The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE
- Conditions
- HIV Infections
- Interventions
- Drug: Standard of Care (SOC) Oral ARTDrug: Oral RPVDrug: Oral CABDrug: RPV-LA Loading DoseDrug: CAB-LA Loading DoseDrug: RPV-LA Maintenance DoseDrug: CAB-LA Maintenance Dose
- Registration Number
- NCT03635788
- Brief Summary
The purpose of this study is to compare the efficacy, safety, and durability of two different strategies to treat participants with a history of sub-optimal adherence and control of their HIV infection: long-acting (LA) antiretroviral therapy (ART) and all-oral standard of care (SOC).
- Detailed Description
This study will compare the efficacy, safety, and durability of two different strategies to treat participants with a history of sub-optimal adherence and control of their HIV infection: long-acting (LA) antiretroviral therapy (ART) with rilpivirine (RPV) LA and cabotegravir (CAB) LA versus all-oral standard of care (SOC).
The study includes four steps. However, per the February 12, 2024, recommendations from the Data and Safety Monitoring Board (DSMB), randomization into Step 2 stopped on February 16, 2024, leaving three steps in the current study protocol.
In Step 1, participants will receive a SOC oral induction regimen consisting of an ART regimen that involves at least 3 drugs for 24 weeks. Participants who achieve milestones will receive conditional economic incentives. With randomization into Step 2 ended, all eligible Step 1 participants will register to Step 3 at the completion of Step 1.
Participants who are currently on Step 2:
Eligible participants in Step 2 Arm A (already on RPV-LA + CAB-LA) will register to Step 3 and continue on this regimen until the end of Step 3 (52 weeks; See protocol for more information). This should happen at the next scheduled study visit after approval of Version 4.0.
Eligible participants in Step 2 Arm B (SOC arm) will register to Step 3 and switch to oral RPV + oral CAB for 4 weeks (optional; see protocol for more information) followed by RPV-LA + CAB-LA Q4 weeks until the end of Step 3 (52 weeks). This should happen at the next scheduled study visit after approval of Version 4.0.
Eligible participants will enter Step 4 and be followed up to 52 weeks on locally sourced oral ART.
Participants will be followed for up to a total of 180 weeks. Study visits, which will occur throughout the study, may include physical examinations; blood, urine, and hair collection; liver function tests; questionnaires; and an electrocardiogram (ECG).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 310
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: LA ART Standard of Care (SOC) Oral ART In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm A: LA ART Oral RPV In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm A: LA ART Oral CAB In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm A: LA ART RPV-LA Loading Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm A: LA ART CAB-LA Loading Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm A: LA ART RPV-LA Maintenance Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm A: LA ART CAB-LA Maintenance Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm B: SOC Oral ART Standard of Care (SOC) Oral ART In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm B: SOC Oral ART Oral RPV In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm B: SOC Oral ART Oral CAB In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm B: SOC Oral ART RPV-LA Loading Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm B: SOC Oral ART CAB-LA Loading Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm B: SOC Oral ART RPV-LA Maintenance Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART. Arm B: SOC Oral ART CAB-LA Maintenance Dose In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART.
