ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

Ban Kiem Tee

Ban Kiem Tee

Dr BK Tee is an HIV section 100 GP with 15 years of clinical experience and 8 years of research participation as the Principal Investigator at The Centre Clinic, Victorian AIDS Council, where he is also the clinical director since 2009. 

 

No HIV practitioner can avoid the onslaught of PrEP. Whether you like it or not, you'll be facing it head on from fellow doctors and patients alike. Yet there are too many vital questions unanswered. Today's session on "How would you like your PrEP" introduces HPTN 067 or ADAPT study that attempts to address the question of optimal dosing and schedule of daily vs "time driven" ( 2 tabs a week + post exposure dose) and "event driven" ( one before and one after). Equally important is the question regarding how to start and stop PrEP ie how many days after starting and stopping PrEP is an individual protected from acquiring HIV.

 
ADAPT STUDY or HPTN 067
 
were conducted in Harlem (US), Silom (Bangkok, Thailand) and Cape Town (South Africa), designed to measure the coverage of sex events, number of tablets (required and taken) and self reported side effects and secondarily, adherence, safety and HIV infections. In other words, it is designed to identify dosing schedules that participants are more likely to follow and if these schedules "influence healthier sexual practices".
 
Apart from the U.S. site, the speakers concluded that Truvada PrEP "coverage" were comparable across the arms although daily dosing proved to produce better adherence. It is important to note that " comparable coverage" in this context does NOT equate to "comparable efficacy". If proven efficacious it will provide easier/cheaper alternative to daily dosing.
 
 
IPERGAY PK SUBSTUDY
 
12 participants received a single double dose TDF/FTC followed by PK sampling of plasma, PBMC, DBS and saliva done at T0, 0.5, 1, 2, 4, 8 and 24 hours.
10 participants had 2 rectal biopsies (including T0) and 2 participants had rectal biopsies at the above time schedule. 
Rectal biopsies were then exposed overnight to CCR5 tropic HIV 1 virus.
 
High concentrations (comparable to ART drug levels) of FTC were detected early at around T0.5 and for TDF at around 24 hours after dosing. However, although all the rectal biopsies were "infected" at baseline this compares to 6/10 of infected biopsies taken after dosing. Unfortunately there were no rectal PK and "infectivity" analysis done with additional post exposure doses to determine the protection conferred by the second and 3rd doses in the Ipergay PrEP regimen.
 
CELL PREP
 
This study extrapolates PrEP protective intracellular concentrations from STRAND and iPREX. 
Participants were given daily TDF/FTC for 30 days to 19 volunteers and bloods taken at days 1,3,7,20,30 and 35,45,60.
Estimated risk reductions were found to be
After dose 1 - 77%
After dose 2- 89%
After dose 3 - 98%
After dose 4 - 98%
Stop +1d - 97%
Stop +3d - 96%
Stop +5d - 93%
Stop +7d - 90%
 
Putting all these together, I believe that we should continue to advocate for daily dosing as it encourages better adherence and good coverage. Patients should continue to use condoms for at least the first 3 doses.
 
However, stopping PrEP continues to be unclear. IPrex rectal PK substudy showed 6 out of 10 "infected" samples after 24 hours despite CellPrEP showing 96% risk reduction up to 3 days after stopping daily dosing. I guess the question remains as to what the period of infectivity is after a mucosal exposure/inoculum.
 
 
Tagged in: IAS2015

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.
 
Pharmacology:
 
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:
 
ECLAIR study 
- 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.
 
HPTN 077 
- 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".
 
HPTN 083
- 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.
 
Watch for:
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."
 
 
 
 
 
Tagged in: IAS2015

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