Varicella,Measles
PCP
• 33%of children,AIDS defining illness
• Peak age 3-6 months
• Highest mortality in <1year of age
• Fever,tachypnea,dyspnea,hypoxia
• CXR:interstitial infiltrates,diffuse alveolar opacities,lobar infiltrates,pleural effusions
PCP
Diagnosis:P.carinii in BAL,tracheal aspirate
Treatment :intravenous IV TMP(20mg/kg/d)SMZ(100mg/kg/d)or Pentamidine(4mg/kg/d)
Prednisolone 2mg/kg/d if PaO2 <70
Secondary prophylaxsis:TMP(150/mg/m2/d)
And SMX(750/mg/m2/d)
Clinical manifestations….
• CNS:HIV Encephalopathy 50-90%perinatal infections
• Progressive or Static encephalopathy• Respiratory tract:LIP (25%)• Related to exposure to EBV• Nodular lymphoid hyperplasia • Progressive alveolar capillary block• Diffuse reticulonodular pattern• Prednisolone 2mg/kg/d
Clinical manifestations….
• GIT:Oral candidiasis
• AIDS Enteropathy
• Chronic diarrhea
• Chronic hepatitis
• pancreatitis
• Cardiovascular system
• Renal disease
Clinical manifestations
• Hematology:anemia 20-70%
• leukopenia 33%
• thrombocytopenia 10-20%
• Malignancy:<2% of cases
• Skin manifestations:nonresponsive seborrheic dermatitis
NATURAL HISTORY
• RAPID PROGRESSORS
• 20-30%• PCP• Failure to thrive• HIV Encephalopathy• Intra partum infection
• SLOW PROGRESSORS
• 15% are asymptomatic till 5yrs
• Lymphadenopathy• Parotitis• INTERMEDIATE
PROGRESSOR 60-75%
DIAGNOSIS
• Children >18months: 3 HIV antibody tests
• Children <18months:HIV nonexposed (parents nonreactive)-3HIV antibody tests
positive HIV infection
negative NO infection
• HIV exposed (mother positive):HIV culture
HIV DNA/RNA PCR
HIV exposed Infant
• Virologic tests, no role of antibody tests
• Neonates sample(not cord blood)
• 48hrs 1-2m 4-6m
• N N N NO HIV
• P P P inutero infection
• N P P intrapartum
• N N P Breast feeding
Diagnosis ….
• Two negative HIV Elisa tests done 1month apart after 6months of age exclude HIV infection in a child with no clinical evidence of disease
MANAGEMENT
• Definitive therapy :HAART
• Supportive care:Nutrition
• Immunisation
• Prophylaxsis
• Treatment of specific secondary infections
• Neuropsycological complications of HIV
TREATMENT
• Baseline investigations:CBP,LFT,Serum amylase,LDH,CXR,Mx,Urine CMV,TOXO serology,quantitative immunoglobulins
• CD4/CD8
• HIV RNA PCR
• HIV Culture
Treatment
• Hit early,hit hard
• NO HALF HEARTED HAART
HAART…
• Prerequisitives for HAART• Definite diagnosis• Counselling of family• Options of therapy• NO CURE , ONLY CONTROL• LIFE LONG/SURVIVES• COST• DRUG COMPLIANCE,ADHERENCE
HAART:When to start
• Treat ALL HIV infected children age<1yr regardless of clinical,immunological virologic status
• Treat ALL HIV infected with clinical symptoms of HIV(Category A,B,C)
• Treat ALL children with evidence of immunesuppresion(immune category 2/3) regardless of age or viral load
HAART:When to start <12m
Clinical category
CD4% Plasma HIV RNA copies
Recommendation
Symptomatic(A,B or C)
OR
<25% Immune category 2/3
Any value treat
Asymptomatic (N)
>25% Immune category 1
Any value Consider treatment
HAART:When to start >12m
Clinical category
CD4% Plasma HIV RNA copies
recommendation
AIDS (C) OR
<15% Any value treat
Mild-mod
A,B OR
15-25% >100,000c/l Consider treat
Asymptomatic( N) AND
>25% <100,000c/l Defer and monitor
HAART …..
