Long-acting cabotegravir-rilpivirine combo shows promise in virologically-suppressed HIV

The long-acting injectable combining the INSTI* cabotegravir and the NNRTI** rilpivirine helped maintain virological suppression in HIV-positive individuals, according to the phase IIb POLAR study presented at ID Week 2020.

Long-acting cabotegravir plus rilpivirine, administered every 2 months, maintained high levels of virologic suppression, had a favourable safety profile, and was well tolerated, said study author Dr Anthony Mills, CEO of the Men’s Health Foundation, Los Angeles, California, US.

Participants in this multicentre, open-label trial were 97 virologically-suppressed HIV-positive individuals (plasma HIV-1 RNA <50 copies/mL at screening) who had previously received antiretroviral therapy (ART) and completed (≥312 weeks) the phase IIb LATTE** study where they received once-daily doses of oral cabotegravir (30 mg) and rilpivirine (25 mg). They were given the option of switching to long-acting intramuscular cabotegravir (600 mg) plus rilpivirine (900 mg) administered every 2 months (n=90) or fixed-dose oral dolutegravir (50 mg) plus rilpivirine (25 mg) QD (n=7) for 12 months.

Median age of participants was 41 years, and the population was primarily male and Caucasian. Median CD4+ cell count at baseline was 842 cells/mm³.

After 12 months of treatment, none of the patients in either group had plasma HIV-1 RNA ≥50 copies/mL. None of the patients experienced virological failure, defined as plasma HIV-1 RNA >200 copies/mL. [ID Week 2020, abstract 116]

Virologic data was unavailable for two patients in the cabotegravir-rilpivirine arm due to discontinuation, one due to drug-related depression and another for loss to follow-up.

Adverse events (AEs) occurred in 96 and 43 percent of patients in the cabotegravir-rilpivirine and dolutegravir-rilpivirine arms, respectively, though the increased incidence in the former was primarily due to injection-site reactions. Seventy-two and 14 percent, respectively, experienced drug-related AEs. Grade ≥3 AEs occurred in nine cabotegravir-rilpivirine recipients. Five cabotegravir-rilpivirine recipients experienced serious AEs, one of which was drug related (injection site extravasation).

The most frequently reported AEs, not including injection-site reactions, among cabotegravir-rilpivirine recipients were nasopharyngitis and upper respiratory tract infection (11 percent each), diarrhoea, and pyrexia (10 percent each).

A total of 1,534 injections were administered over the 12-month period, with 463 injection-site reactions reported, though all were classified as mild or moderate in severity (84 and 16 percent, respectively) and resolved after a median 3 days. The most common injection-site reaction was pain (27 percent).

There were no clinically relevant patterns with regard to clinical laboratory results over the 12-month period, said Mills.

Eighty-eight percent of patients who received long-acting therapy acknowledged their preference for this regimen over the oral therapy they had received during the LATTE study. This was mostly due to the convenience and frequency of administration of the regimen.

“Taken together, these results indicate that long-acting cabotegravir plus rilpivirine … is an efficacious and well-tolerated maintenance therapy for HIV-1 infection that may be preferable to daily oral therapy,” said Mills. However, he cautioned against direct comparisons between the two regimens tested in POLAR due to the small study population and the unequal number of participants in each group.