Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocol

Abstract Background In Malawi and elsewhere in Africa, many children living with HIV are unaware of their status, often because of missed services for the prevention of vertical transmission of HIV (PVTH). Pregnant and breastfeeding women (PBFW) living with HIV frequently go without viral load (VL)...

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Main Authors: Michael E. Herce, Caitlin Cassidy, Alexandra Munson, Jessie K. Edwards, Sarah E. Rutstein, Mitch Matoga, Chimwemwe Kumwenda, Katherine R. Simon, Joep J. van Oosterhout, Carrie M. Cox, Funny Kamanga, Wiza Kumwenda, Sam Phiri, Ethel Rambiki, Agness Thawani, Jacqueline Huwa, Bridget Malewezi, Tisu Mvalo, Agatha Bula, Lameck Chinula, Irving Hoffman, Madeleine A. Squibb, Rose K. Nyirenda, Friday Saidi, Mina C. Hosseinipour, Maganizo B. Chagomerana
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Language:English
Published: BMC 2025-07-01
Series:Implementation Science Communications
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Online Access:https://doi.org/10.1186/s43058-025-00762-5
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author Michael E. Herce
Caitlin Cassidy
Alexandra Munson
Jessie K. Edwards
Sarah E. Rutstein
Mitch Matoga
Chimwemwe Kumwenda
Katherine R. Simon
Joep J. van Oosterhout
Carrie M. Cox
Funny Kamanga
Wiza Kumwenda
Sam Phiri
Ethel Rambiki
Agness Thawani
Jacqueline Huwa
Bridget Malewezi
Tisu Mvalo
Agatha Bula
Lameck Chinula
Irving Hoffman
Madeleine A. Squibb
Rose K. Nyirenda
Friday Saidi
Mina C. Hosseinipour
Maganizo B. Chagomerana
author_facet Michael E. Herce
Caitlin Cassidy
Alexandra Munson
Jessie K. Edwards
Sarah E. Rutstein
Mitch Matoga
Chimwemwe Kumwenda
Katherine R. Simon
Joep J. van Oosterhout
Carrie M. Cox
Funny Kamanga
Wiza Kumwenda
Sam Phiri
Ethel Rambiki
Agness Thawani
Jacqueline Huwa
Bridget Malewezi
Tisu Mvalo
Agatha Bula
Lameck Chinula
Irving Hoffman
Madeleine A. Squibb
Rose K. Nyirenda
Friday Saidi
Mina C. Hosseinipour
Maganizo B. Chagomerana
author_sort Michael E. Herce
collection DOAJ
description Abstract Background In Malawi and elsewhere in Africa, many children living with HIV are unaware of their status, often because of missed services for the prevention of vertical transmission of HIV (PVTH). Pregnant and breastfeeding women (PBFW) living with HIV frequently go without viral load (VL) monitoring and their infants miss key HIV testing milestones for early infant HIV diagnosis (EID). In Malawi, the current standard of care (SOC) involves mostly passive approaches to pediatric HIV diagnosis, relying on mothers presenting to health facilities with their infants. To reach PBFW living with HIV and their infants who miss critical HIV services and who are at higher risk for adverse HIV outcomes, including vertical transmission, we developed the “Point-of-care Active Case finding & Management” or “PAC-Man” model. PAC-Man uses a multifaceted implementation strategy involving task-shifted mobile teams to reach these mother-infant pairs (MIPs) with evidence-based point-of-care (POC) technology for EID and maternal VL testing in the community, linked to back-to-care and antiretroviral therapy (ART) services. Methods We will conduct a hybrid type III effectiveness-implementation incomplete stepped-wedge cluster-randomized trial in 12 clinics in Malawi over a 3-year period to test our strategy. Control periods will reflect SOC. Intervention periods will add PAC-Man to SOC. The primary outcome is reach of infant EID testing by age 6 months in the clinic population. Secondary outcomes include the proportion of infants newly diagnosed with HIV initiating ART and maternal VL testing reach. These outcomes will be assessed using routinely collected clinic data augmented with field surveys enrolling a sample of MIPs randomly selected from each clinic. Implementation outcomes of acceptability, adoption, fidelity, implementation, sustainability, cost, and scalability will be assessed using convergent mixed methods. Discussion Study findings will offer new insights into the effects of differentiated, community-based services for reaching infants unaware of their HIV-positive status and their mothers and characterize the fit of the PAC-Man strategy with the national PVTH program. The study holds promise for improving access to EID and VL testing, and ART, for MIPs currently being missed by traditional facility-based approaches and could suggest a novel approach for use in real-world PVTH programs across Africa. Trial registration This study is registered at ClinicalTrials.gov, NCT06493357.
