Study finds rectal gel to be safe in men, but not as acceptable for daily use

MTN-017: a rectal phase 2 extended safety and acceptability study of tenofovir reduced-glycerin 1% gel.

Cranston RD, Lama JR, Richardson BA, Carballo-Dieguez A, Kunjara Na Ayudhya RP, Liu K, Patterson KB, Leu CS, Galaska B, Jacobson CE, Parikh UM, Marzinke MA, Hendrix CW, Johnson S, Piper JM, Grossman C, Ho KS, Lucas J, Pickett J, Bekker LG, Chariyalertsak S, Chitwarakorn A, Gonzales P, Holtz TH, Liu AY, Mayer KH, Zorrilla C, Schwartz JL, Rooney J, McGowan I; MTN-017 Protocol Team. Clin Infect Dis. 2016 Dec 16. pii: ciw832. [Epub ahead of print]

Background: HIV disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed.

Methods: MTN-017 was a Phase 2, three-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily; or RG-TFV rectal gel before and after receptive anal intercourse (RAI) (or at least twice weekly in the event of no RAI); or daily oral FTC/TDF.

Results: MSM and TGW (n=195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). There were no differences in Grade 2 or higher adverse event rates in participants using daily gel (Incidence Rate Ratio (IRR): 1.09, p=0.59) or RAI gel (IRR: 0.90, p=0.51) compared to FTC/TDF. High adherence (≥80% of prescribed doses as assessed by unused product return and SMS reports) was less likely in the daily gel regimen (Odds Ratio (OR): 0.35, p<0.001) and participants reported less likelihood of future daily gel use for HIV protection compared to FTC/TDF (OR: 0.38, p<0.001).

Conclusions: Rectal application of RG TFV gel was safe in MSM and TGW. Adherence and product use likelihood were similar for the intermittent gel and daily oral FTC/TDF regimens, but lower for the daily gel regimen.

Abstract access   [1]

Editor’s notes: While microbicide gel to prevent HIV in women has not been consistently shown to be effective, scientific efforts to develop a rectal microbicide gel have continued in the hopes of finding a safe and effective product for HIV prevention in men. This paper presents a phase II clinical trial in which gay men and other men who have sex with men across four different countries were randomly assigned to one of three arms: oral pre-exposure prophylaxis (‘daily oral’), topical gel administered before and after receptive anal intercourse (‘RAI’), and topical gel administered daily (‘daily rectal’). The authors found that the rectal gel was safe to use, and was acceptable to participants, although the daily rectal application had lower acceptability and lower adherence than daily oral or the RAI.  This safety, adherence, and acceptability seen in this Phase II study supports further development of the gel as a rectal microbicide candidate, although consideration will need to be given to dosing regimens to maximize adherence. 

Africa [5], Asia [6], Latin America [7], Northern America [8]
Peru [9], South Africa [10], Thailand [11], United States of America [12]
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