Paediatric HIV Resistance Referal Pathway. Mohern Archary Paediatric Infectious Diseases Unit King Edward VIII Hospital / University of KwaZulu Natal

Transcription

1 Paediatric HIV Resistance Referal Pathway Mohern Archary Paediatric Infectious Diseases Unit King Edward VIII Hospital / University of KwaZulu Natal

2 Third line Antiretroviral treatment options in HIV positive children failing Protease Inhibitor (PI) based regimes Ahmed N 1, Pillay A 2, Moodley P 3, Bobat R 2,Archary M 2 1 Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, England 2 Paediatric Infectious Diseases Department,Edward VIII Hospital, Kwazulu-Natal, South Africa 3 National Health Laboratory Services, Kwazulu-Natal, South Africa

3 The overall median mutation scores were (range ) for RTs, and 190 (range ) for PIs. In total, 50% (16/32) had major PI mutations, with one minor PI mutation. The most sensitive drugs were darunavir (25/32), tipranavir (20/32), tenofovir (21/32), zidovudine (20/32) and etravirine (19/32).

4 Paediatric 3 rd line Drugs Birth 1m 1yr 2yr 3yr 4yr 5yr 6yr 7yr 8yr 9yr DRV Oral suspension 100 mg and 75 mg tablet RAL Oral suspension 100mg and 25 mg chewable tablet ETR 25mg, 100mg and 200mg tablet

5 ANTIRETROVIRAL DRUG FORMULATIONS AVAILABLE IN SA DRUG FORMULATION MANUFACTURER RECOMMENDED FORMULATION Tenofovir ATAZANAVIR CAPSULES 300MG ASPEN X ATAZANAVIR CAPSULES 200MG ASPEN X ATAZANAVIR (CAPSULES) 150MG ACTIVO, BMS X ATAZANAVIR (CAPSULES) 100MG ACTIVO, BMS X R WR UK ATAZANAVIR PAED FORMULATION? X DARUNAVIR 300MG ASPEN X DARUNAVIR 75, 150 ASPEN X FOSAMPRENAVIR 700MG GSK X FOSAMPRENAVIR SUSPENSION 50MG/ML GSK X TENOFOVIR 300MG ASPEN, CIPLA, NOVAGEN, SONKE X TENOFOVIR TABLET 250, 200,150 CIPLA, NOVAGEN X TENOFOVIR ORAL POWDER 40mg/scoop ASPEN X RALTEGRAVIR 400MG MSD* X RALTEGRAVIR 100MG MSD RALTEGRAVIR 25mg MSD Application for chewable, scored tablet Application for chewable tablet X X ETRAVIRINE 200, 100mg PHARMACARE X ETRAVIRINE 25MG X

6 TREATMENT OPTIONS FOR THIRD LINE TREATMENT FAILURE IN YOUNG CHILDREN ARE LIMITED

7 When should a HIV infected Child have an HIV resistance testing Infant vertically infected by a mother with treatment failure. Child failing a PI based regimen despite adequate adherence. Child with a complicated NRTI history

8 What to do with a Resistance test result Must ensure that the patient is going to be compliant to the new regimen Must have an available third line regimen to put the patient on.

9 Treatment Failure Paediatric Referral pathway 1. Early recognition of virological failure 2. Early institution of enhanced adherence 3. Appropriate referral for Resistance testing

10 1. Early recognition of virological failure Changing mind sets: Detectable Viral load (on ARV) = call for immediate action (abn Potassium) Each facility to develop systems to identify patients with detectable viral loads Examples of systems: KEH Clinic all bloods performed are recorded by the phlebotomist in a ledger results checked daily when clinic quiet. KwaMashu Polyclinic All lab printed lab results reviewed on a daily basis Laboratory based screening all detectable VL red flagged

11 2. Early institution of enhanced adherence Patients should be called back as soon as possible before next appointment. Dedicated Treatment failure clinic (once a week) Standardised method of enhanced adherence encompassing all the common causes for poor adherence

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13 3. Appropriate referral for Resistance testing Referral to the Paediatric Infectious diseases clinic Thursday at King Edward VIII Hospital Area 1 / 3 Edendale Hospital Area 2 Ngwelezana Hospital Area 3

14 Area 2 - Edendale Area 1/3 King Edward VII Hospital

15 Assess for common causes of poor adherence in children: Inappropriate formulation esp Kaletra syrup in an older child or alluvia (200/50mg tablet) in child who cannot swallow the adult tablet. Inappropriate dose check that the appropriate dose has been prescribed and dispensed. Inappropriate administration crushing of film coated tablets, incorrect volumes given. Change in caregiver or change in the health of the caregiver. Unstable home environment. Non-disclosure of status of the child. Treatment fatigue. Do-not believe that the medication is working.

16 Counselling should be conducted in a nonthreatening manner, focusing on addressing the possible reasons and potential solutions for poor adherence, rather than apportioning blame. Use objective criteria to assess adherence eg adherence to appointment dates, pill counts. Refer the caregiver/patient to appropriate support services eg social worker, psychologist where appropriate.

