ARV and paediatrics: Missing tools, makeshift solutions
13 July 2004
Because there are no FDCs specifically designed for children, she will receive the adult FDC split in half. Although it is the best available solution, breaking tablets means that you cannot be sure that the child always gets the exact dosage required, and for some weight ranges, additional NVP is needed to avoid under-dosage.
Htway Htway is only 10 months old and has HIV. When she started receiving antiretroviral treatment at an MSF clinic in Myanmar, her weight was a mere 3.3 kg and her height was 58cm. She was failing to thrive and was facing one opportunistic infection after another. Htway Htway was receiving cotrimoxazole to ward off PCP, a form of pneumonia, was on other antibiotics to fight Mycobacterium Avian Complex and was receiving treatment for tuberculosis.
Both of the baby's parents are HIV positive, and her father is about to start treatment. During the day the child stays in the MSF feeding centre and the nurses administer the drugs. In the evenings, Htway Htway is looked after by her 14-year-old sister, who is responsible for giving her the drugs.
Choosing the correct ARV regimen for Htway Htway will not be easy for her doctor.
The first, simplest option would be to start Htway Htway on MSF's standard first-line regimen for children: stavudine (d4T), lamivudine (3TC) and nevirapine (NVP) in a fixed-dose combination (FDC) tablet.
But because there are no FDCs specifically designed for children, she will receive the adult FDC split in half. Although it is the best available solution, breaking tablets means that you cannot be sure that the child always gets the exact dosage required, and for some weight ranges, additional NVP is needed to avoid under-dosage.
But for Htway Htway, things are more complicated than that. Her doctor would like to avoid a potential metabolic interaction between NVP and the rifampicin she is receiving for her TB. So a second option would be for her to receive efavirenz instead of nevirapine. But efavirenz is not recommended for children less than three years old or children weighing less than 10 kg - and Htway Htway is both.
A third option would be to use a combination of AZT, 3TC and abacavir, as recommended by WHO for HIV/TB co-infection. But in Myanmar MSF has no access to abacavir as the drug is expensive and there are no low-cost prequalified generic versions. Furthermore, this kind of "triple-nuke" combination has significantly less potency, and 5% of patients develop dangerous hypersensitivity to abacavir.
Eventually, Htway Htway's doctor decides in favour of a fourth option: to use AZT, 3TC and NVP in syrup formulations. In this case, the dose of NVP is increased in order to compensate for the drug interaction with rifampicin (even though there is a lack of guidelines about how to modify the NVP dose in this situation).
Htway Htway now takes her ARV syrups twice daily, and another seven tablets as well. Syrups can be difficult to use, as you need to use several different syrups and get the dosage exactly right using a syringe. Her pill burden is extremely high.
Nevertheless, she is slowly gaining weight and her diarrhoea has stopped. This week her sister will be able to take her home for the first time in months.
What is needed:
Paediatric fixed-dose combinations and breakable tablets, to ease children's adherence to treatment and make dosage easier.
Clearer guidelines and protocols on antiretroviral treatment for children, including further study of drug interaction.