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Introduction: Predictors of neurodevelopment among children who are HIV‐exposed uninfected (CHEU) are poorly understood. Methods: Mothers with and without HIV and their children were enrolled during 6‐week postnatal care visits across seven sites in Kenya between March 2021 and June 2022. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool, including social, language, fine motor and gross motor domains. We used multivariate linear mixed effects models to identify associations between 1‐year neurodevelopment scores, HIV and antiretroviral therapy (ART) exposures, and household factors, adjusted for potential confounders and clustered by the site. Results: At 1‐year evaluation, CHEU (n = 709) and children who are HIV‐unexposed uninfected (CHUU) (n = 715) had comparable median age (52 weeks) and sex distribution (49% vs. 52% female). Mothers living with HIV were older (31 vs. 27 years), had lower education (50% vs. 26% primary) and were more likely to be report moderate‐to‐severe food insecurity (26% vs. 9%) (p < 0.01 for all). Compared to CHUU, CHEU had higher language scores (adjusted coeff: 0.23, 95% CI: 0.06, 0.39) and comparable social, fine and gross motor scores. Among all children, preterm birth was associated with lower gross motor scores (adjusted coeff: −1.38, 95% CI: −2.05, −0.71), food insecurity was associated with lower social scores (adjusted coeff: −0.37, 95% CI: −0.73, −0.01) and maternal report of intimate partner violence (IPV) was associated with lower fine motor (adjusted coeff: −0.76, 95% CI: −1.40, −0.13) and gross motor scores (adjusted coeff: −1.07, 95% CI: −1.81, −0.33). Among CHEU, in utero efavirenz (EFV) exposure during pregnancy was associated with lower gross motor scores compared to dolutegravir (DTG) exposure (adjusted coeff: −0.51, 95% CI: −1.01, −0.03). Lower fine and gross motor scores were also associated with having a single or widowed mother (adjusted coeff: −0.45, 95% CI: −0.87, −0.03) or a deceased or absent father (adjusted coeff: −0.81, 95% CI: −1.58, −0.05), respectively. Conclusions: Biologic and social factors were associated with child neurodevelopment. Despite socio‐demographic differences between CHEU and CHUU, 1‐year neurodevelopment was similar. Addressing IPV and food insecurity may provide benefits regardless of maternal HIV status. DTG use was associated with higher neurodevelopmental scores in CHEU, compared to EFV regimens, potentially contributing to a lack of neurodevelopmental difference between CHEU and CHUU., INTRODUCTION Successful prevention of vertical transmission programmes over the last decade has contributed to a rapidly growing population of almost 16 million children who are HIV‐exposed uninfected (CHEU) around the [...]

Antiretroviral therapy for children living with HIV (CLHIV) under 3 years of age commonly includes lopinavir/ritonavir (LPV/r). However, the original liquid LPV/r formulation has taste and cold storage difficulties. To address these challenges, LPV/r oral pellets have been developed. These pellets can be mixed with milk or food for administration and do not require refrigeration. We developed the population pharmacokinetic (PK) model and assessed drug exposure of LPV/r oral pellets administered twice daily to CLHIV per World Health Organization (WHO) weight bands. The PK analysis included Kenyan and Ugandan children participating in the LIVING studies (NCT02346487) receiving LPV/r pellets (40/10 mg) and ABC/3TC (60/30 mg) dispersible tablets. Population PK models were developed for lopinavir (LPV) and ritonavir (RTV) to evaluate the impact of RTV on the oral clearance (CL/F) of LPV. The data obtained from the study were analyzed using nonlinear mixed‐effects modeling approach. Data from 514 children, comprising a total of 2,998 plasma concentrations of LPV/r were included in the analysis. The LPV and RTV concentrations were accurately represented by a one‐compartment model with first‐order absorption (incorporating a lag‐time) and elimination. Body weight influenced LPV and RTV PK parameters. The impact of RTV concentrations on the CL/F of LPV was characterized using a maximum effect model. Simulation‐predicted target LPV exposures were achieved in children with this pellet formulation across the WHO weight bands. The LPV/r pellets dosed in accordance with WHO weight bands provide adequate LPV exposures in Kenyan and Ugandan children weighing 3.0 to 24.9 kg. [ABSTRACT FROM AUTHOR]

Expansion of access to diagnosis and treatment for human immunodeficiency virus (HIV) and a high incidence of HIV infection in adolescence has resulted in a growing population of adolescents and young adults living with HIV. The prevalence of poor retention in care, insufficient viral suppression and loss to follow-up are higher among adolescents and young adults compared with other age groups. Poor outcomes could be attributed to psychosocial changes during adolescence, but also to poor transitional care from paediatric to adult HIV services. In many countries, transition processes remain poorly defined and unstructured, which may jeopardize treatment adherence and retention. We describe existing definitions of transition and transition frameworks, and key elements of transition as proposed by key national stakeholders in Kenya. Our consensus definition of transition is 'a planned process by which adolescents and young adults living with HIV, and their caregivers, are