ATLAS-2M: Long-Acting Cabotegravir/Rilpivirine Every 2 Months Noninferior to Monthly Dosing

Last year, at the Annual Conference on Retroviruses and Opportunistic Infections (CROI), investigators presented 48-week results of the Antiretroviral Therapy as Long-Acting Suppression (ATLAS) study showing that a regimen of monthly injectable cabotegravir/rilpivirine was noninferior to continued 3-drug oral antiretroviral (ART) therapy in adults with virologically suppressed HIV-1 infections.

Now, at the virtual CROI 2020, an international team of investigators shares 48-week results from ATLAS-2M, which tested out every other month (Q8W) dosing of the intramuscular injection compared with monthly (Q4W) dosing.

Turner Overton, MD, Division of Infectious Diseases, University of Alabama at Birmingham, and presenting author of the ATLAS-2M study, explained how the need for long-acting treatment options is so important for people living with HIV.

“Despite effective oral HIV therapy, we still face challenges achieving viral suppression in some individuals and maintaining durable viral suppression in others,” he told Contagion^®. “There are numerous reasons for these issues, from socioeconomic factors, logistical issues, chaotic factors, drug-drug interactions, pill fatigue and pill burden, and the stigma related to both HIV and HIV therapies.”

The multicenter, open-label, phase 3b noninferiority study evaluated the efficacy and tolerability of Q8W dosing of 600 mg cabotegravir (CAB) plus 900 mg rilpivirine (RPV) long-acting (LA) maintenance therapy compared with Q4W dosing of 400 mg CAB + 600 mg RPV in treatment-experienced adults living with HIV-1 infection.

The primary end point at 48 weeks was the proportion with plasma HIV-1 RNA ≥50 c/mL with a noninferiority (NI) margin of 4%, with a key secondary end point of the proportion with HIV-1 RNA <50 c/mL with an NI margin of -10%.

A total of 1045 participants were randomized 1:1 to receive either CAB+RPV LA Q8W (n = 522) or Q4W (n = 523). The median age of participants was 42 years (range 19-83), 27% were female, and 73% were white. A total of 63% of individuals were naïve to CAB+RPV LA, while 37% transitioned from Q4W CAB+RPV LA in ATLAS.

Investigators found that Q8W dosing was noninferior to Q4W dosing at the 48-week mark for both of the key virologic outcomes—viral suppression (94.3% vs 93.5%) and viral load ≥50 c/mL (1.7% and 1.0%).

The safety profiles of both dosing regimens were similar, with only mild or moderate injection site reactions reported. Two percent of patients withdrew due to an adverse event. Of the ATLAS-2M participants who were treated Q8W and had received >48 weeks of Q4W treatment in ATLAS, 93% (115/124) reported a preference for Q8W dosing.

The ATLAS-2M results support the therapeutic potential of Q8W CAB+RPV LA, investigators concluded.

“Having more options for HIV treatment is wonderful,” Turner told Contagion^®. “This study demonstrates that [Q8W intramuscular] therapy can be highly effective for virologic suppression. As we add more options for virologic suppression for our patients, we can achieve the goals of 95-95-95 or even better.”

The study, “Cabotegravir + rilpivirine every 2 months is noninferior to monthly: ATLAS-2M study,” was presented virtually Monday, March 9, 2020 at CROI 2020.