Of the 2.5 million HIV-positive children in the world in 2007, nearly 90% were in sub-Saharan Africa, according to UNAIDS. Antiretrovirals (ARVs) are developed for adults, most clinical trials are in adults, with doses and dosage forms designed for adults. But children cannot be dosed like small adults, as their metabolic capacity to absorb ARVs is not simply proportional to their weight. Safety, efficacy and dosage need to be determined via specific pediatric trials. Most ARVs were developed in tablet form, yet these are impractical for children under five, who require special liquid formulations. While older children can take tablets, those intended for adults often contain too large a dose.

The treatment of children has always been integral to Abbott´s HIV research. Abbott conducted clinical studies of its protease inhibitor (PI) HIV medicines in children at the same time as it studied them for adult use, and both of Abbott´s PIs are available around the world in liquid formulations. Abbott´s new, lower-strength tablet formulation, Aluvia® (lopinavir/ritonavir), is the only co-formulated protease inhibitor tablet that can be used in children. The tablets do not require refrigeration and can be taken with or without a meal. The WHO recommends lopinavir/ritonavir as the preferred treatment for children who no longer respond to first-line HIV medicine.

Bristol-Myers Squibb currently produces pediatric formulations of Videx® (didanosine), Zerit® (stavudine) and Sustiva® (efavirenz), and is working with the Pediatric Aids Clinical Trials Group to develop Reyataz® (atazanavir) for infants from 3 months old to 18 years. It is also developing Sustiva® oral solution for children from 3 months to 16 years. Sustiva capsules are currently approved for use in children 3 years and older.

Gilead Sciences is working to advance development of a pediatric formulation of tenofovir. To address issues with the initial formulation, Gilead has developed a new heat-stable encapsulated sprinkle formulation for future studies. Two Phase III studies in pediatrics are currently enrolling patients.

GlaxoSmithKline has developed a number of ARV liquid formulations for children, all available at not-for-profit prices in the world´s poorest countries. GSK has also committed to support four pediatric clinical trials in resource-poor countries to determine the best ways to expand access to HIV/AIDS treatment. The development of oral solutions for its combination therapies, Combivir® and Trizivir®, is complicated because two key components (zidovudine and lamivudine) require different pH ranges to maintain stability, and daily dosing issues associated with abacavir have hampered a Kivexa® pediatric formulation.

In 2007, GSK gained European Commission approval for new scored tablets for Epivir, Combivir and Ziagen. This will enable children above 14kg of weight to benefit from a solid dosage form. Scored tablets enable ARVs to be broken into two smaller doses which simplifies treatment for children. Tablets are often easier to store and distribute, and also less complicated to administer than the liquid formulations currently available – particularly when two or three medicines are combined in one pill. For example, a child weighing 20kg can now take half a tablet of Combivir in the morning and the second half in the evening in combination with another ARV, instead of requiring 8ml of Epivir solution twice a day plus 12ml of Retrovir solution three times daily.