1. Prescription and Use of Paediatric Antiretroviral Drugs (ARVs) for the Treatment of HIV in Children

2. Prescribing ARVs Key Questions: How do we select the appropriate regimen? How do we select the most effective ARV formulations? How do we prescribe appropriate doses of each formulation based on the child’s weight?

3. Three Steps to Prescribing Ped ARVs Once a child has been identified as eligible for ART and prepared to initiate treatment, there are three steps to prescribing ARVs: 1.Identify the proper regimen to prescribe based on National Guidelines and clinical condition of the child 2.Select which ARV formulations to use based on the regimen selected 3.Use the Paediatric ARV Dosing Chart to prescribe the proper amount of each formulation based on the child’s weight

4. Review of Regularly Used ARVs Drug ClassDrug NameAbbreviation NRTIZidovudineAZT AbacavirABC Stavudined4T Lamivudine3TC NNRTINevirapineNVP EfavirenzEFV Protease Inhibitor (PI) Lopinavir + Ritonavir LVP/r

5. Step 1: Identify the right regimen Select the appropriate regimen based on the national ART guidelines: AZT based regimen should always be used to initiate children on 1 st line, unless the child is anemic

6. Step 2: Choose the right formulations Pediatric ARVs are available in three kinds of formulations: 1.Oral suspensions i.e. AZT syrup 2. Single drug tablets i.e. 3TC 150mg 3.Fixed-dose combination tablets i.e. Triomune Baby (d4T 6mg + 3TC 30mg + NVP 50mg) 6

7. Step 2: Choose the right formulations AZTABCd4T3TCNVPEFVLPV/r Single Drug Formulations AZT syrup ABC syrup d4T syrup 3TC syrup NVP syrup EFV syrup LPVr syrup AZT 100mg ABC 60mg d4T 15mg 3TC 150mg NVP 200mg EFV 200mg LPVr 125mg AZT 300mg - d4T 20mg -- EFV 100mg LPVr 250mg Fixed-Dose Combinations AZT / 3TC / NVP 60/30/50mg AZT / 3TC 60/30mg ABC / 3TC 60/30mg d4T / 3TC / NVP 6/30/50mg d4T / 3TC / NVP 12/60/100mg d4T / 3TC 6/30mg d4T / 3TC 12/60mg Many different products are available to choose from…

8. Step 2: Choose the right formulations However, fixed-dose combinations should always be used when possible due to their many advantages over oral suspensions and single tabs: Easier to dose, as you do not have to give instructions for multiple drugs Better control in administration than oral solutions More versatile – can be crushed, dispersed in food or water, or swallowed as a tablet More neutral taste Lower tablet burden/volumes Easier to check adherence Easier to transport/store with no need for refrigeration Easier to order due to reduced number of formulations

9. Step 2: Choose the right formulations Fixed-dose combinations can and should be used to build every recommended regimen: Recommended Regimen Regimen using fixed-dose combinations AZT + 3TC + NVP AZT/3TC/NVP 60/30/50mg AZT + 3TC + EFV AZT/3TC 60/30mg + EFV (200mg or 100mg) AZT + 3TC + LPVr AZT/3TC 60/30mg + LPVr (solution / 125mg) ABC + 3TC + NVP ABC/3TC 60/30mg + NVP (solution / 200mg) ABC + 3TC + EFV ABC/3TC 60/30mg + EFV (200mg or 100mg) ABC + 3TC + LPVr ABC/3TC 60/30mg + LPVr (solution / 125mg) d4T + 3TC + NVP d4T/3TC/NVP 6/30/50mg d4T + 3TC + EFV d4T/3TC 6/30mg + EFV (200mg or 100mg) d4T + 3TC + LPVr d4T/3TC 6/30mg + LPVr (solution / 125mg)

10. Fixed-dose combination tablets can be split, crushed, and most of them dispersed in water: FormulationCan be split?Can be crushed? Can be dispersed in water? AZT/3TC/NVP 60/30/50mg AZT/3TC 60/30mg ABC/3TC 60/30mg d4T/3TC/NVP 6/30/50mg d4T/3TC 6/30mg X X

11. Step 2: Choosing the right formulation Fixed-dose combination tablets can be split, crushed, and most of them dispersed in water: FormulationCan be split?Can be crushed? Can be dispersed in water? AZT/3TC/NVP 60/30/50mg AZT/3TC 60/30mg ABC/3TC 60/30mg d4T/3TC/NVP 6/30/50mg d4T/3TC 6/30mg X X

12. Exercise 1 – Administering FDC tablets Take three fixed dose combination tablets: Split the first one in half Crush the second with a spoon Put the third in a cup and add a few MLs of water—watch it dissolve in the water Which was difficult to do? Which is easiest to teach to a mother of an HIV+ child?

