Long-Acting Drug Delivery Systems for ART Optimization in Children Living with HIV-1 II (LADDS II) (R61/R33 Clinical Trial Not Allowed)

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.