Evaluation of a Differentiated Point-of-care Active Case Finding & Management Model to Eliminate Mother-to-Child Transmission of HIV in Malawi (PAC-Man)

UNCPM 22401 - Evaluation of a Differentiated Point-of-care Active Case Finding & Management Model for the Elimination of Mother-to-Child Transmission of HIV in Lilongwe and Mangochi, Malawi

Purpose: To conduct a hybrid effectiveness-implementation stepped-wedge trial to:

1. Estimate the effect of the PAC-Man model, compared to SOC, on the proportion of infants who receive timely EID testing.
2. Estimate the effect of the PAC-Man model, compared to SOC, on the proportion of pregnant and breastfeeding women living with HIV who receive guideline-adherent viral load testing.
3. Compare implementation outcomes between the PAC-Man model and SOC.

Participants: The total study sample size is 2,426, including 2,304 mother-infant pair (MIP) survey participants, 48 high-risk pregnant/breastfeeding women living with HIV for in-depth interviews (from high-risk MIPs who participated in a survey); 10 PMTCT policy makers and Ministry of Health (MOH)/ President's Emergency Plan for AIDS Relief (PEPFAR) implementing partner senior managers for key informant interviews; and about 48-64 professional and lay health providers for focus group discussions and implementation actor surveys.

To rigorously evaluate the PAC-Man model, investigators will use a hybrid (type 3) effectiveness-implementation incomplete stepped-wedge trial design. The hybrid incomplete stepped-wedge design is a rigorous quasi-experimental design that allows for incremental "rollout" of the PAC-Man model and serial measurement of both health outcomes (for infants and mothers in Objectives 1 and 2, respectively), as well as implementation outcomes (Objective 3). The incomplete stepped-wedge design is more efficient than a complete design, minimizes costs, and reduces participant burden, without sacrificing statistical precision. Using this design, sequential crossover from control (i.e., the SOC) to intervention (i.e., SOC plus the PAC-Man model) takes place at each 'step' using cluster randomization until all clusters (defined as a group of "sites," or health facilities plus the surrounding communities in its catchment area) receive the intervention. The 12 sites included in our study will be divided into 4 clusters of 3 sites each.

Study Overview

• Status: Recruiting
• Conditions: HIV Prevention
• Intervention / Treatment: Behavioral: PAC-Man; Behavioral: Standard of Care

Detailed Description

PAC-Man Model:

PAC-Man represents an integrated differentiated services delivery (DSD) model for mothers and infants that brings the following three evidence-based practices into the community for elimination of mother to child transmission (EMTCT): 1) pediatric active case finding using novel point-of-care (POC) early infant diagnosis (EID) technology; 2) same-day antiretroviral therapy (ART) initiation for infants newly diagnosed with HIV infection; and 3) maternal viral load (mVL) testing and back-to-care services. PAC-Man uses a mobile approach to offer EMTCT services in the community and reach "high risk" MIPs in which the mother living with HIV did not initiate ART, started ART late during pregnancy or breastfeeding, dropped off treatment following ART initiation, was unsuppressed on ART, was identified with HIV infection for the first-time during the post-partum period, and/or did not return with her infant for EID testing. Because these evidence-based practices are already recommended by the Ministry of Health and will be functioning at the site and not the individual level, delivering the PAC-Man model will be done under the auspices of routine care, applying an overarching implementation strategy of creating new mobile care teams equipped with new diagnostic technology who deploy the m-PIMA™ in community settings.

PAC-Man Implementation Approaches:

The overall implementation strategy being evaluated in this study is the creation of mobile care teams to deploy m-PIMA™ and provide EMTCT services in the community. Complementing this overarching strategy will be two sub-strategies used to enhance PAC-Man adoption: 1) task shifting of active case finding, EID and mVL testing, ART initiation, and back-to-care services to community health workers (CHWs), community nurses, and HIV diagnostic assistants; and 2) changing service sites to convenient locations in the community to overcome barriers to EID and mVL delivery. These strategies are intended to work in concert with the above evidence-based practices to integrate PAC-Man into the EMTCT program.

• Study Type: Interventional
• Enrollment (Estimated): 2426
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Herce, MD, MPH; Phone Number: 9198435996; Email: michael_herce@med.unc.edu

Study Locations

• Malawi
  • Lilongwe, Malawi
    • Recruiting
    • Area 18 Health Centre
    • Contact: Chimwemwe Kumwenda; Phone Number: +265-999-265626; Email: ckumwenda@unclilongwe.org
  • Monkey Bay, Malawi
    • Recruiting
    • Monkey Bay Community Hospital
    • Contact: Chimwemwe Kumwenda; Phone Number: +265-999-265626; Email: ckumwenda@unclilongwe.org
  • Central Region
    • Lilongwe, Central Region, Malawi
      • Not yet recruiting
      • Bwaila Hospital
      • Contact: Michael Herce, MD, MPH; Phone Number: 9198435996; Email: michael_herce@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

The criteria for Enumerated MIP Cohort is as follows:

Inclusion Criteria:

• Enrolled in the national EMTCT program at a study site in the 12 months preceding a survey.

