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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 3 rd in order of infected cases 16% of all new cases occur in children<15yr.

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Pediatric HIV

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  1. Pediatric HIV Dr.Bujji Babu M.D.

  2. 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

  3. 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

  4. 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

  5. TRANSMISSION • Transfusion related 30% • Vertical 70% • In utero 30-40% • Intrapartum 50-70% • Breast feeding 14-29%

  6. Clinical features • Failure to thrive 100% • Fever 95% • Recurrent/persistent LRT 86% • Recurrent diarrhea 45% • Lymphadenopathy 40% • Hepatosplenomegaly 75% • CNS involvement 13%

  7. Clinical manifestations • INFECTIONS:bacterial • viral • fungal • parasitic • Organ specific:CNS, GIT, Pulmonary, renal, hematology,CVS, Skin,Malignancy • Ophthalmology

  8. CDC Pediatric HIV Classification

  9. CDC Revised Pediatric HIV Classification:Immune categories

  10. CLINICAL MANIFESTATIONS • Infections:recurrent bacterial infections persistent pneumonias Opportunistic infections: PCP MAC Oral Candidiasis,Cryptosporidiosis Disseminated CMV,Herpes,Varicella,Measles

  11. 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

  12. 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)

  13. 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

  14. Clinical manifestations…. • GIT:Oral candidiasis • AIDS Enteropathy • Chronic diarrhea • Chronic hepatitis • pancreatitis • Cardiovascular system • Renal disease

  15. Clinical manifestations • Hematology:anemia 20-70% • leukopenia 33% • thrombocytopenia 10-20% • Malignancy:<2% of cases • Skin manifestations:nonresponsive seborrheic dermatitis

  16. 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% NATURAL HISTORY

  17. 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

  18. 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

  19. 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

  20. MANAGEMENT • Definitive therapy :HAART • Supportive care:Nutrition • Immunisation • Prophylaxsis • Treatment of specific secondary infections • Neuropsycological complications of HIV

  21. TREATMENT • Baseline investigations:CBP,LFT,Serum amylase,LDH,CXR,Mx,Urine CMV,TOXO serology,quantitative immunoglobulins • CD4/CD8 • HIV RNA PCR • HIV Culture

  22. Treatment • Hit early,hit hard • NO HALF HEARTED HAART

  23. HAART… • Prerequisitives for HAART • Definite diagnosis • Counselling of family • Options of therapy • NO CURE , ONLY CONTROL • LIFE LONG/SURVIVES • COST • DRUG COMPLIANCE,ADHERENCE

  24. 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

  25. HAART:When to start <12m

  26. HAART:When to start >12m

  27. 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

  28. HAART… • What to start…… • Protease inhibitor based: 2NRTI and 1PI • NNRTI based regimes:2NRTI and 1NNRTI • NRTI Based regimes:3NRTI

  29. 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

  30. 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

  31. Recommended HAART regimes in children • NRTI based regime • Strongly recommended:none • Alternative regime:ZDV plus 3TC plus abacavir • Use in special circumstances:2NRTI

  32. HAART… • NEVER USE • ZDV,d4T antagonistic action • d4T,ddC Toxicity concern • ddI,ddc Toxicity concern • ddC,3TC Toxicity concern • Monotherapy resistance concern

  33. 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.

  34. 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

  35. 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

  36. 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)

  37. When to change drugs • Clinical considerations • Progressive neurodevelomental deterioration • Growth failure • Disease progression • Drug toxicity or intolerance • Superior new drug regimes

  38. 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

  39. 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

  40. Supportive care… • Passive immunisation • VZIG<72hrs of exposure • Measles Ig<6days. • PROPHYLAXSIS • Primary Secondary • PCP PCP,CMV, • DMAC candidiasis,cryptococcosis

  41. PCP Prophylaxsis

  42. 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)

  43. HIV and TUBERCULOSIS • Adult type picture • PPD >5mm positive • Asymptomatic childPPD,CXR,contact • Positive Contact :6RH • Positive Contact plus PPD>5mm:9RH • SYMPTOMATIC:9-12 m ATT

  44. 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 PROGNOSIS

  45. 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

  46. Strategies to improve Adherence • Initial interventional strategies • Medication strategies • Follow up intervention strategies

  47. 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.

  48. Thank you

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