17 Treatment Failure on Efavirenz (or NVP) Regimen All patients should be referred for intensified adherence as outlined above. Address and rectify potential reasons for poor adherence. Monthly follow-ups focusing on reinforcing adherence, accessing adherence to visit dates Repeat HIV Viral load after 3 months of intensified adherence If still has HIV Viral load >1000 copies/ml discuss with clinician experienced with Paediatric ART or refer to mother hospital for assessment. Change to second-line ART when all measures have been put in place to ensure optimal adherence.

18 Paediatric HIV resistance clinic Who: Paediatric Infectious disease team When: Thursday mornings Where: Family clinic building, King Edward VIII Hospital For whom: patients that require HIV resistance testing and possible 3 rd line ARV s

19 Requirements From Area 1 By appointment only Referral letter Completed forms: NHLS HIV drug resistance testing form Motivation for Third line form

20 How to contact the Paediatric ID team Area 1/3 Telephonically: King Edward VIII Hospital switchboard /3245 Paediatric ID registrar in Ward N2A Electronically: HIV resistance clinic will reply with date of appointment and necessary forms Can contact us for any advice regarding changing to 2 nd line (even if pts not to be seen in specific clinic)

21 Area 2 referrals to EDH Telephonically: Khanyisa Clinic in Edendale Hospital / Paediatric ID registrar/senior medical officer in Khanyisa Clinic Electronically: fathima.naby@gmail.com/kevin.spicer@kznhealth.gov.za HIV resistance clinic will reply with date of appointment and necessary forms Can contact us for any advice regarding changing to 2 nd line (even if pts not to be seen in specific clinic) Advanced Clinical Care 23/04/2014

22 NHLS HIV drug resistance form

23 Motivation form

24 Completed motivation form and genotype should be sent to: A recommendation will be communicated directly to the site. Recommended regimen will be sent directly to the referring hospital.

25 Summary: Identify patient Patient seen at clinic Resistance testing done Make an appointment Send electronic copies Follow up visit the Paed ID team Complete necessary documents Motivation for 3 rd line or advice on mx

26 Summary Third line options in children are limited. All efforts should be made to ensure durability of available regimens.

27 SS Currently 17 year old female First presentation to care 31/1/2005 (8 years) Perinatally HIV-infected WHO stage 1; Immunologically stage 3 CD4 198 (11.9%) Started D4T/3TC/EFV on 27/5/2005 Did well initially: remained virally suppressed Bloods 8/2/08: VL < 25 copies/ml and CD4 562 (27.4%)

28 Date Jul 08 Aug 08 Continued. Ongoing adherence concerns: Living with aunt, mom looking after her ill mother Little in way of treatment support Only disclosed to when 12y6m Dec 08 Mar 09 Oct 09 Feb 10 May 10 Oct 10 Feb 11 Age 12y4m 12y5m 12y7m 12y11 13y6 13y10 14y1 14y7 14y10 CD4 # CD4% VL DRT on 25/08/2008: No resistance detected Changed to second line 16/3/2011

29 True/false The resistance test showed no resistance - she should not have switched regimens (T/F)

30 What second line regimen would you have chosen? 1. AZT/3TC & LPV/r 2. TDF/3Tc & LPV/r 3. AZT/ABC & LPV/r 4. AZT/ddi & LPV/r

31 At what age would you use TDF in Adolescent patients? 1. Pregnant 12 yr old 2. Non-pregnant 14 yr old 3. Pregnant 16yr old 4. Non-pregnant 16yr old 5. 1, 3 and 4

32 TDF can safely be used in: Pregnant adolescents > 12 years and > 40 kg Non-pregnant adolescents > 15yrs and > 40kg Monitoring renal function (cgfr) in adolescents < 15yrs requires calculation using the Counahan Barrat formula: (height(cm)x40) / creatinine

33 On second line. Well clinically Date Oct 11 April 12 June 12 Sep 12 Nov 12 May 12 CD4# CD4% VL Vomiting and unable to swallow alluvia 200/50, switched to 100/25mg Ongoing poor adherence and missed appointments

34 Seen in July 2013 LMP April 2013 Pregnant, does not want to explore the option of TOP O/E HOF about 16 weeks She has not taken ART since realized she was pregnant Advised by her sister that ART may be harmful to the baby

35 Booked ANC Further progress. Male infant born Birth PCR negative Received kal/azt/3tc 3m: Baby admitted: kwashiorkor, GE, LRTI(diluting formula) PCR negative 13 Oct Nov Dec Jan Mar Apr 2014 VL CD4 (%) 106 (9.9%) 163 (11.7%) Changed to combivir and aluvia Has defaulted visits again since May DRT: No resistance detected

36 Regarding the infant prophylaxis 1. NVP as a single drug for 6 weeks. 2. AZT/3TC/Kaletra is safe 3. NVP for 12 weeks 4. AZT/NVP for 6 weeks

37 What would you advise the mother regarding Breastfeeding 1. Breastfeeding is contra-indicated when the mother is not virally suppressed 2. Continue breastfeeding but stop NVP at 6 weeks 3. Continue breastfeeding but stop NVP at 12 weeks 4. Continue breastfeeding and NVP for as long at viral load is > 1000copies/ml

38 Will you do a birth PCR? 1. Yes 2. No

39 When will you repeat the HIV test? 1. As this infant tested PCR negative at 6 weeks, no further HIV testing is required as he is not breastfeeding. 2. At 18 months 3. On admission for Kwashiokor 4. At 9 months