Exclusion Criteria:

• None.

The criteria for Enumerated MIP Field Survey is as follows:

Inclusion Criteria:

• Age 16 years or older.
• Enrolled in the national EMTCT program at a study site in the 12 months preceding a survey.

Exclusion Criteria:

• Documented transferred out from a site prior to the field survey.
• Participated previously in the field survey.
• Decline informed consent.

The criteria for In-Depth Interviews is as follows:

Inclusion criteria:

• Age 16 years or older.
• Met high-risk criteria for PAC-Man model.
• Participated in a field survey.

Exclusion criteria:

• Decline informed consent.

The criteria for Focus Group Discussions is as follows:

Inclusion criteria:

• Age 18 years or older.
• MOH or implementing partner professional or lay health worker at a study site (such as nurses, community health workers, health surveillance assistants, and HIV diagnostic assistants)
• Generally familiar with the PAC-Man model and/or EMTCT/ EID service delivery at their site.

Exclusion criteria:

• Decline informed consent.

The criteria for Key Informant Interviews is as follows:

Inclusion criteria:

• Age 18 years or older.
• HIV/ EMTCT policy maker OR MOH/ PEPFAR implementing partner senior manager.
• Generally familiar with HIV and/or EMTCT/ EID service delivery.

Exclusion criteria:

• Decline informed consent.

The criteria for Implementation Actor Questionnaires is as follows:

Inclusion criteria:

• Age 18 years or older.
• Professional or lay health provider at a study site.
• Generally familiar with HIV and/or EMTCT/ EID service delivery at their site.
• Participated in a focus group discussion.

Exclusion criteria:

• Decline informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PAC-Man Model; PAC-Man represents an integrated DSD model for mothers and infants that brings the following three evidence-based practices into the community for EMTCT: 1) pediatric active case finding using novel POC EID technology; 2) same-day ART initiation for infants newly diagnosed with HIV infection; and 3) mVL testing and back-to-care services. PAC-Man uses a mobile approach to offer EMTCT services in the community and reach "high risk" MIPs. Delivering the PAC-Man model will be done under the auspices of routine care, applying an overarching implementation strategy of creating new mobile care teams equipped with new diagnostic technology who deploy the m-PIMA in community settings.	Behavioral: PAC-Man; PAC-Man represents an integrated DSD model for mothers and infants that brings the following three evidence-based practices into the community for EMTCT: 1) pediatric active case finding using novel POC EID technology; 2) same-day ART initiation for infants newly diagnosed with HIV infection; and 3) mVL testing and back-to-care services. PAC-Man uses a mobile approach to offer EMTCT services in the community and reach "high risk" MIPs. Delivering the PAC-Man model will be done under the auspices of routine care, applying an overarching implementation strategy of creating new mobile care teams equipped with new diagnostic technology who deploy the m-PIMA in community settings.
Active Comparator: Standard of care (control arm); Routine care as provided by the Ministry of Health.	Behavioral: Standard of Care; Routine care as provided by Ministry of Health.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of infants who receive EID testing by age 6 months	Proportion of infants exposed to HIV who receive EID testing by age 6 months among the enumerated cohort of MIPs with infants at least 6 weeks old at all study sites.	Within 12 months of MIP enrollment in the national EMTCT program