13. Step 2: Choose the right formulation When using fixed-dose combinations, you only require the following pediatric formulations at your facility: Fixed-dose combinationsSingle formulations 1. AZT/3TC/NVP 60/30/50mg6. EFV 200mg 2. AZT/3TC 60/30mg7. EFV 100mg 3. ABC/3TC 60/30mg8. NVP solution (for use with ABC) 4. d4T/3TC/NVP 6/30/50mg9. LPVr solution 5. d4T/3TC 6/30mg10. LPVr 125mg * Will also need NVP 200mg, but that is also used for adults so should be readily available

14. Step 3: Prescribe the right dose The first step in dosing ARVs for children is determining the weight of the child—doses need to be increased as the child grows There are 6 major weight ranges to use when dosing: 3 – 5.9kg 6 – 9.9kg 10 – 13.9kg 14 – 19.9kg 20 – 24.9kg 25kg and above You must weigh a child each time he/she comes to the clinic to check if he/she has reached the next weight range

15. Step 3: Prescribe the right dose Weight ranges (kg) 3-5.96-9.910- 13.9 14- 19.9 20- 24.9 25- 29.9 AZT 3TC NVP (60/30/50mg) AZT/3TC (60/30mg) 11.522.531 adult tab ABC/3TC (60/30mg) 11.522.531 adult tab d4t 3TC NVP (6/30/50mg) d4t/3TC (6/30mg) 11.522.531 adult tab The number of tablets included in the table above is given twice daily Dosing of fixed-dose combinations is harmonized across drug types…

16. Step 3: Prescribe the right dose Dosing aide provides number of tablet to give for each formulation (including CTX) across all weight ranges:

17. Exercise 2:Use your Paediatric ARV Dosing Chart to answer the following about dosing FDCs: 17 1.For a 9kg child on the regimen AZT + 3TC + NVP: a.Which formulation would you use for this child? Triple FDC b. What is the average daily dose of this formulation? 1.5 BD c. How many tablets should you dispense for 30 days? 90 tablets

18. Exercise 2: Dosing Ped FDCs (continued) 2.For a 16kg child on the regimen ABC + 3TC + EFV: a.Which formulations would you use for this child? Dual FD of ABC + 3TC, and single dose tablet of EFV b. What is the average daily dose of these formulations? ABC/3TC 2.5 BD, 300mg of EFV c. How many tablets of each formulation should you dispense for 30 days? ABC + 3TC = 150 tablets For EFV, first need to decide on the best formulation for the patient. Is there a 300 mg tablet? NO.

19. Exercise 3 – Dosing syrups vs FDCs 19 You have a patient who weighs 5 kg. You prescribe a regimen of AZT/3TC/NVP. 1 st : Calculate the AM and PM dose if you were to use syrups. What is the total volume needed for a 30-day supply? AZT = 360 ml, 3TC = 180 ml, NVP = 300 ml 2 nd : Calculate the AM and PM dose if you were to use FDCs. What is the total number of tablets needed for a 30-day supply? FDC = 60 tablets

20. We need to consider what the patient will have to go home with…

21. Using FDCs for lead-in NVP dosing 21 Current recommendation for any patient initiating NVP-based ART for the first time is to dose the NVP once daily for the first two weeks to reduce risk of associated rash During 2 week lead in period, children should get the appropriate triple FDC as the AM dose, and the equivalent dual FDC for the PM dose MorningAZT/3TC/NVP EveningAZT/3TC

22. Exercise 4 – Lead-in dosing with FDCs 22 4 year old child Weight 12.5kg Eligible for ART Formulation? Dose? Lead-in? AZT/3TC/NVP 60/30/50mg 2 am / 2 pm Initiate lead- in for 2 weeks 28 tabs of triple FDC, 28 tabs of dual FDC Initiate full ART 120 tabs of triple FDC Follow up 120 tabs of triple FDC until weight increases to 15kg

23. Case Study Practice Let’s examine a few real cases and correctly determine: – What regimen should they be given? – What formulations should you use? – How much would you prescribe of each formulation?

