ABSTRACT
Background: Children living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CHEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in CLHIV/CHEU. This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among CLHIV/CHEU admitted with severe acute malnutrition. Methods: This is an open label randomized controlled trial involving 300 children; 76 CLHIV and 224 CHEU. The participants are being randomized to receive 1 week of ceftriaxone (n = 150) or standard-of-care (ampicillin/gentamicin) (n = 150), in addition to other routine care. The trial's primary outcome is in-hospital mortality. Secondary outcomes are: length of hospitalization; weight-for-height, weight-for-age and height-for-age z-scores; and pattern/antimicrobial sensitivity of pathogens. In addition, 280 severely malnourished children of unknown serostatus will be tested for HIV at admission to determine the prevalence and factors associated with HIV-infection. Furthermore, all the CLHIV on LPV/r will each provide sparse pharmacokinetic (PK) samples to evaluate the PK of LPV/r among malnourished children. In this PK sub-study, geometric means of steady-state LPV PK parameters [Area Under the Curve (AUC) 0-12h , maximum concentration (Cmax) and concentration at 12 h after dose (C12h)] will be determined. They will then be put in pharmacokinetic-pharmacodynamic (PK-PD) models to determine optimal doses for the study population. Discussion: This study will ascertain whether antibiotics with higher sensitivity patterns to common organisms in Uganda and similar settings, will produce better treatment outcomes. The study will also provide insights into the current pattern of organisms isolated from blood cultures and their antimicrobial sensitivities, in this population. In addition, the study will ascertain whether there has been a significant change in the prevalence of HIV-infection among children presenting with severe malnutrition in the WHO recommended option B plus era, while determining the social/structural factors associated with HIV-infection. There will also be an opportunity to study PK parameters of antiretroviral drugs among severely malnourished children which is rarely done, and yet it is very important to understand the dosing requirements of this population. Trial Registration: ClinicalTrials.gov, identifier: NCT05051163.
ABSTRACT
BACKGROUND: The present study aims to understand the socioeconomic and physical activity impact of the COVID-19 pandemic on children living with perinatally acquired HIV (PHIV) and without HIV (HIV-) in Kampala (Uganda). METHODS: The authors included children aged 10-18 years who filled out questionnaires at baseline (2017-2018, prepandemic) and 2 years later (March 2020-January 2021, pandemic) in an observational cohort study at Joint Clinical Research Centre (Kampala). Physical activity energy expenditure was calculated using a youth compendium from the National Collaborative on Childhood Obesity Research. Descriptive and standard test statistics including Kruskal-Wallis were used. RESULTS: One hundred and ninety-eight children from Kampala Uganda were included prepandemic (101 PHIV and 97 HIV-); 131 (71 PHIV and 60 HIV-) had information collected during the pandemic. At baseline, median and interquartile range age was 13 years (11; 15), and 52% were females. During the pandemic, overall weekly physical activity increased by a median of 854 minutes (interquartile range: 270-1890), and energy expenditures increased by 16% in both PHIV and in HIV- (P < .001 for groups overall prepandemic vs pandemic). CONCLUSIONS: The authors found in this Ugandan cohort of children that children engaged in more physical activity. Further research is warranted to understand the long-term effects of the pandemic on children's well-being.