- Primary Outcome Measures
Name Time Method Occurrence of regimen failure in Step 2 From after Step 2 randomization to Step 2, Week 48 Regimen failure is defined as the occurrence of the first of the following two events at any time post randomization and Step 2, week 48, visit:
* Virologic failure (defined as confirmed HIV-1 RNA \>200 copies/mL after Step 2 randomization)
* Permanent discontinuation of randomized study treatment
- Secondary Outcome Measures
Name Time Method Number of participants with plasma HIV-1 RNA level less than 50 copies/mL and less than or equal to 200 copies/mL at scheduled study visits on Steps 1 and 2 Measured from Step 1 entry through Step 2, Week 52 Summarized and tabulated by Step, study visit, and randomized treatment
Frequency of AEs during Steps 1 and 2 Measured from Step 1 entry through Step 2, Week 52 AEs will be graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
Frequency of new drug-resistance mutations in participants with virologic failure in Step 2 Measured from after Step 2 randomization through Step 2, Week 52 Summarized and tabulated by randomized treatment
Occurrence of the treatment-related failure in Step 2 at any time post randomization and week 48 visit from after Step 2 randomization to Step 2, Week 48 Time will be measured from the Step 2 randomization to the first of the following events: virologic failure or treatment discontinuation due to adverse event (AE)
Summary score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 Step 2 randomization, Step 2 weeks 24 and 48 Summarized and tabulated by randomized treatments
Occurrence of virologic failure in Step 2 at any time post randomization and week 48 visit from after Step 2 randomization to Step 2, Week 48 Virologic failure is defined as confirmed HIV-1 RNA greater than 200 copies/mL after Step 2 randomization
Frequency of Injection Site Reactions (ISR) during Step 2 Measured from Step 2 randomization through Step 2, Week 52 Summarized and tabulated by reaction site
Summary of participant self-reported dichotomous preference questionnaire Step 2 week 48 Summarized and tabulated by randomized treatment
Number of participants with virologic non-success from after Step 2 randomization to Step 2, Week 48] Virologic non-success will be defined by the US Food and Drug Administration (FDA) Snapshot algorithm
Occurrence of discontinuation of randomized treatment in Step 2 Measured from after Step 2 randomization through Step 2, Week 48 Time will be measured from Step 2 at any time post randomization to Step 2 week 48 visit
Frequency of missed or delayed injections for participants who received LA ART in Step 2 Measured from Step 2 randomization through Step 2, Week 52 Delayed injection is defined as 8 days beyond scheduled injection day.
Summary scores of HIV Treatment Adherence Self-Efficacy Scale in Step 1 and Step 2 Measured from Step 1 through Step 2, Week 52 Summarized and tabulated by Step
Trial Locations
- Locations (31)
University of Pittsburgh CRS
🇺🇸Pittsburgh, Pennsylvania, United States
Northwestern University CRS
🇺🇸Chicago, Illinois, United States
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
🇺🇸Boston, Massachusetts, United States
Vanderbilt Therapeutics (VT) CRS
🇺🇸Nashville, Tennessee, United States
Columbia P&S CRS
🇺🇸New York, New York, United States
University of Colorado Hospital CRS
🇺🇸Aurora, Colorado, United States
University of Southern California CRS
🇺🇸Los Angeles, California, United States
UCLA CARE Center CRS
🇺🇸Los Angeles, California, United States
Alabama CRS
🇺🇸Birmingham, Alabama, United States
UCSD Antiviral Research Center CRS
🇺🇸San Diego, California, United States
Harbor-UCLA CRS
🇺🇸Torrance, California, United States
Ucsf Hiv/Aids Crs
🇺🇸San Francisco, California, United States
The Ponce de Leon Center CRS
🇺🇸Atlanta, Georgia, United States
Univ. of Florida Jacksonville NICHD CRS
🇺🇸Jacksonville, Florida, United States
Massachusetts General Hospital CRS (MGH CRS)
🇺🇸Boston, Massachusetts, United States
Johns Hopkins University CRS
🇺🇸Baltimore, Maryland, United States
Washington University Therapeutics (WT) CRS
🇺🇸Saint Louis, Missouri, United States
New Jersey Medical School Clinical Research Center CRS
🇺🇸Newark, New Jersey, United States
Jacobi Med. Ctr. Bronx NICHD CRS
🇺🇸Bronx, New York, United States
Weill Cornell Chelsea CRS
🇺🇸New York, New York, United States
Case Clinical Research Site
🇺🇸Cleveland, Ohio, United States
Weill Cornell Uptown CRS
🇺🇸New York, New York, United States
Ohio State University CRS
🇺🇸Columbus, Ohio, United States
Greensboro CRS
🇺🇸Greensboro, North Carolina, United States
Chapel Hill CRS
🇺🇸Chapel Hill, North Carolina, United States
SUNY Stony Brook NICHD CRS
🇺🇸Stony Brook, New York, United States
Cincinnati Clinical Research Site
🇺🇸Cincinnati, Ohio, United States
Houston AIDS Research Team CRS
🇺🇸Houston, Texas, United States
University of Washington AIDS CRS
🇺🇸Seattle, Washington, United States
Puerto Rico AIDS Clinical Trials Unit CRS
🇵🇷San Juan, Puerto Rico
Penn Therapeutics, CRS
🇺🇸Philadelphia, Pennsylvania, United States