Improving HIV Prevention Among Heterosexual Cisgender Men Seeking STI Services in Malawi (NJIRA)

Improving HIV Prevention Among Heterosexual Cisgender Men Seeking STI Services in Malawi: Examining the Benefits, Acceptability, and Associated Costs of a Systems-navigator-delivered Integrated Prevention Package

To evaluate the potential benefit(s), acceptability, and associated costs of a systems navigator-delivered HIV prevention intervention in promoting and supporting persistent use of evidence-based HIV pre-exposure prophylaxis (PrEP) among heterosexual cisgender men receiving care for sexually transmitted infections (STIs) in Lilongwe, Malawi.

Study Overview

• Status: Enrolling by invitation
• Conditions: HIV Infection; Sexually Transmitted Infections; Pre-exposure Prophylaxis; Systems Navigation
• Intervention / Treatment: Other: PrEP eligibility assessment; Diagnostic test: Rapid HIV antibody testing prior to provision and/or refill of PrEP; Other: PrEP follow-up with a PrEP nurse in accordance with contemporary PrEP guidelines; Behavioral: Evaluation of barriers and facilitators to ongoing PrEP use; Other: Point of contact STI testing to inform counseling regarding ongoing PrEP care engagement; Other: Tracing for any missed PrEP visits; Other: Offering a PrEP "restart" kit for cisgender men who choose to discontinue PrEP during the follow-up period

• Study Type: Interventional
• Enrollment (Estimated): 215
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: erica hamilton; Phone Number: 919-544-7040; Email: ehamilton@fhi360.org
• Study Contact Backup: Name: Michelle Robinson; Phone Number: 919-544-7040; Email: mrobinson@fhi360.org

Study Locations

• Malawi
  • Lilongwe, Malawi
    • Malawi CRS
    • Contact: Lameck Chinula, M.B.B.S.; Phone Number: 265-8614587; Email: lchinula@unclilongwe.org
    • Principal Investigator: Mitch Matoga, MBBS, MSc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Cisgender adult and adolescent cisgender men who meet all of the following criteria are eligible for inclusion in this study as a participant initiating PrEP:

   • Age ≥18 years, or age 15-17 (with assent and parent/guardian consent)
   • Able to provide informed consent
   • No plans to move outside study area for at least 26 weeks after study enrollment
   • Willing to provide contact/locator information, including phone number, to facilitate tracing
   • Willing to participate in study activities, including specimen collection
   • Willing to participate in study activities, including systems navigation, counseling, and point of contact STI testing
   • Sought STI clinic services within 7 days of enrollment
   • Initiated on PrEP at STI clinic within 7 days of enrollment
   • Reports at least one cisgender female sex partner in the 6 months prior to enrollment
   • Self-identifies as heterosexual

2. Individuals who meet all of the following criteria are eligible for inclusion in this study as other key stakeholders:

   • Age ≥18 years at the enrollment visit
   • Able to provide informed consent
   • Involved in provision of clinical service navigation, systems navigation, STI or HIV care or prevention (including clinic management or oversight), or development of HIV prevention policy or programs at local or national level

Exclusion Criteria:

1. Cisgender adult and adolescent men who meet any of the following criteria are ineligible for inclusion in this study as a participant initiating PrEP:

   • Appearance of psychological disturbance or cognitive impairment that would limit the ability to understand study procedures, as determined by the investigators
   • Any other condition that, in the opinion of the investigators, would make participation in the study unsafe, or otherwise interfere with the conduct of the study
   • Current participation in any HIV prevention study or other study considered to interfere the interpretation of study outcomes (see Section 4.4).

2. Individuals who meet any of the following criteria are ineligible for inclusion in this study as other key stakeholder:

   • Appearance of psychological disturbance or cognitive impairment that would limit the ability to understand study procedures, as determined by the investigators
   • Any other condition that, in the opinion of the investigators, would make participation in the study unsafe, or otherwise interfere with the study activities

