HIV in Children and early detection

2. HIV in Children and early detection CBSK ZNA Koningin Paola Kinderziekenhuis ARC: ZNA/UZA/ITG Philip Maes – Bart Peeters – Myriam Willems – Elke De Belder 21 December 2006

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10. Child with HIV: what to do?

11. Child with HIV: what to do? Don’t panic and Phone: 03/280.21.12!

12. HAART Highly Active Anti Retroviral Therapy  Dramatic fall in child and adult mortality from HIV infection in Europe  Very expensive  major impact on the family  Wide variation in prescribing practice across Europe: from 50% to 97% in different countries  Problems of compliance/adherence

13. Diagnosis • ELISA • Western Blott • PCR • virale lading

14. Guidelines for HAART in HIV + children U.S.A.: 1993: Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children: convened by the NPHRC, HRSA & NIH 1998: CDC: MMWR: April 17, 1998/Vol.47/No. RR-4 2005: Most recent update Nov. 05, 2005. Europe: 09/99: Current evidence for the use of Pediatric Antiretroviral Therapy - A PENTA Analysis Belgium: National Pediatric Working group every 3 months with review of the guidelines once a year

17. When to start HAART ?

18. When to start HAART ? What HAART to start with ?

19. When to start HAART ? What HAART to start with ? When to change HAART ?

20. When to start HAART ? - No randomised trial evidence is available - So decisions to start are based on: clinical disease stage? viral load ? CD4% ? cfr.: CDC 1994 Revised classification system for HIV infection in children less than 13 years of age. - AIDS stadium or not ? - Age ?

21. Basic principles for HAART in HIV + children 1. Importance of clinical trials in children 2. Management of prescribing HAART is becoming increasingly complex and should wherever possible be directed in specialised centres by a multidisciplinary team 3. Regular monitoring (clinical/biochemical/psycho-social)

22. Basic principles for HAART in HIV + children 4. Factors to be considered before starting HAART: - availability, tolerability, efficacy, formulation, and side effect profile of currently available drugs, including dosage frequency, and impact on school, family, and social life - dosage in function of the farmacokinetic, complex differences in absorbtion, distribution and metabolism between neonates, infants, children, adolescents and adults

23. Basic principles for HAART in HIV + children 4. Other factors to be considered before starting HAART: - interactions with other medications and food - development of antiretroviral resistance, and planning for subsequent drug regimens when virological or clinical failure occurs - a detailed understanding of the families medical and social circumstances are critical to the successful introduction and maintenance of combination antiretroviral therapy

24. Personal conclusions HAART in HIV + children • HAART, 95% compliance necessary • 50% success is very good • universal problem • motivation • if you try to get ideality, you get realityif you try to get reality, you get shit • hit hard, hit early • compliance - adherence - ? • Another way to look at it: “living met HIV”

25. Personal conclusions Adherence in HIV + children • Bad taste of the medication • Difficult medicationscheme • Food advise • Quantity of pills, size of pills • Adverse events • Child • Adaption of living to the medicationscheme • Environment is not aware of the diagnosis • Therapy duration

26. daily confrontation with sickness • daily struggle with the medication • altered motivation when the child is going better • Child is sometimes to young to understand the necessity of the medication • QOL • The weather • Sleep/rest • Fight with partner • Seasons • Relationdoctor- patient • Function of the multidisciplinary team • Accesability of the hospital • Influence of alternative medicines, healers, religious leaders, gossip in the community

28. Table 1: 1994 Revised HIV pediatric classification system: Immune categories based on Age-specific CD4+ T-cells count and %

29. Table 2: 1994 Revised HIV pediatric classification system: Clinical categories Category N: Not symptomatic Children who have no signs or symptoms considered to be the result of HIV infection or who have only one of the conditions listed in Category A Category A: Mildly symptomatic Children with 2 or more of the following conditions but none of the conditions listed in categories B and C. - lymfadenopathy ( 0.5 cm at more than two sites; bilateral = 1 site) - hepatomegaly - splenomegaly - dermatitis - parotitis - recurrent of persistent upper respiratory infection, sinusitis or otitis media