• 1. HIV RNA level is raised or increasing
>5 fold raise in <2years of age
>3 fold raise in >2years of age• 2.CD4 absolute number or percentage is found to
be declining rapidly to Immune category 2• 3.Clinical disease• 4.All children with HIV RNA>100,000c/ml• 5.Children >30months with HIVRNA>10,000c/ml
HAART…
• What to start……
• Protease inhibitor based: 2NRTI and 1PI
• NNRTI based regimes:2NRTI and 1NNRTI
• NRTI Based regimes:3NRTI
Recommended intial HAART in children
• PI BASED REGIME :
• Strongly recommended
• 2NRTI and Lopinavir/ritonavir or nelfinavir or ritonavir
• Alternative:2NRTI and Ampenavir(child>4yr) or indinavir
Recommended HAART regimes for initial therapy
• NNRTI BASED REGIMES:
• Strongly recommended:
• children>3y 2NRT plus efavirenz
• Children <3y 2NRTI plus nevirapine
• Alternative regime:2NRTI plus nevirapine
Recommended HAART regimes in children
• NRTI based regime
• Strongly recommended:none
• Alternative regime:ZDV plus 3TC plus abacavir
• Use in special circumstances:2NRTI
HAART…
• NEVER USE
• ZDV,d4T antagonistic action
• d4T,ddC Toxicity concern
• ddI,ddc Toxicity concern
• ddC,3TC Toxicity concern
• Monotherapy resistance concern
HAART….
• How to monitor…• Basal tests:CD4, plasma viral load, CBP,LFT• CD4,plasma viral load is assessed at
4wk,12wk,3monthly there after• If a 10 fold decrease in viral load is not seen
at the end of 12wk DRUG RESISTANCE• Change or add new drugs.
HAART…
• Syr zidovudine:160mg/m2/dose
• 2mg/kg/dose 6th hourly
• Syr lamivudine:100mg/m2/dose
• 4mg/kg/12th hourly
• ZDV plus 3TC: COMBIVIR(300/150)
• VIRAMMUNE
When to change drugs
• Virologic considerations:<10%decrease in viral load
• HIV RNA not suppressed to undetectable levels after 4-6m of HAART
• Repeated detection of HIV RNA in children who had undetectable levels initially
When to change drugs
• Immunological considerations:
Change in immune class
Persistent decline of CD4 % by5%
Rapid decline in absolute CD4
count(>30% decline in<6m)
When to change drugs
• Clinical considerations
• Progressive neurodevelomental deterioration
• Growth failure
• Disease progression
• Drug toxicity or intolerance
• Superior new drug regimes
When and What drugs to be changed
• Assess and review adherence• Never ever change one drug• Add 2 new drugs of different category• Consider overlap of drug resistance pattern• Consider drug interactions• Quality of life• If dose of drug is decreased do not reduce below
thearapeutic range
Supportive care
• IMMUNISATION:standard pediatric immunisation schedule.
• No live Vaccines (no OPV,BCG)
• Varicella and MMR can be given to immune categories 1 and 2 (but not 3)
• PCV(Pneumococcal conjugate vaccine) is given 2,4,6 and15 months.Booster PPV 5yrs
Supportive care…
• Passive immunisation
• VZIG<72hrs of exposure
• Measles Ig<6days.
• PROPHYLAXSIS
• Primary Secondary
• PCP PCP,CMV,
• DMAC candidiasis,cryptococcosis
PCP Prophylaxsis
Birth to 4-6wk
HIV exposed
No 1month
4-6wk to 1yr
HIV exposed
yes 3 monthly
1-5yr HIV infected
CD4<500 or<15%
yes 3-4monthly
6-12yr HIV infected
CD4<200 or<15%
yes 3-4monthly
Supportive care
• Nutrition :high calorie high protein diet
NG feeds,TPN• Hygeine :importance of hand washing
Avoid raw/under cooked food(salmonella)
Avoid drinking or swimming in a lake,river water or being in contact with young farm animals(cryptosporidium)
• Risk of pets (toxoplasma, bartonella)
HIV and TUBERCULOSIS
• Adult type picture
• PPD >5mm positive
• Asymptomatic childPPD,CXR,contact
• Positive Contact :6RH
• Positive Contact plus PPD>5mm:9RH
• SYMPTOMATIC:9-12 m ATT
PROGNOSIS
• WORST:>75%die<3y• PCP,MAC• Encephalopathy• Wasting syndrome• Poor :>30% die <3yr• Persistent fever,oral
thrush,Hb<8g%,• Platelets<100,000/mm• Serious bacterial
infections
• Better :LIP,• Lymphadenopathy• Hepatomegaly• Splenomegaly• Parotitis• Median survival of
vertically infected child 8-9yrs
Management of HIV exposed infant
• ZDV from birth to 6wks
• Avoid breast feeding
• No live vaccines
• HIV DNA /RNA PCR and HIV culture at 48hrs,1-2m and 4-6m of age
• If HIV infected offer HAART
• PCP prophylaxsis from 6wk to 1yr
Strategies to improve Adherence
• Initial interventional strategies
• Medication strategies
• Follow up intervention strategies
CONCLUSION
• Mean survival in children < adults
• Cost of standard care as per western guidelines is high
• Prevention of Perinatal infection,
• Primary prophylaxsis and effective management of oppurtunistic infections is the most cost effective in Indian scenerio.
Thank you