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A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure on TLD in Sub-Saharan Africa (RESOLVE)

Primary Purpose

HIV Infections, AIDS, Virologic Failure

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Maintenance on TLD treatment strategy
Individualized Care treatment strategy
Immediate Switch
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring ART, Medication Adherence, Drug resistance, Dolutegravir

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 15 years and above
  • Enrolled in HIV care at one of the study clinics
  • History of two HIV-1 RNA viral load measurements >1,000 copies/mL while on TLD
  • On TLD as first-line ART for at least 12 months

  • Lives within 100 kilometers of study clinic

    • Pregnant women are eligible for enrollment.

Exclusion Criteria:

  • Plans to transfer out of the clinic within the next 48 weeks
  • Plans to move out of the study catchment area within the next 48 weeks
  • On TLD as second-line or third-line ART

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Maintenance on TLD

    Individualized Care

    Immediate Switch

    Arm Description

    Participants will undergo routine enhanced adherence counseling (EAC) at the enrollment visit (Week 0) and will be maintained on TLD. At Week 24, participants will undergo phlebotomy for repeat plasma HIV-1 RNA viral load testing. If the HIV-1 RNA viral load is >1,000 copies/mL, the participant will be switched to protease inhibitor (PI)-based second-line ART. Otherwise, the participant will be continued on TLD. Participants will continue to have routine care visits, EAC, and viral load monitoring at intervals determined by the clinic as per national guidelines. At study completion, participants will undergo plasma HIV-1 RNA viral load testing at Week 48. For pregnant participants randomized to the Maintenance on TLD arm, the second visit will be completed at Week 4, rather than Week 24.

    Participants will undergo routine EAC, point-of-care urine tenofovir (TFV) testing, and genotypic resistance testing (GRT) at enrollment. Participants will return when GRT results are available for a treatment decision. Side effects and tolerance will also be assessed. All information will be used to make an optimal treatment recommendation with participant input. Participants will have an additional study visit at Week 24 and will continue to have routine care visits, adherence counseling by the clinic, and viral load monitoring at intervals determined by the clinic per national guidelines. Participants will undergo plasma HIV-1 RNA viral load testing at Week 48.

    Participants will undergo routine EAC and a switch from TLD to PI-based second-line ART at the enrollment visit (Week 0). Participants will have an additional study visit at Week 24. Participants will continue to have routine care visits and viral load monitoring at intervals determined by the clinic per national guidelines. At study completion, participants will undergo plasma HIV-1 RNA viral load testing at Week 48.

    Outcomes

    Primary Outcome Measures

    Viral suppression at 48 weeks
    A plasma HIV-1 RNA viral load <50 copies/mL (FDA-snapshot definition)

    Secondary Outcome Measures

    Full Information

    First Posted
    May 6, 2022
    Last Updated
    October 18, 2023
    Sponsor
    Massachusetts General Hospital
    Collaborators
    Mbarara University of Science and Technology, University of KwaZulu, University of California, San Francisco, National Institute of Allergy and Infectious Diseases (NIAID)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05373758
    Brief Title
    A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure on TLD in Sub-Saharan Africa
    Acronym
    RESOLVE
    Official Title
    A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure for Individuals on Tenofovir, Lamivudine, and Dolutegravir (TLD) in Sub-Saharan Africa
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2023 (Anticipated)
    Primary Completion Date
    May 1, 2027 (Anticipated)
    Study Completion Date
    May 1, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Massachusetts General Hospital
    Collaborators
    Mbarara University of Science and Technology, University of KwaZulu, University of California, San Francisco, National Institute of Allergy and Infectious Diseases (NIAID)