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
Active Comparator: Standard of care PrEP services; Standard of care (SOC) PrEP services include PrEP eligibility assessment, rapid HIV antibody testing prior to provision and/or refill of PrEP, and PrEP follow-up with a PrEP nurse in accordance with contemporary PrEP guidelines. Specifically, SOC services do not generally include point of contact STI testing (with the exception of rapid syphilis and Hepatitis B antigen testing, if kits are available, at PrEP initiation) nor tracing for missed PrEP visits. Participants randomized to the SOC condition will receive these standard PrEP services.	Other: PrEP eligibility assessment; PrEP eligibility assessment; Diagnostic test: Rapid HIV antibody testing prior to provision and/or refill of PrEP; Rapid HIV antibody testing prior to provision and/or refill of PrEP; Other: PrEP follow-up with a PrEP nurse in accordance with contemporary PrEP guidelines; PrEP follow-up with a PrEP nurse in accordance with contemporary PrEP guidelines
Experimental: Intervention package PrEP services; The intervention package is integrated into PrEP visits and includes evaluation of barriers and facilitators to ongoing PrEP use, point of contact STI testing to inform counseling regarding ongoing PrEP care engagement, tracing for any missed PrEP visits, and offering a PrEP "restart" kit for cisgender men who choose to discontinue PrEP during the follow-up period. Recognizing increasingly cyclical PrEP use patterns, navigators serve as a direct entry point to retain or re-engage participants in HIV prevention care.	Other: PrEP eligibility assessment; PrEP eligibility assessment; Diagnostic test: Rapid HIV antibody testing prior to provision and/or refill of PrEP; Rapid HIV antibody testing prior to provision and/or refill of PrEP; Other: PrEP follow-up with a PrEP nurse in accordance with contemporary PrEP guidelines; PrEP follow-up with a PrEP nurse in accordance with contemporary PrEP guidelines; Behavioral: Evaluation of barriers and facilitators to ongoing PrEP use; Evaluation of barriers and facilitators to ongoing PrEP use; Other: Point of contact STI testing to inform counseling regarding ongoing PrEP care engagement; Point of contact STI testing to inform counseling regarding ongoing PrEP care engagement; Other: Tracing for any missed PrEP visits; Tracing for any missed PrEP visits; Other: Offering a PrEP "restart" kit for cisgender men who choose to discontinue PrEP during the follow-up period; Offering a PrEP "restart" kit for cisgender men who choose to discontinue PrEP during the follow-up period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect of a systems-navigator facilitated HIV prevention package on PrEP persistence among heterosexual cisgender men seeking STI clinical services in Lilongwe, Malawi	Consistent with this primary study objective, the following endpoint will be assessed: Persistent PrEP use across all three modalities (LAI, daily oral, or event-driven PrEP), where persistence is defined as adherence to any PrEP modality through 26 weeks, comparing proportions in intervention and control arm participants. LAI: Receive on-time injections (+/- 7-day window for the first injection and 14-day window thereafter)	26 weeks
To assess the effect of a systems-navigator facilitated HIV prevention package on PrEP persistence among heterosexual cisgender men seeking STI clinical services in Lilongwe, Malawi	Consistent with this primary study objective, the following endpoint will be assessed: Persistent PrEP use across all three modalities (LAI, daily oral, or event-driven PrEP), where persistence is defined as adherence to any PrEP modality through 26 weeks, comparing proportions in intervention and control arm participants. Daily Oral: Have protective PrEP concentration detected at designated study follow-up visits, based on intraerythrocytic Tenofovir-diphosphate collected as dried blood spot; Tenofovir-diphosphate concentrations associated with ≥4 doses/week will be classified as adherent.	26 weeks
To assess the effect of a systems-navigator facilitated HIV prevention package on PrEP persistence among heterosexual cisgender men seeking STI clinical services in Lilongwe, Malawi	Consistent with this primary study objective, the following endpoint will be assessed: Persistent PrEP use across all three modalities (LAI, daily oral, or event-driven PrEP), where persistence is defined as adherence to any PrEP modality through 26 weeks, comparing proportions in intervention and control arm participants. Event-driven: Self-reported PrEP adherence (2+1+1), in the past 30 days, assessed through self-report of PrEP use and sex acts at study follow-up visits.	26 weeks
To assess the effect of a systems-navigator facilitated HIV prevention package on PrEP persistence among heterosexual cisgender men seeking STI clinical services in Lilongwe, Malawi	Consistent with this primary study objective, the following endpoint will be assessed: Persistent PrEP use across all three modalities (LAI, daily oral, or event-driven PrEP), where persistence is defined as adherence to any PrEP modality through 26 weeks, comparing proportions in intervention and control arm participants. Event-driven: Self-reported PrEP adherence (2+1+1), in the past 30 days, assessed through intraerythrocytic Tenofovir-diphosphate concentrations.	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Engagement with system navigators: Proportion of intervention arm participants engaged by systems navigator within 7-days of enrollment visit (defined as any contact, i.e. text exchange, in-person communication)	7 days
