Today's satellite presentation on "Injectable Options and Preventable Confusion: An update and interactive Discussion on the Pipeline on Antibodies, Long Acting ARVs and Vaccines" was certainly interactive but possibly missed the mark a little, on preventing confusion. Much heated discussion after the presentations centered around the bioethics and science of designing efficacy and effectiveness trials.
The presentation was divided into 3 different updates: Preventive HIV Vaccines, Broadly Neutralizing Antibodies and Long Acting Injectable Antiretrovirals for PrEP. The first 2 left me high and dry (a little too scientific and non clinical for my liking) but it was the third that I was really there for.
Professor Myron Cohen reminded us of the promising results of the LATTE trials proving the efficacy of Cabotegravir and Rilpivirine dual therapy vs a triple therapy regimen.
A compartmental pharmacological evaluation on LA Rilpivirine in 66 HIV negative volunteers showed peak concentrations at days 6-8 and present in plasma and genital tract to day 84, importantly with proven tolerability.
LA Cabotegravir ( previously known as GSK 744, which has very similar molecular configuration to Dolutegravir) shows very favorable attributes for PrEP: high genetic barrier and long half life allowing 1-3 monthly injectable dosing. Its effectiveness as a PrEP agent has been proven in Vaginal Challenge in Rhesus (Andrew et al CROI 2014) and Pigtail Macaques (Radzio et al CROI 2014).
LA formulation involves nanosuspensions (sustained drug levels) rather than large boluses with tapering plasma concentrations.
Ongoing efficacy studies:
- is a randomized placebo controlled trial of GSK 744 in the U.S. Which is nearing completion. 120 men, mostly MSM with low to moderate risk are given 4 weeks of oral dosing followed by 3 injections and followed for 52 weeks.
- is a phase IIa study to evaluate the safety and tolerability and PK of injectable Cabotegravir in men and women. It has a follow up phase between week 41-81 to evaluate what is called the "Tail Phase".
- phase 2B/3 is a double blind safety and Efficacy Study of quarterly injectable GSK 744 vs daily oral Truvada PrEP in MSM and transgender women. It's an interesting 3 step study which finishes with an open label Truvada PrEP to cover the "Tail" on the last injection. This is the study to look out for.
Long Acting PrEP Concerns
- tolerance of 2 injections of 4 miles each, ? Every 2 months
- safety as the drug can not be "removed" once injected
- The "Tail" ie how to manage discontinuation as subtherapeutic levels of ARV threatens resistance in HIV is acquired.
Monday 20 July 14.30 a 16.00 session on "how would you like your PrEP".
HPTN 067 ADAPT study on NON DAILY PrEP:
"This session presents latest findings from the HPTN 067 ADAPT trial of non-daily PrEP in Cape Town, Bangkok, and Harlem. The study findings have deep implications for PrEP rollout, related to flexibility in dosing, engagement with PrEP and factors leading to disengagement, forgiveness for missed doses, and how to start and how to stop PrEP, and patterns of sexual activity among women and MSM. Combined with emerging information from pharmacokinetics studies and the Ipergay study, this session provides an outstanding opportunity to discuss the safety, efficacy, and utility of non-daily regimens, and provide a perspective on overall flexibility in PrEP dosing. Directed toward practitioners who are prescribing PrEP, program implementers, advocates and policy makers, the objective of the session is to improve our understanding and practice of PrEP rollout, including how PrEP use can be adapted to different patterns of sexual activity."