James Nuttall Paediatric Infectious Diseases Unit Red Cross Children s Hospital

Transcription

1 James Nuttall Paediatric Infectious Diseases Unit Red Cross Children s Hospital Paediatric HIV Infection Symposium, August 21, 2010, Red Cross Children s Hospital

2 Overview of talk The 2010 paediatric guidelines in context Goals & objectives Key changes & their practical implications Clinicians (nurses & doctors, dieticians) Pharmacists Counsellors Managers Concluding remarks

3 The 2010 Paediatric guidelines in context The South African Antiretroviral Therapy (ART) programme, known as the Comprehensive Care Management, Treatment and Support (CCMTS) programme was launched in 2003 Government has adopted a new outcome based approach to accelerate attainment of the objectives outlined in the MTSF (Medium term Strategic Framework) one of the objectives being to improve the health profile of all South Africans. The 10 point plan of the Health Sector is aimed at creating a well functioning health system capable of producing improved health outcomes

4 DOH SA 10-point plan (2009) 1. Provision of Strategic Leadership and creation of a Social Compact for better health outcomes 2. Implementation of the National Health Insurance (NHI) 3. Improving the Quality of Health Services 4. Overhauling the health care system and improve its management 5. Improved Human Resources Planning, Development and Management 6. Revitalisation of infrastructure 7. Accelerate implementation of the HIV & AIDS and Sexually Transmitted Infections National Strategic Plan and increase focus on TB and other communicable diseases 8. Mass mobilisation for better health for the population 9. Review of Drug Policy 10. Strengthen Research and Development

5 Goals of the guidelines Achieve best health outcomes in the most costefficient manner Implement nurse-initiated treatment Decentralise service delivery to PHC Integrate services for HIV, TB, MCH, SRH and wellness Diagnose HIV earlier Prevent disease progression Avert AIDS related deaths Retain patients on lifelong therapy Prevent new infections among children, adolescents and adults Mitigate the HIV and AIDS impact

6 Specific objectives To prioritise ARVs for Patients with CD4 < 200 or with sever disease irrespective of CD4 Patients co-infected with TB/HIV Pregnant women with CD4 350 for lifelong ART and CD4 > 350 for prophylaxis To test all HIV exposed children < 1 year age and treat all those found to be HIV infected To standardise 1 st and 2 nd line therapy for children, adolescents and adults in the public and private sector To reduce the use of stavudine (d4t ) To expand the use of FDC and co-packaged formulations To enable nurses to initiate ARVs for treatment and prevention To enable PHC facilities to initiate, manage, monitor and refer patients

7 Old & New guidelines 1. Introduction 2. Clinical features of HIV-infection 3. Caring for HIV-exposed children 4. Caring for HIV-positive children 5. Nutrition support 6. HIV and AIDS clinical manifestations and complications 7. Other conditions and opportunistic infections 8. Paediatric palliative care 9. Caring for the terminal child 10. Antiretroviral therapy (ART) 11. Adherence 12. Post-exposure prophylaxis (PEP) 13. Legal issues 14. Counselling 15. Disclosure to children 1. Introduction 2. Identifying children with HIV infection 3. HIV testing in children 4. Care for the child with possible or confirmed HIV infection 5. Nutritional support 6. Anti-retroviral therapy (ART) 7. Adverse reactions to ART 8. System specific conditions & complications in HIVinfected children & opportunistic infections 9. Paediatric palliative care 10. Considerations for ART in adolescents 11. PEP & safe working practices 12. Psychosocial support 13. Legal issues 14. Counselling 15. Adherence 16. Disclosure to children

8 2. HIV TESTING IN CHILDREN Which children should be tested for HIV infection? All HIV-exposed infants Children with: Clinical features suggestive of HIV infection Acute illnesses, especially if severe All children with the following IMCI classifications: Suspected symptomatic HIV infection or possible HIV infection All children diagnosed with TB or who have a history of TB treatment Family and social history: Parental request to test the child Father or sibling with HIV infection Death of mother, father or sibling When the mother s HIV status is unknown and her whereabouts are unknown When the child may have been wet-nursed or breastfed by a woman of unknown or positive HIV status When the child may have experienced or been at risk of sexual assault When it is in the best interest of the child where the child is being considered for foster or adoption placement

