Optimizing Research to Speed Up Availability of Pediatric Antiretroviral Drugs and Formulations

Abstract

Globally 1.8 million children are living with human immunodeficiency virus (HIV), yet only 51% of those eligible actually start treatment. Research and development (R&D) for pediatric antiretrovirals (ARVs) is a lengthy process and lags considerably behind drug development in adults. Providing safe, effective, and well-tolerated drugs for children remains critical to ensuring scale-up globally. We review current approaches to R&D for pediatric ARVs and suggest innovations to enable simplified, faster, and more comprehensive strategies to develop optimal formulations. Several approaches could be adopted, including focusing on a limited number of prioritized formulations and strengthening existing partnerships to ensure that pediatric investigation plans are developed early in the drug development process. Simplified and more efficient mechanisms to undertake R&D need to be put in place, and financing mechanisms must be made more sustainable. Lessons learned from HIV should be shared to support progress in developing pediatric formulations for other diseases, including tuberculosis and viral hepatitis.

Keywords: HIV; antiretrovirals; children; formulations; research.

Figure 1.

Development and introduction of fixed-dose combinations for children living with human immunodeficiency virus. Abbreviations: ARV, antiretroviral; FDC, fixed-dose combination; PK, pharmacokinetic; SOC, standard of care; SRA, stringent regulatory authorities; Tx, treatment.

Figure 2.

Strategies to innovate research and speed up collection of critical data to develop and introduce pediatric drug and formulations more rapidly. Abbreviations: ARV, antiretroviral; HIV, human immunodeficiency virus; PIP, pediatric investigation plan; PK, pharmacokinetic; PSP, pediatric study plan; WHO, World Health Organization.

Figure 3.

Translating novel approaches: potential immediate applications to the development of dolutegravir/tenofovir alafenamide/emtricitabine. Abbreviations: DTG, dolutegravir; EMA, European Medicines Agency; FDA, Food and Drug Administration; FDC, fixed-dose combination; F/TAF, emtricitabine/tenofovir alafenamide; FTC, emtricitabine; IMPAACT, International Maternal Pediatric Adolescent AIDS Clinical Trials; LBW, low birth weight; MPP, medicines patent pool; PHTI, Paediatric HIV Treatment Initiative; PK, pharmacokinetic; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.