Delineating Patterns of Sexualized Substance use and its Association with Sexual and Mental Health Outcomes Among Young Gay, Bisexual and Queer Men in Singapore: A Latent Class Analysis


 Background: Young gay, bisexual, and other men who have sex with men (YMSM) are vulnerable to the risks associated with sexualized substance use. This is a novel study in Singapore that aims to classify patterns of sexualized substance use among YMSM, and investigate its association with sexual and mental health outcomes. Methods: In this cross-sectional study among 570 YMSM aged 18 to 25 years old, latent class analysis (LCA) conducted to identify classes with similar patterns of sexualized substance use, across which measures of inconsistent condom use, recent STI diagnoses, past suicide ideation and depression severity were compared. Results: LCA revealed three classes of YMSM based on types of substances ever used in sexualized contexts, which we labelled as ‘substance-naïve’, ‘substance-novice’, and ‘chemsex’. Substance-naïve participants (n=404) had only ever used alcohol, while substance-novice participants (n=143) were primarily amyl nitrite users with a small proportion who reported using chemsex-related drugs. Chemsex partiipants (n=23) comprised individuals who had mostly used such drugs. Those in the chemsex group were more likely to report recent unprotected anal sex with casual partners, depression severity and a history of suicide ideation.Conclusions: Findings of this study highlight how the use of varying substances in sexualized contexts may be classified and characterized by different sexual and mental health outcomes. Health promotion efforts should be differentiated accordingly to address the risks associated with sexualized substance use among YMSM.

The PCYCS is a prospective cohort study exploring the syndemic risks associated with HIV and other sexually transmitted infections (STI) acquisition among YMSM in Singapore. This study was a partnership between Action for AIDS Singapore (AFA), one of Singapore's longest-running community-based organizations serving the health of GBMSM, and the National University of Singapore (NUS). To be eligible for this cohort, participants had to be HIV-negative or unsure of their HIV status, between the ages of 18 to 25 years old, Singapore citizens or permanent residents, and identify as gay, bisexual, or queer men at the point of recruitment, which spanned across May to September 2019. Participants were asked to self-report these attributes. Assuming a population of 210,000 GBMSM in Singapore (32), we targeted recruitment of at least 384 participants to achieve a 95% con dence level and 5% margin of error. However, 600 participants were targeted for recruitment to account for potential attrition at each follow-up for this cohort study.
Participants were invited to participate in this study through a recruitment yer that was disseminated through both online (e.g. social media) and o ine (e.g. at the organization's o ce or outreach activities) channels by a network of community-based organizations in Singapore who are engaged in health advocacy-related activities for GBMSM. Participants who were interested in participating and were eligible for the study signed up through an enrolment link with their self-reported alias, contact details, date of birth, gender, HIV status, sexual orientation, and their residence status. An AFA staff member subsequently veri ed the eligibility of participants who had signed up prior to sending them a unique identi er, and a link for the baseline survey.
It was imperative for the team to ensure that participants' identities their data would remain con dential, as drug use and sexual relations between men are criminalized in Singapore. To do so, the researchers ensured that no staff member from AFA or NUS had full access to either the enrolment details held by AFA which contained aliases and contact details of participants, and the baseline survey results held by NUS. Both sets of data were only linked by the unique identi er which participants entered at the beginning of the survey. Upon completion of the survey, a NUS staff member provided AFA with the unique identi ers who had completed the baseline survey, and an SGD20.00 (approximately USD15.00) cash reimbursement was given to the participant. A total of 570 participants were recruited at the baseline of the cohort; the response rate could not be established as it was not possible to ascertain the total number of eligible participants that the recruitment yers had reached. Participants could also refer their friends to participate in the survey and be reimbursed SGD5.00 (approximately USD3.75) for each eligible individual successfully referred and who had completed the baseline survey; a total of 171 (30.0%) of participants were recruited through referrals.

Ethics declaration
Ethics approval was obtained from the institutional review board at the National University of Singapore (NUS-IRB Reference Code S-19-007) prior to data collection.

