November 2, 2004
“HIV treatment for adults is slowly becoming easier, with increasing availability in developing countries of a three-drug cocktail in one tablet. But children who need treatment still have to drink large amounts of foul tasting syrup or swallow large tablets – that's if they can actually access treatment at all. Children with HIV are generally not interesting for pharmaceutical companies, but some generic companies are developing more child-friendly ARV treatments. International agencies need to push this issue higher up the agenda and governments will need to remove barriers to the use of generic products.”
Children with HIV/AIDS are being neglected. Doctors treating them have very limited choices of drugs at their disposal, and so around 50 percent of children with HIV/AIDS die before the age of two.
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. Although children represent only six percent of HIV infections, they account for 17 percent of deaths due to AIDS.
In wealthy countries, relatively few children are being born with HIV, due in large part to the success of efforts to prevent mother-to-child transmission. Some pediatric formulations (such as syrups) do get developed and manufactured for this market. However, because of a lack of commercial interest, these formulations are not available for children in developing countries because they are either too expensive or simply not registered and/or marketed. Further, developing countries also need different formulations better adapted to their context, such as chewable and breakable tablets. At present these pediatric formulations are lacking.
There are several major problems facing clinicians:
First, there is the problem of diagnosis. Most serological methods used to diagnose HIV are not reliable for children under 18 months. Virological confirmation tests are needed but these tests are expensive, need sophisticated lab facilities and thus are not available.
CD4 (the white blood cell targeted by HIV) is also difficult, since most of the commercially available CD4 count machines are not adapted for use in young children.
The second critical challenge is the lack of pediatric formulations of antiretrovirals (ARVs), which makes determining and administering doses complex and burdensome and often leads to over- or under-dosing. As children grow, doses must be adjusted but this is difficult in the absence of pediatric formulations. For children under 10 kilos, difficult-to-measure syrups are used, often in large quantities. 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.
There are no pediatric fixed-dose combinations. This means that children do not have the possibility to take one pill twice a day, like adults do. Some studies are looking at once-daily tablets. Projects are underway at public drug producers such as the Government Pharmaceutical Organization in Thailand and the generic company Cipla in India.
However, since there is no lucrative potential market, European and US-based companies (and even some generic companies) are, for the most part, not interested in developing pediatric formulations adapted to poor countries. This is why the leadership and involvement of governments and international organizations such as the World Health Organization (WHO) and UNICEF is so critical.
A third major problem is the lack of simple guidelines and tools to facilitate prescription. Currently, doses are determined according to weight or body surface. 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. Standardized dosing charts can help avoid miscalculation and can support prescribing of ARVs.
The fourth major challenge is the high price of the pediatric formulations that do exist. Both first- and second-line ARV treatment for children costs several times more than for adults. 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 for a 14 kg children).
Further examples of problems include: Merck does not offer any reduced, differential price for its efavirenz syrup, and there are no WHO pre-qualified generic versions of d4T oral solution.
MSF began treating children with ARVs in early 2002. By the middle of 2004, only 5 percent of MSF patients were children under 13. MSF is seeking to increase the numbers of children under treatment, but our efforts are frustrated by the lack of proper tools.
MSF is committed to fighting for the development of appropriate, practical and affordable diagnostics and drug formulations to facilitate widespread treatment of children with AIDS.
© 2013 Doctors Without Borders/Médecins Sans Frontières (MSF)