Outcomes of the PLHIV With Suboptimal Viral Suppression to Injectable Long-acting Antiretrovirals (SUPLA)

A Phase 3 Study Comparing Clinical Outcomes in People Living With HIV (PLHIV) With Suboptimal Adherence Treated With Injectable Long-acting Antiretrovirals Versus Oral Antiretrovirals

This study aims to determine whether people living with HIV (PLHIV) with suboptimal medical adherence can achieve better viral suppression with long-acting antiretrovirals (LA) compared to all-oral antiretrovirals.

Study Overview

• Status: Recruiting
• Conditions: HIV-1-infection; Non-Adherence, Medication
• Intervention / Treatment: Drug: cabotegravir/rilpivirine (600mg/ 900mg); Drug: Antiretroviral Combinations

Detailed Description

This is an open-label, multi-center, randomized, active-controlled, superiority trial on 40 adult subjects who had been diagnosed to have HIV infection for at least 12 months before enrollment but with suboptimal viral suppression despite antiretroviral treatment (ART), with the latest HIV-1 viral load ≥ 200 copies/mL. Participants' eligibility will be assessed through a review of their medical records, and individuals with established resistance to cabotegravir or rilpivirine will be excluded. Enrolled participants will then be randomized 1:1 to either "Delayed Switch to LA Treatment Group" or "Immediate LA Treatment Group" on enrollment. The "Delayed Switch to LA Treatment Group" will also switch to LA on week 24. The proportion of participants with HIV-1 RNA <200 copies/mL at week 24 in the two study groups will be compared. Psychologic assessments including self-stigma and depression assessment will also be performed on day1, at week 24 and week 52.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nan-Yu Chen, MD, PhD; Phone Number: 8450 +886 3 3281200; Email: nanyuchen@cgmh.org.tw

Study Locations

• Taiwan
  • Keelung, Taiwan, 204
    • Recruiting
    • Chang Gung Memorial Hospital, Keelung
    • Contact: Nan-Yu Chen; Email: nanyuchen@cgmh.org.tw
  • Taipei, Taiwan, 105
    • Recruiting
    • Chang Gung Memorial Hospital, Taipei
    • Contact: Nan-Yu Chen; Email: nanyuchen@cgmh.org.tw
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital, Linkou
    • Contact: Nan-Yu Chen; Phone Number: 8450 +886 3 3281200; Email: nanyuchen@cgmh.org.tw
  • Taoyuan, Taiwan, 330
    • Recruiting
    • Taoyuan General Hospital, Ministry of Health and Welfare
    • Contact: Chien-Yu Cheng, MD, PhD; Email: s841060@gm.ym.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing to sign the written informed consent form for male and female participants aged 18 and above.
• At the time of enrollment, diagnosed with HIV infection for a minimum of 12 months.
• Under oral antiretroviral treatment (ART), which can be irregular or interrupted, with the most recent viral load ≥ 200 copies/mL.
• Body weight ≥ 35Kg.
• Willing to maintain contact with the research team throughout the study (provide accurate and reachable phone numbers, social accounts like Line, or reliable contact information of family or friends).
• Willing to receive gluteal (buttocks) drug injections.
• Willing to transition back to oral medication or follow the recommended treatment prescription according to the then-current national treatment guidelines after discontinuation of long-acting injectable drugs.

Exclusion Criteria:

• For those currently undergoing oral antiretroviral therapy, who have started or restarted oral ART for less than six consecutive months before screening.
• Previously undergone HIV drug resistance testing and known to have resistance mutations to either cabotegravir or rilpivirine.
• Unable to commit to maintaining contact with the research team throughout the study.
• Individuals who cannot receive treatment for hepatitis B during the period of transitioning to long-acting injections, if they are hepatitis B carriers.
• Individuals with buttock fillers.
• Women who are planning to become pregnant, pregnant, or currently breastfeeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate Long-Acting Injectable Treatment Group; Immediate switch to long-acting injectable antiretrovirals on enrollment	Drug: cabotegravir/rilpivirine (600mg/ 900mg); Immediate switch from oral antiretroviral to long-acting injectables; Other Names: Cabenuva
Active Comparator: Delayed Long-Acting Injectable Treatment Group; Keep on standard all-oral antiretrovirals on enrollment for 24 weeks, then switch to long-acting injectable antiretrovirals	Drug: Antiretroviral Combinations; Standard all-oral antiretroviral combinations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV-1 RNA <200 copies/mL	Percentage of study participants with plasma HIV-1 RNA <200 copies/mL at week 24	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV-1 RNA <50 copies/mL	Percentage of study participants with plasma HIV-1 RNA <50 copies/mL at week 24, 52	Week 24, week 52
HIV-1 RNA <200 copies/mL	Percentage of study participants with plasma HIV-1 RNA <200 copies/mL at week 52	Week 52
Change of plasma HIV-1 viral load	Change of plasma HIV-1 RNA at week 24, 52	Week 24, week 52
Change of CD4 count	Change of CD4 count at week 24, 52	Week 24, week 52
Occurrence of HIV and non-HIV related conditions	Percentage of study participants with HIV and non-HIV related conditions occurrence	Week 24, week 52
Lost F/U rate	Lost follow-up rate at every target visit	up to week 96
Usage of outreach drug delivery service	Percentage of study participants who use the outreach drug delivery service	up to week 52
Resistant variant emergence	Resistant variant emergence detection if HIV-1 viral load ≥200 copies/mL	Week 24, week 52
Adverse events	Incidence and severity of adverse events (AEs)	Week 24, week 52
Discontinuation due to AEs	Discontinuation due to AEs at week 24, 52	Week 24, week 52
Change of depression score	Change of depression score at week 24, 52	Week 24, week 52
Change of self-stigma score	Change of self-stigma score at week 24, 52	Week 24, week 52
Change of metabolic parameters	Change of metabolic parameters (body weight, BMI) at week 24, 52	Week 24, week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieved ART trough level assessment	Use liquid chromatography- mass spectrometry to determine rilpivirine and cabotegravir concentrations in stored remaining plasma specimen collected at each visit	Week 52
Change of acceptability score	Acceptability assessment for long-acting injectable antiretrovirals	Day1 (post-injection), week 24, 52 for the immediate LA treatment group; week 24 (post-injection), and week 52 for the delayed switch to LA group.
Delayed injections	Percentage of delayed injections (>7 days after the target visit)	up to week 52
HIV-1 RNA <50 copies/mL	Percentage of study participants with plasma HIV-1 RNA <50 copies/mL	Week 72, week 96

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Taoyuan General Hospital
• Investigators: Principal Investigator: Nan-Yu Chen, MD, PhD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: HIV-1, non-adherence
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Anti-Retroviral Agents; Rilpivirine; Cabotegravir
• Other Study ID Numbers: 202301496A3; MOHW113-CDC-C-114-000106 (Other Grant/Funding Number: Taiwan Centers for Disease Control)

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
• product manufactured in and exported from the U.S.: No