Injectable cabotegravir-rilpivirine sustains benefit in HIV patients, with or without oral lead-in

An oral lead-in (OLI) regimen consisting of cabotegravir + rilpivirine (CAB+RPV) did not seem to have an effect on HIV patients who switched from a daily oral dolutegravir/abacavir/lamivudine (ABC/DTG/3TC) regimen to a monthly injectable CAB+RPV long-acting (LA) therapeutic regimen, given the similar efficacy, safety, and tolerability profiles observed with or without OLI, according to the 124-week results of the phase III FLAIR* trial presented at HIV Glasgow 2020.

“[These findings suggest] that CAB+RPV LA, with or without OLI, is a well-tolerated and effective maintenance therapy [in this setting],” said the researchers.

These results come on the heels of the 96-week FLAIR results reflecting the noninferiority of the monthly injectable CAB+RPV regimen to oral ABC/DTG/3TC therapy. [CROI 2020, abstract 482]

ART-naive participants who have achieved virological suppression (HIV-1 RNA <50 copies/mL) with ABC/DTG/3TC during a 20-week induction phase were included in the FLAIR maintenance phase (n=566). These patients were randomized 1:1 to either continue with ABC/DTG/3TC or switch to LA. Prior to transitioning, participants who switched to LA were given an OLI of CAB+RPV QD for ≥4 weeks.

At week 100, patients receiving oral ABC/DTG/3TC therapy entered the extension switch phase, wherein they were given the option to withdraw from their current regimen or switch to LA therapy – either directly (direct-to-inject [DTI] arm; n=111) or with a 4-week OLI (OLI arm; n=121). [HIV Glasgow 2020, abstract O414]

At week 112, one patient in the DTI arm had confirmed virological failure (ie, two consecutive HIV-1 RNA ≥200 copies/mL). By week 124, one participant in the DTI arm and another in the OLI arm had HIV-1 RNA ≥50 copies/mL.

Nonetheless, a majority of the participants in both the DTI and the OLI arms maintained virological suppression (99 percent and 93 percent, respectively) at week 124, as per FDA Snapshot algorithm.

Adverse events (AEs) leading to treatment discontinuation were uncommon in both the DTI and the OLI arms (n=0 and 2, respectively). Only one patient in the DTI arm discontinued owing to a reported lack of efficacy, while five from the OLI arm withdrew due to other reasons.

The most common AE in the DTI and the OLI arms was injection site reactions (n=576 and 338, respectively), which were mostly mild in severity (n=478 and 271, respectively). The rates of serious AEs were comparable between the DTI and the OLI arms (n=4 and 5, respectively). There was only one report of a grade 4 drug-related AE (ie, mixed cellularity Hodgkin’s lymphoma) occurring in the DTI arm. “Overall, CAB+RPV LA was well-tolerated,” noted the researchers.

Given the sustained virologic suppression in almost all participants and the favourable safety and tolerability profiles observed in both study arms in the extension switch phase, these findings suggest that the switch to a monthly injectable CAB+RPV regimen maintains it effect regardless of the presence or absence of an OLI, they said.