Pediatric Formulations for ARVs

Partnership Objective

Make antiretroviral viral medicines available to children with HIV/AIDS in developing countries in sub-Saharan Africa and Asia.

In the case of ARVs, children cannot be dosed like small adults, as their metabolic capacity to absorb ARVs is not simply proportional to their weight. In the case of ARVs, children cannot be dosed like small adults, as their metabolic capacity to absorb ARVs is not simply proportional to their weight. Copyright Bristol Myers Squibb

What are the health needs and challenges?

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.

Description of partnership activities and how they address needs and challenges

This partnership researches and develops new medicines and/or new formulations of existing medicines to treat children with HIV/AIDS, especially in developing countries in sub-Saharan Africa and Asia. In some cases, partners have signed licensing, patent and/or technology transfer agreements with generic drug manufacturers in South Africa, India and Brazil to make existing HIV/AIDS medicines available in developing countries at lower costs.

AbbVie, first as Abbott, has a long-standing commitment to the treatment of children with HIV. In 2007, AbbVie (as Abbott) launched the first lower-strength tablet formulation of lopinavir/ritonavir in the developing world (Uganda) before making the product available in developed countries. The lopinavir/ritonavir tablet is the only co-formulated protease inhibitor tablet that can be used in children (generic versions of this tablet formulation have been made available subsequent to 2007). The tablets do not require refrigeration and can be taken with or without a meal, an important advance in delivering HIV medicine in developing countries. The tablet is easier for children to take than its liquid formulation, which has been used in Africa since 2001. The lower-strength tablet is sold at half the price of the original formulation in 69 countries, including all of Africa.  AbbVie is developing a sprinkle formulation of norvir, suitable for use in children living with HIV. The new powder has no alcohol or propylene glycol, has significantly improved shelf life from the liquid formulation currently in use, and will not require refrigeration.

Bristol-Myers Squibb produces pediatric formulations of Videx® (didanosine), Zerit® (stavudine) and Sustiva® (efavirenz) and works with the Pediatric AIDS Clinical Trials Group to develop Reyataz® (atazanavir) for infants from 3 months old to 18 years. Sustiva capsules are currently approved for use in children 3 years and older. Sustiva is currently approved in the US for treatment of HIV-1 infection in combination with other ARVs in adults and children 3 months or older who weigh at least 3.5 kg and for patients 3 years and older in other parts of the world.  Bristol-Myers Squibb has studied a capsule sprinkle approach to dosing of Sustiva in children 3 months of age and older. For more information about Bristol-Myers Squibb’s initiatives to expand access to medicines for people with HIV/AIDS and people in developing countries click here

Since 2009, GlaxoSmithKline's ARV interests have been managed by ViiV Healthcare, a new HIV company founded with the singular purpose of research and development of HIV treatments. ViiV Healthcare has developed a number of ARV liquid formulations for children, all available at access prices in the world's poorest countries. ViiV Healthcare has also committed to support multiple paediatric clinical trials in resource-poor countries to determine the best ways to expand access to HIV/AIDS treatment..

In 2010 ViiV Healthcare announced a partnership with Clinton Access Health Initiative (CHAI) and Mylan Laboratories to develop the fixed dose combinations abacavir/lamivudine for the treatment of infants and children. In this innovative partnership ViIV Healthcare, Mylan and CHAI worked to bring respective expertise to develop a taste masked and dispersible product that was deemed of high clinical significance. In 2013, the WHO highlighted ABC/3TC as a key medicine for the treatment of infants and children. ViiV Healthcare conducted the technical development of the product and provided finance and project management support for Mylan to develop and file the product. Mylan filed the product with the FDA in October 2013.

Recognising that 66% of the over 3 million children living with HIV worldwide do not have access to appropriate care and medicines, ViiV Healthcare has granted royalty-free voluntary licences for paediatric formulations of its existing and pipeline HIV medicines (including Dolutegravir), in order to ensure that children in all least-developed, all low-income, and all sub-Saharan African countries (where 99% of all children with HIV live) are able to receive high-quality, low-cost medicines.

ViiV Healthcare also supports collaborative research trials in resource-poor settings to understand public health issues such as prevention of mother-to-child HIVtransmission and HIV-TB co-infection. In total, at the end of 2012, 93 clinical trials were underway; 14 of the 93 trials are paediatric studies. African countries participating in the paediatric studies include Malawi, South Africa, Tanzania, Uganda, Zambia and Zimbabwe.

As part of its ongoing work to deliver innovation in paediatric HIV treatment and care, ViiV Healthcare established a £10 million Paediatric Innovation Seed Fund. This fund specifically supports partnerships with organizations that focus on the evidence base for paediatric care and treatment, the research and development of paediatric fixed-dose combination (FDC) products, and formulations for the treatment of infants and children living with HIV. Examples of partnerships developed to improve access to treatment and care include:

  • The ViiV Healthcare-Elizabeth Glaser Pediatric AIDS Foundation Partnership to increase early detection of HIV and improve access to antiretroviral therapy for HIV-positive infants and young children; strengthen government leadership and policies around paediatric HIV/AIDS; and improve the quality and use of paediatric care to advance the effectiveness of its services.
  • The ViiV Healthcare-amfAR TREAT Asia program to optimize the quality of healthcare for infants and children living with HIV across Asia through the development of clinical data to support optimal paediatric treatment guidelines.

Partnership information

Company(ies) AbbVie , Bristol-Myers Squibb , GlaxoSmithKline

Partner(s) Amfar’s TreatAsia Program, Aspen Pharmacare, Clinton Health Access Initiative, Elizabeth Glaser Pediatric AIDS Foundation, Emcure Pharmaceuticals, Mylan, Positive Action for Children Fund Grantees, Ranbaxy, ViiV Healthcare

Type of Partner(s) Generic Manufacturers, NGOs, Other Business, PDPs

Therapeutic Focus Women and Children's Health, Infectious Diseases

Disease(s) Children's Health, HIV/AIDS

Program Type(s) Availability of Treatment - Technology Transfer - Manufacturing and Entrepreneurial Know-How, Research & Development - Development of Treatments, Research & Development - Pediatric R&D

Targeted Population(s) Children, People with low income

Region(s) South Asia, Sub-Saharan Africa

Number of Countries 49

Country(ies) Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Ghana, Guinea, Guinea-Bissau, India, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, Somalia, South Africa, South Sudan, Sudan, Swaziland, Tanzania, The Gambia, Togo, Uganda, Zambia, Zimbabwe

Start Date 2007

Anticipated completion date Ongoing