Case study No. 9. Development of simple and appropriate formulations for scale-up of HIV treatment for children: an example from the CHAPAS-1 trial

Abstract

Whilst there has been considerable progress in antiretroviral (ARV) drug options for adults, the development of affordable drugs in appropriate formulations for children has lagged behind. Where liquids are available they are costly, have short shelf-lives, and are difficult to transport and store. As a result divided adult fixed-dose combination (FDC) tablets (combining 2 or 3 drugs into 1 pill) have been frequently given to children in resourcelimited settings. Parts of adult tablets, although acceptable for older children, prevent reliable and easy adjustment of dose as a child grows and often contain suboptimal ratios of drugs for young children, risking either toxicity or underdosing and the development of drug resistance. This is a particular concern given that many children face a lifetime requirement of ARVs and key first line drugs like nevirapine (NVP) and lamivudine (3TC) are highly susceptible to resistance. The CHAPAS-1 trial investigated the appropriate dosing of, and adherence to, a new FDC specifically for children, Triomune Baby (50mg NVP; 6mg stavudine (d4T); 30mg 3TC) and Triomune Junior (double Baby dose). Pharmacokinetic (dosing) data from a subset of children in CHAPAS-1 showed the ratio of drugs contained within Triomune Baby/Junior to be appropriate for African children. Data were submitted to the US Food and Drug Administration (FDA) as part of the approval process for use of the tablets in Africa. These combination tablets are the first licensed specifically for children under 12 years and are now widely available throughout Africa. They are dosed according to simple weightband tables, now endorsed and standardised across different ARV regimens by World Health Organisation