Management of HIV in Children: Challenges and Outcomes

Abstract

Background: An estimated 1.7 million children aged 0-14 years were living with HIV in 2021 globally with over 90% of them in Sub-Saharan Africa. Infants and children with HIV disproportionately contribute to mortality due to the aggressive nature of paediatric HIV, late presentation to care, suboptimal or unpalatable antiretroviral drug formulations and low levels of ART adherence. Gaps in the health system are responsible for preventable HIV infections in children as well as delayed linkage to care leading to poor outcomes. It is important to clearly characterize clinical and virologic outcomes and identify modifiable factors that undermine the effectiveness of antiretroviral therapy (ART) in infants and children including the impact of delayed diagnosis. Objectives: To determine the impact of delayed diagnosis on survival benefit of early ART in infants with HIV, define early and long-term response to ART in children with HIV and determine factors associated with clinical outcomes in ART-treated children. Methods: Three prospective studies involving HIV-1 infected infants and children were conducted between 2004 and 2016. In the Paediatric Adherence Study (PAD) an observational prospective study, 149 HIV-1 infected children aged 18 months to 12 years with advanced clinical disease were enrolled and initiated on ART at the Kenyatta National Hospital in 2004-2006. Children were followed prospectively for >15 years for clinical (morbidity, growth, mortality) immunologic (CD4 count and %) and virologic (HIV-1 plasma RNA, genotypic drug resistance mutations) outcomes. In the Optimizing HIV-1 Therapy- (OPH-03), a randomized controlled trial 99 HIV-1 infected infants aged between 0 and 5 months were enrolled and initiated on ART at the Kenyatta National Hospital between 2006 and 2008. In the pre-randomization phase of 24 months children were followed 3-monthly while on antiretroviral therapy and monitored for clinical parameters (mortality, morbidity, growth), immunologic (CD4) and virologic (plasma HIV-1 RNA, HIV-1 reservoir) outcomes. At 24 months children were randomized to either treatment interruption or continued ART. After a short interruption period (3 months) all children resumed ART. For this analysis only the 24-month pre-randomization phase is considered. In the Paediatric Urgent Start of HAART (PUSH), a randomized controlled trial 193 HIV-1 infected infants and children < 12 years of age hospitalized for severe illness were enrolled from 4 facilities (KNH and Mbagathi District Hospital, Kisumu County Hospital and JOOTRH) between 2013 and 2015 and randomized to urgent (within 48 hours) or post-stabilization (within 14 days) ART. Children were followed up prospectively for 2 years for clinical, immunologic and virologic monitoring. As part of this study we collected serial plasma samples for CMV viral load and used the entire population of children to determine the impact of high CMV viraemia on clinical outcomes. For this analysis we consider pooled analysis of children in both arms of the study in the first 12 months of follow-up.