PrEP - new alternatives to tenofovir / ftc"

Alternative PrEP Regimen

Maraviroc + FTC may be the first alternative PrEP regimen to become available. Obviously this is great for people who for some reason cant take or tolerate TDF/FTC.

Roy Gulick presented 48 week data from HPTN 069 - a RCT   double blinded safety and tolerability trial comparing four treatments arms

      Maraviroc alone

      maraviroc + FTC

     maraviroc + TDF

     Tenofovir DF + FTC

THIS WAS NOT A TRIAL OF EFFICACY

406 HIV-ve MSM older than 18 years deemed to be at some risk for acquiring HIV ( needed to have a self reported history of unprotected anal intercourse with either a known HIV+ve man or a man of unknown HIV sero-status within the previous 90 days.) were randomised to one of the four arms and followed up for 48 weeks. 28% were black, 22% latino. eGFR at enrolment needed to be > 70.

Maraviroc was studied because it was an available ARV, it was already known to be concentrated in rectal tissue, and it was known to be well tolerated.

Findings - All arms were well tolerated - no significant safety or tolerability differences were found. There were 5 seroconvresions in the study- 2 of these had no detectable drug; the other three had detectable drug and these were all in the maraviroc alone arm. But this study was not set up to look at efficacy.

Injectable Cabotegravir - PrEP Study in Monkeys but with Intravenous challenge.

Could Cabotegravir LA protect against IV transmission of HIV?  Long acting Depot CAB injection would suit IV drug users but would it work?

Three arms  injected with CAB LA with varying doses at week 0 and week four. one group received only one dose at week 0.  IV challenge given at week 2.    8 macaques in each group     Five macaques remained untreated as controls.

All 5 macaques were found to be infected one week after challenge

two 50mg doses given at week 0 and 4weeks resulted in 7 out of 8 macaques remaining uninfected

one 50mg dose at week 0 resulted in all 8 macaques in that group remaining uninfected

one 25mg dose at week0 plus one 50mg dose at week 4 resulted in 6 out of 8 macaques remaining uninfected

Notwithstanding the difficult to explain single infection in the first group these results suggest that adequate dosing with CAB LA will protect IVDU's from IV infection with HIV. Fwurther study ill be done.

ECLAIR - Long acting Injectable PrEP   Safety and PK study

This would be great for a subsection of our patients at some stages in their lives.

Phase 2a randomised trial of Cabotegravir LA - INSTI . Doses based on Phase 1 data, supported by animal studies. 127 patients randomised receive injections given at 3 monthly intervals of CAB LA or saline.

There was a 4 week induction period of oral therapy. Safety tolerability and PK was assessed through the trial until the 41 week endpoint.

Avaerage age 30. 57% white

Both oral and LA doses were well tolerated. Absorption rates were faster than expected higher peaks and lower troughs with 21% falling below the IC90. Most significant AE's were injection site reactions in the active treatment arms. There weren't many problems with the saline injections. ISR's lasted 5 days on average. There were two seeroconversions - one receiving saline, the other occurring in the followup phase of the CAB LA group. The dose is being reviewed in light of the PK data.

Topical Rectal microbiocide - MTN 017

Phase 2 three period randomised sequence open label safety acceptability

comparing rectally applied reduced glycerine 1% tenofovir with oral TDF/FTC

in each 8 week study period 195  MSM > 18yrs with a history of being ano-receptive either used the topical rectal gel daily; used the rectal gel before and after anoreceptive sex; or took TDF/FTC orally. Participant switched method every 8 weeks with a "washout " period of one week between each change.

Subjects were given lots of support to be adherent - eg daily texts to ensure daily use of the rectal gel . Very frequent interviews and questionairres. Adherence was objectively by collecting blood, rectal fluid and rectal tissue samples. Adherence was found to consistent with >80% of expected doses taken/used.

138 were screened "out" because of the presence at enrolment of STI's or HIV infection

There were few AE's. All methods were well tolerated. All methods were "liked" by the participants. There was found to be high levels of adherence in all arms. Further studies will now be done.