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Engagement with system navigators: Proportion of intervention arm participants engaged by systems navigators at least once after the initial engagement during the first 26 weeks following initiation of PrEP.	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Engagement with system navigators: Proportion of intervention arm participants with attempted engagement by systems navigators at least once after the initial engagement during the first 26 weeks following initiation of PrEP.	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Engagement with system navigators: Mean (standard error) number of contacts (text, telephone call, home visit, other) with intervention arm participants made with systems navigators (mean contacts per participant) during first 26 weeks following initiation of PrEP.	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Uptake of self-test/pill pack ("re-start" kit) among those to whom it is distributed (through end of study participation): Proportion who self-report use of HIV self-test	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Uptake of self-test/pill pack ("re-start" kit) among those to whom it is distributed (through end of study participation): Proportion who self-report use of PrEP pill pack	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Uptake of self-test/pill pack ("re-start" kit) among those to whom it is distributed (through end of study participation): Proportion who self-report use of HIV self-test in conjunction with/prior to initiation of PrEP pill pack	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Acceptability and barriers among key stakeholders, including participants enrolled as seronegative PrEP initiators and other key stakeholders: Acceptability based on quantitative surveys (participants enrolled as seronegative PrEP initiators only)	26 weeks
To assess acceptability and barriers of implementing a systems-navigator delivered HIV prevention package among key stakeholders in the clinic and heterosexual cisgender men initiating PrEP at STI clinics	Consistent with this primary study objective, the following endpoint will be assessed among participants in the intervention arm only: Acceptability and barriers among key stakeholders, including participants enrolled as seronegative PrEP initiators and other key stakeholders: Perceived facilitators and barriers to implementation of the intervention will be assessed through individual semi-structured interviews.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the feasibility of a future randomized controlled trial	Consistent with this secondary study objective, the following endpoint will be assessed, considering all enrolled HIV seronegative participants: Calendar time to enroll 200 participants	52 weeks
To assess the feasibility of a future randomized controlled trial	Consistent with this secondary study objective, the following endpoint will be assessed, considering all enrolled HIV seronegative participants: Proportion of participants retained at each [eligible] study visit	52 weeks
To assess the feasibility of a future randomized controlled trial	Consistent with this secondary study objective, the following endpoint will be assessed, considering all enrolled HIV seronegative participants: Complete all study visits through 26 weeks, 39 weeks, and 52 weeks (among participants eligible for longer follow-up)	52 weeks
To assess the feasibility of a future randomized controlled trial	Consistent with this secondary study objective, the following endpoint will be assessed, considering all enrolled HIV seronegative participants: Proportion of PrEP visits on the same day as study visits, by PrEP modality	52 weeks
To assess the feasibility of a future randomized controlled trial	Consistent with this secondary study objective, the following endpoint will be assessed, considering all enrolled HIV seronegative participants: Proportion of participants completing 30-day Timeline Follow-back at quarterly study visits	52 weeks
To assess the feasibility of a future randomized controlled trial	Consistent with this secondary study objective, the following endpoint will be assessed, considering all enrolled HIV seronegative participants: Time to complete each study visit	52 weeks
To assess the feasibility of a future randomized controlled trial	Consistent with this secondary study objective, the following endpoint will be assessed, considering all enrolled HIV seronegative participants: Additional time (at PrEP visits) engaging with systems navigators	52 weeks

Collaborators and Investigators

• Sponsor: HIV Prevention Trials Network
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Division of AIDS, US National Institute of Allergy and Infectious Diseases
• Investigators: Study Chair: Sarah Rutstein, MD, PhD, University of North Carolina, Chapel Hill; Study Chair: Mitch Matoga, MBBS, MSc, UNC Project Malawi

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: HIV; PrEP; STI; Malawi; Cisgender; Heterosexual; Lilongwe; Systems Navigation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Urogenital Diseases; Genital Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies; HIV Antibodies
• Other Study ID Numbers: HPTN 112; UM1AI068619-17 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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