9 1. IDENTIFYING CHILDREN WITH HIV INFECTION Early infant diagnosis Every contact with the health care service should be used to ensure that every child s HIV-exposure status is known and documented on the Road to Health Card 6-week immunisation visit 10-week immunisation visit Breastfeeding HIV-exposed infants

10 2. HIV TESTING IN CHILDREN Which tests in which situations? Antibody tests HIV rapid tests To detect HIV exposure in child <18 mths of age To exclude HIV exposure (seroreversion) (non-breastfeeders) To diagnose HIV infection in child 18 mths of age (non breastfeeders): 2 different tests required HIV laboratory ELISA Confirmatory test in children >18 mths of age with positive HIV rapid test / discrepant rapid test results PCR tests DNA PCR For diagnosis of HIV infection in HIV exposed infants (& breastfeeding children) RNA PCR/viral load VL > (>4 log) confirms HIV diagnosis <18 mths of age Initiation of ART should not be delayed while awaiting the result of the confirmatory viral detection assay

11 2. HIV TESTING IN CHILDREN Implications Clinicians: nurses & doctors Provider-initiated testing at every opportunity Counsellors HIV testing? Managers Documentation & monitoring

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13 5. ANTI-RETROVIRAL THERAPY (ART) Eligibility criteria Fast-track criteria 1 st -line regimens Monitoring 2 nd -line regimens Concomitant tuberculosis

14 5. ANTI-RETROVIRAL THERAPY (ART) Eligibility criteria All children less than 1 year of age Children 1 to 5 years: Clinical Stage 3 or 4 OR CD4 25% or absolute CD4 count < 750 cells/µl Children 5 years to 15 years: Clinical Stage 3 or 4 OR CD4 350 cells/µl Social criteria At least one identifiable caregiver who is able to supervise the child for administering medication (all efforts should be made to ensure that the social circumstances of vulnerable children, e.g. orphans, are addressed so that they too can receive treatment) Disclosure to another adult living in the same house is encouraged so that there is someone else who can assist with the child s ART

15 5. ANTI-RETROVIRAL THERAPY (ART) Fast-track criteria (initiate ART within 2 wks of eligibility) Children less than 1 year age Stage 4 MDR or XDR TB CD4 <15% OR <200 cells/µl Social criteria At least one identifiable caregiver who is able to supervise the child for administering medication (all efforts should be made to ensure that the social circumstances of vulnerable children, e.g. orphans, are addressed so that they too can receive treatment) Disclosure to another adult living in the same house is encouraged so that there is someone else who can assist with the child s ART

16 5. ANTI-RETROVIRAL THERAPY (ART) Eligibility: Implications Clinicians (Nurses & Doctors) Early infant diagnosis (also < 6 weeks of age) Increased community-based ART initiation in young infants In infants, initiation of ART should not be delayed while awaiting the result of the baseline viral load (confirmatory diagnostic test) Clinical staging & CD4 counts at diagnosis Tracing & acting on results: fast-track criteria Clear referral channels Counsellors Caregiver pre & post-test counselling Managers Training of nurses & doctors at level 1 & 2

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18 Standardised Paediatric HIV stationery (W. Cape DOH, 2009)

19 5. ANTI-RETROVIRAL THERAPY (ART) 1 st -line regimens Regimen 6 months up to 3 years 1 st -line d4t+ 3TC + LPV/r Over 3 years and >10kg d4t + 3TC + EFV 1 st -line Drugs Comments All infants and children under 3 years Children 3 years or over Currently on d4t based regime with no side effects ABC + 3TC + LPV/r ABC + 3TC + EFV Can continue Substitute once lipodystrophy suspected

20 5. ANTI-RETROVIRAL THERAPY (ART) Monitoring At initial diagnosis Check HIV result Document weight and height Screen for TB symptoms Do the CD4 count Purpose Ensure that the National testing algorithm including HIV DNA PCR and HIV viral load (RNA) for infants and children < 18 months has been followed To monitor growth and development and identify eligibility for ART To identify TB- HIV co-infection To identify eligibility for ART Hb or FBC is available To detect anaemia or neutropaenia

