www.hivandhepatitis.com

CROI 2016: On-Demand Rectal Microbicide Gel Has Reasonable Acceptability -- Daily Less So

Results from the MTN-017 study of 1% tenofovir gel as a rectal microbicide were presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2016)last week in Boston. The study compares the safety and acceptability of oral tenofovir/emtricitabine (Truvada) PrEP with the rectal gel either in daily use or used before and after the participant has anal sex as the receptive partner.

[Produced in collaboration with Aidsmap.com]

The study found that the rate of adverse events of any severity was exactly the same as for oral PrEP for daily use, and somewhat lower during occasional use. However, though participants rated the gel as almost as easy to use as oral PrEP, and said that they would be willing to use the gel again during sex (though not daily), there was no disguising the fact that, if offered the choice between the gel and the pill as the one PrEP method they could use, most participants would choose the pill.

The encouraging safety and adherence results, however, may help this product move further towards a full acceptability study.

The MTN-017 Study

MTN017 was conducted between 2013 and 2015 at 8 sites in 4 countries: Pittsburgh, Boston, and San Francisco, as well as San Juan, Puerto Rico, in the U.S.; Bangkok and Chiang Mai in Thailand; Lima, Peru; and Cape Town, South Africa.

The study had a so-called crossover design, meaning that every participant used all 3 PrEP regimens in turn. After a screening visit, participants used one of the 3 methods (oral PrEP, daily gel, or gel before and after sex) for 8 weeks, with clinic visits on day 1, after 4 weeks, and after 8 weeks. They then waited for a week before using the second method for 8 weeks, then waited another week and used the third method.

The researchers selected 195 participants from 349 who were screened for the study. The most common reason for not being selected were ineligible lab results (such as poor kidney function), but 8 people were found to already have HIV (2.3%) and 3 were screened out for possible acute HIV symptoms.

Adherence was measured by product returns and by participants responding to SMS text reminders, but free drug levels were also measured in blood, rectal fluid, and rectal biopsies, and intracellular drug levels were assessed in rectal tissue and in T-lymphocytes.

The average age of the 195 participants was 31.1 years, and the average age at individual sites ranged from 22.8 in Cape Town to 35.9 in San Francisco. On average 80% had a college education or were attending college (apart from at Cape Town, where it was 27%).

Notably, this study managed to enroll a significant proportion of trans women. While 73% of participants defined themselves as gay or bisexual men, there were 4 cisgender women (2%), 19 people who defined themselves as trans women, and another 30 who described themselves as "other" or declined to define their gender. So this study included somewhere between 10% and 25% trans people.

Safety, Acceptability, Adherence, and HIV Infections

In terms of safety, the rectal gels were at least as safe as the Truvada pill. The percentage of participants who experienced adverse events of grade 2 or above (i.e., more than "mild") was 34% among oral pill users, 33% among daily rectal gel users, and 30% among sex-associated gel users.

In terms of subjective acceptability, however, the oral pill was more popular than the gel. Scores from 1 (dislike) to 10 (like) for general impression of the product, ease of use, and intention to use it again if it became available were added up. If the score for oral Truvada was regarded as 100%, then the score for generally liking the product was only 28% for daily-use gel and 37% for before-and-after sex gel.

The gel’s scores for ease of use were better, with a score of 56% for the daily gel (again compared with 100% for oral Truvada) and 76% for before-and-after sex use. For intention to use in the future, the score was 38% for daily gel and 70% for before-and-after sex. The 70% and 76% scores did not differ, statistically speaking, from the Truvada scores.

Adherence was defined as the proportion of participants who used the pill or gel more than 80% of the time. In terms of self-report and product returns, 94% of pill users and 93% of before-and-after sex gel users achieved at least 80% adherence, but only 83% of those using gel daily.

Drug level measurements confirmed the self-reports: the percentage of participants with detectable tenofovir in plasma and issues was 94% for oral Truvada and 80% for the daily gel. Levels were not given for the before-and-after-sex gel, as these would vary with use.

There were 4 HIV infections during the study, 3 of them in Cape Town, though 1 of these was diagnosed 82 days after his last product use. The other 3 infections were distributed 1:1:1 in terms of the regimen the participant was allocated to at the probable time of infection. Of these, 2 participants had HIV resistance mutations to the NNRTI class of drugs, which could not be PrEP-related as the PrEP regimen did not include NNRTIs.

Tenofovir gel is not the only one being evaluated as a possible rectal microbicide. A study of gel containing the drug dapivirine, which was also used in the vaginal ring studies presented at CROI, is underway.

Presenter Ross Cranston of the University of Pittsburgh told the conference, "These results support further study of 1% rectal gel tenofovir as a microbicide for HIV prevention in men who have sex with men and transgender women."

2/29/16

Reference

R Cranston, J Lama, BA Richardson, et al. MTN-017: Rectal Phase 2 Extended Safety and Acceptability Study of 1% Tenofovir Gel
.Conference on Retroviruses and Opportunistic Infections. Boston, February 22-25, 2016. Abstract 108LB.