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Paediatric HIV

Paediatric HIV. Dr. Russell Pierre Senior Lecturer, Consultant Paediatrician University of the West Indies. MOH 3 rd Annual HIV Clinical Management & ARV Therapy Training Workshop 29-31 March 2006. Objectives. At the end of this presentation participants should be able to:

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Paediatric HIV

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  1. Paediatric HIV Dr. Russell Pierre Senior Lecturer, Consultant Paediatrician University of the West Indies MOH 3rd Annual HIV Clinical Management & ARV Therapy Training Workshop 29-31 March 2006

  2. Objectives At the end of this presentation participants should be able to: • Understand the pathogenesis of HIV in infants and children • Recognise common presenting features of paediatric HIV • Understand the strategies for management of HIV-affected infants and children • Appreciate the application of paediatric HIV/AIDS management in the Jamaican context

  3. Philosophy • Life-cycle / developmental approach to issues of diagnosis and treatment • Public-health approach to management • Prevention of HIV • Prevention of acute illnesses / opportunistic infections • Preservation of immune function • Improving quality of life • Palliative care issues

  4. Historical perspective • Paediatric HIV first recognised in 1986 in Jamaica • ‘Pioneers’ who initiated individual ‘pockets’ of paediatric HIV care • 2002: Development of Pediatric Infectious Diseases Clinics in Greater Kingston region coordinated by Prof CDC Christie & the implementation of the Kingston Pediatric & Perinatal Program Overall Aim: Reduce MTCT Improve survival & QOL of infected children and adolescents • 2003: Program received a major boost in therapeutic and laboratory support through Clinton HIV/AIDS Initiative and Global Fund • 2003-present: Established clinics in St. Ann’s Bay, Cornwall Regional, Mandeville, and MayPen Hospitals through outreach and preceptorship training

  5. JAMAICA Pediatric AIDS Cases & Deaths (1982 - 2004) Source: Ministry of Health, Jamaica

  6. Historical perspective • Dramatic fall in incidence of new cases of paediatric infections in US • Paediatric ARV History • 1988 – monotherapy with AZT • 1994 – dual therapy • 1998 – triple therapy with HAART

  7. Key differences from infected adults • Perinatal transmission • Effect of virus on immature immune system • Virologic response • CD4+ response – reliance on CD4% to determine severity of immunologic deterioration • Clinical presentation • Diagnostic challenge in < 18 months

  8. Possible routes of transmission In-utero At Birth During breastfeeding

  9. Other modes of transmission • Sexual – abuse, exploitation, experimentation, consensual • Transfusion (rare in Ja) • Intravenous drug use (rare in Ja)

  10. Natural history of paediatric HIV Newborns: most studies – generally well at birth Virologic response: increases rapidly in initial 2-3 months then slowly declines to virologic set-point after several months to years Immunologic response: brisk and variable T cell proliferation; hence cannot rely on absolute CD4+ as marker of immune deficiency; CD4+ percent <15% indicative of severe immune deficiency Virologic set-point: state of in-vivo equilibrium between viral production and elimination

  11. Virologic response Child Adult Time (years) Infection

  12. Natural history of paediatric HIV Pattern of Clinical Progression Asymptomatic Mild to Moderate Severe

  13. Natural history of paediatric HIV Patterns of Progression Rapid 20 % Intermediate 70 % Slow 10 %

  14. Rapid Progressors • PCP • FTT • CNS invovlement • Chronic GE • Recurrent infections • CMV infection • Persistent candidiasis

  15. Progression to AIDS Early onset – perinatal infections in infants < 12 months Commonest manifestations: • recurrent pneumonia • recurrent diarrhoea • growth failure • neurological abnormalities

  16. Slow Progressors • Generally well until late childhood • Some completely asymptomatic • Few---progress to AIDS • Main problems : pneumonia / Lymphocytic interstitial pneumonitis (LIP), stunting

  17. Clinical manifestations

  18. Generalised, persistent lymphadenopathy

  19. Dermatitis

  20. Mucocutaneous Candidiasis

  21. Recurrent lower respiratory tract infections • Bacterial pneumonia • Community acquired infections • Need to always consider tuberculosis • Increased occurrence of LRTI associated with LIP

  22. Pneumocystis jiroveci pneumonia (PCP)

  23. Lymphocytic Interstitial Pneumonitis

  24. Chronic lung disease

  25. Wasting / FTT / Malnutrition

  26. Hepatosplenomegaly

  27. Neurodevelopmental abnormalities • Developmental delay • Developmental regression • Spasticity, hyperreflexia • Impaired cognitive function • CT scan brain: generalized cortical atrophy with ventricular enlargement and calcified basal ganglia (arrow) • (Ref. D. Carli C et al, Ann Neurol 34(2): 198-205, 1993.)