21 5. ANTI-RETROVIRAL THERAPY (ART) Monitoring At routine follow-up visits Document weight and height Check that CD4 has been done in the last 6 months WHO clinical Staging Purpose To monitor growth and development and to see if they have become eligible for ART To see if they have become eligible for ART To see if they have become eligible for ART Screen for TB symptoms To identify TB / HIV co-infection

22 5. ANTI-RETROVIRAL THERAPY (ART) Monitoring If eligible for ART Purpose ALT if starting on a NVP based regimen If ALT raised, do HepBSAg and avoid NVP HB or FBC is available if starting on an AZT based regimen If less then 8g/l refer

23 5. ANTI-RETROVIRAL THERAPY (ART) Monitoring On ART Height + weight + development Clinical Stage CD4 at month 6, 1 year into ART and then every 12 months VL at month 6, 1 year into ART, and then every 12 months ALT if on NVP and develops rash or jaundice FBC at month1, 2 and 3 if on AZT Purpose To monitor response to ART To monitor response to ART To monitor response to ART To monitor response to ART To identify problems with adherence To identify NVP toxicity To identify AZT toxicity

24 5. ANTI-RETROVIRAL THERAPY (ART) 1 st -line regimens & monitoring: Implications Clinicians (Nurses & Doctors) Abacavir ARV dosing chart for children 12 mthly CD4 & viral load (in stable patients) Pharmacists Drug supply, ARV dosing chart for children & side effects Counsellors Caregiver adherence counselling Updated training on new regimens: formulations, administration & side effects Managers Training of nurses & doctors at level 1 & 2 Linking PMTCT follow-up clinics to ART sites

25 5. ANTI-RETROVIRAL THERAPY (ART) 2 nd -line regimens: virological monitoring VL <400 routine follow-up and adherence support VL repeat VL after 6 months step-up adherence support if VL still VL >1000 begin step-up adherence support & repeat VL after 3 months: VL <400 as above VL as above VL >1000 see next slide

26 5. ANTI-RETROVIRAL THERAPY (ART) 2 nd -line regimens: virological monitoring Viral load still >1000 after 3 months: Child on NNRTI-based regimen + adherence >80% switch to 2 nd line regimen Child on boosted PI-based regimen reinforce adherence (monitor VL 3-mthly) if VL >5000, adherence >80% change therapy, preferably guided by resistance testing Child previously on unboosted PI (ritonavir) motivate for resistance testing, switch to 2 nd line regimen

27 5. ANTI-RETROVIRAL THERAPY (ART) 2 nd -line drug regimens Regimen 6 months up to 3 years 1 st -line d4t+ 3TC + LPV/r 2 nd -line AZT + ddi + NVP/EFV Over 3 years and >10kg d4t + 3TC + EFV AZT + ddi + LPV/r 1st-line Drugs Comments All infants and children under 3 years Children 3 years or over 2 nd -line Children above 3 years Failed ABC + 3TC + EFV Failed on AZT or ddi based regime Failed on LPV based regimen or failing any 2 nd line Infants under 3 years failing 1 st line ABC + 3TC + LPV/r ABC + 3TC + EFV AZT + ddi + LPV/r ABC + 3TC + LPV/r Refer Refer Specialist advice necessary and/or hospital referral Specialist advice necessary and/or hospital referral

28 5. ANTI-RETROVIRAL THERAPY (ART) 2 nd -line regimens: Implications Clinicians (Nurses & Doctors) Flexibility around VL monitoring for children who are unsuppressed: 3-6 monthly Referral criteria for specialist opinion Continued use of didanosine in 2 nd -line (cf. adults) Criteria for & access to genotyping & new drugs Holding strategies Pharmacists Drug supply, ARV dosing chart for children & side effects Counsellors Caregiver adherence counselling Updated training on new regimens: formulations, administration & side effects Managers Enabling role for specialist / tertiary services: genotyping & new drugs

