July 13, 2004
International pharmaceutical industries and governments are failing to develop and produce AIDS medicines and diagnostic tools suited to children, claimed Doctors Without Borders/Médecins Sans Frontières (MSF) today at the XV International AIDS Conference in Bangkok. However, the organization reported getting good clinical results in treating children by utilizing creative techniques to educate children and their caretakers about HIV and help them adhere to treatment.
"Children who need treatment have to drink great amounts of foul-tasting syrup or swallow large tablets, and that's only if they are even able to access treatment in the first place," said Dr. David Wilson, Medical Coordinator of MSF programs in Thailand. "Commercial pharmaceutical companies do not bother to develop pediatric formulations of AIDS medicines because children are not an attractive market."
The large success of efforts to prevent transmission of the virus from mother to child in developed countries means that relatively few children are being born with HIV in wealthy countries. The resulting lack of a profitable market means that pediatric formulations are in short supply despite the growing need for them in developing countries. The only hope on the horizon is that some generic companies are developing fixed-dose first-line therapies.
The estimated worldwide number of children with HIV/AIDS was over 2.5 million in 2003. In the same year, 700,000 children under the age of 15 were newly infected with HIV/AIDS, 88.6% of whom live in sub-Saharan Africa. Their prognosis is not good. Approximately 50% of children with HIV/AIDS die before the age of two. MSF began treating children with ARVs in December 2000 and by March 2004 about 5% of MSF patients were children under 13. Although MSF is not yet treating large numbers of children, MSF teams have created innovative tools, such as health diaries, treatment calendars, and fairy tales about "Devimmon," a witch that is a metaphor for HIV, to help children adhere to treatment.
MSF is committed to doing better for children but our efforts are frustrated by the lack of proper tools.
The first challenge is to know if children are HIV positive. Standard serological tests are not reliable in infants of less than 18 months. In addition, monitoring CD4 is also difficult, since most of the commercially available CD4 machines are not adapted for use on young children. The second critical challenge is the lack of pediatric formulations of ARVs, which makes determining and administering doses complex and burdensome. Currently, doses are determined according to weight or body surface and must be adjusted as the child grows.
In developing countries, there are no standardized dosing schedules, and doctors and other health professionals have no simple guidelines for treatment of HIV in children. In most cases, bad-tasting, difficult-to-measure syrups are used for children under 10 kilos. For older children, a dosing chart is used to calculate dose by weight.
Syrups and oral solutions are not suitable for use in older children because of the large volumes needed, but low dosage tablets and capsules are not produced for most ARVs. In practice, this means that caregivers are forced to measure syrups and cut and crush adult formulations.
Those pediatric formulations come at a high price. While the fixed-dose version of d4T/3TC/NVP for adults is available for about US$200 per patient per year, the best price for the same drugs in pediatric formulations is approximately US$1,300 (oral solutions and syrups). There are no pediatric fixed-dose combinations.
For the second-line regimen of AZT/ddI/NFV, the adult yearly price is from US$1,228 but for pediatric dosages, the same regimen in powder and syrup formulations costs at least US $2,846 per patient per year.
There are some ongoing studies looking at once-daily tablet and/or syrup formulations for children. However, without a lucrative market, companies are not allocating enough resources to make quick progress.
"Unless there is increased pressure on drug makers and intervention from governments, it will be years before new therapies are available," stated MSF pharmacist Fernando Pascual. "We are committed to fighting for the development of practical diagnostics and child-friendly drug formulations."
© 2013 Doctors Without Borders/Médecins Sans Frontières (MSF)