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
BackgroundChildren 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 o...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Pediatrics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2022.880355/full |
| _version_ | 1818218623436587008 |
|---|---|
| author | Victor Musiime 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 |
| author_facet | Victor Musiime 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 |
| author_sort | Victor Musiime |
| collection | DOAJ |
| description | BackgroundChildren 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.MethodsThis 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.DiscussionThis 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 RegistrationClinicalTrials.gov, identifier: NCT05051163. |
| first_indexed | 2024-12-12T07:26:42Z |
| format | Article |
| id | doaj.art-1a2da7135e614374a13a7f2da6a17d8c |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-12T07:26:42Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-1a2da7135e614374a13a7f2da6a17d8c2022-12-22T00:33:08ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-06-011010.3389/fped.2022.880355880355Strategies 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 StudyVictor Musiime0Victor Musiime1Andrew Kiggwe2Judith Beinomugisha3Lawrence Kakooza4Josam Thembo-Mwesige5Sharafat Nkinzi6Erusa Naguti7Loice Atuhaire8Ivan Segawa9Willy Ssengooba10Jackson K. Mukonzo11Esther Babirekere-Iriso12Philippa Musoke13Department of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, UgandaDepartment of Research, Joint Clinical Research Centre, Kampala, UgandaMakerere University Lung Institute, College of Health Sciences, Makerere University, Kampala, UgandaMakerere University Lung Institute, College of Health Sciences, Makerere University, Kampala, UgandaMakerere University Lung Institute, College of Health Sciences, Makerere University, Kampala, UgandaMakerere University Lung Institute, College of Health Sciences, Makerere University, Kampala, UgandaMakerere University Lung Institute, College of Health Sciences, Makerere University, Kampala, UgandaMwanamugimu Nutrition Unit, Directorate of Paediatrics and Child Care, Mulago National Referral Hospital, Kampala, UgandaMwanamugimu Nutrition Unit, Directorate of Paediatrics and Child Care, Mulago National Referral Hospital, Kampala, UgandaMakerere University Lung Institute, College of Health Sciences, Makerere University, Kampala, UgandaBSL 3 Mycobacteriology Laboratory, Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, UgandaDepartment of Pharmacology and Therapeutics, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, UgandaMwanamugimu Nutrition Unit, Directorate of Paediatrics and Child Care, Mulago National Referral Hospital, Kampala, UgandaDepartment of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, UgandaBackgroundChildren 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.MethodsThis 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.DiscussionThis 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 RegistrationClinicalTrials.gov, identifier: NCT05051163.https://www.frontiersin.org/articles/10.3389/fped.2022.880355/fullHIVHIV exposed childrensevere acute malnutritionmortalityantibioticsAfrica |
| spellingShingle | Victor Musiime 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 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 Frontiers in Pediatrics HIV HIV exposed children severe acute malnutrition mortality antibiotics Africa |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | HIV HIV exposed children severe acute malnutrition mortality antibiotics Africa |
| url | https://www.frontiersin.org/articles/10.3389/fped.2022.880355/full |
| work_keys_str_mv | AT victormusiime strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT victormusiime strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT andrewkiggwe strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT judithbeinomugisha strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT lawrencekakooza strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT josamthembomwesige strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT sharafatnkinzi strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT erusanaguti strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT loiceatuhaire strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT ivansegawa strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT willyssengooba strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT jacksonkmukonzo strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT estherbabirekereiriso strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy AT philippamusoke strategiestoreducemortalityamongchildrenlivingwithhivandchildrenexposedtohivbutareuninfectedadmittedwithsevereacutemalnutritionatmulagohospitalugandaredmothivamixedmethodsstudy |