Because HIV transmission in young children has largely been eliminated in high-income countries due to effective prevention of mother-to-child transmission (PMTCT) interventions, little market incentive exists for pharmaceutical companies to develop antiretroviral (ARV) drugs adapted for children. The World Health Organisation (WHO) recommends immediate antiretroviral therapy (ART) for all HIV-positive children less than two years old, but the safety and correct dosing of key ARVs have not been established in very young children, and appropriate child-adapted formulations do not exist. Current paediatric ARV formulations are unpalatable for these children, are impractical for caregivers due to multiple liquid preparations that have to be adjusted according to weight, and have undesirable interactions with tuberculosis (TB) drugs.
"There are millions of children with HIV-related disease in low- and middle-income countries, but their needs are absent from the HIV research and development agenda, and this is largely because they are poor and voiceless and do not represent a lucrative market," said Dr. Bernard Pécoul, executive director of DNDi. "Working with partners, we hope to help fill this terrible gap and offer improved treatment options for children with HIV and AIDS."
Last year, Médecins Sans Frontières/Doctors Without Borders (MSF), UNITAID, and other organisations called upon DNDi to apply its expertise to paediatric HIV and AIDS based on its track record in delivering new medicines for neglected diseases. DNDi, a not-for-profit R&D organization, develops new treatments for neglected patients suffering from sleeping sickness, leishmaniasis, Chagas disease, and malaria.
"Our medical teams in the field have for years faced difficulty treating young children with HIV due to the lack of appropriate treatment tools," says Dr. Unni Karunakara, International President of MSF. "We will do everything possible to accelerate the development of and access to improved formulations for children with HIV and AIDS, and look forward to being able to introduce better, affordable medicines to treat HIV-positive babies and children where we work."
After an in-depth needs assessment and consultation with experts - including those from endemic countries such as South Africa, Uganda, Cote d'Ivoire, and Thailand, and from public sector research institutions such as the US National Institutes of Health, UK Medical Research Council, and Agence Nationale de Recherche sur le Sida in France - ideal specifications for improved treatments were developed. There is consensus around the need to develop an improved first-line protease inhibitor-based regimen for children under three years of age, irrespective of prior exposure to ARVs, and this will be DNDi's first priority.
Ideally, this new first-line paediatric HIV therapy needs to be easy to administer and better tolerated by children than current drugs, as well as heat stable, easily dispersible, and dosed once daily or less. It must also carry minimal risk for developing resistance and be suitable for infants and very young children, with minimum requirements for weight adjustments. Finally, any new formulations must be compatible with TB drugs, and, importantly, affordable.
"Paediatric HIV has indeed been a neglected area for innovation in drug development," said Dr. Gottfried Hirnschall, director of WHO's HIV and AIDS Department. "Children's access to HIV treatment has been low with only 28% of the children in need of HIV treatment receiving it at the end of 2009. WHO appreciates DNDi's focus on new paediatric HIV treatments, and we look forward to working together to deliver more and better medicines for children in need."
DNDi's paediatric HIV programme will be led by the newly appointed Marc Lallemant, MD, formerly head of the Programs for HIV Prevention and Treatment (PHPT), a clinical research consortium of Chiang Mai University, Harvard School of Public Health, and IRD (Institut de Recherche pour le Développement), based in Chiang Mai, Thailand. He has studied and conducted research on HIV in pregnant women and children and on the prevention of mother-to-child transmission of HIV since 1985. Dr. Lallemant led two major clinical trials on PMTCT (PHPT 1 and 2), which served as the basis for WHO recommendations for PMTCT in resource-limited settings. He is also involved in paediatric HIV research with PENTA, the European clinical research network and the NIH-funded International Maternal Paediatric Adolescent AIDS Clinical Trials Group (IMPAACT).
"Children living with HIV- related disease are a neglected population, and paediatric AIDS can be considered a neglected disease," says Dr. Lallemant. "While we must make every effort to eliminate new HIV infections among infants through large-scale access to PMTCT and maternal ART, we cannot neglect the millions of children currently and newly infected with the virus who are in dire need of treatment today."
