Utilization of post-exposure prophylaxis potentially contributed to the changes of risk behaviors among men who have sex with men in China

Background The HIV infection status among men who have sex with men (MSM) in China is a cause for concern. Post-exposure prophylaxis (PEP) serves as a highly effective biomedical preventive measure against HIV infection. Substantial evidence has established an association between PEP utilization and risk behaviors among MSM, but whether the utilization of PEP has an impact on risk behaviors remains unknown. This study sought to elucidate the impact of PEP usage on risk behaviors among MSM and provide recommendations for developing targeted HIV prevention programs. Methods A cohort study was conducted in Qingdao, China, from April 2021 to January 2022. Participants were enlisted by volunteers from community-based organizations through a snowball sampling method. Face-to-face interviews were conducted to collect sociodemographic and behavioral information of participants. The study encompassed a retrospective investigation, baseline survey, and follow-up survey, representing periods before, during, and after PEP usage, respectively. Generalized estimating equations, fitting a Poisson regression model, were applied to scrutinize changes in risk behaviors of MSM during and after PEP usage, in comparison to before PEP usage. Results A total of 341 MSM were recruited in the cohort study, with 179 individuals completing the follow-up survey. In comparison to before PEP usage, there was a significant increase in the proportion of Rush Popper usage (17.6% vs. 23.8% vs. 29.6%) and commercial sexual partners (10.9% vs. 17.6% vs. 21.8%) among MSM during and after PEP usage. Before PEP usage, 88.7% of MSM reported having ≥3 temporary sexual partners in the last 6 months. This proportion exhibited no significant change during PEP usage (91.8%), but it significantly increased to 97.8% after PEP usage (P < 0.05). Notably, there was a significant decrease in group sex during and after PEP usage compared to before PEP usage (30.8% vs. 21.4% vs. 21.2%). Conclusion The utilization of PEP may impact risk behaviors among MSM, potentially leading to increased Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage, accompanied by a decrease in group sex. Further research is imperative to elucidate the impact of PEP utilization on MSM and develop targeted HIV prevention programs.


Introduction
Men who have sex with men (MSM) have always constituted a key population for HIV infection due to risk behaviors, such as recreational drug use, participation in group sex, and engaging in unprotected anal sex (1).Globally, the median HIV prevalence among MSM was 7.5%, significantly surpassing that of general adult population aged 15-49 years, which was 0.7% (2).The HIV prevalence in China remains relatively low, with the majority of newly reported HIV infections in recent years attributed to sexual behavior.Notably, the proportion of HIV transmission through homosexual sex has seen a substantial increase, escalating from 2.5% in 2006 to 25.6% in 2022 (3).Among MSM in China, the HIV prevalence has reached 7.0%, with certain regions exceeding 20.0%, indicating a concerning HIV epidemic within this population (4).
Initially, the HIV prevention and control measures for MSM in China primarily focused on health education, promoting condom use, and encouraging regular HIV testing.These measures have achieved notable success, contributing to significant improvements in HIV knowledge and testing rates among MSM.However, challenges such as condom-related stigma (5), sexual sensation (6), and risk perception (7) have resulted in only about half of MSM in China consistently using condoms during sexual activities, implying a persistent high risk of HIV infection in this population.Therefore, in order to achieve the goal of ending the AIDS epidemic by 2030, the promotion of biomedical preventive measures is indispensable.
Post-exposure prophylaxis (PEP) is a biomedical preventive measure used to block HIV infection following exposure, with its efficacy substantiated in numerous studies (8,9).Initially employed for occupational post-exposure prevention (10), PEP expanded to non-occupational settings with the spread of HIV (11).Currently, multiple guidelines on PEP recommend individuals at risk of HIV infection to initiate PEP for prevention within 72 hours of HIV exposure (12-14).The global promotion and application of PEP have spurred its demand among MSM in China.In 2016, Chinese Center for Disease Control and Prevention (CDC) designated PEP as a crucial measure for HIV prevention among MSM (15).MSM can access PEP through diverse channels, including hospitals, pharmacies, and Blued app (a MSM social media).
Substantial evidence has established an association between PEP utilization and risk behaviors among MSM (16)(17)(18).The engagement in risk behaviors prompts MSM to use PEP, yet whether the utilization of PEP has an impact on risk behaviors of MSM remains unknown.A cohort study was conducted among MSM using PEP in Qingdao from 2021 to 2022, with the objective of comprehending the impact of PEP usage on the risk behaviors of MSM.The findings aim to provide recommendations for the development of targeted HIV prevention measures.

