Background Pre-exposure prophylaxis (PrEP) is a promising and effective tool to prevent human immunodeficiency virus (HIV) transmission; however, context-specific data to guide optimal implementation are currently lacking in China. This study aims to systematically collect comprehensive, empirical data to determine effective ways to implement PrEP among at-risk men who have sex with men (MSM) in China. Methods The CROPrEP project, a real-world study of PrEP use, will recruit 1000 high-risk HIV-negative MSM participants from four cities in China, who will be able to choose between daily or event-driven dosing regimens, according to their preference. Participants will be followed up at months 1, 3, 6, 9, and 12 for PrEP provision, clinical evaluation, laboratory testing (e.g., emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) concentrations, and HIV/sexually transmitted infections), alongside detailed, self-administered online questionnaires regarding sexual behaviors, adherence, and attitudes. Online weekly notes will be used to record pill use and sexual practice. Various measurements will be triangulated to assess adherence, including: self-reported adherence, pill count, and drug concentration. A propensity score matching model will be fitted to examine the effectiveness of PrEP use in HIV seroconversion compared with non-PrEP users selected from a local expanding cohort study of HIV-1-negative MSM at participating research centers. Analyses using a generalized estimating equation model will focus on elucidation of the cascade of PrEP implementation, effectiveness, safety, and possible effects of PrEP use on sexual behaviors. This study will provide a comprehensive assessment of real-world PrEP use among Chinese MSM, to develop guidelines and strategies for PrEP implementation in China. Discussion The CROPrEP project is the first study of the TDF/FTC combination as PrEP in China, which will provide primary data on PrEP implementation, including: the cascade of PrEP use, “real-world” effectiveness, adherence, and safety. The findings from this study have potential to be vital for promoting the integration of PrEP within the portfolio of HIV prevention interventions and developing guidance on PrEP implementation in China. Trial registration ChiCTR-IIN-17013762 (Chinese Clinical Trial Registry). Date of registration: 8 December 2017.

IntroductionPre-exposure prophylaxis (PrEP) reduces the risk of HIV infection among men who have sex with men by up to 99%. However, in real-world settings, PrEP users may exhibit risk compensation after uptake of PrEP, including more condomless anal intercourse (CAI) and increased sexually transmitted infection (STI) acquisition. HIV self-testing (HIVST) decreases CAI among men who have sex with men (MSM) by providing awareness of the HIV status of oneself and one’s sexual partners. Here, we describe the rationale and design of a randomised waitlist-controlled trial to examine the impact of HIVST on risk compensation among PrEP users.Methods and analysisThe study is a two-arm randomised waitlist-controlled trial with 1000 HIV-negative MSM in four major cities in China who will be taking oral PrEP (involving tenofovir disoproxil fumarate/emtricitabine) either daily (n=500) or in an event-driven regimen (n=500). The participants will be randomised (1:1) to either the immediate HIVST intervention arm (HIVST plus standard facility-based counselling and testing from 0 to 12 months) or the waitlist arm (standard facility-based counselling and testing from 0 to 6 months, then crossover to receive the HIVST intervention in months 7–12). Participants will provide blood samples to assess the incidence of syphilis and herpes simplex virus type 2 (HSV-2) during a follow-up. The primary outcomes will be the occurrence of CAI, number of sexual partners and incidence of syphilis and HSV-2 during a follow-up. The secondary outcomes will be the HIV and STI testing frequency and STI treatment adherence during a follow-up. The planned start and end dates for the study is 26 December 2018 and 31 December 2020.Ethics and disseminationThe Medical Science Research Ethics Committee of The First Affiliated Hospital of China Medical University has approved the study (IRB(2018)273).Trial registration numberChiCTR1800020374