Rectal microbicide gels, applied either daily or before and after sex, are currently being investigated as an option for HIV pre-exposure prophylaxis (PrEP). Given that many people who have anal sex already use lube, one hope is for an HIV-prevention product that people could essentially use in place of a lube. But can gels provide enough coverage across rectal tissue if people don’t use an applicator?
Studies of rectal tenofovir microbicide gels, such as the MTN-017 study, provide rectal-specific applicators for people to use to insert the gel. Although applicators deliver a precise dose, they may challenge product acceptability by being bulky, inconvenient and unappealing to users.
“Use of applicators does not mimic real world lubricant use during sex,” explained Eugenie Shieh, MD, from The Johns Hopkins Hospital.
If a rectal microbicide gel is approved for HIV PrEP, finding an effective application that works in the lives of potential users will be crucial to its success.
At CROI 2016, Shieh presented results from a study investigating whether a gel, applied by men in the way they would normally apply lube, could deliver a similar volume, in the same areas of the colon, as gel delivered by an applicator. Five men with a history of receptive anal intercourse used a radiolabeled gel that could later be detected on a SPECT/CT body scan.
Participants tested three different deliveries: gel via applicator (3.5 or 10 mL) and a radiolabeled lube (up to 10 mL) that they were told to apply as they normally would before sex. After applying the lube, participants were asked to “simulate anal intercourse” with an artificial phallus (which would effectively push the lube into the colon).
Although this was a small study, her team found that manual dosing delivered a smaller amount of gel that was retained in the colon, with more variability between users. About 3% of the gel was retained inside the colon after manual gel use. This is compared to 95% of gel retained in the colon with a 10 mL dose delivered by applicator, and 88% of gel retained with a 3.5 mL applicator dose.
“For manual dosing, the dose retained was 32-fold less than the 10 mL applicator dosing,” explained Shieh.
The researchers also measured how far the gel distributed along the colon by looking at the SPECT/CT scan images and using a computer algorithm to estimate concentrations of the gel. Shieh reported that the manual and applicator distributions were similar, but that manual dosing was associated with less consistent distribution of gel across the colon.
Shieh concluded that rectal microbicides applied as a lube “may not provide adequate drug concentrations or reliable mucosal coverage where needed,” and that, “lube dosing may require a different formulation than applicator dosing.” Increasing the concentration of the drug contained in the microbicide lube, from 1% (the percentage of tenofovir currently being tested as a rectal microbicide) to 10% may help, said Shieh, but that “ultimately, the feasibility of manual dosing will vary with each rectal microbicide.”