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Abstract
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.
- HIV
- HPV
- anti-infective agents
- clinical trial
- epidemiology
Data availability statement
Data are available upon reasonable request.
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Data availability statement
Data are available upon reasonable request.
Footnotes
Handling editor Jonathan Ross
Collaborators LIMIT-HPV study team members: Affiliated with the Division of Cancer Epidemiology, McGill University, Montréal, Canada: Allita Rodrigues (study coordinator), Natalia Morykon and Raphaela Rodrigues (management of subject participation and specimen collection), and Sheila Bouten, Samantha Shapiro and Olga Tsyruk (data management); affiliated with Clinique OPUS: Roger Leblanc; affiliated with Clinique Médicale Urbaine du Quartier-Latin: Benoit Trottier (clinical collaborators); affiliated with the Research Institute of the McGill University Health Centre, Montréal, Québec, Canada: Christina de Castro and Karène Proulx-Boucher (study coordination and management of subject participation) and Guillaume Theriault (specimen collection); affiliated with the Service de Microbiologie Médicale et service d’Infectiologie, Départements de Médecine et de Biologie médicale, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada: Julie Guénoun and Émilie Comète (HPV testing and genotyping).
Contributors ELF, AdP, JET, FC and P-PT conceived and designed the study. MZ managed the study. CL drafted the manuscript under the supervision of ELF, AdP and MZ. All authors interpreted the data, critically reviewed the manuscript and approved the final version.
Funding This work was supported by the Canadian Institutes of Health Research (CIHR) (grant MOP-137066 to AdP and ELF; grant FDN-143347 to ELF), the Canadian Cancer Society Research Institute (grant 703 032 to ELF) and an HIV/HPV grant from the HIV/AIDS network of Fonds de Recherche du Quebec – Sante (FRQ-S; to AdP). CarraShield Labs (St Petersburg, Florida) provided gel supplies and non-latex condoms at no cost. The CIHR and CarraShield Labs were not involved in study design or data collection and were not and will not be involved in data analysis or preparation of results. AdP holds a salary award (chercheur-boursier) from FRQ-S.
Competing interests AdP received honoraria for consulting on HIV antiretroviral regimen for ViiV Healthcare, and received grants from CIHR and FRQ-S, outside the submitted work. ELF reports personal fees from Roche and Merck, outside the submitted work. ELF and MZ hold a patent related to the discovery of 'DNA methylation markers for early detection of cervical cancer', registered at the Office of Innovation and Partnerships, McGill University, Montreal, Quebec, Canada (October 2018). FC has received grants through his institution from Merck Sharp & Dohme, Becton Dickinson and Roche to conduct evaluation of HPV diagnostic tests, as well as honoraria from Merck and Roche for lectures on HPV. JET is an employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc, Kenilworth, New Jersey, USA.
Provenance and peer review Not commissioned; externally peer reviewed.
Author note JET's affiliation changed prior to completion of the study. His new affiliation is Department of Pharmacoepidemiology, Merck Research Laboratories, West Point, Pennsylvania, USA 19486.