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