Rectal products for PrEP: Are they an option?
BETA is attending and reporting from the 2017 International AIDS Society conference on HIV Science this week in Paris, France from July 23 to 26—bringing you the latest news, updates, and research on HIV treatment and prevention.
Rectal microbicides are topical products—like gels, enemas or suppositories—designed to prevent the acquisition of sexually transmitted infections including HIV when used daily or before sex. Although there are not any topical HIV prevention products on the market, much investment has been (and is being) made in finding a topical product that is effective and that people like and will use.
At the IAS 2017 conference this week, Ian McGowan, MD, PhD, FRCP, from University of Pittsburgh, discussed the need for (and challenges associated with) topical HIV prevention products, and a separate team of researchers presented promising findings from a very early study of a rectal HIV-prevention douche.
Although we already have one highly effective method of pre-exposure prophylaxis (PrEP), it would be beneficial for people to have a choice in the type of PrEP product that works for them (akin to how women have options in contraceptives). And, rectal PrEP options might be ideal for people having anal sex if they can replace products that are already being used.
“I would argue that topical products are behaviorally congruent. People use gels and enemas for anal sex. This might be a good way to deliver a [PrEP HIV prevention] product,” said McGowan.
A rectal douche containing an HIV-prevention drug is one strategy that is currently being investigated. E. D. Weld, from Johns Hopkins University School of Medicine, and colleagues shared information during a poster session about a small study, with six HIV-negative men, of a rectal douche containing tenofovir.
Because many people douche before anal sex, a medicated douche may be a valuable HIV prevention tool for people who struggle with oral PrEP or prefer a topical method, said Weld.
In the study, participants used the douche and then the researchers collected tissue and plasma samples over the following week to determine if, to what extent, and for how long the drug permeated the colon tissue and lingered in the body. The researchers also used imaging to detect how the drug was distributed in the colon.
The product was generally well-tolerated by participants, and the majority of participants (5 out of 6) reported that they would be very likely to use it if it could protect them from HIV. All of the participants said that they would be either “very likely” or ”likely” to use it before receptive anal intercourse if it were available and if it protected against HIV.
The drug was delivered effectively throughout the colon as measured by imaging, and drug concentrations exceeded the level for effective protection by more than 10-fold.
Although this product, and other rectal PrEP products may demonstrate success in early studies, there are many challenges in bringing these types of PrEP products to market.
No rectal microbicide products have advanced to phase 2B or 3 effectiveness studies, shared McGowan. Topical PrEP gels have proved only moderately successful in clinical trials, and many issues have surfaced related to product acceptability and adherence.
As we consider the disappointing adherence to topical PrEP gels in clinical trials, it’s worthwhile to consider the obvious mismatch between what consumers want and the product they are asked to use in clinical trials.
“Consumer preference is another big issue,” said McGowan. “This is what we’ve been told the last decade that the consumer wants: They want a sexy, lubricant-like product that protects them. And yet, up to 2017, this is what they get [shows picture of a sterile-looking medical device]. It hasn’t set the world on fire, and we don’t have the resources to do something better. This is really a commercial issue.”
Another challenge is posed by the requirements for future PrEP research. Because we already have one highly effective method of PrEP, the bar is higher for investigational PrEP products. Candidate PrEP products must demonstrate effectiveness through “non-inferiority” studies, which are typically large, expensive clinical trials.
In the absence of new design strategies, demonstration of rectal microbicide efficacy “may not be possible,” said McGowan, suggesting that it might be time to re-think how the scientific community evaluates how useful and worthwhile HIV prevention products are.
In the same session, Jessica Haberer, from Massachusetts General Hospital, spoke to this point by sharing that in public health, there is a balance between acceptability and efficacy.
“We would all love to have a perfect formulation of PrEP that everyone takes, and that works perfectly, but in reality we really just need to find what’s going to work for individuals. And even if that formulation isn’t 100% efficacious, if they are using it more, they’ll get more benefit than a formulation that may be more efficacious, but not working for them as an individual. Marrying those two concepts is important,” she said.