How viable is a self-administered CAB+RPV injection in virally suppressed adults with HIV-1?

A substudy of the phase III FLAIR study has found comparable efficacy and pharmacokinetics for cabotegravir (CAB) plus rilpivirine (RPV) via subcutaneous (SC) administration relative to those via intramuscular (IM) gluteal injections among virally suppressed individuals living with HIV-1.

While SC injection can be self-administered at home, most participants still favour IM. However, some of them express interest in the option of self-administration.

“CAB and RPV pharmacokinetic parameters following 12 weeks of SC abdominal injections were similar to those following IM gluteal injections,” said lead author Dr Ronald D’Amico, senior medical director in medical affairs at ViiV Healthcare, US, who presented the findings at the recent AIDS 2024.

“SC injections led to a higher incidence and longer duration of injection-site reactions (ISRs), resulting in lower acceptability of and satisfaction with SC injections compared with IM injections,” he added.

Participants of the phase III FLAIR study who gave consent for this substudy were administered IM injections during screening, three SC injections from day 1 to week 8, and again IM injections at week 12. The study staff oversaw all injections based on the FLAIR study regimen and schedule (Q4W, CAB plus RPV 400 mg/600 mg).

Subsequently, D’Amico and his colleagues examined several outcomes, which included safety, tolerability, efficacy, pharmacokinetics, and patient-reported outcomes.

In total, 93 virally suppressed adults living with HIV-1 consented to the substudy and received SC injections. Of these, 19 percent were female sex at birth, 23 percent were aged 50 years, and 20 percent were Black. [AIDS 2024, abstract OAB2604]

Plasma exposures to CAB plus RPV were similar between SC and IM injections, with 90 percent confidence intervals of geometric least square mean ratios within the 0.80‒1.25 bioequivalence limits.

Eighty-four of the 93 participants (90 percent) maintained HIV-1 RNA less than 50 copies/mL, and only two (2 percent) had HIV-1 RNA equal to 50 copies/mL. None of the individuals with HIV-1 showed virologic failure during the duration of the substudy.

SC vs IM injections

At week 9, more than half of the participants (n=50/85, 59 percent) preferred IM injections. The most common reasons were less injection site swelling (n=29/50, 58 percent) and fewer nodules (58 percent).

On the other hand, a few of the participants (n=29/85, 34 percent) favoured SC injection because of convenience (n=25/29, 86 percent). More than half of these individuals (n=51/87, 59 percent) were “extremely” or “very” interested in self-administration.

Pain was the most frequent SC-related ISR, occurring in 48 percent on injections. This was followed by nodules (34 percent) and erythema (26 percent). The median duration of these ISRs were 10 days, but the median induration (33 vs 26 days) and nodule durations (39 vs 9 days) were longer with SC than with IM administration. Of note, five participants (5 percent) withdrew due to an SC-related ISR.

“Most participants favour IM administration over SC administration. As a result, further development of this treatment regimen for SC self-administration will not be pursued,” D’Amico said.

“ViiV Healthcare, however, remains committed to evaluating alternative drugs for the potential for self-administration,” he added.