Optimizing the Delivery of HIV nPEP

Optimizing the Delivery of HIV Post-exposure Prophylaxis: A Randomized Controlled Trial of Text Messaging Support and Physician to Nurse Task-shifting

Despite decades of traditional prevention efforts based on behavior change and condom use, Ontario has seen over 700 new HIV infections annually over the past 10 years. Post-exposure prophylaxis (PEP) is one such approach, in which uninfected persons use 28 days of antiretroviral medications (ARVs) shortly after an HIV exposure to minimize the risk of acquiring HIV. PEP is highly efficacious, is considered a standard of care intervention based on medical and ethical grounds, and is supported by treatment guidelines. Yet several implementation challenges have limited its clinical and public health impact in Ontario, where no formal PEP policy exists. Our proposal seeks to optimize two aspects of delivering PEP for sexual exposures (nPEP). Results will inform the development of a standardized approach to nPEP both province-wide and elsewhere.

Thus study has pragmatic, multicenter randomized controlled trial using a 2x2 factorial design to determine whether the proportion of nPEP patients that successfully complete follow-up:

1. is higher among those receiving mobile phone-based text messaging support than among those receiving standard care; and
2. is non-inferior among those receiving care from a sexual health clinic nurse compared to those receiving hospital-based physician care.

The prospective, randomized, non-blinded, 2x2 factorial trial that will enroll 318 study participants in Toronto. In Intervention A, we will randomize half of study participants to a text messaging support service ('WelTel'), in which a trained, community-based counselor provides standardized weekly 'check-in' messages during their 12-week course of PEP follow-up. The other half will receive standard care, which does not include any form of active outreach or reminders outside of scheduled appointments. In Intervention B, we will randomize half of participants to receive nurse-led care for PEP follow-up at a local sexual health clinic; the other half will receive standard care by a hospital-based ID physician. The specific activities for each follow-up visit will be clearly defined in a medical directive. In keeping with Ontario legislation on medical directives, nurses will review cases with their authorizing physician or nurse practitioner on a routine basis.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: nPEP; Behavioral: Text Messaging Support; Other: Nurse-Led nPEP

• Study Type: Interventional
• Enrollment (Anticipated): 434
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Darrell HS TAN, MD, FRCPC, PhD; Phone Number: 416-864-5568; Email: darrell.tan@gmail.com
• Study Contact Backup: Name: Attia Qamar, BME; Email: Attia.Qamar@unityhealth.to

Study Locations

• Canada
  • Toronto, Canada
    • Recruiting
    • Crossways Sexual Health Clinic (TPH)
    • Contact: Natalie Fawcett, BSN, MSN, NP; Email: Natalie.Fawcett@toronto.ca
    • Principal Investigator: Allison Chris, MD CCFP FRCPC
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • HIV Prevention Clinic (Toronto General Hospital)
      • Contact: Karla Fisher, BSc, MSc; Email: Karla.Fisher@uhn.ca
      • Principal Investigator: Isaac Bogoch, MD MS FRCPC
    • Toronto, Ontario, Canada
      • Recruiting
      • Positive Care Clinic (St. Michael's Hospital)
      • Contact: Attia Qamar, BME; Email: Attia.Qamar@unityhealth.to
      • Principal Investigator: Darrell Tan, MD FRCPC, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be 18 years or older
2. Be known or presumed to be HIV-uninfected at baseline
3. Be initiated on PEP by a healthcare provider in the past six days for a sexual exposure to a known or suspected HIV-infected source
4. STAGE 1 only: Own a mobile phone with text messaging capabilities on which they are willing to potentially receive messages from the text messaging service
5. Be capable of communicating verbally and via text in English
6. Be planning to continue their follow-up locally or be willing to have follow-up study visits conducted remotely; either by telephone or via an encrypted video conferencing system (such as Zoom for healthcare).
7. Be referred to a sexual assault center and provided with necessary counselling and support services if presented for nPEP following sexual assault.

Exclusion Criteria:

