Long-Acting Antiretrovirals

Talk by Professor Ian McGowan on long-acting ARVs (LAARVs).

-       Research from NYC (MSM) indicates high rates of willingness, and that a majority would prefer an injection.

-       Research from Africa (women) indicates that injection/implant/vaginal ring (as PrEP) would be preferred.

Current development of LAARVs is both for treatment and prevention.

Requirements for LAARVs as injection:

-       Infrequent dosing (every 2-3 months)

-       Practical injection volume (<4mL)

-       Doesn’t require cold-chain storage

Rilpivirine and cabotegravir most likely candidates of current generation of medications.

-       Have only been evaluated in the context of clinical trials (phase 1 and 2); adherence data likely to vary in the real world (and depending on whether being given as PrEP or treatment)

-       Tolerability good; patient satisfaction overall good

-       Efficacy signal in cabotegravir (animal studies)

-       Injection-site reactions reasonably frequent over time (highest at first injection)

-       Long-acting rilpirivine detectable in tissue (plasma/endocervical and vaginal fluid) up to >500 days (!) later – which is concerning for risk of resistance. Therefore cabotegravir more promising for use as long-acting PrEP (and phase 3 studies planned) – cabotegravir involves 4 week oral lead-in then Q8 weekly injection.

Novel NRTI “EFdA” also promising based on animal modelling; currently at phase 1 studies in humans. Animal models indicate that long-acting formulation could be effective up to 1yr.

As mentioned elsewhere – TAF silicone tubing implant and biodegradable implants both promising for use as PrEP.

Main challenges with LAARVs:

-       Safety (need oral lead-in)

-       Acceptability (needs real-world data)

-       Adherence

-       Resistance

-       Pharmacokinetics

-       Delivery