Oral Lead-In Likely Not Needed When Switching to Injected Cabotegravir/Rilpivirine for HIV Patients

By Marilynn Larkin

November 12, 2021

NEW YORK (Reuters Health) - In patients with HIV, switching to long-acting intramuscular injections of cabotegravir plus rilpivirine (CAB/RPV) had similar safety and efficacy with and without an oral lead-in, according to the latest results of the FLAIR study.

"These data represent the longest period of follow-up within the phase 3 clinical trial program, contributing to our understanding that long-acting CAB/RPV remains safe and effective out to 124 weeks," Dr. Chloe Orkin of Royal London Hospital in the UK told Reuters Health by email.

"Excitingly, the participants who received the CAB/RPV without the oral lead in did just as well as those who had the four-week oral lead-in," she said. "Consequently, the European Medicines Agency has allowed the drug to be prescribed with or without the oral lead-in, another big paradigm shift for people with HIV who wish to or need to avoid oral therapy."

As reported in The Lancet HIV, the FLAIR study is an ongoing phase 3, randomized, open-label, multicenter trial. Participants (median age about 37; 78% men; about 75% white) who were virologically suppressed (HIV-1 RNA <50 copies per mL) during the 20-week induction phase with standard of care were randomly assigned to continue the standard-of-care oral regimen or switch to long-acting CAB/RPV in the 100-week maintenance phase (283 per group).

Participants receiving long-acting therapy at baseline were given cabotegravir (30 mg) plus rilpivirine (25 mg) once daily, after an oral lead-in for at least four weeks before the first injection. In the extension phase, they could choose to continue long-acting cabotegravir (400 mg) plus rilpivirine (600 mg) every four weeks from week 100, or withdraw.

Participants in the oral group could choose to switch to long-acting therapy, either direct-to-injection or with a four-week oral lead-in, or withdraw.

Ninety-two percent of participants transitioned to long-acting CAB/RPV in the extension phase: 48% in the direct-to-injection group and 52% in the oral lead-in group.

Eighty-six percent of those in the long-acting treatment group continued that regimen into the extension phase. Ninety-nine percent of direct-to-injection participants and 93% of those on oral lead-in remained virally suppressed at week 124.

Eighty percent of those in the long-acting group remained suppressed at week 124: 5% had HIV-1 RNA of 50/mL or more and the rest had no virological data.

Adverse events leading to withdrawal occurred in one participant in the direct-to-injection group and two in the oral lead-in group after 24 weeks of CAB/RPV, and 15 (5%) in the long-acting group up to week 124. No deaths occurred in the extension phase.

Overall, CAB/RPV adverse event type, severity, and frequency were similar across all groups.

Injection site reactions (mostly mild-to-moderate) were the most common adverse event, occurring in 21% of injections in the extension switch population and 21% of injections in the long-acting group, leading to withdrawal in 2% of participants in each group.

A spokesperson for ViiV Healthcare commented in an email to Reuters Health that the findings were "further reinforced in a recent presentation conducted at the European AIDS Clinical Society conference where an abstract with the pooled analysis of FLAIR, ATLAS and ATLAS-2M were presented that highlighted that no major safety signals were identified during the oral lead-in phase."

Starting with monthly CAB/RPV injections directly is currently not approved by the US Food and Drug Administration, and the company recommends that clinicians in the US follow the protocol outlined in the label. The company is waiting for a decision from the FDA based on a supplementary new drug application that included data from the FLAIR 124 study.

The European Commission's recent update to the Summary of Product Characteristics for the two drugs means patients and clinicians have the choice of starting long-acting injections directly or after the oral initiation phase.

The study was funded by ViiV and Janssen Research and Development. Seven coauthors are employees of ViiV, four are employees of Janssen, three are employees of Glaxo Smith Kline, and Dr. Orkin and several other coauthors have received fees from ViiV.

SOURCE: https://bit.ly/3BYW8p7 and https://bit.ly/30gDtbe The Lancet HIV, online October 14, 2021.