ATLAS: Long-Acting Cabotegravir + Rilpivirine Non-Inferior to Oral ART at 48 Weeks

The 48-week results of the ATLAS study indicate that the regimen of monthly injectable cabotegravir/rilpivirine is non-inferior to continued 3-drug oral antiretroviral (ART) therapy in adults with virologically suppressed HIV-1 infections.

The findings of the study were presented in an oral abstract presentation at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019). Contagion® spoke exclusively to Susan Swindells, MBBS, who presented the findings at the meeting (see video).

“The study was partnered by a study called FLAIR, which was a similar design in patients who were just starting anti-HIV therapy," said Dr. Swindells, an investigator on the study. "They had very similar results: high levels of suppressions in both arms, patients liked it, and both studies went extremely well.”

Antiretroviral Therapy as Long-Acting Suppression (ATLAS), was a phase 3, open-label, multicenter study, which enrolled 616 participants who had HIV-1 RNA <50 c/mL for > 6 months without virologic failure on oral ART regimens of either 2 nucleoside reverse transcriptase inhibitors plus 1 integrase strand transfer inhibitor (NRTI + ISTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), or a protease inhibitor (PI).

At the point of enrollment, the participants were randomized 1 to 1 to continue current ART or switch to the treatment arm.

The participants enrolled in the study had a median age of 42 years. The abstracts also note that 33% of participants were female and 68% were white. At baseline, 50% of participants were on a 2 NRTI + 1 NNRTI regimen, 33% on an INSTI regimen, and the remaining 17% were on a PI regimen.

The 308 patients in the treatment arm received oral cabotegravir 30 mg + rilpivirine 25 mg once daily for 4 weeks for safety monitoring. Then, the participants went on to receive single 3 mL loading doses of cabotegravir long-acting (LA) 600 mg (200 mg/mL) and rilpivirine long-acting 900 mg (300 mg/mL) via intramuscular injection, followed by 2 mL intramuscular injections every 4 + 1 weeks of cabotegravir LA 400 mg and rilpivirine long acting 600 mg.

At week 48, 5 participants (1.6%) in the cabotegravir/rilpivirine arm and 3 (1.0%) in the control arm had HIV-1 RNA >50 c/mL, meeting the primary endpoint of non-inferiority using the US Food and Drug Administration’s snapshot algorithm with a 6% non-inferiority margin.

The study investigators also report that the cabotegravir/rilpivirine arm was non-inferior to the current ART arm for the key secondary endpoint of HIV-1 RNA <50 c/mL (93% vs 95%).

During the study 3 cabotegravir/rilpivirine group participants and 4 current ART group participants had confirmed virologic failure (CVF).

In the cabotegravir/rilpivirine arm, 231 participants reported injection site pain, with 4 participants (1%) withdrawing as a result. Incidences of grade 3/4 and serious adverse events (AEs) were similar between the 2 study groups with 35 AEs reported in the cabotegravir/rilpivirine arm and 23 reported in the current ART group. Additionally,1 death was reported in the current ART arm.

The investigators also note that of the 275 cabotegravir/rilpivirine arm participants completing an HIV Treatment Satisfaction Questionnaire at week 48, 98% reported being more satisfied with long-acting cabotegravir and rilpivirine compared with their daily oral treatment at study entry.

The 48-week results of ATLAS indicate that the long-acting regimen of cabotegravir/rilpivirine was non-inferior to current ART treatment and generally well tolerated, with low rates of serious adverse events.

"Once this option gets rolled out, then it’s going to be another choice for patients, that’s the biggest clinical implication," said Dr. Swindells. "Now, they’re going to have this other option, instead of taking a pill everyday they can come to the clinic and get their injection and then they’re good to go for a month. And based on our experience with the study and the patient at our clinic, some people are going to really like that. So, it’s nice for patients to have an alternative, a choice."

The study, “Long-Acting Cabotegravir + Rilpivirine as Maintenance Therapy: ATLAS Week 48 Results,” was presented at the Annual Conference on Retroviruses and Opportunistic Infections (CROI), on March 7, 2019, in Seattle, Washington.