24. Case 1 Osofia is 3 month old and weighs 5 kg. She was given single dose NVP for PMTCT but went on to get HIV infected. Currently you don’t have kaletra syrup at your facility. Initiate the patient on treatment in the recommended way. What regimen should she be given? AZT/3TC/NVP What formulations should you use? Triple FDC of AZT/3TC/NVP and Duo fixed dose AZT/3TC How much would you prescribe of each formulation? Triple FDC AZT/3TC/NVP-1 od and AZT/3TC 1 od If you are giving them a 14-day supply, how many tablets should you give them of each formulation? AZT/3TC/NVP 14 tablet and AZT/3TC -14 tablets

25. Case 2 IBU is a 6 month old infant who is HIV positive. He received NVP syrup for prophylaxis. He is not anemic and the weight is 6 kg. You have all the drugs available in the facility. What regimen should they be given? AZT/3TC/Kaletra What formulations should you use? FDC- AZT/3TC and Syrup for kaletra How much would you prescribe of each formulation? AZT/3TC- 1.5 BD and Kaletra 1.5 mls BD If you are giving them a 30-day supply, how many tablets should you give them of each formulation? AZT/3TC 90 tablets and Kaletra 90mls for 30 days

26. Case 3Mary is 4 years old and weighs 15 kg. She was diagnosed with HIV. She is anemic and you don’t have abacavir in your facility. What criteria would you use to determine if Mary is eligible for ARVs? CD4 %- less than 25% or CD count <750 or WHO clinical stage 3 or 4 If she is eligible for ARVs What regimen should she be given? D4T/3TC/NVP What formulations should you use? Triple FDC of D4T/3TC/NVP baby and Duo FDC D4T/3TC baby How much would you prescribe of each formulation? D4T/3TC/NVP 2.5 A.M. and D4T/3TC 2.5 P.M. If you are giving her a 14-day supply, how many tablets should you give her of each formulation? D4T/3TC/NVP 35 tablets and D4T/3TC 35 tablets If she comes back for after 14 days as she has tolerated the drugs what formulation would you give, what dose and how many tablets would you dispense for 30 days? D4T/3TC/NVP baby, 2.5 BD and 150 mg

27. Case 4 Aki is a 7 year old HIV positive boy. He is anemic and is eligible to start ARV’s. You have abacavir in you facility. He is 18 kg. What regimen should they be given? ABC/3TC/NVP or ABC/3TC/EFV What formulations should you use? Duo FDC for ABC/3TC and single tablets NVP or Duo FDC ABC/3TC and single tablet EFV How much would you prescribe of each formulation? ABC/3TC 2.5 BD and Tab NVP 1 in morning and 0.5 in Evening Or ABC/3TC 2.5 BD and Tab EFV(600mg) 0.5 mg od If you are giving them a 30-day supply, how many tablets should you give them of each formulation? ABC/3TC 150 tablets and NVP 45 tablets Or ABC/3TC 150 tablets and EFV 15 tablets

28. Case 5 Popo is a 9 year old boy who is HIV+. He is not on ARVs and was diagnosed with TB. His weight is 21kg. He is eligible to start ARVs. When would you start him on ARVs 2-8 weeks after initiation of anti TB treatment What regimen should they be given? AZT/3TC/EFV What formulations should you use? Dou FDC AZT/3TC and single tablet EFV How much would you prescribe of each formulation? AZT/3TC 3BD and EFV (600mg) 0.5 od If you are giving them a 30-day supply, how many tablets should you give them of each formulation? AZT/3TC 180 tablets and EFV(600mg) 15 tablets

29. Summary Use the national ART guidelines to select which regimen to use – Always check for anemia to determine if AZT is acceptable When selecting formulations, always use fixed-dose combinations where possible – Easier to dose and better for the patient Always take the child’s weight, and use the Ped ARV dosing chart to determine how much to prescribe of each formulation