A combination of two long-acting injectable anti-HIV drugs
taken once monthly had a very low rate of treatment failure and a favourable
safety profile, according to results from two phase III trials presented at this
week’s Conference on Retroviruses and Opportunistic Infections (CROI
2019) held in Seattle.
Dual injections of cabotegravir, an experimental integrase
inhibitor, and the non-nucleoside reverse transcriptase inhibitor (NNRTI)
rilpivirine, currently available as a pill (Edurant), maintained viral
suppression among treatment-experienced people switching from a standard oral
regimen and among previously untreated people after a short three-drug
What’s more, study participants expressed a high level of
satisfaction with monthly injections compared with daily pills, and nearly all
said they would prefer to use the injectable method, reported Dr Susan
Swindells of the University of Nebraska Medical Center and Dr Chloe Orkin of
Queen Mary University of London.
The phase II LATTE trials previously demonstrated that a
simplified oral regimen of cabotegravir plus rilpivirine is effective as
maintenance therapy. This supported the evaluation of injectable formulations
of the two drugs in previously untreated patients. As reported at the 2016
International AIDS Conference, 91% of people who received the injections every
4 weeks and 92% of those who did so every 8 weeks had undetectable viral load
at week 48.
This set the stage for larger phase III trials. ATLAS
(Antiretroviral Therapy as Long-Acting Suppression) evaluated injectable
cabotegravir plus rilpivirine in people who switched from a standard oral
antiretroviral combination with an undetectable viral load, while FLAIR (First
Long-Acting Injectable Regimen) tested the injectables in people starting HIV
treatment for the first time.
Cabotegravir and rilpivirine were administered as two
separate intramuscular jabs, with the buttocks being the preferred injection
site. All injections were given by health care providers. Patients were asked
to return to their clinics each month and were given a seven-day window in
which to do so. Adherence was good in both studies, with almost all
participants receiving monthly treatment within this window.
Use of injectable therapy would be “a big paradigm
shift” in how we offer treatment, according to Orkin. “It can be done
– we haven’t done it in HIV, but it’s done in other areas of medicine,”
she said, pointing out that long-acting depot formulations are widely used for
psychiatric drugs and contraception is commonly administered as injections
every month or two.