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Day 4’s morning session was focused largely on PrEP, making it interesting and relevant to the Australian context.
Chloe Orkin (from the Royal London Hospital) began by providing a brief summary of the current situation and future prospects for PrEP.
She noted the current use (as PrEP) of standard antiretrovirals; the development of new compounds from existing classes (e.g. EFdA [NRTI]; dapivirine, MIV-170 and IQP-0528 [NNRTIs]; cabotegravir and MK-2048 [IIs]; and entry inhibitors [vivriviroc, 5P12-RANTES, PIE-12, nifviroc and trimer-D-peptide]); as well as new compounds from new classes (VRC01 and griffithsin [Neutralising antibodies]).
She also mentioned novel means of drug formulation that’re being developed: rings, inserts, suppositories, gels, films, soft implants, injections and douche/enema.
Sheena McCormack (University College London) presented an update on the evidence for PrEP effectiveness.
She began by presenting the a summary of currently available evidence as below, reminding us that overall (especially in MSM) PrEP is very effective; that adherence was a major factor in many of the studies where effectiveness was less good (particularly in young black MSM in the USA and in heterosexual populations).
She focused on the PROUD (continuous truvada as PrEP; immediately or deferred) study which looked at effectiveness, risk compensation and STI rates This study showed an effectiveness of 86% (90% CI 64-96%), with NNT = 13 (90% CI 9-23) – Dr McCormack commented that this compares favourably with other medications (such as statins) that’re approved for preventive measures. She also commented that some of those in the immediate intervention (PrEP) arm had significantly more unprotected anal intercourse than those in the deferred arm, and that rates of unprotected anal intercourse in both arms were relatively high. In that study, a rectal STI indicated a 1 in 6 risk of HIV infection in the following year.
Australia’s EPIC study was mentioned, particularly with regard to the fact that it targeted those at high risk of HIV.
She provided a summary of worldwide PrEP demonstration projects between 2011-2015:
- 32 projects in 16 countries
- 8478 participants with 7061 cumulative years exposure
- Total HIV seroconversions n=67
à Highest rates in MSM 18-25 years (7.7/100 person-years)
à However available intracellular data showed undetectable or very low tenofovir levels in nearly all of those with seroconversion while on PrEP.
Episodic vs daily dosing – the importance of choice to effectiveness
HPTN 067/ADAPT study was mentioned: this study compared the use of daily, twice weekly (and another tablet after sex) and episode-driven PrEP in 3 populations (Harlem MSM/TGW; Bangkok MSM/TGW; Cape Town WSM). It showed that in the Bangkok population (who were generally better educated and suffered less social disadvantage) there was little difference in effectiveness between treatment arms, whereas adherence was much poorer for event-based PrEP in the other two arms (compared with continuous PrEP). This suggests that a choice of event-based or continuous PrEP may be useful depending on the population in question, and that if a population is likely to be adherent to episodic PrEP, this may produce cost-savings (less drug used overall).
HIV infection despite PrEP
Those two cases of HIV being contracted despite good adherence (and adequate drug levels) were mentioned, including the “Toronto case” and the second case recently reported of a MSM acquiring a strain of resistant HIV. This reinforces the importance of reminding those on PrEP that it is not 100% effective.
Possible use of maraviroc as PrEP
HPTN 069/ACTG 5305 (Phase II Study of Maraviroc-Based Regimens for HIV PrEP in MSM) was discussed. In this study of n=406 MSM, people were randomised to oral maraviroc (MVC) only; MVC+FTC; MVC+TDF or TDF+FTC. 5 seroconversions occurred (4 in MVC-only arm), but in 4 of those plasma drug levels were low or undetectable.
Dapivirine-impregnated vaginal ring as PrEP
ASPIRE (n=2629; 27% risk reduction) and Ring (n=1959; 31% reduction) studies. Both in Africa.
However risk reduction was 60% in women >25 years of age; based on further data from the studies poor adherence was thought to be responsible for the poorer effectiveness in younger women.
Dr McCormack also mentioned the possibility of including contraceptive drugs in the PrEP vaginal ring to provide combined PrEP/contraceptive effect.
- Overwhelming evidence of effectiveness of biological efficacy of TDF+/-FTC – which is not compromised by STI or risk compensation.
- Population effectiveness not compromised by resistance (to date)
- Heterosexuals have a choice of drug; MSM have a choice of regimen; women will soon have a choice of delivery method.