Efficacy of a carrageenan gel in preventing anal human papillomavirus (HPV) infection: interim analysis of the Lubricant Investigation in Men to Inhibit Transmission of HPV Infection (LIMIT-HPV) randomised controlled trial.

Background Carrageenan, a non-toxic gelling agent derived from red algae, has potent anti-human papillomavirus (HPV) activity in in vitro and animal studies. We assessed, in an interim analysis, the efficacy of a carrageenan-based gel in reducing the risk of new detections of anal HPV among gay, bisexual and other men who have sex with men (gbMSM). Methods The LIMIT-HPV study (Lubricant Investigation in Men to Inhibit Transmission of HPV Infection) is a phase IIb, double-blind, placebo-controlled randomised controlled trial conducted in Montreal, Canada. gbMSM were randomly assigned (1:1) to receive a carrageenan-based or placebo gel. Participants were instructed to apply the gel to the anus, condom and/or partners’ penis before and—as required—during receptive anal intercourse. Questionnaire data and anal samples were collected at 0, 1, 2, 3, 6, 9 and 12 months. We estimated new detections of anal HPV infection(s) detected via Linear Array using Cox proportional hazards models. Results Participants recruited from February 2016 to December 2019 were randomly assigned to the carrageenan (n=127) or placebo (n=128) arm. The efficacy and safety analyses included 201 and 210 participants. The median follow-up time was 7.6 months (range: 0–28.5) in the carrageenan group and 9.3 months (range: 0–40.7) in the placebo group. The HR for new detections was 1.21 (95% CI 0.86 to 1.70): 69.4% and 65.1% new detections of HPV in the carrageenan and placebo arms, respectively. More adverse events were reported in the carrageenan (59.8%) compared with the placebo (39.8%) arm. Conclusions The interim analysis did not demonstrate a protective effect of carrageenan on the risk of new detections of anal HPV infection among gbMSM. Carrageenan gel use was associated with a higher proportion of adverse events. Given these findings and the (assumed) low probability that a beneficial effect would be found by the study’s end, the trial was terminated as recommended by the Data Safety and Monitoring Board. Trial registration number NCT02354144.