Benefits, drawbacks of injectable HIV regimens highlighted in new study
The antiviral activity and safety of long-acting cabotegravir and rilpivirine, when given every 2 months, was noninferior to once-monthly administration of the combination among adults with HIV-1, according to results from the global phase 3 ATLAS-2M study presented during CROI 2020.
Study findings
The trial demonstrated that the injectable regimen of cabotegravir (ViiV Healthcare) plus rilpivirine (Janssen Pharmaceuticals) – which are both injectable medications indicated for HIV – kept the viral load below the limit for detection in more than 90% of people, according to Rajesh T. Gandhi, MD, member of the Infectious Diseases Division at Massachusetts General Hospital and professor of medicine at Harvard Medical School.
The regimen also provided “similar results to once-monthly injection of the drugs,” he told Healio.
In the phase 3 trial, Edgar Turner Overton, MD, professor of medicine at the University of Alabama at Birmingham, and colleagues randomly administered the injectable regimen to adults with HIV-1 infection, a suppressed viral load and a virus that was not resistant to cabotegravir or rilpivirine. Investigators measured HIV-1 RNA levels using the FDA Snapshot algorithm at week 48, administering an injectable regiment of cabotegravir and rilpivirine every 2 months in 522 participants and every month in 523 participants.
The effectiveness of the regimen, as indicated by levels of plasma HIV-1 RNA greater than 50 copies/mL at week 48, was similar in the 1-month (1%) and 2-month (1.7%) arms of the study (95% CI, –0.6 to 2.2). Virologic suppression in the 1-month (93.5%) and 2-month (94.3%) arms were also similar (95% CI, –2.1 to 3.7).
Confirmed virologic failure (CVF), defined as successive viral loads greater than 200 copies/mL, in the ATLAS-2M study was detected in 1.5% of patients in the 2-month arm and 0.4% of patients in the monthly arm. Resistance mutations associated with rilpivirine, cabotegravir or both agents were identified in five of the eight instances of CVF in the 2-month arm and both of the two CVF instances in the 1-month arm.
The rate of serious adverse events was comparable in the 1-month (3.6%) and 2-month (5.2%) arms. The rate of withdrawals due to adverse events was also similar among the 1-month and 2-month arms, with rates of 2.5% and 2.3%, respectively.
Not only does this option show efficacy, but findings from the LATTE-2 study presented at the International AIDS Conference in 2018 revealed that the long-acting injectable ART regimen of cabotegravir and rilpivirine was highly acceptable and tolerable in patients with HIV-1 infection.
Overall, both the 4-week and 8-week dosing regimens were highly acceptable, tolerable and patients were highly satisfied compared with the daily oral regimen, according to the study.
Medication adherence is essential for individuals with HIV to have successful therapy over a lifetime, the researchers said. These data indicated that a long-acting regimen could be an alternative for many patients to overcome challenges tied to taking daily, oral medication.
What this means for clinicians
An important benefit of injectable HIV regimens like the one examined in ATLAS-2M is that people do not have to take daily oral medications, according to Gandhi.
“This is particularly helpful for people who have difficulty remembering to take a daily medication, people who have swallowing difficulties, people who have just had surgery and are not taking oral medications, and people who just don’t want to take a medicine every day,” he said.
However, the injectable regimens are not without drawbacks, according to Gandhi. They cannot be self-administered and there is potential for resistance if people miss doses.
“People with difficulty adhering with daily oral therapy may benefit from the injections,” Gandhi told Healio. “However, another important issue is the fact that, if patients stop taking the injections, they must switch quickly to oral therapy. If not, the injectable drugs leave the body slowly, which may select for drug-resistant HIV, which is more difficult to treat.”
References:
Margolis DA, et al. Safety, Efficacy and Durability of Long-acting CAB and RPV as Two Drug IM Maintenance Therapy for HIV-1 Infection: LATTE-2 Week 160 Results. Presented at: HIV Glasgow; Oct. 28-31, 2018; Glasgow, Scotland.
Murray M, et al. Abstract THPEB042. Presented at: International AIDS Conference; July 23-27, 2018; Amsterdam.
Overton E, et al. Abstract 34. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.
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