1. Creatinine clearance <30 mL/min (using Cockcroft-Gault formula)
2. Enrolled in any other clinical trial of an HIV prevention intervention
3. Prior participation in this clinical trial for a previous episode of nPEP
4. Known co-infection with chronic hepatitis B at enrollment
5. Current or planned pregnancy or breastfeeding
6. Use of a medication whose co-administration with Biktarvy is contraindicated (dofetilide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifampicin, rifabutin, rifapentine, modafinil, dexamethasone, metformin, St. John's Wort)
7. Concomitant use of HIV pre-exposure prophylaxis (PrEP)
8. Stage 2 only: Concomitant use of any non-prescription medication, supplement, vitamin or natural remedy which the patient is unwilling to discontinue during Biktarvy® administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ARM 1 = TEXT MESSAGING SUPPORT; PEP will be delivered by ID physician and participants will receive weekly text message "check-ins" and optional automated text appointment reminders via the WelTel system.	Drug: nPEP; Participants will receive Bictegravir/emtricitabine/tenofovir alafenamide 50/200/25mg (Biktarvy®) one tablet once daily as study drug to complete a 28 day course of PEP.; Other Names: Bictegravir/emtricitabine/tenofovir alafenamide; BIC/FTC/TAF; Biktarvy; Behavioral: Text Messaging Support; Text messaging support service ('WelTel'): community-based counselors will provides standardized weekly 'check-in' messages during the participants 12-week course of nPEP follow-up. Participants in the text-message arm will also have the option of receiving generic non-specific automated text reminders of their upcoming appointments in the form of "Don't forget about tomorrow".
EXPERIMENTAL: ARM 2 = NO TEXT MESSAGING SUPPORT; PEP will be delivered according to the standard of care by an infectious diseases physician. Participants will not receive text message reminders or "check-in".	Drug: nPEP; Participants will receive Bictegravir/emtricitabine/tenofovir alafenamide 50/200/25mg (Biktarvy®) one tablet once daily as study drug to complete a 28 day course of PEP.; Other Names: Bictegravir/emtricitabine/tenofovir alafenamide; BIC/FTC/TAF; Biktarvy
EXPERIMENTAL: ARM 3 = NURSE-LED nPEP; PEP will be delivered by a sexual health clinic nurse operating under a medical directive.	Drug: nPEP; Participants will receive Bictegravir/emtricitabine/tenofovir alafenamide 50/200/25mg (Biktarvy®) one tablet once daily as study drug to complete a 28 day course of PEP.; Other Names: Bictegravir/emtricitabine/tenofovir alafenamide; BIC/FTC/TAF; Biktarvy; Other: Nurse-Led nPEP; nPEP follow-up is provided by nurse-led care at a local sexual health clinic instead of a hospital-based ID physician.
ACTIVE_COMPARATOR: ARM 4 = ID PHYSICIAN-LED nPEP,; PEP will be delivered according to the standard of care by an infectious diseases physician.	Drug: nPEP; Participants will receive Bictegravir/emtricitabine/tenofovir alafenamide 50/200/25mg (Biktarvy®) one tablet once daily as study drug to complete a 28 day course of PEP.; Other Names: Bictegravir/emtricitabine/tenofovir alafenamide; BIC/FTC/TAF; Biktarvy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported completion of a full course of PEP medications and receipt of a final HIV test result from their nPEP provider 12 weeks after the index exposure	Determined by patient completion of acceptability questionnaire and evidence of HIV test result	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability of TAF/FTC/ELV/cobi-based nPEP]	Collection of adverse events	12 weeks
Completion of each scheduled follow-up activity (blood tests and clinic visits)	Measured by study visit attendance on CRFs	12 weeks
Diagnosis of incident HIV	Determined through laboratory analysis of blood, urine and mucosal swab samples	12 weeks
Sexually transmitted infections (gonorrhea, chlamydia, syphilis, hepatitis B and C)	Determined through laboratory analysis of blood sample	12 weeks
Self-reported sexual risk-taking behaviour	The following activities will be captured in a questionnaire: number of unprotected vaginal/anal sex acts, and for men who have sex with men, score on a HIV risk index (based on the validated HIRI-MSM)	12 weeks
Numbers and types of linkages made by PEP providers to other forms of healthcare	Number of participants referred to psychiatry/mental health services and; Number of participants referred to addictions/substance services	Week 12
Patient satisfaction with their PEP experience	Collected using a patient survey	12 weeks
Inquiries from participants to the PEP provider outside of scheduled follow-up	the number of times participants contacted their healthcare provider outside of scheduled follow-up	12 weeks
PEP-related referrals for physician consultation	Number of times a participant randomized to the nurse-led arm had to be referred to a physician; captured on the sexual health clinic documentation.	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of cost on heathcare system	Prospective collection of cost data during the trial to inform a future health economic analysis from the perspective of the healthcare system.	Week 12

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR); CIHR Canadian HIV Trials Network
• Investigators: Principal Investigator: Isaac I Bogoch, MD, FRCPC, MSc, Toronto General Hospital

Publications and helpful links

General Publications

• Palmer MJ, Henschke N, Villanueva G, Maayan N, Bergman H, Glenton C, Lewin S, Fonhus MS, Tamrat T, Mehl GL, Free C. Targeted client communication via mobile devices for improving sexual and reproductive health. Cochrane Database Syst Rev. 2020 Jul 14;8(8):CD013680. doi: 10.1002/14651858.CD013680.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 4, 2021
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): August 1, 2023

Study Registration Dates

• First Submitted: August 21, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (ACTUAL): August 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide
• Other Study ID Numbers: CTN 287

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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