Investigating whether long-acting injectable medications will be more successful for people who are non-adherent to their HIV medications than oral regimens.

Treatment Category:  Treatment Experienced

Study Description

This four-step study compares Long-Acting (LA) Injectable Antiretroviral Therapy (ART) to standard of care (SOC) oral ART in previously non-adherent individuals.

Step 1 is the induction phase, and all participants receive study-provided SOC oral ART. Participants receive financial incentives for meeting study-specified goals.
Step 2 is the randomization phase and participants are randomized 1:1 to receive LA ART or continue on SOC for 52 weeks.
Step 3 is the crossover/continuation phase. Participants randomized to LA ART will continue that therapy, and eligible SOC participants will cross over to receive LA ART for 52 weeks.
Step 4 is the observational phase that switches participants who received at least one LA ART injection and are no longer eligible for injections back to locally sourced oral SOC ART for 52 weeks.

Study Status  

Why is this study being done?

  • This study is investigating if LA injectable ART will be more successful for people who are non-adherent to their HIV medications than oral SOC 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 SOC arm.

Who can join?
People living with HIV (PLWH) who are 18 years of age or older who

  • Have been prescribed anti-HIV medications (ART) for at least 6 months
  • Have an HIV viral load greater than 200 copies
  • Show evidence of non-adherence to their HIV medications by either:
    • Poor virologic response within the last 18 months (viral load greater than 200 copies at two time points at least 4 weeks apart)
    • Loss to clinical follow-up within the last 18 months, with ART non-adherence for at least 6 consecutive months
  • Have no active hepatitis B or C
  • Are willing to receive injections in the gluteus muscles (buttocks).

What do I need to do in the study?

Step 1: Induction (24 Weeks)
All study participants will be prescribed an individualized oral study-provided 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 weeks 4, 8, 12, 16, and 20. Participants whose viral load is <50 copies at week 20 will be eligible for randomization to Step 2 at their week 24 visit.

Step 2: Randomization to LA ART Versus Oral SOC (52 Weeks)
Participants will have a 50% chance of receiving either:

Oral cabotegravir and oral rilpivirine daily for 4 weeks.
–    During this 4-week oral phase, participants 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:
Continue taking SOC oral ART for 52 weeks.

Step 3: LA ART Continuation/Crossover to LA ARV (52 weeks)
Participants continue LA ART injections every 4 weeks for 52 weeks.

SOC/Crossover Arm:
Participants with an HIV RNA <50 copies at Step 2 week 48 or 52 are eligible to cross-over to LA ART.

Step 4: Observation on SOC for Participants Who Received at Least One Dose of LA ART (52 weeks)
This step is for participants that received at least one dose of LA ART and discontinued injections for any reason.

Duration of Study:
Steps 1-3 combined are a total of 128 weeks. Step 4 lasts 52 weeks.

What treatments or drugs are involved with this study?
The study provides oral and LA injectable cabotegravir and rilpivirine in Steps 1-3. Standard of care oral ART will need to be locally sourced.