Medical Chronicle recently hosted a CPD-accredited, one-hour webinar on HIV in 2022: Paediatric update. The webinar is sponsored by Cipla and was presented by Dr Leon Levin. Dr Leon Levin is a paediatrician who has been treating HIV infected infants, children and adolescents for the past 26 years and is currently Senior Technical Advisor in Paediatrics at Right to Care NGO. 

Dr Leon Levin gave an insightful HIV paediatric update

 

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