Strategies to Reduce Mortality Among Children Living With HIV and Children Exposed to HIV but Are Uninfected, Admitted With Severe Acute Malnutrition at Mulago Hospital, Uganda (REDMOTHIV): A Mixed Methods Study

Victor Musiime; Andrew Kiggwe; Judith Beinomugisha; Lawrence Kakooza; Josam Thembo-Mwesige; Sharafat Nkinzi; Erusa Naguti; Loice Atuhaire; Ivan Segawa; Willy Ssengooba; Jackson K Mukonzo; Esther Babirekere-Iriso; Philippa Musoke

doi:10.3389/fped.2022.880355

Strategies to Reduce Mortality Among Children Living With HIV and Children Exposed to HIV but Are Uninfected, Admitted With Severe Acute Malnutrition at Mulago Hospital, Uganda (REDMOTHIV): A Mixed Methods Study

Front Pediatr. 2022 Jun 24:10:880355. doi: 10.3389/fped.2022.880355. eCollection 2022.

Authors

Affiliations

¹ Department of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
² Department of Research, Joint Clinical Research Centre, Kampala, Uganda.
³ Makerere University Lung Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
⁴ Mwanamugimu Nutrition Unit, Directorate of Paediatrics and Child Care, Mulago National Referral Hospital, Kampala, Uganda.
⁵ BSL 3 Mycobacteriology Laboratory, Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
⁶ Department of Pharmacology and Therapeutics, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.

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 (C_max) and concentration at 12 h after dose (C_12h)] 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.

Keywords: Africa; HIV; HIV exposed children; antibiotics; mortality; severe acute malnutrition.

Associated data

ClinicalTrials.gov/NCT05051163