Propelling the Pediatric HIV Therapeutic Agenda With Science, Innovation, and Collaboration

Abstract

Background:A number of well-described obstacles to the pediatric therapeutic agenda have resulted in substantial delays in the introduction of new medications, formulations, strategies, and approaches to treat infants, children, and adolescents living with HIV.Setting:Global landscape.Methods:The authors will provide a summary of current and emerging initiatives to accelerate the pediatric therapeutic agenda including illustrative case studies of innovations and scientific discovery in diagnosis and treatment of very young children with HIV infection.Results:The challenges posed by rapid physiologic and developmental changes that characterize the trajectory of childhood as well as the complex regulatory and fiscal milieu of HIV therapeutics have hampered pediatric HIV therapeutic research. Recent efforts to accelerate this agenda include prioritizing agents and formulations, defining dosing by weight bands, applying innovative study designs, synergizing work across research networks to achieve common goals, and the establishment of a global prioritized research agenda. A case study of initiatives to diagnose and effectively treat newborns and infants will illustrate the critical role of basic science research and novel approaches to study design and implementation that are informing global efforts to end AIDS.Conclusions:A pediatric therapeutic agenda informed by basic science and achieved through innovation and global cooperation is essential to achieve an AIDS-free generation.

Neurodevelopment at 11 months after starting antiretroviral therapy within 3 weeks of life

“…Solid or dispersible formulations would certainly improve adherence. 42,43 Our findings do not suggest neurotoxicity from ART.…”

The promise of paediatric dolutegravir

“…In 2019, fewer than 55% of the estimated 1.8 million children living with HIV (CLHIV) received life‐saving antiretroviral therapy (ART) [1]. Children in low‐ and middle‐income countries (LMIC) continue to have limited access to optimal paediatric ART [2], and viral load suppression (VLS) rates among children remain unacceptably low [3]. To achieve the UNAIDS 95‐95‐95 benchmarks for all ages by 2030 [4], there is a pressing need for LMIC to have access to robust, affordable and child‐friendly paediatric ART regimens [2].…”

“…This includes children who are newly initiating HIV treatment, those who are virologically suppressed on non-DTG regimens, and individuals who experience virological failure on a non-DTG regimen. ART coverage and viral load suppression in children continue to lag that in adults [3], and paediatric DTG promises to advance epidemic control across this vulnerable group. DTG10, in particular, provides clear advantages for the child, the caregiver and healthcare provider and the broader health system, including the ARV market.…”

“…ART coverage and viral load suppression in children continue to lag that in adults [3], and paediatric DTG promises to advance epidemic control across this vulnerable group. DTG10, in particular, provides clear advantages for the child, the caregiver and healthcare provider and the broader health system, including the ARV market.…”

Safety and Efficacy of Starting Antiretroviral Therapy in the First Week of Life

“…World Health Organization [ 5 ] and other international pediatric guidelines [ 6–8 ] recommend prompt initiation of ART regardless of clinical, immunologic, and virological status [ 7–9 ]. However, HIV testing immediately following birth does not occur in most countries [ 10 , 11 ], available drug formulations are limited in the first month of life [ 10–13 ], and there are limited pharmacokinetic (PK), safety, and efficacy data for neonatal ART [ 12 , 13 ].…”