30. Table 2: 1994 Revised HIV pediatric classification system: Clinical categories Category B: Moderately symptomatic Children who have symptomatic conditions, other than those listed for category A or category C, that are attributed to HIV infection. Examples of conditions in clinical category B include, but are not limited to, the following: - Anemia (<8gr/dl), neutropenia (<1000/mm³), or thrombocytopenia (<100000/mm³) for  30 dd - bacterial meningitis, pneumonia or sepsis (single episode) - candidiasis, orofaryngeal persisting for > 2 mm in children aged > 6 mm - cardiomyopathy - CMV infection with onset before age 1 month - diarrhea, recurrent or chronic - hepatitis, nephropathy - HSV stomatitis, recurrent (I.e. > 2 episodes/year) - HSV bronchitis, pneumonitis or esofagitis with onset before age 1 month - Herpes Zoster involving at least two distinct episodes or more than one dermatome - LIP or pulmonary lymphoid hyperplasia complex - ... Category C: Severe symptomatic Children who have any condition listed in the 1987 surveillance case definition for acquired immunodeficiency syndrome, with the exception of LIP

31. Table 3:Association of baseline CD4 T cell % with long-term risk for death in HIV- infected children

32. Table 4:Association baseline # HIV RNA Copy with long-term risk for death in HIV-infected children

33. Table 5:Association baseline # HIV RNA copy & CD4 T cell % with long term risk for death in HIV infected children

34. Table 8: Indications for initiation of antiretroviral therapy in children >12 mm with HIV infection (Nov 26,2003) OR OR OR AND AND

35. Concensus Belgian National Pediatric Group • < 6 mm of age: Start a treatment from the moment the infection has been confirmed by: - 2 positive elements: - Clinical status (Cat. C) - DNA-PCR - RNA-PCR - Culture - 2 positive virological results taken on 2 different samples

36. Concensus Belgian National Pediatric Group • > 6 mm of age: decision to treat depends on clinical criteria and/or biological criteria - clinical: Cat. C and B (except 1 pneumonia) - immunological: - CD4 <20% if > 1y - CD4 <25% if < 1y -  abs. # CD4 ( >30% in <6months) - virological: - <1y: V.L. > 100.000 c/ml - >1y: V.L. > 150.000 c/ml

38. What HAART to start with ? • Nucleoside Reverse Transcriptase Inhibitors • Non-Nucleoside reverse Transcriptase Inhibitors • Nucleotide reverse transcriptase Inhibitors • Protease Inhibitors • Fusion Inhibitors

39. Mechanism of Action NRTIworks here PI works here Protease NNRTIworks here Viralassembly Translation Proteincleavage RNA and reversetranscription Transcription Injectionof capsidcontents Integrase DNA RNA Provirus(circularstructure) Maturation Integration of ProvirusDNA into Host DNA FI works here HIV particle Binding CompletedHIV particle Adapted from HIV/AIDS Handbook. 4th ed. Boston: Total Learning Concepts, 1999; Ritchie DJ. In: Powderly WG, ed. Manual of HIV Therapeutics. Philadelphia: Lippincott-Raven, 1997:33-41.

41. Concensus Belgian National Pediatric Group • < 6 mm of age:  2 NRTIs + NVP • >6 mm of age: advanced stage: - Cat. C - Immunological stage 3 - V.L. > 300.000 c/ml  2NRTIs + 1 PI mild stage:  2NRTIs + 1 NNRTI

42. “Doctors should pay attention with the fact that patients often lie when they are telling that they’ve taken their medication.” Hippocrates (460-377 BC)

45. Mother to child transmission of HIV: impact of measures of prevention

46. Pregnancy and HIV infection in 2005 • > 90% of pediatric infections are acquired by mother to child transmission • 40.106 persons are infected by HIV globally • In Belgium35% of the HIV infected persons are women.80 % in childbearing age (15-40 years) % women • Subsaharian Africa 50% • SE Asia 30% • Europe 20%

47. HIV mother to child transmission rates in prospectively followed cohorts

48. When does mother to child transmission occur ? Postpartum transmission through breast feeding: risk estimated at 3 to 9 % /year, about 25 to 40 % of the total risk

49. How is the timing of HIV vertical transmission established ? in utero transmission peripartum transmission transmission by breastfeeding + at < 48 hours neg at < 48 h + after 1 week neg at < 1 month + thereafter If breastfeeding HIV detection (PCR DNA)

50. Risk factors for mother to child transmission of HIV • age • ethnicity • - parity no correlation with risk Demographic and behavioural • unprotected sexual • intercourse during pregnancy • - IV drug abuse • Severity of illness in the mother • evaluated by: • - clinical stage • immunodeficiency • viremia Increased risk clinical immunological virological • acute HIV infection • STD