  28. Recurrent or persistent upper respiratory tract infection, sinusitus or otitis media Parotitis Recurrent diarrhoea Bacterial sepsis Organ-specific dysfunction CDC. 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR, 1994. 43 (No. RR-12): p. 1-10 Clinical manifestations

  29. Reducing the impact of HIV on children

  30. AIM Increase survival & Improve quality of life

  31. Give a child a chance Early Intervention is the key

  32. Framework for a comprehensive approach to manage HIV in infants children Prevent unintended pregnancy in HIV + women Prevent MTCT Prevent HIV in women Provide accessible treatment, care and support for HIV-infected women, their infants and families

  33. Key aspects of management • Prevention of HIV infection • Early diagnosis • Early detection – high index of suspicion • Prevention (& timely treatment) of common childhood illnesses • Prevention and early treatment of opportunistic infections • HAART – preserve / restore immune system • Palliative care • Multidisciplinary management approach

  34. Management of HIV-exposed infant • ARV prophylaxis (pre- and post-exposure) • Breastfeeding alternatives • Follow-up and monitoring • PCP prophylaxis – Cotrimoxazole • Diagnosis of HIV infection • Immunizations – National EPI recommendations • Nutrition • Growth & development • Clinical evaluation for stigmata of HIV infection • Challenges – follow-up, adherence to prophylaxis, stigma of non-breastfeeding

  35. Diagnosis of HIV infection in exposed infant • Serial qualitative DNA PCR is currently the accepted standard for early diagnosis • DNA-PCR [2 consecutive readings] • 1-2 months • 3-6 months • Antibodies (Elisa) • 12 months in non-breastfed infant • Others – RNA PCR, p24, viral culture • Passive transfer of maternal Ig G leads to detectable antibody in uninfected children for up to 18 months • Antibody tests e.g.ELISA not diagnostic until 18 months unless negative

  36. Lancet 2004; 364: 1865-71

  37. Diagnosis of HIV infection in child HIV Elisa with confirmatory Western blot [> 18 months of age]

  38. Classification of paediatric HIV/AIDS CDC Clinical Category • N– asymptomatic • A– mildly symptomatic • B– moderately symptomatic • C– severely symptomatic – AIDS defining conditions CDC 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR, 1994. 43 (No. RR-12): p. 1-10

  39. Classification of paediatric HIV/AIDS CDC Immune Category CD4%, and age-specific CD4 count • 1 –  25% [none/mild suppression] • 2 – 15 – 24%[moderate suppression] • 3 – < 15%[severe suppression]

  40. Classification of paediatric HIV/AIDS WHO Staging System • Clinical Stage 1 (asymptomatic) • Clinical Stage 11 (mild to moderate) • Chronic diarrhoea • Candidiasis • FTT • Persistent fever • Recurrent severe bacterial infections • Clinical Stage 111(severely symptomatic) • AIDS defining conditions • Severe FTT • Progressive encephalopathy • Malignancy • Recurrent sepsis

  41. Comprehensive management of HIV-infected child • Multidisciplinary management approach • Prevention (& timely treatment) of common childhood illnesses • Regular ambulatory care • Growth & development monitoring • Immunizations – National EPI guidelines; influenza, pneumococcal • Nutrition & food safety

  42. Comprehensive management of HIV-infected child • Prevention and early treatment of opportunistic infections • Cotrimoxazole • Fluconazole • Azithromycin • Aciclovir • Isoniazid • IVIG • Palliative care

  43. Antiretroviral Therapy Preserve and restore immune system

  44. Who, when, what, how??? • Several guidelines: Caribbean, Jamaican, WHO, DHHS………….. • Bottom-line issues for consideration • Feasible • Accessible • Affordable • Safe • Sustainable • Practical

  45. Practical guidelines • Any HIV-infected infant or child with AIDS defining condition or severe immunosuppression (CD4 < 15%) • All HIV-infected infants < 12 months of age, regardless of clinical, immunologic or virologic parameters • All others – discuss and consider treatment according to guidelines

  46. Practical considerations • Limited range of paediatric formulations in Jamaica • Initiation of therapy & adherence in children is caregiver – dependent • Treatment options are limited • Aim for practical, simplified regimes

  47. Effectiveness of interventions in treating Paediatric HIV/AIDS The Jamaican Experience

  48. Collaborators • Kingston Pediatric & Perinatal HIV/AIDS Program (KPAIDS) Team • University of the West Indies; University Hospital of the West Indies • Jamaica Ministry of Health – Bustamante Hospital for Children, Comprehensive Health Centre, Spanish Town Hospital, National AIDS Program • Elizabeth Glaser Pediatric AIDS Foundation (EGPAF), Pfizer Foundation

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