Brief Description:

This study will compare Long-Acting (LA) Injectable Antiretroviral Therapy (ART) to standard of care (SOC) oral ART in previously non-adherent PLWH.

Purpose of this Study/treatment:

This study is investigating if Long-Acting Injectable ART will be more successful for people who are non-adherent to their HIV medications than oral standard of care regimens. The main advantages of LA ART in this population include infrequent dosing and directly observed therapy. A challenge for participants is that, to be eligible to receive LA ART, they will need to attain virologic suppression through adherence to their SOC oral medications. Financial incentives will be used during the first 20 weeks of the study to motivate participants to be adherent to an oral regimen until they are eligible to be randomized to either the LA ART arm or the standard of care arm.

This study has 4 steps:

Step 1: Induction- up to 24 Weeks

During the first step of the study, all study participants are prescribed an individualized oral ART regimen. In addition to financial compensation for attending study visits, participants will receive a financial incentive (bonus) if they attend their week 2 visit and achieve specific drops in their viral loads at the remaining Step 1 study visits. Participants whose viral load is <200 copies starting at week 12 will be eligible for randomization. Participants have until the Step 1 week 20 to achieve a viral load eligible for randomization. If randomized, they will have a 50% chance of either receiving LA ART or continuing on oral SOC until the end of the Step 2. Participants who do not have <200 copies will not be eligible for randomization and will be discontinued from the study.

Step 2: Randomization to LA ART vs. Oral SOC- 52 Weeks

LA ART Arm:

After discussion between the participant and the site study doctor, some participants randomized to the LA ART arm may be prescribed oral cabotegravir 30mg and oral rilpivirine 25mg daily for four weeks and some participants may immediately start LA ART. Those participants who are started on oral cabotegravir and rilpivirine, are monitored for side effects. Those who tolerate the oral medication will receive the LA form of cabotegravir and rilpivirine as intramuscular injections in the buttocks every 4 weeks for 48 weeks.

SOC Arm:

Participants randomized to the standard of care arm will continue taking SOC oral ART for 52 weeks.

Step 3: LA ART Continuation/Crossover to LA ARV- 52 weeks

LA ART Arm:

Participants continue LA ART injections every 4 weeks for 52 weeks.

SOC/Crossover Arm:

Participants with an HIV RNA <200 copies at Step 2 week 48 or 52 are eligible to cross-over to LA ART. After discussion between the participant and the site study doctor, some participants may be prescribed oral cabotegravir 30mg and oral rilpivirine 25mg daily for four weeks and some participants may immediately start LA ART. Those participants who are started on oral cabotegravir and rilpivirine, are monitored for side effects. Those who tolerate the oral medication will receive the LA form of cabotegravir and rilpivirine as intramuscular injections in the buttocks every 4 weeks for 48 weeks. If participants do not want to cross-over the LA ART, they are discontinued from the study at the end of Step 2.

Step 4: Observation on SOC for participants who received at least one does of LA Art- 52 weeks and are not receiving CAB/RPV through their clinic.

This step is for participants that received at least one dose of LA ART and discontinued injections for any reason. Oral SOC ART will not be provided by the study.

Requirements to Enter Step 1 of the Study:

The complete list of inclusion/exclusion criteria are in the protocol, including exclusionary medications. Below is an abbreviated list of the requirements.

Inclusion:

  • PLWH who are 18 years of age or older.
  • Prescribed ART for at least 6 months.
  • Screening HIV RNA is greater than 200 copies.
  • Women must not be pregnant, planning to become pregnant, or breastfeeding. Women who can become pregnant must agree to use 1 form of effective birth control.
  • There is evidence of non-adherence to their HIV medications. Non-adherence to HIV medications will be defined as having one of the two criteria below:
  1. Poor virologic response within the last 18 months (defined as <1 log10 decrease in HIV-1 RNA from the participant’s historical baseline value or HIV-1 RNA >200 copies/mL at two time points at least 4 weeks apart) in individuals who have been prescribed ART for at least 6 consecutive months.
  2. Lost to clinical follow-up within the last 18 months with ART non-adherence for ≥6 consecutive months. Lost to clinical follow-up is defined as either no contact with provider or missed 2 or more appointments in a 6-month period. ART non-adherence is defined as a lapse in ART ≥7 days (consecutive or non-consecutive), in the 6-month period where they were lost to clinical follow-up per participant report.

Exclusion:

  • Previous use of cabotegravir.
  • Uncontrolled seizures.
  • Advanced liver disease.
  • Unwilling to receive injections in the buttocks.
  • Active Hepatitis B infection.

Treatment:

Step 1: The first up to 24 weeks of treatment will consist of at least 3 HIV medications. One of those drugs must be a protease inhibitor or an integrase inhibitor.

Step 2: LA ART Arm:

Receiving oral medications:

Weeks 0-4: Oral cabotegravir 30 mg and rilpivirine 25mg daily

Weeks 4-52: LA Injectable cabotegravir and rilpivirine every 4 weeks.

Not receiving oral medications:

Weeks 0-52: LA Injectable cabotegravir and rilpivirine every 4 for 52 weeks.

SOC arm:

Participants will continue their oral ART regimen from Step 1 for 52 weeks.

Step 3: LA ART Arm:

Participants continue LA Injectable cabotegravir and rilpivirine every 4 weeks for 52 weeks.

Crossover arm:

Participants with an HIV RNA <200 copies cross-over to the LA regimen.

Receiving oral medications

Weeks 0-4: Oral cabotegravir 30 mg and rilpivirine 25mg daily

Weeks 4-52: LA Injectable cabotegravir and rilpivirine every 4 weeks.

Not receiving oral medications:

Weeks 0-52: LA Injectable cabotegravir and rilpivirine every 4 weeks

Step 4: Participants who received at least one injection and transitioned off LA injectable before the end of Step 3 will enter Step 4. Participants will take oral ART locally-sourced.

Duration of Study:

The study lasts between 128-180 weeks.

Sites: