Recreational Drug use and Risk of HIV Infection Among Young Men Who Have Sex with men: A Cross-Sectional Study in Tianjin, China


 Background- Recreational drug use among young men who have sex with men (YMSM) was a public health issue of worldwide concern. Evidence had shown the relevance between recreational drug use and human immunodeficiency virus (HIV) infection. This study aimed to investigate the current prevalence state of recreational drug use among YMSM in Tianjin, discern the characteristics of YMSM who used recreational drugs or not and examine the interaction effect of recreational drug use and unprotected anal intercourse (UAI) on HIV infection.Methods- In 2018, a cross-sectional study was conducted in Tianjin, China. The snowball sampling method was used to recruit YMSM. Participants were recruited from gay bars, gay bathhouses, social network sites (WeChat, QQ, gay chat website), gay apps and peer referrals. Structured questionnaires were used to collect data.Results- A total of 1075 YMSM met the eligibility criteria and were included in the study eventually. The overall HIV prevalence was 4.3% (46/1075). Of all the recreational drugs involved in this study (rush poppers, methamphetamine, capsule No.0), rush poppers (406/517,78.5%) were the most popular among YMSM in Tianjin. Compared with non-drug users, drug users were more likely to have first sex earlier, be bisexual, be male sex worker (MSW), have a higher education level, seek sex partners through physical venues, engage in UAI, have sexually transmitted infection (STI), and receive HIV testing. Moreover, recreational drug use and UAI were associated with the increased risk of HIV infection [adjusted OR:3.6 (95%CI: 1.7-7.6) and 4.9 (95%CI: 2.2-10.4), respectively]. There was additive interaction of recreational drug use and UAI on HIV infection [relative excess risk due to interaction (RERI): 6.949 (95%CI: 0.011‐13.887); attributable proportion due to interaction (AP): 0.809 (95%CI: 0.578‐1.039)].Conclusions- Recreational drug use was common and correlated with HIV infection among YMSM in Tianjin. There was an urgent need to build novel targeted HIV prevention strategies to discern and reduce recreational drug use among YMSM in China.


Introduction
The prevalence of human immunode ciency virus (HIV) infection had been low among the general population over the past three decades. However, the burden of HIV infection was disproportionately concentrated among men who have sex with men (MSM) [1,2]. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, among Asia and the Paci c, MSM contribution to 44% of new HIV infections in 2019 [3]. Additionally, evidence of global HIV infection showed that HIV infection was converging among young men who have sex with men (YMSM) [4,5]. Compared with the older MSM, YMSM were in their sexually active period and might have more sexual activities. Moreover, owing to freshness, thrill-seeking and peer in uence [6][7][8][9], they were more likely to use recreational drugs when engaging in sexual behaviors. Data from World Health Organization (WHO) also indicated that YMSM were more vulnerable to HIV and had a greater HIV risk than heterosexual young people or older MSM [10], which implied they were a special population to be concerned.
Recreational drug use among MSM was a public health issue of worldwide concern. Due to China's effective legal control and intensive regulations on drugs over recent years [11], the utilization rate of traditional drugs (heroin, opium) had signi cantly decreased. Unlike traditional drugs, the legal de nitions of recreational drugs were often vague and imprecise. So these drugs were not being well controlled by relevant drug legislation [12]. There was an increase in the use of recreational drugs in China [11,13,14]. Using recreational drugs helped MSM deal with shame and vulnerability issues they might have from outside. Some drugs like rush popper could relax the anal sphincter, reduce anal pain and help MSM quickly expand blood vessels to reach orgasm in a short period, improving the sexual experience [15]. However, a growing body of research indicated that recreational drug use was associated with increased risk of unprotected anal intercourse (UAI) [16][17][18], intimate partner violence (IPV) [19], group sex [17] and HIV/sexually transmitted infection (STI) [11,[19][20][21][22]. Moreover, MSM could ensue dependent and abuse in recreational drugs after long-term continuous use [23]. In the context of HIV treatment, recreational drug using among HIV-positive individuals had been proved to be associated with non-adherence of antiretroviral treatments (ARTs) [24][25][26]. That meant if the HIV-positive individuals were treated with ARTs and still used recreational drugs at the same time, they would become more infectious to other individuals when engaging in sexual behaviors [17].  [27].
China was a country with traditional Confucianism as its main social values [28]. Sexual behaviors between men in China were taboo both politically and by family/cultural tradition. Although not illegal, YMSM endure stigma and discrimination by both the family and society [29,30]. This had set obstacles to explore the behavioral characteristics of YMSM in China. However, the corresponding research was still necessary and had very important practical signi cance. The ndings of this study should contribute to the eld of proposing novel targeted prevention and intervention measures on reducing recreational drug use and HIV infection among YMSM.

Recreational drugs
Recreational drugs were also known as "club drugs". In this study, recreational drug use was de ned as the use of any type of drugs (one or more) at some time before or during sexual behaviors over the past 6 months.
The recreational drugs involved rush poppers, methamphetamine and capsule No.0. Rush poppers were aphrodisiac gas composed of volatile nitrite. Its main function was to relax the smooth muscles. Originally, rush poppers were emergency medicine for heart disease. MSM used them to expand blood vessels and reduce the perception of pain, for the smooth muscles were also distributed around the anus. Methamphetamine, known as crystal meth, was a central nervous system stimulant and widely used as an illicit drug. It had a high potential for abuse. Capsule No.0, the main ingredient was 5-MeO-MiPT, was psychedelic in the tryptamine class. It was known for producing greater tactile, bodily, and sexual effects than other psychedelics. "Capsule No.0" was a code name among MSM in China. During the implementation of the study, Tianjin City CDC and Tianjin Shenlan CBO had established a cooperative relationship of mutual assistance, complementarity and mutual bene t. Tianjin City CDC's support for the Tianjin Shenlan CBO was mainly re ected in data reporting, technical support, funds management and staff training to improve professional pro ciency. Besides, Tianjin City CDC undertook data veri cation; provided HIV con rmation, CD4 and viral load test; supervise the implementation process and quality control.

Research Design
Tianjin Shenlan CBO was a formally community-based organization that provided community-based support services (including HIV testing, counseling and psychological support) for MSM. The organization had a good in uence and a high reputation among MSM in Tianjin. Therefore, staff in the organization were able to contact with MSM expediently, which facilitated the collection and authenticity of data.

Participants And Data Collection
The snowball sampling method was used to recruit YMSM. Participants were recruited from gay bars, gay bathhouses, social network sites (WeChat, QQ, gay chat website), gay apps and peer referrals.
Inclusion criteria were: (1) > 16 and ≤ 24 years old, (2) biologically male, (3) having sex with another man in the past one year, (4) able to complete investigation, (5) understanding informed consent and privacy issues.
Data were collected by trained staff of the Tianjin Shenlan CBO. The staff of the organization mostly were also MSM, so they could truly experience what the participants underwent, which would be a bene t for smooth unhindered communication with participants. Participants were invited to the Tianjin Shenlan CBO's public health advisory service center for community-based support services. When participants came to the public health advisory service center for counseling or testing, experienced staff would conduct a face-to-face interview with participants. During this period, a structured questionnaire was completed by the participants under the guidance of the staff.
The content of the questionnaire included, (1) Socio-demographics data: age, self-reported sexual orientation, ethnicity, educational level, marital status, occupations, the local residence time in Tianjin. (2) Sexual behaviors: age of sexual debut, UAI over the past 6 months, routes to seek sex partners, awareness of HIV-related knowledge, any STI over the past 12 months, HIV testing history over the past 12 months.
(3) Info of recreational drug use over the past 6 months.

Hiv Laboratory Test
Before testing, YMSM would choose to collect blood or saliva. Patrons' oral mucosal exudate test (Mano Bio-Pharmaceutical Co., Ltd, Beijing, China) was used for the former and a blood rapid detection reagent (Wan Fu Biotechnology Co., Ltd, Guangzhou, China) for the latter. In addition, 5 ml of blood sample was collected from those who get any positive tests above. Then, the blood sample was sent to Tianjin CDC to perform enzyme-linked immunosorbent (ELISA; Wan Tai Biological Pharmaceutical Co., Ltd, Beijing, China). HIV infection was by con rmed Western blot (WB) assay (MP Biomedical Asia Paci c Pte Ltd, Singapore).

Statistical Methods
Category variables were described by frequencies and proportions. For the general demographic characteristics, differences were calculated using Pearson's chi-squared test or Fisher's exact test. The univariate and multivariate logistic regression model was performed to evaluate (1) the associations between recreational drug use and each factor (2) risk of recreational drug use and UAI on HIV infection.
Variables for the multivariate model were based on the results of univariate analysis. Variables with a value less than 0.1 were selected into the multivariate model. Odds ratios (OR), adjusted odds ratios (aOR) and their 95%CI of the variables were estimated. Strati ed analysis among participants engaging in UAI or not engaging in UAI were performed to check the consistency of ORs of recreational drug use for the risk of HIV infection across subgroups. For the model where data separation occurred and the maximum likelihood method failed to converge, the rth statement was added into SAS logistic model procedure to make it converge.
The additive interaction of recreational drug use and UAI on HIV infection risk was tested to explore possible enhancing effects of drug use on UAI-associated risk of HIV infection. Additive interaction was estimated using indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). If there was signi cant additive interaction, the 95% CI of RERI and AP would not include 0, or 95% CI of S would not contain 1. i.e., recreational drug use enhanced the risk of UAI on HIV infection. All the data analyses were performed in SAS version 9.4 (SAS Institute Inc., Cary, NC).

Characteristics of the participants
A total of 1075 YMSM met the eligibility criteria and were included in the study eventually. Con rmed by the laboratory test, 46 participants were HIV-positive and the overall HIV prevalence was 4.3% (46/1075).
Among all the participants, the mean age was 21.5 ± 1.7 years (ranging from 16 to 24 years); 98.7% were homosexuals; 97.6% were ethnically Han; 99.3% were unmarried; 46.7% were students; 59.2% had a university degree or above; 48.1% used recreational drugs (at least one type); 84.7% had been lived in Tianjin for more than 2 years; 82.7% were seeking sexual partners through the internet; 97.3% had a good understanding of HIV-related knowledge; 49.6% engaged in UAI over past 6 months, 2.9% had STI over past 12 months and 70.6% received HIV testing over past 12 months (Table 1). c. Partner-seeking meant the routes for YMSM to seek sex partners. YMSM who reported mainly using the QQ, WeChat, gay apps, gay chat rooms to seek sexual partners were de ned as internet-based while seek sexual partners in gay bathrooms, bars, parks, public toilets were de ned as physical venues.
d. Knowledge represented whether YMSM have a good understanding of HIV-related knowledge. It was classi ed by the score of 8 questions about HIV (for example, the main transmission route of HIV). If the participant's answer was correct, it was counted as one point, otherwise zero. The result of HIV-related knowledge was de ned as knowing if the total score was no less than 6 while less than 6 was de ned as unclear.
e. UAI was the history of unprotected anal intercourse over the past 6 months.
f. STI was the history of sexually transmitted infection over the past 12 months.
g. Testing history was the HIV testing history over the past 12 months.

Types Of Recreational Drugs Used By Ymsm
In this study, 517 YMSM reported using at least one type of recreational drug over the past 6 months. The proportion of recreational drug use was 48.1% (517/1075). Among drug users, 411 (79.5%) used only one type of drug while 106 (20.5%) were polydrug users. Rush poppers (406/517,78.5%) were the most commonly used recreational drug (Table 2).

Characteristics Of Ymsm Who Used Recreational Drugs Or Not
Among drug users and non-drug users, the HIV prevalence were 7.0% (36/517) and 1.8% (10/558), respectively ( =0.001). Univariate analysis showed age of sexual debut, sex orientation, occupations, routes to seek sex partners, HIV-related knowledge, STI history and HIV testing history were statistical signi cance between the two categories (

Subgroup analysis of recreational drug use on HIV infection risk
In the subgroup analyses, among YMSM who engaged in UAI, the multivariable aOR of recreational drug use on HIV infection was increased to 5.5 (95%CI: 2.2-13.7) while the aOR using the entire study population was 3.6 (95%CI: 1.7-7.6) ( Table 4). Among YMSM who did not engage in UAI, the multivariable aOR of recreational drug use on HIV infection was attenuated to 1.1 (95%CI: 0.3-4.3).

Additive interaction between recreational drug use and UAI on HIV infection risk
From the results of the subgroup analysis, we inferred that there might be an interaction between recreational drug use and UAI. Making the non-UAI and non-drug user group as the reference, recreational drug use increased the aOR of UAI on HIV infection from 1.5 (95%CI: 0.4-5.4) to 8.5 (95%CI: 2.9-24.8) with a signi cant additive interaction (RERI: 6.949, 95%CI: 0.011-13.887; AP: 0.809, 95%CI: 0.578-1.039) ( Table 5). (310/1122). Using recreational drugs such as rush poppers might generate "cognitive escape", which was characterized by avoidance from thought related to HIV infection. Consequently, YMSM were more likely to engage in sexual risk behaviors like UAI, group sex even IPV and could potentiate further HIVtransmissions in the community [33].
In this study, drug users might have rst sex earlier. YMSM were in the period of transition from adolescence to adulthood. Their mind was not mature enough. Premature sexual behaviors at this period had a greater impact on their substance use after adulthood [34].Compared with other groups, students might less likely to use recreational drugs and MSW were more likely to use drugs. Because of the specialness of their profession, MSW would use recreational drugs more frequently [35]. Drug users were more likely to have higher education. The impact of education levels on drug use mostly laid in extensive social networking and availability for drugs [7]. One study also found that it was di cult for those with university education levels to attain an appropriate support network for avoiding recreational drug use, thus leading to drug use [36]. Our data showed that drug-users were more likely to be bisexual. A YMSM was bisexual meant that YMSM had more sexual partners than those who were homosexual. Meanwhile, faced discrimination from both heterosexual and homosexual individuals, bisexual YMSM might be more likely to use substances before sex, because they may rely on substances to cope with stigma. But it remained unclear if bisexual YMSM were more or less likely to use substances before sex with different types of partners [37].
In this study, YMSM using recreational drugs were more likely to nd sexual partners based on physical venues (gay bars, parks, and gay bathhouses). YMSM nding sexual partners through the internet-based route accounted for a large proportion (889/1075, 82.7%), which was consistent with the ndings in China [38] and in the United States [39][40][41]. The proportion of recreational drugs used among YMSM seeking sexual partners through the internet-based route was 45% (400/889). However, the proportion of YMSM using recreational drugs who sought sex partners through physical venues was much higher (117/186,62.9%). As another name for recreational drugs was "club drug", it was originally used in physical venues (parties, clubs). We speculated that the use of recreational drugs symbolized the trust and intimacy between YMSM. The relationship between YMSM seeking sexual partners based on physical venues might be more stable, and this sensation would prompt YMSM to use recreational drugs to increase sexual experience [17]. Due to anonymity and the instability of the relationship, the proportion of recreational drug use might decline among YMSM who sought sexual partners based on the network.
Recreational drug use and UAI had been proved to be the independent risk factors on HIV infection in numerous studies. Moreover, our study found that there was an additive interactive effect between recreational drug use and UAI on HIV infection risk, with important public health implications.
Recreational drug use ampli ed the effect of UAI on HIV infection risk to further increase the prevalence of HIV. This provided a hint for future HIV prevention, that is, reducing the occurrence of UAI and the risk of HIV infection by reducing the use of recreational drugs.
The results showed that drug users were more likely to have been tested for HIV in the past. This might be the result of increasing scope of relevant knowledge dissemination as China continued to improve HIV prevention. YMSM no longer avoided HIV testing, and their health awareness had also been continuously improved. They were willing to know their HIV infection status, which prompted the emergence of detection behaviors. Some studies had also pointed out that the feeling of guilt and the fear of HIV infection caused by conducting high-risk sexual behaviors would also prompt the detection of HIV [42,43].
One other study suggested that social apps might be leveraged to promote HIV testing among YMSM [39]. Regardless of the reason for detection, prompting the YMSM to conduct regular testing was a key step in controlling the spread of HIV. This was also a positive factor found in this study and was closely related to China's investment in HIV prevention and control.
The Important aspect of future HIV prevention and control should focus on continuing to expand the promotion of HIV prevention, eliminate the society's bad perception of HIV, and reduce the stigma of YMSM. In addition, in the analysis of the types of recreational drugs, we found that rush was used at the highest frequency, which was consistent with other studies [15,21,44]. Therefore, it was necessary to proactively develop control and intervention programs that aimed at drug use among YMSM in China.
This suggested that the management should improve the legal system for the prevention and control of recreational drugs and strengthen the control of distribution channels.
This research has several limitations. First, in this study, the snowball sampling method was used to recruit participants, which may have certain tendentiousness. However, we recruited participants in a variety of ways (gay bars, gay bathhouses, social network sites, gay apps and peer referrals) to increase the representativeness. Second, the cross-sectional study design prevented us from making causal inferences about recreational drug use and HIV infection. Hence longitudinal investigations were needed to understand the association between them. Further, our data collection adopted a real-name registration system (ID card number, mobile phone number and ngerprint information were involved). Due to the privacy of some questions (such as whether you had ever had STI), the participants might have concealed the actual situation which may result in social expectation bias. We conducted an interviewstyle questionnaire collection to avoid this. Besides, all staff had received professional training to ensure the authenticity of the data. Community-Based Organization; RERI: relative excess risk due to interaction; AP: attributable proportion due to interaction; S: synergy index; OR: odds ratio; AOR: adjusted odds ratio.