Rectal douches are at an earlier stage in development. This could be a combination antiretroviral/antibiotic prevention product to stop HIV and STIs in gay men and other people who have anal sex, used both before and after anal sex.
There had been some research on the acceptability of this idea around the time of the iPrEx study, but with the success of oral PrEP, enthusiasm for lubes and douches ebbed. Now, with concern about high and rising rates of STIs in the gay community, some of them associated with PrEP, the idea of a douche that could help prevent both HIV and STIs has regained traction.
A poster from Alex Carballo-Diéguez reported on douching practices among people who have anal sex, recruited from the gay dating app Grindr in the United States. Of the 4751 respondents, 78% reported having been the receptive partner in anal sex in the last three months. Of these, 80% reported douching before having receptive anal sex and 27% reported douching afterwards (in addition to or instead of beforehand).
Survey respondents were very interested in the idea of a douche to prevent HIV and STI. Ninety-eight per cent of men who currently douche and 94% of men who do not said that would be very interested in such a product.
One technical issue is that although men reported an average of three douche applications before sex (most used an enema bottle or shower attachment), they didn’t hold the water inside for very long (mostly for less than a minute). So a rectal douche would have to deliver drug fast to the tissues.
Ethel Weld of Johns Hopkins University reported on the first phase I study of a rectal douche, called DREAM-01 (not to be confused with the DREAM vaginal ring study). This study recruited 18 gay men for an initial safety, acceptability and drug absorption study, using a gel containing just the anti-HIV drug tenofovir as studies of this in rectal lubricants have been done before.
Previous studies had found that many common sexual lubricants caused rectal cell damage by being too concentrated. They are hyper-osmolar, which means they tend to cause cell damage by drawing the water out of them. Because of this the study tested three different douche formulations, a standard one given in two sizes of enema (220 mg and 660mg) and a more dilute formulation given in a 660mg dose.
The participants used one dose of each formulation, with a month in between doses during which blood and tissue samples were taken. Some participants had CT scans to see how far up the gut the enema travelled.
Interestingly it was the smaller enema dose that was associated with the larger number of reported adverse events, though most of these were mild and this version of the douche remained highly acceptable to participants. There were only two adverse events that the investigators judged to be caused by the gel; some bleeding in one case and a feeling of rectal discomfort and dryness in the other. Tissue biopsies showed no evidence of cell damage.
The douches achieved adequate coverage, i.e. they travelled as far up the colon as semen was likely to go.
Drug concentration inside tissue cells was ten to 1000 times in excess of that required to suppress HIV but in all cases was well below suppressive levels in blood; this means the drug in the gel gets where it needs to locally but is not absorbed systemically. This is what you want if the gel contains an anti-STI antibiotic as avoiding significant concentrations in blood is the way to avoid generating resistant bacteria.
In tests using explants, tissue cells taken from the rectum after the douche was used and then cultured with HIV, found that the tenofovir within cells suppressed HIV effectively for at least six hours and had significant effect for up to 24 hours. Viral suppression was linked to tissue concentrations, with the hypo-osmolar one achieving the highest concentrations, though this douche formulation was slightly less popular than the other two.
The conclusion is that an anti-HIV and anti-STI rectal enema/douche would be acceptable, would achieve high tissue concentrations of preventative drug for a useful period after sex, and that – at least in the lab dish – it suppresses HIV replication.