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Tenofovir Rectal Gel Safe and Acceptable in Study of MSM and TGW
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Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
Tenofovir 1% rectal gel proved safe and largely acceptable in an international study that enrolled 195 men who have sex with men (MSM) and transgender women (TGW) [1]. Participants preferred applying the gel before and after sex rather than every day in this phase 2 trial, MTN-017.
Antiretroviral gels have protected nonhuman primates from viral exposure, MTN-017 researchers noted, but 1% tenofovir gel developed for vaginal use proved neither safe nor acceptable when applied rectally. MTN-017 used a reduced-glycerin formulation of 1% tenofovir gel that was safe and acceptable when applied for 7 straight days by 11 men and 3 women [2].
MTN-017 recruited 195 HIV-negative MSM or TGW who reported receptive anal intercourse. There were four sites in the United States, two in Thailand, and one each in Peru and South Africa. The trial evaluated three regimens: 1% tenofovir rectal gel used daily, 1% tenofovir rectal gel used 12 hours before and after receptive anal intercourse or at least once weekly (the RAI arm), and a daily tenofovir/emtricitabine (TDF/FTC) tablet. A crossover design randomized all participants to use each of the three study regimens for 8 weeks, with a 1-week washout between regimens. Researchers defined adherence as taking more than 80% of doses as evaluated by product returns, interview, and sometimes drug-level testing.
Of the 195 recruited participants, 187 could be evaluated. Nineteen participants were TGW and 4 were women. Age averaged 31.1 years, and 80% had a college education. Grade 2 to 4 adverse events developed in one third of participants while taking each regimen.
Generalized estimating equation models determined that, compared with TDF/FTC pills, participants proved significantly less likely to like daily rectal gel (odds ratio [OR] 0.28, P < 0.001) or RAI gel (OR 0.37, P = 0.002). They felt daily rectal gel was harder to use than tablets (OR 0.56, P = 0.08), while RAI gel compared more favorably with tablets in ease of use (OR 0.76, P = 0.46). Participants said they were significantly less likely to use daily gel than tablets (OR 0.38, P < 0.001) but not significantly less likely to use RAI gel than tablets (OR 0.70, P = 0.23).
Drug level testing showed that 80.2% of participants used the daily rectal gel faithfully, while 94.3% took their TDF/FTC tablets daily. Adherence determined by product return and interview calculated less than 80% adherence by 6% of participants when taking TDF/FTC pills, 7% when using RAI rectal gel, and 17% when using daily rectal gel.
The MTN-017 investigators concluded that rectal tenofovir gel was safe when used daily or before and after receptive anal intercourse, that adherence to all study products was high, but that participants preferred before-and-after use to daily use. The researchers proposed that their results "support further study of 1% rectal gel tenofovir as a rectal microbicide for HIV prevention in MSM and TGW."
References
1. Cranston R, Lama J, Richardson BA et al. MTN-017: Rectal phase 2 extended safety and acceptability study of 1% tenofovir gel. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 108LB.
2. McGowan I, Cranston RD, Duffill K, et al. A phase 1 randomized, open label, rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of three formulations of tenofovir 1% gel (the CHARM-01 study). PLoS One. 2015;10:e0125363. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125363
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