Creating Rectal Microbicides People Desire, How Do We Get There?

Greetings  from Vancouver where the weather ( I am sorry to make you jealous) is absolutely gorgeous.

An interesting  satellite session on Rectal Microbicides, presented today by the Microbial Trials Network (MTN). Despite the proven effectiveness of PrEP there is still enthusiasm from sectors of the community for continued development of this alternative prevention tool. Not all MSM will be able to or want to take daily Tenofovir/FTC. Anal sex is also widely practiced by heterosexual couples particularly in Africa so there is much potential for use by these couples for the same reasons  vaginal microbicides are important.

The first ever Phase II trial to assess safety and acceptability of a rectal microbicide, MTN017 has just  been completed and was discussed by protocol chair Dr  Ross Cranston of University of Pittsburgh. Subjects were MSM and transgender females in multiple global locations

There were three treatment arms –

1.daily oral TDF/FTC

2.daily rectal reduced glycerin (RG)  tenofovir 1% gel (Phase 1 studies of ordinary tenofovir 1% gel found that when applied rectally it was associated with siginificant bloating, abdominal pain and diarrhoea. A reduced glycerin preparation was made which caused less osmosis in the rectum)

 or

3. RG TFV 1% gel used only before and after sex.

 Alll participants trialled all three methods and reported back on likelihood of ongoing use and ease of use. Data will likely be published in Feb 2016.

Several interesting ethical questions about the conduct of rectal microbicide trials  were raised by  Dr Ndebele of Medical Research Council of Zimbabwe. Most importantly, now that PrEP has proven to be so effective, should it also be provided as part of the comprehensive prevention package to trial participants, along with condoms and counselling regarding safe sex ?

I tend to think it should, as did most of the rest  of the audience, given UNAIDS Guidelines on ethical standards for HIV Prevention trials state “ participants should be offered state of the art risk reduction methods as they become available.”

This obviously raises many issues such as

- impact of cost

- the ethics of providing PrEP to participants in countries where there is little chance it will be available anytime soon and then withdrawing their access at the end of study and

- if uptake of PrEP were high amongst participants it would seem unlikely that you would be able to assess the efficacy of the microbicide.So what’s the point !

Dr Ian Mc Gowan another lead investigator discussed likely future directions for the MTN. This includes attempting to find a gel which could be used as a lube rather than inserted with the unpopular applicator currently used. The possibly of developing an alternative drug dapavirine which is more potent than tenofovir was also discussed.

The session wrapped up with a panel discussion between community representatives from the trial sites in the US, Canada and South Africa.

 They discussed

- how important  the development of rectal microbicides was for them as an alternative method for HIV prevention

- the importance of getting the product right so that it was an acceptable alternative

-the need for researchers to engage and invest in the community so that community members can participate meaningfully in trials  and

-the need for a gel that could be used both vaginally and rectally, being  useful for women for both types of sex and also to avoid the stigma for MSM in many countries when buying a product that idenitfied them as being engaged in anal sex.

It will be interesting to see how the MTN  goes. There are significant challenges and probably some sectors who will be sceptical of the need for rectal microbicides. However the more choices people have the better I think !

Slides for some of these presentations available on the IAS2015 website by clicking on the session on the Programme at a Glance.