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spelling doaj-art-13bbe74fc3404b49b97d111dba0b30d22025-08-20T04:02:55ZengBMCImplementation Science Communications2662-22112025-07-016111910.1186/s43058-025-00762-5Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocolMichael E. Herce0Caitlin Cassidy1Alexandra Munson2Jessie K. Edwards3Sarah E. Rutstein4Mitch Matoga5Chimwemwe Kumwenda6Katherine R. Simon7Joep J. van Oosterhout8Carrie M. Cox9Funny Kamanga10Wiza Kumwenda11Sam Phiri12Ethel Rambiki13Agness Thawani14Jacqueline Huwa15Bridget Malewezi16Tisu Mvalo17Agatha Bula18Lameck Chinula19Irving Hoffman20Madeleine A. Squibb21Rose K. Nyirenda22Friday Saidi23Mina C. Hosseinipour24Maganizo B. Chagomerana25Institute for Global Health and Infectious Disease, School of Medicine, University of North CarolinaDepartment of Epidemiology, Gillings School of Public Health, University of North CarolinaDepartment of Neurology, School of Medicine, University of North CarolinaDepartment of Epidemiology, Gillings School of Public Health, University of North CarolinaInstitute for Global Health and Infectious Disease, School of Medicine, University of North CarolinaUNC Project-Malawi, University of North CarolinaUNC Project-Malawi, University of North CarolinaBaylor College of Medicine Children’s Foundation MalawiPartners in HopeBaylor College of Medicine Children’s Foundation MalawiUNC Project-Malawi, University of North CarolinaUNC Project-Malawi, University of North CarolinaPartners in HopeLighthouse TrustLighthouse TrustLighthouse TrustMothers2MothersUNC Project-Malawi, University of North CarolinaUNC Project-Malawi, University of North CarolinaUNC Project-Malawi, University of North CarolinaInstitute for Global Health and Infectious Disease, School of Medicine, University of North CarolinaInstitute for Global Health and Infectious Disease, School of Medicine, University of North CarolinaMinistry of HealthUNC Project-Malawi, University of North CarolinaInstitute for Global Health and Infectious Disease, School of Medicine, University of North CarolinaInstitute for Global Health and Infectious Disease, School of Medicine, University of North CarolinaAbstract Background In Malawi and elsewhere in Africa, many children living with HIV are unaware of their status, often because of missed services for the prevention of vertical transmission of HIV (PVTH). Pregnant and breastfeeding women (PBFW) living with HIV frequently go without viral load (VL) monitoring and their infants miss key HIV testing milestones for early infant HIV diagnosis (EID). In Malawi, the current standard of care (SOC) involves mostly passive approaches to pediatric HIV diagnosis, relying on mothers presenting to health facilities with their infants. To reach PBFW living with HIV and their infants who miss critical HIV services and who are at higher risk for adverse HIV outcomes, including vertical transmission, we developed the “Point-of-care Active Case finding & Management” or “PAC-Man” model. PAC-Man uses a multifaceted implementation strategy involving task-shifted mobile teams to reach these mother-infant pairs (MIPs) with evidence-based point-of-care (POC) technology for EID and maternal VL testing in the community, linked to back-to-care and antiretroviral therapy (ART) services. Methods We will conduct a hybrid type III effectiveness-implementation incomplete stepped-wedge cluster-randomized trial in 12 clinics in Malawi over a 3-year period to test our strategy. Control periods will reflect SOC. Intervention periods will add PAC-Man to SOC. The primary outcome is reach of infant EID testing by age 6 months in the clinic population. Secondary outcomes include the proportion of infants newly diagnosed with HIV initiating ART and maternal VL testing reach. These outcomes will be assessed using routinely collected clinic data augmented with field surveys enrolling a sample of MIPs randomly selected from each clinic. Implementation outcomes of acceptability, adoption, fidelity, implementation, sustainability, cost, and scalability will be assessed using convergent mixed methods. Discussion Study findings will offer new insights into the effects of differentiated, community-based services for reaching infants unaware of their HIV-positive status and their mothers and characterize the fit of the PAC-Man strategy with the national PVTH program. The study holds promise for improving access to EID and VL testing, and ART, for MIPs currently being missed by traditional facility-based approaches and could suggest a novel approach for use in real-world PVTH programs across Africa. Trial registration This study is registered at ClinicalTrials.gov, NCT06493357.https://doi.org/10.1186/s43058-025-00762-5HIV/AIDSStepped-wedge trialHybrid effectiveness-implementation trialMalawiEarly infant diagnosisPrevention of vertical transmission of HIV
spellingShingle Michael E. Herce
Caitlin Cassidy
Alexandra Munson
Jessie K. Edwards
Sarah E. Rutstein
Mitch Matoga
Chimwemwe Kumwenda
Katherine R. Simon
Joep J. van Oosterhout
Carrie M. Cox
Funny Kamanga
Wiza Kumwenda
Sam Phiri
Ethel Rambiki
Agness Thawani
Jacqueline Huwa
Bridget Malewezi
Tisu Mvalo
Agatha Bula
Lameck Chinula
Irving Hoffman
Madeleine A. Squibb
Rose K. Nyirenda
Friday Saidi
Mina C. Hosseinipour
Maganizo B. Chagomerana
Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocol
Implementation Science Communications
HIV/AIDS
Stepped-wedge trial
Hybrid effectiveness-implementation trial
Malawi
Early infant diagnosis
Prevention of vertical transmission of HIV
title Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocol
title_full Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocol
title_fullStr Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocol
title_full_unstemmed Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocol
title_short Study design and procedures for a hybrid effectiveness-implementation incomplete stepped-wedge cluster-randomized trial to evaluate a differentiated point-of-care HIV diagnosis and management model for the prevention of vertical transmission of HIV in Malawi: The PAC-Man trial protocol
title_sort study design and procedures for a hybrid effectiveness implementation incomplete stepped wedge cluster randomized trial to evaluate a differentiated point of care hiv diagnosis and management model for the prevention of vertical transmission of hiv in malawi the pac man trial protocol
topic HIV/AIDS
Stepped-wedge trial
Hybrid effectiveness-implementation trial
Malawi
Early infant diagnosis
Prevention of vertical transmission of HIV
url https://doi.org/10.1186/s43058-025-00762-5
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