While some advances are being made in antiretroviral therapy (ART) coverage for pediatric populations, significant gaps remain. Currently available ART regimens for children have limitations and result in suboptimal viral suppression. Infants and young children achieve even lower rates of viral suppression and are more likely to experience subsequent viral rebound. Key factors underlying these suboptimal viral suppression outcomes include suboptimal regimen potency, poor adherence in all pediatric populations, often the result of poor regimen tolerability, lack of appropriate formulations, and poor palatability of many of the existing formulations. Additional factors contributing to limitations in treatment efficacy include high rates of pre-treatment drug resistance, hypervariable antiretroviral (ARV) drug exposures in early life due to ontogeny of drug metabolizing enzymes and transporters, significant and pervasive stigma, and non-disclosure of HIV status affecting mothers living with HIV, all of which can perpetuate poor virologic suppression rates and associated morbidity and mortality. While the roll out of a promising daily pediatric friendly oral dolutegravir formulation is underway in many low- and middle-income settings and presents the prospect of improving dismal viral suppression rates in this population, its impact is still limited by factors common to daily oral ART including stigmatization concerns and persistent adherence challenges.
Long acting ARVs represent a major therapeutic advance for people living with HIV across the age spectrum. They offer the prospect of enhanced treatment convenience and improved treatment adherence and stigma reduction, potentially removing a key barrier to maintenance of viral suppression. A combination of two long-acting injectable drugs has received regulatory approval for 2-monthly administrations for the treatment of HIV-1 in adults and adolescents and is being investigated in younger children. Another long-acting drug was also recently approved for 6-monthly administration in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current ART regimen. Despite such remarkable progress, further advances are needed to fully realize the promise of long-acting treatment for HIV treatment and sustained effort is necessary to accelerate their introduction in pediatric populations.
Long-Acting Drug Delivery Systems (LADDS) that can overcome limitations of daily oral ART are needed to significantly simplify dosing requirements and optimize ART outcomes in infants and children through achievement and maintenance of consistent and effective drug levels and suppression of HIV replication. Stimulating critical optimization and preclinical activities at an earlier stage in the product development lifecycle could significantly facilitate and accelerate introduction of promising LADDS platforms to young pediatric populations, often the last ones to benefit from treatment innovations.