Support for Long-Acting Cabotegravir plus Rilpivirine With or Without Lead-In

After 100 weeks, long-acting cabotegravir plus rilpivirine (LA CAB/RPV) was safe with or without an oral lead-in period to an extension phase of 24 additional weeks, according to a paper published in The Lancet HIV.

Investigators from Royal London Hospital evaluated switching participants from standard of care oral regimens to LA CAB/RPV via direct-to-injection or oral lead-in pathways. This was the longest duration of follow up (124 weeks) for this combination in the Phase III program, study author Chloe Orkin told Contagion. This was a part of the ongoing FLAIR study which takes place throughout 11 countries.

Participants with HIV who had never used antiretroviral therapy (ART) were randomly assigned to continue the standard of care, or switch to LA CAB/RPV, where they received a cabotegravir (30 mg) plus rilpivirine (25 mg) once daily oral lead-in for at least 4 weeks before first injection. From there, the participants could choose to continue long-acting cabotegravir (400 mg) plus rilpivirine (600 mg) every 4 weeks from week 100 or withdraw. Additionally, standard of care participants were given the option at week 100 to withdraw or switch to long-acting therapy, either the direct-to-injection or with a 4 week oral lead in.

By week 100, 92 percent of participants made the transition to LA CAB/RPV in the extension phase, the study authors reported, noting 111 from the direct-to-injection group and 121 in the oral lead-in group. Additionally, they observed that a majority (86 percent) of those randomized to the long-acting therapy group continued the long-acting regiment into the extension phase.

The study authors determined that 1 participant in each extension switch group had 50 or more HIV-1 RNA copies per mL, but 99 percent of the direct-to-injection group and 93 percent in the oral lead-in group remained suppressed at the 124 week mark. The investigators noted that the lower suppression rates among the oral lead-in group were driven by “non-virological reasons.”

Among the participants randomized to the long-acting group, 80 percent of participants remained suppressed at 124 weeks. There were 14 participants who had HIV-1 RNA 50 or more copies per mL, including five additional participants since the week 96 analysis, the study authors wrote. The remainder of the oral lead-in participants had no virological data, they added.

Adverse events that caused a participant to withdraw were uncommon, the study authors said, and occurred in 3 participants in the extension switch group (1 in direct-to-injection, 2 in the oral lead-in group) after 24 weeks of CAB/RPV therapy, plus 15 participants in the long-acting group after 124 weeks. There were no deaths during the extension phase.

The groups shared similar adverse event types, severity, and frequency, the study authors reported, noting that injection site reactions were the most common. That occurred in 21 percent of injections in the extension switch population and 21 percent of the long-acting group. They reactions were mostly mild-to-moderate in classification, the investigators continued, and they decreased in incidence over time.

Adherence to the dosing schedule remained high during the extension phase of the study, the investigators also observed, writing that 97 percent of injections were administered within 7 days before or after the intended dosing visit date.

“Findings from the present study serve as proof of principle for direct-to-injection LA CAB/RPV, supporting the initiation of LA CAB/RPV with or without the oral lead-in,” the study authors concluded. “These findings also show that LA CAB/RPV continues to be an effective and durable maintenance therapy for virologically suppressed people with HIV over 124 weeks.”