With the success of antiretrovirals (ARVs) and the approval of innovative new options for treatment and prevention, there is a public perception that HIV is no longer a problem. However, HIV is still a global health concern, and particular attention is needed for children living with HIV and the development of new, more effective, pediatric treatments.
Almost 2 million children around the world are living with HIV, and approximately 160,000 children and adolescents (< 15 years of age) were newly diagnosed with HIV in 2021. Just over 50% of children living with HIV have access to treatment(compared with ~75% of adults) and a lower proportion compared with adults have an appropriate response to therapy (i.e., virus suppression). In addition, fewer antiretrovirals (ARVs), the mainstay of HIV therapy, are available in appropriate formulations for infants and young children compared with the approved ARVs for adults.
Newer ARVs, including better tolerated, more effective combination therapy, are desperately needed for the pediatric HIV population. Despite regulatory requirements and incentives from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to develop new pediatric medicines, challenges remain in formulation development, operationalization of clinical trials and access and supply of pediatric ARVs. ViiV Healthcare is committed to addressing these challenges to find new and better ways to develop age-appropriate HIV medicines
One formulation does not fit all
Many of us who work in pediatric drug development believe the ideal pediatric oral formulation is one that meets the needs of children from infants to young adolescents. Achieving that is easier said than done. The development of specific age-appropriate ARV formulations can be quite complex, especially when combining two to threeARVs into one formulation. We can’t treat children like small adults when it comes to getting the doses and ratio of medicine correct and maintaining acceptable safety and efficacy across different ages and weights.Also, some HIV medicines have a taste that children would not like, and creating a “good” tasting medicine for global use must consider varying cultural influences and preferences on what is acceptable.
More needs to be done globally to draw attention to children living with HIV and address the unmet need for new and better age-appropriate HIV medicines
Other considerations for pediatric oral formulations are storage requirements, use of water (or other diluents) and devices (e.g., syringe and cup) for administration. The preference for new oral ARVs is the development of a dispersible tablet that can be reconstituted in water. As HIV treatment moves into long-acting injectable formulations, additional challenges arise which require early planning to address the needs of dose, dosing intervals, injection site, and drug vial sizes.
Support for pediatric clinical trials has to start early
ViiV Healthcare (ViiV HC), a company 100% dedicated to people living with and vulnerable to acquiring HIV, has taken innovative approaches to addressing the challenges in development, access, and supply of pediatric HIV treatment. A group of pediatric drug development experts at ViiV HC advise adult development teams to ensure that the needs of future pediatric development programs are addressed. We start working on oral and long-acting pediatric formulations for new development programs as early as initial adult clinical trials with investigational ARVs. Clinical pharmacological data from these early clinical trials provides data that can be used in developing models to support the dose prediction in children. Enabling work to support pediatric clinical trials such as phase I trials of new formulations or different injection sites is also completed well in advance to ensure the seamless start of pediatric clinical trials.
Global partnerships are going to be the key to success for children LHIV
Global partnerships have helped overcome challenges and barriers to developing new HIV pediatric treatments for children and making them accessible. By partnering with global pediatric networks including the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) and Penta, ViiV HC has expedited clinical trials in the areas of the world where most children with HIV live, such as low- and middle-income countries (LMIC) in Southeast Asia, South America, and Africa.
To facilitate access to new pediatric ARVs in LMIC, we have created unique partnerships. Specifically, we have partnered with non-governmental organizations such as the Clinton Health Access Initiative, Medicines Patent Pool, and Unitaidto expedite the generic development and registration of pediatric formulations of ARVs such as dolutegravir. To facilitate product development, ViiV HC and our partners provide incentives to generic manufacturers, such as funding for development and transfer of technological know-how, and, in turn, the generic manufacturers commit to accelerating product development of these pediatric ARVs. This approach has the potential to reduce the time it takes for availability of new pediatric ARVs in LMIC.
Leaving no person living with HIV behind
ViiV Healthcare’s mission is to leave no person living with HIV behind. By creating innovative pediatric ARV formulations and engaging in global partnerships, we are ensuring that the children living with HIV, one of the most vulnerable populations, are not left behind. Our pediatric programs led to FDA approval for pediatric oral formulations of ARV treatments that are easier to administer and taste good to children. In the past couple of years, we were able to deliver a simple, dispersible tablet of dolutegravir, a key component of HIV therapy, to the global population of children living with HIV and single dispersible tablet containing the combination of dolutegravir, abacavir and lamivudine, which is a complete treatment regimen. Shortly after the approval of the first ever long-acting ARV treatment option for adults, cabotegravir+rilpivirine, this regimen was approved for adolescents in the US and elsewhere around the world.
By taking innovative and collaborative approaches to product development and global partnerships, ViiV HC is closing the treatment gap between adults and children living with HIV. As we continue to work to end the HIV epidemic, more needs to be done globally to draw attention to children living with HIV and address the unmet need for new and better age-appropriate HIV medicines.
