Evaluation of a Differentiated Point-of-care Active Case Finding & Management Model to Eliminate Mother-to-Child Transmission of HIV in Malawi
NCT Number: NCT06493357
Acronym: PAC-Man
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: HIV Prevention
Interventions: BEHAVIORAL: PAC-Man|BEHAVIORAL: Standard of Care
Sponsor: University of North Carolina, Chapel Hill
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 2426
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-07
Completion Date: 2027-12-31
Locations: Bwaila Hospital, Lilongwe, Central Region, Malawi

Summary:
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.

Primary Outcome Measures: 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: 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)