A5359: The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE - A Phase III Study to Evaluate Long-Acting Antiretroviral Therapy in Non-adherent HIV-Infected Individuals

HIV Treatment

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 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 injectable ART (cabotegravir and rilpivirine injections) 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 SOC oral ART for 52 weeks.

· This study is looking at whether LA Injectable ART will be more successful for people who are non-adherent to their HIV medications than SOC oral 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 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.

People living with HIV who are 18 years of age or older.

· Prescribed anti-HIV medications (ART) for at least 6 months.

· Evidence of non-adherence to their HIV medications by one of the two criteria below:

o Poor virologic response within the last 18 months (viral load greater than 200 copies/mL at two time points at least 4 weeks apart)

o Lost to clinical follow-up (no contact or missed two appointments in 6 months) within the last 18 months with ART non-adherence (lapse in ART more than 7 days) in the 6-month period

· No previous use of cabotegravir.

· No active hepatitis B.

· Willing to receive injections in the buttocks.

Step 1: Induction (up to 24 Weeks

All study participants will receive oral ART either provided by the study or through prescription by their provider for up to 24 weeks.

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 study visits. Starting at Week 4, participants whose viral load is less than 200 copies will be eligible for randomization to Step 2.

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

Participants will have a 50% chance of either receiving:

LA ART Arm:

(Optional lead-in) 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:

o LA form of cabotegravir and rilpivirine (known as Cabenuva) as intramuscular injections in the buttocks every 4 weeks for 48 weeks.

OR

SOC Arm:

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 less than 200 copies are eligible to cross-over to LA ART (with optional oral lead-in).

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.

The study provides oral and LA injectable cabotegravir and rilpivirine in Steps 1-3. Standard of care oral ART may be study provided or locally sourced for Steps 1-2.

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

Important Notice: Please remember to obtain local IRB approval prior to the distribution of any protocol-specific information including study specific recruitment tools developed for providers and participants.