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)