To watch the replay of this webinar and still earn a CPD point, go to: https://event.webinarjam.com/go/replay/474/519k1umra63a3qtv  

Email john.woodford@newmedia.co.za to let him know that you have watched the replay. 

 The following article is based on Dr Levin’s presentation. 

The differences in HIV between adults and children​ are: 

• Viral Loads​ 
• CD4 counts​ 
• Response to therapy​ 
• Pharmacokinetics​ 
• Lack of trial data​ 
• Adherence issues​ 
• Drug formulations​ 
• Taste issues​. 

In terms of CD4 counts in children​, for those <5 years we look at CD4 percentage, while for those >5 years we look at the CD4 absolute count​. 

Adherence​ 

Adherence depends greatly on the simplicity of the regimen​, such as twice- or once-daily dosing, and a reduced number of pills. Volumes of liquids should be easy to measure​. Twice daily does not mean 12 hourly. It requires education​. Taste issues​ can be a problem. One can try to disguise taste with peanut butter, sweet soft foods, chocolate milk, etc​. 

Don’t always start highly active antiretroviral therapy (HAART) on the first visit​. 

Some tablets must be swallowed whole – they can’t be crushed or chewed​. Ritonavir tablets can be crushed. 

To monitor adherence​, you can monitor pharmacy records​, ask patients to bring their medication to each visit​, use a treatment chart​, and ask the patient​ in a nonjudgmental way if they are taking their meds. 

Drug formulations​ 

In terms of solutions vs tablets/capsules, try change to capsules/tablets as soon as possible​ 

Lopinavir/ ritonavir (LPV/r tablets) can’t be crushed. 

Dolutegravir (DTG) and ritonavir (RTV) tablets can be crushed​. Ritonavir powder​ is available, as are LPV/r pellets​. LPV/r solution should be kept in fridge until dispensed. Thereafter, it is stable at room temp for 42 days​. 

Drug dosing 

Increase doses as the child grows​, using body surface area (BSA), weight​ and a dosing chart. 

New regimens for DOH 2019​ 

From 1 month of age, 1st Line. 

3-20kg: abacavir (ABC), lamivudine (3TC)​, LPV/r 

20kg and over: ABC, 3TC, DTG​. 

From 10 years and 35kg​ - Tenofovir​, lamividine​, dolutegravir, tenofovir, lamivudine and dolutegravir 

(TLD)​. 

Once DTG dispersible is available then it will be ABC/3TC/DTG from 3kg and 4 weeks of age. 

New paediatric formulations 

Lopinavir/ritonavir pellets 

This is the same technology (Melt Extrusion) as LPV/r tablets except much smaller​. Sprinkle pellets onto a spoon of soft food​. Pellets can’t be stirred, crushed, dissolved/ dispersed in food, or chewed​. This is better tolerated than LPV/r solution​.  

Patients less than six months don’t tolerate pellets well and risk of aspiration – so don’t use​. After six months, there is still a slight after-taste but better tolerated​. This is available in public and private sectors.​ 

In Department of Health (DoH), it is used for patients >6 months not tolerating LPV/r solution.​ Link to Video: https://tinyurl.com/y3vjjpfw ​   

Ritonavir (RTV) heat stable powder 

The use of RTV solution in paediatrics​ is super-boosting lopinavir/ritonavir when used with rifampicin​, as a booster with atazanavir and darunavir​. 

Pros​:  

• Shelf life of 36 months​ 
• Doesn’t need to be stored in a fridge​ 
• 100mg dosing per sachet​ 
• Can be sprinkled over soft food (apple sauce or vanilla pudding) or mixed with liquid (water, chocolate milk, or infant formula).​ 
• Alcohol- and propylene glycol-free. 

Cons: 

• Tastes terrible​ 
• Must be used within 2 hours of mixing with food or liquid​ 
• If dosed at < 100mg is very complicated to reconstitute​. If used with food must administer the entire 100mg dose​. 

RTV solution is no longer available. RTV powder is freely available​. 

Abacavir /3TC 120/60 tablets​ 

• Scored and dispersible ​ 
• Can be used from 3kg till 25kg​ 
• Will replace all other paediatric 3TC and ABC formulations​ 
• Is given once daily​ 
• At 25kg can use ABC/3TC 600/300 tablets​ 
• Two generics are registered in SA​ 
• Is available in the private sector​ 
• Is on the new DoH tender​ 
• Western Cape and Eastern Cape are already are using it. ​ 
• Is cost effective​. 

DTG paediatric formulations​ 

DTG dispersible tablets​: 

• 10mg scored generic tabs​ 
• Can be used from 4 weeks of age and 3kg​ 
• Two generics lodged with SAHPRA. Hopefully will be registered any day now​ 
• Will become part of the paediatric guidelines as soon as available in SA.  

Abacavir/lamivudine/lopinavir/ritonavir 4 in 1 

• Cipla/ DNDi​ 
• 30/15/40/10mg powder​ 
• Actually tastes quite nice 
• Has been registered by SAHPRA 
• Will probably be used for patients not tolerating LPV/r solution or failing DTG regimens. 

Tenofovir alefenamide (TAF) 

This is a prodrug of tenofovir​. It has less effect on kidneys and bones especially when used with a booster like ritonavir​. It is a very small formulation​, 10mg if used together with CYP450 inhibitors eg RTV or COBI​; 25mg if not given with CYP450 inhibitors. It can be given from six years and 25Kg. Might be associated with weight gain​. 

TAF/FTC/DTG 

It is available in 25mg/200mg/50mg​ as a tiny tablet​, and children love it​. It can be used from six years and 25kg​. You should still monitor renal function​ and watch weight gain​. 

At 35kg can switch to TLD​. At least two generics have been registered by SAHPRA​ and should be available within the next few months​. 

Abacavir +3TC Backbone​ 

3TC has a side effect​ of pure red cell aplasia - anaemia, however this is very rare​. 

Abacavir can have a hypersensitivity reaction​. Therefore​, if you stop abacavir for a suspected hypersensitivity reaction, you can never give the patient abacavir again​. 

This may or may not be accompanied by rash​. Systemic symptoms may be severe​ and present as a multisystem disorder​. This is usually in first six weeks of treatment​ and becomes visibly worse with each dose​. There have been fatalities with rechallenge​. 

Hypersensitivity reaction (HSR) is linked to human leukocyte antigen (HLA) B*5701​ allele. A blood test is available in South Africa but is not frequently requested​. HLA B*5701 is rare in the black population​ and HSR has a prevalence of 5% in whites, 0.2% in blacks​. 

Switching from EFV to DTG​ must be >20kg​. 

Antiretroviral treatment in special populations​ 

Neonates: 

• Get expert advice in every case​ 
• LPV/r can’t be used until the baby is 14 days old (or 14 days after expected date of birth in prems)​ 
• Abacavir not registered <3 months​ 
• No therapeutic dose of nevirapine (NVP) in neonates​ 
• NVP less effective in those under three years​ 
• Invariably there will be non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance due to
• Prevention of mother-to-child transmission (PMTCT​). 

HAART and adolescence​: 

Issues in this age group are: 

• Adherence​ 

• Disclosing diagnosis​ (adolescent groups​ and group therapy have a role to play) 

Summary 

Children are different yet the same​. They respond very well to ART, we just need to get them to take it​. These new wonderful paediatric formulations are going to make a major difference​. Please upgrade your patients’ regimens. Please make use of our Right to Care helplines:  

HIV: 082 352 6642 

TB: 063 698 6543