Study design and participants
This cohort study conducted in Qingdao comprises three components: a baseline survey, a retrospective investigation, and a follow-up survey.MSM aged 18 years and above, residing in Qingdao, who were HIV-negative, and utilized PEP in the last 6 months were recruited through a snowball sampling method.Between April and August 2021, volunteers from local communitybased organizations (CBOs) recruited eligible MSM to conduct the baseline and retrospective survey.During this period, participants were asked to recommend individuals around them to participate.Recruitment took place in diverse venues such as bars, bathhouses, and parks, etc.The follow-up survey was conducted 6 months later.During this period, CBOs stayed in touch with study participants via WeChat, encouraging their engagement in the follow-up.
To improve the cooperation and data quality, this study employed volunteers from local CBOs as investigators.These volunteers maintained close connections with the local MSM community, resulting in increased cooperation during the investigation.Comprehensive training sessions were uniformly provided to all investigators, ensuring the acquisition of specific investigation skills.On-site surveys were conducted in separate rooms to safeguard the privacy of participants.

Measures
All data were collected through face-to-face interviews.The following information was collected: sociodemographic characteristics (age, marital status, registered residence, education, occupation, income, and sexual orientation), Rush Popper usage in the last 6 months (how to use, where to use, how often to use), sexual behaviors in the last 6 months (temporary sexual partners, commercial sexual partners, unprotected anal sex, group sex, etc.), HIV infection status, PEP usage.
All participants had utilized PEP in the last 6 months during the baseline survey, categorizing this phase as during PEP usage.Subsequently, the retrospective and follow-up surveys were designated as before and after PEP usage, respectively.

Statistical analysis
Two researchers independently entered and verified the raw data using EpiData3.1 software and created a database.Statistical analyses were performed using R4.2.3 software.Descriptive analyses were conducted to describe the sociodemographic characteristics of study participants.The chi-square test was employed to compare sociodemographic differences between followers and those lost to follow-up.Outcome variables in this study encompassed various risk behaviors potentially facilitating HIV transmission, such as Rush Popper usage, temporary sexual partners, commercial sexual partners, group sex, and so on.Generalized Estimating Equations fitting a Poisson regression model, were used to analyze changes in outcomes during and after PEP usage compared to before PEP usage.Comparing during PEP with before PEP sought to discern the possible short-term impact of PEP utilization on MSM.Comparing after PEP with before PEP aimed to understand the stable impact of PEP utilization on risk behaviors among MSM.Variables with statistical significance were further stratified by sociodemographic characteristics.All statistical tests were two-sided and were statistically significant at P < 0.05.

Study population
In the cohort study, a total of 341 MSM were recruited, with 179 of them completing the follow-up survey.Both the follow-up and loss of follow-up groups predominantly consisted of individuals aged 19-29 years, unmarried, registered in Qingdao, holding a college degree or higher, employed full-time, earning an average monthly income of ≥5,000 RMB, and identifying with a homosexual orientation.Notably, statistical differences were observed in age and average monthly income between the two groups, while the other characteristics showed no statistically significant differences (Table 1).

Change in temporary sexual partners
Before PEP usage, 88.7% had ≥3 temporary sexual partners in the last 6 months.During PEP usage, this proportion was 91.8%, showing no significant change compared to before PEP usage (P > 0.05).However, subgroup analysis indicated a significant increase in this proportion among individuals with a college or higher degree during PEP usage (RR = 1.063, 95% CI:

