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

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?

Three Steps to Prescribing Ped ARVsOnce 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

Review of Regularly Used ARVs

Drug Class Drug Name Abbreviation

NRTI Zidovudine AZT

Abacavir ABC

Stavudine d4T

Lamivudine 3TC

NNRTI Nevirapine NVP

Efavirenz EFV

Protease Inhibitor (PI)

Lopinavir + Ritonavir

LVP/r

Step 1: Identify the right regimen

AZT + 3TC + (NVP or EFV)*

ABC + 3TC + (NVP or EFV)*

Preferred

1st Alternative

2nd Alternative

If AZT or d4T used in 1st Line

1st Line Therapy

d4T + 3TC + (NVP or EFV)*

If ABC used in 1st Line

ABC + 3TC + LPV/r

2nd Line Therapy

* For all infants exposed to NVP in PMTCT, LPV/r should be substituted into 1st line for NVP or EFV

(AZT or d4T) + 3TC + LPV/r

Recommended ART Regimensfor Children

Select the appropriate regimen based on the national ART guidelines:

AZT based regimen should always be used 

to initiate children on 1st line, unless the child is anemic

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

Step 2: Choose the right formulations

AZT ABC d4T 3TC NVP EFV LPV/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 6/30/50mgd4T / 3TC / NVP 12/60/100mg

d4T / 3TC 6/30mgd4T / 3TC 12/60mg

Many different products are available to choose from…

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

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)

Fixed-dose combination tablets can be split, crushed, and most of them dispersed in water:

Formulation Can 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

Step 2: Choosing the right formulationFixed-dose combination tablets can be split, crushed, and most of them dispersed in water:

Formulation Can 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

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?

Step 2: Choose the right formulationWhen using fixed-dose combinations, you only require the following pediatric formulations at your facility:

Fixed-dose combinations Single formulations

1.  AZT/3TC/NVP 60/30/50mg  6.  EFV 200mg

2.  AZT/3TC 60/30mg  7.  EFV 100mg

3.  ABC/3TC 60/30mg  8.  NVP solution     (for use with ABC)

4.  d4T/3TC/NVP 6/30/50mg  9.  LPVr solution

5.  d4T/3TC 6/30mg  10.  LPVr 125mg

* Will also need NVP 200mg, but that is also used for adults so should be readily available

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

Step 3: Prescribe the right dose

Weight ranges (kg)

3-5.9 6-9.9 10-13.9

14-19.9

20-24.9

25-29.9

• AZT 3TC NVP (60/30/50mg)

• AZT/3TC (60/30mg)

1 1.5 2 2.5 3 1 adult tab

• ABC/3TC (60/30mg)

1 1.5 2 2.5 3 1 adult tab

• d4t 3TC NVP (6/30/50mg)

• d4t/3TC (6/30mg)

1 1.5 2 2.5 3 1 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…

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

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 FDCb. What is the average daily dose of this formulation?

1.5 BDc. How many tablets should you dispense for 30 days?

90 tablets

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 EFVb. What is the average daily dose of these formulations?ABC/3TC 2.5 BD, 300mg of EFVc. 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.

Exercise 3 – Dosing syrups vs FDCs

19

You have a patient who weighs 5 kg. You prescribe a regimen of AZT/3TC/NVP.

1st: 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 

2nd: 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

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

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

Morning AZT/3TC/NVP Evening AZT/3TC 

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

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?

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

Case 2 IBU is a 6 month old infant who is HIVpositive. He received NVP syrup for prophylaxis.He is not anemic and the weight is 6 kg. Youhave 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

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 4If 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

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 orDuo 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 OrABC/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

• Case 5 Popo is a 9 year old boy who is HIV+. He is not on ARVsand was diagnosed with TB. His weight is 21kg. He is eligible to start ARVs.• When would you start him on ARVs2-8 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

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