FLAIR Trial Results Advance Possibility for Long-Acting ART

One of the hurdles faced by people living with HIV who are on antiretroviral therapy (ART) is the necessity of taking daily pills, which can lead to nonadherence and prevent the virus from being suppressed. Scientists have been working on solutions, 1 of which is the idea of a long-acting injectable drug or drugs that would free patients from the burden and possible stigma of sticking to an oral medication regimen.

In a new study published in The New England Journal of Medicine, investigators at Queen Mary University of London’s Department of Infection and Immunity and colleagues set out to determine whether a long-acting injectable formulation consisting of the integrase inhibitor cabotegravir and non-nucleoside reverse transcriptase inhibitor rilpivirine is noninferior to a daily pill consisting of dolutegravir, abacavir and lamivudine.

The First Long-Acting Injectable Regimen (FLAIR) study consisted of 566 adults with HIV who had never taken ART before and had viral RNA levels of at least 1000 copies per milliliter at the beginning of the trial. The median age was 34 years, and 22% were female. All subjects received dolutegravir/abacavir/lamivudine oral induction therapy for 20 weeks, then were randomly split into 2 arms: 1 arm continued with the daily oral therapy and the other arm switched to the long-acting injectable formulation, receiving monthly shots.

At 48 weeks, there was scant difference between the 2 groups when it came to viral suppression: 2.5% in the oral-therapy arm had HIV RNA levels of 50 copies per milliliter or higher, while 2.1% in the injectable group did. This indicates that long-acting injectables are noninferior to oral therapy when it comes to maintaining viral suppression.

Injection-site reactions were the most common adverse effect in the injectables arm of the trial. 86% of participants experienced at least 1 reaction, typically pain. Most of the adverse reactions reported were mild or moderate, peaking around the week 4 injections with 71% of subjects noting them and decreasing substantially by week 48 (20%). The injection-site reactions lasted a median of 3 days and led to 2 participants dropping out of the trial. Other adverse reactions considered to be drug related, such as headache and fever, were experienced by 28% of those taking the injectables vs. 10% of those taking the oral medication.

“The results of this trial show a pathway for patients who have not previously received antiretroviral therapy to reach and maintain HIV-1 suppression with oral induction therapy and a subsequent transition to monthly injectable therapy,” the FLAIR authors wrote, adding that even though the participants in the injectables arm experienced adverse effects at a higher rate than those in the oral-therapy arm, “....effects associated with starting a new treatment (as opposed to continuing the same treatment) may have contributed to the observed differences--a possibility consistent with observations in previous switch studies.”

The investigators noted that 91% of participants preferred the long-acting injectables to the oral regimen, even after receiving the injection a dozen times; however, they pointed out the possibility of selection bias, as the enrolled participants already had expressed a willingness to be given the injectables at the start of the trial. “The potential clinical role of the long-acting regimen remains to be fully defined for the spectrum of patients with HIV-1 infection, particularly those who have adherence challenges, in different practice settings,” they wrote. Additional trials continue to explore the adoption of long-acting ART regimens in patients who have previously taken ART and those who have demonstrated difficulty with adherence, and are following subjects for longer than 48 weeks.