HIV in pediatric
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Paediatric’s HIV
Koh Kian Chuan
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Virus classification
Group: Group VI (ssRNA-RT)
Order: Unassigned
Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Lentivirus
Species
•Human immunodeficiency virus 1•Human immunodeficiency virus 2
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HIV
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pathophysiology
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Introduction• By the end of 2006, estimated 2.3million children <15 years old
living with HIV with an estimated half a million new infections occurring in children
• Children < age 12 years old constituted 1.5% of total reported cases for 2006, those aged 13-19 years 1% and those aged 20-29 years 2.7%
• Vast majority of paediatric HIV infections are acquired vertically
• In developed countries, number of children of HIV positive mothers newly infected with HIV has dramatically decreased with a perinatal transmision rate of <1% a result of antiretroviral (ARV) prophylaxis and the use of highly active antiretroviral therapy (HAART) for pregnant HIV infected mother
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Prevention of mother to child transmission
• 3 components of treatment or prophylaxis (antepartum, intrapartum and neonatal)
• Longer courses of ARV prophylaxis
• Therapy beginning earlier in pregnancy
• Combination regimens
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Factors associated with higher transmission rate
• Maternal– Low CD4 counts– High viral load– Advanced disease – Seroconversion during pregnancy
• Fetal– Premature delivery
• Delivery and procedures– Invasive procedures eg episiotomy– Fetal blood sampling or amniocentesis– Vaginal delivery– Rupture of membrane >4 hrs– chorioamnionitis
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Investigation at birth
• FBC
• HbsAg, Hepatitis C, Toxoplasmosis, CMV, VDRL serology
• LFT, RFT
• HIV DNA PCR
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• Feeding
– not to breastfeed
– Against mixed feeding
• Immunization
– All infants born to HIV infected mothers should receive routine childhood immunisation at the usual recommended age
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• BCG
– Administered to HIV infected infants in the first month of life is associated with low rates of complications
– Complications: lymphadenitis
disseminated infection
IRIS (immune reconstitution inflammatory syndrome)
– Very little data on effectiveness of BCG in HIV infected children
• Polio
– OPV (live attenuated vaccine)--Rare complication: vaccine –associated paralytic poliomyelitis (VAPP)
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• MMR– Live attenuated vaccine
– Risk of adverse reaction following vaccination was no different HIV infected and uninfected children
– Studies on Immunogenicity of MMR vaccine in HIV infected children –noted impairment of Ab response with only half developing protective Ab level
• Hepatitis B – Recombinant vaccine
– No significant adverse event
– Immunogenicity: poorer response rate in HIV infected children with only 25-50% developing protective antibodies
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• Hib– Conjugated polysaccharide vaccine– Safe and immunogenic
• DTP– Safe and immunogenic
• Pneumococcal vaccine– Children infected with HIV have a markedly increased risk
of pneumococcal infection– Both PPV and PCV are safe– ~ 65-100% of HIV infected children developed protective
Ab after PCV vaccination– ART and PPV –independent protective effect against
pneumoccocal disease regardless of CD4 count
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• Varicella vaccine
– Safe and good immunogenicity
–2 doses with 2 months interval
–omit in those with severe immunosuppression (CD4<15%)
Despite vaccination, remember long term protection may not be achieved in severe immunosuppression ie, they may still be at risk of acquiring infections!
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• Precautions recommended for live-attenuated vaccines:
– BCG should not be given in symptomatic HIV infected infants or children (WHO stage 2,3,4) as they are at higher risk of developing disseminated disease
– OPV should be replaced by injectable Inactivated Polio Vaccine
– MMR should be given as per schedule except to those who have severe immunosuppression(CD4<15%)
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Common Clinical features
• Persistent lymphadenopathy
• Hepatosplenomegaly
• Failure to thrive
• Developmental delay
• Recurrent infections (respiratory, skin, gastrointestinal)
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Clinical and Laboratory monitoring of perinatally exposed infant
• Clinical monitoring
– Physical growth
– Developmental milestones
– Early detection of opportunistic infections
– Review of immunization
– Adverse effects of drug therapy
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Virologic and serologic monitoring
• HIV PCR DNA is done at 14-21 days, at 1-2 months of age, and at 4-6 months of age
• Serologic testing after 12 months of age
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Primary PCP prophylaxis• Recommended for infants with indeterminate HIV infection status starting
4-6 weeks of age till they are determined to be HIV-uninfected or presumptively uninfected
• Primary TMP-SMX prophylaxis should be continued until at least 1 year of age for HIV-infected infants and then re-evaluated
• Further use of prophylaxis is guided by clinical staging and CD4%
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Management of HIV infected infants, children and adolescents
• Monitoring of disease progression
– Clinical
– Immunologic- CD4 count and %
– Virologic – plasma viral load assay
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Antiretroviral therapy
• At least 3 drugs
• Monotherapy and dual ART- found Not to provide sustained viral suppression, increased risk of resistance
• Benefits of HAART:– Reduce mortality by 67-80%
– Halt progression to AIDS by 50%
– Reduce hospitalization rate by 68-80%
– Reduce incidence of opportunistic infections by 62-93%
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When to initiate therapy
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Monitoring of HIV infected child on treatment
• Clinical: adherence, drug adverse effects, and improvements in height, weight and development
• Virologic : plasma viral load monitored at week 8, week 12 and every 4-6 months thereafter or whenever there is significant decline in CD4 + T cells
• Immunologic: CD4 should be monitored 3-4 monthly
– CD4% expected to increase ranging from 5-10% at 6 months with continued rise through 1st 2-3 years of HAART
– Patients with discordant responses should be referred to paediatric infectious diseases specialist
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Immune reconstitution inflammatory syndrome
• Characterized by paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating ART and results from restored immunity to infectious and non-infectious agents
• Proposed definition:– Decrease in HIV-1 RNA level from baseline– increase in CD4+ cells from baseline– Clinical symptoms consistent with inflammatory process– Clinical courses not consistent with
• Expected course of previously diagnosed OI• Expected course of newly diagnosed OI• Drug toxicity
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Treatment failure
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Follow up
• Every 3-4 months, if just commencing or switching HAART then every 2 weeks
• Ask about medications
• Side effects: vomiting, abdominal pain, jaundice
• Examine: growth, HC, pallor, jaundice, oral thrush
• FBC, CD4, viral load every 3-4 months
• RFT,LFT,CA/PO4 (amylase if on didanosine) 6monthly
• Referral to social welfare
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• Thank you