empowered with knowledge and skills to enable them to independently manage their health.' Transition should begin soon after disclosure of HIV status until an adolescent gains the necessary knowledge and skills and is willing to move to adult services, or by 25 years of age. Proposed key elements of transition are: target ages for milestone achievement; readiness assessment; caregiver involvement and communication with adult clinics; flexibility to return to adolescent or paediatric clinics; group transition; and considerations for adolescents with special needs. Retention in care, linkage to care and viral suppression are important markers of transition success. Proposed definitions and key elements could provide a framework for structuring transition programmes in other countries. L'acces elargi au diagnostic et au traitement du virus de I'immunodeficience humaine (VIH) et l'incidence elevee de l'infection par le VIH a l'adolescence ont entraine une hausse de la population d'adolescents et de jeunes adultes atteints du VIH. La prevalence de mauvais continuums de soins, de suppressions virales insuffisantes et d'interruptions du suivi est plus elevee chez les adolescents et les jeunes adultes que dans d'autres groupes d'age. Ces mauvais resultats peuvent etre attribues aux changements psychosociaux qui interviennent a l'adolescence, mais aussi a la mediocrite de la transition entre les services de soins pediatriques et adultes du VIH. En Afrique subsaharienne, les processus de transition sont mal definis et peu structures, ce qui peut nuire au respect et a la poursuite des traitements. Nous decrivons ici les definitions existantes de la transition et des cadres de transition, ainsi que les elements cles de la transition proposes par les principales parties prenantes nationales du Kenya. Notre definition consensuelle de la transition est: << processus planifie qui permet aux adolescents et aux jeunes adultes atteints du VIH, ainsi qu'a leurs aidants, de disposer des connaissances et competences necessaires pour gerer leur sante de maniere autonome >>. La transition devrait debuter peu apres la communication de la seropositivite et durer jusqu'a ce que l'adolescent ait acquis les connaissances et competences necessaires et qu'il souhaite passer a des services pour adultes, ou jusqu'a l'age de 25 ans. Les elements cles proposes de la transition sont: ages cibles pour le franchissement de certaines etapes; evaluation de la maturite; implication des aidants et communication avec les services pour adultes; possibility de revenir a des services pediatriques ou pour adolescents; transition de groupe; prise en compte des adolescents ayant des besoins speciaux. Le continuum de soins, le lien entre les soins et la suppression virale sont d'importants marqueurs de la reussite de la transition. Les definitions et elements cles proposes peuvent offrir un cadre pour structurer les programmes de transition dans d'autres pays. La ampliacion del acceso al diagnostico y tratamiento del virus de la inmunodeficiencia humana (VIH) y la alta incidencia de la infeccion por el VIH en la adolescencia han dado lugar a una poblacion creciente de adolescentes y adultos jovenes que viven con el VIH. La prevalencia de una retencion inadecuada en la atencion, la supresion viral insuficiente y la perdida de seguimiento son mayores entre los adolescentes y los adultos jovenes en comparacion con otros grupos de edad. Los resultados negativos pueden atribuirse a cambios psicosociales durante la adolescencia, pero tambien a una atencion de transicion deficiente de los servicios pediatricos a los servicios para adultos con VIH. En Africa subsahariana, los procesos de transicion siguen siendo mal definidos y desestructurados, lo que puede suponer un riesgo para el cumplimiento y la retencion del tratamiento. Describimos las definiciones existentes de transicion y los marcos de transicion, asi como los elementos clave de la transicion propuestos por las principales partes interesadas a nivel nacional en Kenia. Nuestra definicion consensuada de transicion es 'un proceso planificado mediante el cual los adolescentes y adultos jovenes que viven con el VIH, y sus cuidadores, son capacitados con conocimientos y habilidades que les permiten manejar su salud de manera independiente'. La transicion debe comenzar poco despues de la revelacion del estado serologico respecto al VIH hasta que el adolescente adquiera el conocimiento y las habilidades necesarias y este dispuesto a trasladarse a los servicios para adultos, o a la edad de 25 anos. Los elementos clave de la transicion propuestos son: edades objetivo para el logro de los hitos; evaluacion de la preparacion; participacion de los cuidadores y comunicacion con las clinicas para adultos; flexibilidad para regresar a las clinicas para adolescentes o pediatricas; transicion de grupos; y consideraciones para los adolescentes con necesidades especiales. La retencion en la atencion, la vinculacion a la atencion y la supresion viral son marcadores importantes del exito de la transicion. Las definiciones propuestas y los elementos clave podrian proporcionar un marco para estructurar los programas de transicion en otros paises., Introduction Expansion of paediatric antiretroviral therapy (ART) and treatment services has improved survival among children living with human immunodeficiency virus (HIV). However, globally, HIV-associated mortality among adolescents 15-19 years of [...]