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of infants who receive EID testing by age 2 months	Proportion of infants exposed to HIV who receive EID testing by age 2 months among the enumerated cohort of all MIPs with infants at least 6 weeks old at all study sites.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of infants who receive EID testing by age 12 months	Proportion of infants exposed to HIV who receive EID testing by age 12 months among the enumerated cohort of all MIPs with infants at least 6 weeks old at all study sites.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of high-risk infants who receive EID testing by age 6 months	Proportion of infants with high-risk mothers exposed to HIV who receive EID testing by age 6 months among all high-risk MIPs with infants at least 6 weeks old at all study sites.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of infants who initiate ART	Proportion of infants newly diagnosed with HIV who initiate ART ≤60 days from EID sample collection among the enumerated cohort of all infants.	Within 12 months of MIP enrollment in the national EMTCT program
Median infant results return time	Median number of days from infant EID sample collection to results returned to caregivers.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of infants newly diagnosed with HIV	Proportion of infants newly diagnosed with HIV among the enumerated cohort of all infants.	Within 12 months of MIP enrollment in the national EMTCT program
Median age at ART initiation among infants	Median age in months at ART initiation among infants who test positive for HIV.	Within 12 months of MIP enrollment in the national EMTCT program
Median time to ART initiation among infants	Median number of days to ART initiation among infants who test positive for HIV.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of infants who initiate ART the same day as diagnosis	Proportion of infants newly diagnosed with HIV who initiate ART on the same day as EID results received among the enumerated cohort of all infants.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of infants with HIV retained in care at 3 months post-ART initiation	Proportion of infants with HIV who are retained in care at 3-months post-ART initiation.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of infants with HIV retained in care at 6 months post-ART initiation	Proportion of infants with HIV who are retained in care at 6-months post-ART initiation.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of MIPs reached with viral load testing	Proportion of mothers living with HIV who received MOH-recommended 6-monthly VL testing during pregnancy and breastfeeding among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of high-risk MIPs reached with viral load testing	Proportion of high-risk MIPs living with HIV who received MOH-recommended 6-monthly VL testing during pregnancy and breastfeeding among all high-risk MIPs from the enumerated cohort.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of MIPs virally suppressed at 6 months	Proportion of mothers with viral suppression (<1,000 copies of HIV per ml.) at 6 months after EMTCT enrollment among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of high-risk MIPs virally suppressed at 6 months	Proportion of high-risk mothers with viral suppression (<1,000 copies of HIV per ml.) at 6 months after EMTCT enrollment among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of MIPs virally suppressed at 12 months	Proportion of mothers with viral suppression (<1,000 copies of HIV per ml.) at 12 months after EMTCT enrollment among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of high-risk MIPs virally suppressed at 12 months	Proportion of high-risk mothers with viral suppression (<1,000 copies of HIV per ml.) at 12 months after EMTCT enrollment among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of MIPs retained in care at 6 months	Proportion of mothers who are retained in care (≥1 clinic encounter within the last 180 days) at 6 months after EMTCT enrollment among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of MIPs retained in care at 12 months	Proportion of mothers who are retained in care (≥1 clinic encounter within the last 180 days) at 12 months after EMTCT enrollment among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of MIPs who resumed ART	Proportion of mothers who had documented treatment interruption (i.e., a treatment gap ≥28 days) who later resumed ART among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Proportion of MIPs who received enhanced adherence counseling	Proportion of MIPs who had unsuppressed viral load and then completed enhanced adherence counselling among the enumerated cohort of all MIPs.	Within 12 months of MIP enrollment in the national EMTCT program
Adoption - proportion of sites that adopt the PAC-Man model	Number of trained sites that deliver the PAC-Man intervention divided by the total number of trained sites. Study endline sustainability survey is conducted at the end of the trial once all study sites have been randomized to receive the intervention.	6-12 months after sites switch to intervention; study endline (Approximately 12 months from the time that last study sites are switched to the intervention)
Adoption - proportion of providers who adopt the PAC-Man model	Number of trained providers who deliver the PAC-Man intervention divided by the total number of trained providers. Study endline sustainability survey is conducted at the end of the trial once all study sites have been randomized to receive the intervention.	6-12 months after sites switch to intervention; study endline (Approximately 12 months from the time that last study sites are switched to the intervention)
Implementation - cost per pediatric case	Incremental cost of PAC-Man implementation per pediatric HIV case identified, compared to standard of care. Study endline sustainability survey is conducted at the end of the trial once all study sites have been randomized to receive the intervention.	6-12 months after sites switch to intervention; study endline (Approximately 12 months from the time that last study sites are switched to the intervention)
Implementation - cost per unsuppressed MIP	Incremental cost of PAC-Man implementation per pregnant and breastfeeding woman with unsuppressed viral load identified, compared to standard of care. Study endline sustainability survey is conducted at the end of the trial once all study sites have been randomized to receive the intervention.	6-12 months after sites switch to intervention; study endline (Approximately 12 months from the time that last study sites are switched to the intervention)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Michael Herce, MD, MPH, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Herce ME, Cassidy C, Munson A, Edwards JK, Rutstein SE, Matoga M, Kumwenda C, Simon KR, van Oosterhout JJ, Cox CM, Kamanga F, Kumwenda W, Phiri S, Rambiki E, Thawani A, Huwa J, Malewezi B, Mvalo T, Bula A, Chinula L, Hoffman I, Squibb MA, Nyirenda RK, Saidi F, Hosseinipour MC, Chagomerana MB. 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. Implement Sci Commun. 2025 Jul 28;6(1):78. doi: 10.1186/s43058-025-00762-5.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: July 8, 2024
• First Posted (Actual): July 10, 2024

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: HIV Treatment
• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: 24-0561; 1P01HD112215 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with The University of North Carolina at Chapel Hill (UNC).
• IPD Sharing Time Frame: Beginning 9 and continuing for 36 months following publication
• IPD Sharing Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No