    4. Oversight

    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.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The RESOLVE trial is an open, parallel arm, randomized clinical trial which aims to determine the optimal strategy for management of virologic failure on first-line antiretroviral therapy (ART) with tenofovir, lamivudine, and dolutegravir (TLD) in sub-Saharan Africa. The primary outcome of interest will be viral suppression to <50 copies/mL at 48 weeks using the FDA snapshot definition. The study will be conducted in Uganda and South Africa.
    Detailed Description
    The RESOLVE trial is an open, parallel arm, randomized clinical trial which will be conducted at public-sector HIV clinics in Uganda and South Africa. We will enroll individuals with HIV age 15 and above who have had two HIV-1 RNA viral load results >1,000 copies/mL while on TLD as first-line antiretroviral therapy and who have been on TLD for at least 12 months. Participants will be randomized using an equal allocation ratio of 1:1:1 across three study arms : 1) Maintenance on TLD with switch to protease inhibitor (PI)-based second-line ART if virologic failure persists past six months, 2) Individualized Care with regimen choice based on results of genotypic resistance tests and urine tenofovir adherence assays, or 3) Immediate Switch to PI-based second-line ART. Randomization will be stratified by clinic and prior exposure to non-nucleoside reverse transcriptase inhibitors. We will follow participants for one year with study visits at enrollment, Week 24, and Week 48. The primary outcome of interest will be viral suppression to <50 copies/mL at 48 weeks using the FDA snapshot definition.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV Infections, AIDS, Virologic Failure
    Keywords
    ART, Medication Adherence, Drug resistance, Dolutegravir

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    648 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Maintenance on TLD
    Arm Type
    Experimental
    Arm Description
    Participants will undergo routine enhanced adherence counseling (EAC) at the enrollment visit (Week 0) and will be maintained on TLD. At Week 24, participants will undergo phlebotomy for repeat plasma HIV-1 RNA viral load testing. If the HIV-1 RNA viral load is >1,000 copies/mL, the participant will be switched to protease inhibitor (PI)-based second-line ART. Otherwise, the participant will be continued on TLD. Participants will continue to have routine care visits, EAC, and viral load monitoring at intervals determined by the clinic as per national guidelines. At study completion, participants will undergo plasma HIV-1 RNA viral load testing at Week 48. For pregnant participants randomized to the Maintenance on TLD arm, the second visit will be completed at Week 4, rather than Week 24.
    Arm Title
    Individualized Care
    Arm Type
    Experimental
    Arm Description
    Participants will undergo routine EAC, point-of-care urine tenofovir (TFV) testing, and genotypic resistance testing (GRT) at enrollment. Participants will return when GRT results are available for a treatment decision. Side effects and tolerance will also be assessed. All information will be used to make an optimal treatment recommendation with participant input. Participants will have an additional study visit at Week 24 and will continue to have routine care visits, adherence counseling by the clinic, and viral load monitoring at intervals determined by the clinic per national guidelines. Participants will undergo plasma HIV-1 RNA viral load testing at Week 48.
    Arm Title
    Immediate Switch
    Arm Type
    Experimental
    Arm Description
    Participants will undergo routine EAC and a switch from TLD to PI-based second-line ART at the enrollment visit (Week 0). Participants will have an additional study visit at Week 24. Participants will continue to have routine care visits and viral load monitoring at intervals determined by the clinic per national guidelines. At study completion, participants will undergo plasma HIV-1 RNA viral load testing at Week 48.
    Intervention Type
    Other
    Intervention Name(s)
    Maintenance on TLD treatment strategy
    Intervention Description
    Management of virologic failure on TLD using the Maintenance on TLD strategy
    Intervention Type
    Other
    Intervention Name(s)
    Individualized Care treatment strategy
    Intervention Description
    Management of virologic failure on TLD using the Individualized Care strategy
    Intervention Type
    Other
    Intervention Name(s)
    Immediate Switch
    Intervention Description
    Management of virologic failure on TLD using the Immediate Switch strategy
    Primary Outcome Measure Information:
    Title
    Viral suppression at 48 weeks
    Description
    A plasma HIV-1 RNA viral load <50 copies/mL (FDA-snapshot definition)
    Time Frame
    48 weeks post-enrollment (visit window spanning 42 to 54 weeks post-enrollment)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    15 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age 15 years and above Enrolled in HIV care at one of the study clinics History of two HIV-1 RNA viral load measurements >1,000 copies/mL while on TLD On TLD as first-line ART for at least 12 months Lives within 100 kilometers of study clinic Pregnant women are eligible for enrollment. Exclusion Criteria: Plans to transfer out of the clinic within the next 48 weeks Plans to move out of the study catchment area within the next 48 weeks On TLD as second-line or third-line ART
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Suzanne McCluskey, MD
    Phone
    617-726-9488
    Email
    smccluskey@mgh.harvard.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Suzanne McCluskey, MD
    Organizational Affiliation
    Massachusetts General Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure on TLD in Sub-Saharan Africa

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