Discussion
This study investigated changes in risk behaviors among MSM across three stages: before, during, and after PEP usage.The findings revealed significant changes in risk behaviors among MSM after PEP usage.Notable increases were observed in Rush Popper usage, temporary sexual partners, and commercial sexual partners.These changes could be attributed to either the utilization of PEP or broader behavioral shifts within the MSM community.Regardless of the underlying cause, this phenomenon raises concerns for HIV prevention and control among MSM.If PEP usage contributes to increased risk behaviors among MSM, it implies a potential risk compensation linked to PEP usage.Further research is essential to elucidate whether promoting PEP is genuinely beneficial for HIV prevention in MSM.However, given the absence of a parallel control group for those not using PEP in this study, the observed changes may also reflect general behavioral shifts within the entire population during the study period, potentially unrelated to PEP utilization.If this is the case, it underscores the escalating risk behaviors among MSM in Qingdao.The World Drug Report 2022 indicated a global rise in the use of recreational drugs and associated adverse consequences (19).Due to their stimulant and hallucinogenic effects, the use of recreational drugs could potentially facilitate high-risk sexual behaviors among MSM, elevating the risk of HIV transmission in this population (20)(21)(22).Recreational drug use exhibited regional variations influenced by legal systems, economic status, and drug cultures (23).In China, Rush Popper emerged as the primary recreational drug among MSM, readily accessible and easily obtained through the Internet.In this study, the proportion of MSM using Rush Popper ≥1 time/week significantly increased both during and after PEP usage, suggesting that PEP may contribute to heightened Rush Popper use in this population.This finding aligns with the observed increase in Rush Popper usage among MSM in China (24,25), implying a broader shift within the MSM community.The HIV interventions in China primarily targeted individuals injecting traditional drugs, with limited emphasis on recreational drug users (26).These results suggested an urgent need to strengthen the intervention of recreational drug use such as Rush Popper.
As a sexual minority, some MSM were influenced by the traditional Chinese marriage culture, leading them to enter into marriages (27).This subgroup acts as a bridge across from homosexual to heterosexual transmission of HIV, thereby contributing to the expansion of HIV transmission.Shandong Province, the birthplace of Confucianism, is deeply influenced by traditional values and exhibits a pronounced stigmatization of homosexual orientation (28).In this study, individuals who were married/divorced/widowed constituted approximately onefourth of the population.The proportion of temporary and commercial sexual partners in this group increased significantly after PEP usage, potentially escalating the risk of HIV transmission to females.Due to social discrimination and privacy concerns, some MSM reported a heterosexual/bisexual orientation.In contrast, those who reported homosexual orientation had a higher self-identification.The Rush Popper usage, temporary sexual partners, and commercial sexual partners in this group increased significantly after PEP usage, indicating an increasing risk of HIV infection.Compared to traditional HIV prevention measures like condom use, PEP represented a relatively recent and underutilized biomedical HIV preventive measure (29, 30).It was not until 2020 that the Chinese CDC issued guidelines on PEP (31).The high cost of PEP, without compensatory measures, increased the likelihood that MSM of higher socioeconomic status would be aware of and utilize PEP (32).In this study, a notable increase in the proportion of temporary and commercial sexual partners was observed after PEP usage among individuals with higher education levels, full-time professionals, and those with higher monthly incomes.Furthermore, younger MSM, known for being more sexually active and less risk-averse, exhibited significant increases in Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage.These findings implied the importance of accompanying PEP promotion with intensified HIV prevention education for MSM, with a specific focus on the above vulnerable groups.
The present study demonstrated a significant decrease in the proportion of individuals engaging in group sex >5 times in the last 6 months both during and after PEP usage, compared with before PEP usage.In part, it might be explained by the fact that PEP users realized the risks of group sex and consequently curtailed such activities.But since no further investigations were conducted in this study, there was no definite evidence to support this speculation.Alternatively, this decline could be linked to various restrictions imposed during the COVID-19 epidemic, such as quarantine and traffic restrictions, which hindered MSM from gathering and consequently led to a reduction in group sex within this population.In particular, older individuals were more significantly impacted by the lockdown measures during the COVID-19 epidemic, due to their preference for offline searching for sexual partners, which was similar to the findings of Wang et al. (33).In addition, the 1.002-1.128),rising from 86.6% to 99.3%.After PEP usage, the proportion of individuals with ≥3 temporary sexual * 1.323 (1.121-1.562)** * Risk ratio calculated using generalized estimating model fitting Poisson regression.PEP, post-exposure prophylaxis; RR, risk ratio; CI, confidential interval.*P < 0.05; * * P < 0.01; * * * P < 0.001.