29 Relevant scenarios of paediatric treatment failure and resistance Main problem areas Children failing 1 st line L/r (or failing soon after switching to 2 nd line NNRTI after failing 1 st line L/r) NRTI resistance (& NNRTI resistance) Archived NNRTI resistance in PMTCT-exposed Children failing 2 nd line L/r after previous exposure to unboosted PI (ritonavir) More extensive PI resistance including lopinavir ± NRTI resistance Children failing 2 nd line L/r (after 1 st line NNRTI) Frequently no significant PI resistance

30 Holding strategies? Scenario: child needs to change ART but is currently unable to (e.g. unresolved adherence issues, inability to swallow tablets, needing a new ARV drug that lacks paediatric dosing data or formulations Includes: Structured Treatment Interruption (CHER, PENTA 11) Non-suppressive regimen: lamivudine monotherapy Reduces accumulation of further resistance mutations leading to broad cross-resistance in drug class, especially NRTI (& NNRTI) Temporary solution Dependent on adequate CD4 count Lack of paediatric data

31 Accessing new ARV drugs New generation PI Darunavir (DRV, Prezista) Approved for children >6yrs of age, requires RTV boosting, not co-formulated Current potential utility as 2 nd line PI after previous PI failure: Few PI-experienced children have >1 DRV RAM susceptibility is high Tibotec submitting 75 & 150 mg tabs to MCC, 300mg tabs are registered, suspension under investigation Available from Tibotec free-of-charge on individual patient review basis with Sec 21 clearance New ARV drug class: Integrase inhibitors: Raltegravir Initial clinical studies are encouraging, chewable tabs & oral granules for suspension in Pk studies New generation NNRTI: Etravirine Suspension under investigation, Y181C NVP-associated mutation reduces susceptibility to ETR

32 6. ADVERSE REACTIONS TO ART Abacavir hypersensitivity reaction 2 of: fever rash gastrointestinal symptoms (e.g. D+V, abdominal pain) constitutional symptoms (e.g. fatigue, myalgia) respiratory symptoms (e.g. dyspnoea, cough, pharyngitis) Symptoms worsen immediately after dose Early consultation with health care provider Avoid stopping therapy without consultation if possible. Also avoid ongoing use / re-challenge as risk of mortality Lipodystrophy syndrome Low threshold for switching from stavudine or zidovudine to abacavir (or tenofovir in older children/adolescents)

33 6. ADVERSE REACTIONS TO ART Implications Clinicians & pharmacists Awareness & training on identification & management of suspected abacavir hypersensitivity reaction & lipodystrophy Counsellors Careful explanations to caregivers & patients

34 10. CONSIDERATIONS FOR ART IN ADOLESCENTS Adolescence: years of age Two distinct groups of HIV-infected adolescents Adolescents who have been infected around birth Those who acquire HIV through unprotected sex Post pubertal / 15 years of age Adult staging, ART eligibility criteria & drug regimens Adherence & disclosure

35 Role of tenofovir in paediatric / adolescent patients Current limitation in children is formulation (300mg tablet) & dosing (8 mg/kg/day recommended for children) Less concern than previously regarding reductions in bone mineral density and renal toxicity in children Alternative to first-line ABC in children >35 kg and/or >15 yrs, ideally in established puberty Alternative to ABC in older children switching from stavudine for mitochondrial toxicity In 2 nd -line or subsequent regimens guided by genotyping

36 10. CONSIDERATIONS FOR ART IN ADOLESCENTS Implications Clinicians & pharmacists Treatment simplification / adult regimens once-daily / fixed dose combinations Counsellors Managers Adolescent days / Youth clinics

37 Concluding remarks Long awaited and struggled for greatly improved guidelines Eligibility criteria Drug regimens Important linkages with & implications of revised PMTCT & adult guidelines Training needs Emphasis on the role of nurses Shifts Diagnosis & ART initiation should be increasingly occurring at level 1 & 2 community based facilities Specialist/tertiary role at level 3 should increasingly be management of sick young infants & children, complex HIV/TB & other OIs, consultation on treatment failure/genotyping/new regimens, refining policy & guidelines, research