Variable measures
The survey collected sociodemographic information from respondents, including age (in years), ethnicity (Chinese vs non-Chinese), gender (cisgender vs noncisgender), sexual orientation (gay vs non-gay), and monthly household income (SGD5000 and above vs below SGD5000; SGD5000 is approximately USD3668.94). As the YMSM in our sample included respondents who were still schooling, educational attainment and gross monthly personal income were omitted as variables, though they were collected in the baseline survey. Household income was thus collected and utilized as a proxy variable for socioeconomic status among participants.
Participants were asked if they had ever used a series of substances in sexual contexts, including alcohol, poppers, meth, GHB/GBL as well as other ED medication or drugs (e.g. Viagra, Cialis, 'black ants'). For sexual health outcomes, participants were asked about their patterns of unprotected anal sex, as well as STI diagnoses in the last six months. Unprotected anal sex with casual partners in the last six months was coded as a binary variable (yes vs no), and was derived from a series of questions that solicited frequency of self-reported condom use through a ve-point Likert scale from 1 to 5, with 1 being that they did not use condoms and 5 being that they had always used condoms; this question was repeated for permutations of oral and anal sex with regular, casual, and sex worker partners in the last six months. Participants who had not used condoms all the time with casual and sex worker partners in the last six months were coded as 'yes' under this variable. Participants who also reported being tested positive for either gonorrhoea, syphilis, chlamydia, genital herpes, genital warts or hepatitis C were assigned as having been diagnosed with an STI in the past six months through a binary (yes vs no) variable.
For mental health outcomes, both depression severity and past suicide ideation were measured. Depression severity, which was measured through the wellestablished, nine-item patient health questionnaire-9 (PHQ-9) validated by Kroenke and colleagues (33,34). Participants were asked "over the last 2 weeks, how often have you been bothered by any of the following problems?" to a total of nine statements, to which they could respond to four possible answers on a Likert scale; 1 being not at all and 4 being nearly every day. Depression severity was measured as an index that was the sum score of all nine items, with a minimum score of 0 and a maximum score of 27. Cronbach's alpha of the scale was reported as 0.92. Participants were also asked about their suicide-related behaviors, including if they had ever contemplated suicide by responding to three possible answers: yes, no, or prefer not to say.

Statistical analysis
Statistical analysis was carried out using the statistical software STATA version 15 (Stata Corp, College Station, TX, USA). We employed descriptive statistics to identify trends in sample characteristics. Latent class analysis was performed with STATA's gsem function to delineate classes of drug use in sexualized contexts. The chosen variables included a history of using alcohol, poppers, meth, GHB/GBL as well as other ED medication or drugs (e.g. Viagra, Cialis, 'black ants') in sexualized contexts. A latent class model was employed, whereby the conditional item probabilities for each class and class probabilities were estimated through maximum likelihood procedures. A posteriori probabilities were calculated using the predict post-estimation command. In order to determine the number of clusters, models with consecutively increasing were estimated and compared using both Akaike and Bayesian information criteria (AIC and BIC), but BIC was favored given its reliance on both the log-likelihood and the adjusted sample size (35). Given that the three-class model had the lowest AIC and BIC values, it was thus reported in this study. A summary of goodness-of-t statistics are provided in Supplementary Table S1. Entropy, which provides a measure of how well individuals t into each class, was also taken into account to determine the t of the model. Following identi cation of latent classes, we sought to determine the association between varying classes with outcome variables of unprotected anal sex, STI diagnoses, depression severity and past suicide ideation while adjusting for key sociodemographic covariates. We employed multivariable Poisson regression models with robust sandwich variances to compute the crude prevalence ratio (PR) and adjusted prevalence ratio (aPR) estimating these outcome variables. Statistical signi cance was set at p<0.05. Analysis for this study was not pre-registered and the results reported here should be considered exploratory.
With regard to the outcome variables of the study, participants reported a mean score of 7.9 (SD=6.79) on depression severity, while most participants had ever contemplated suicide (n=308, 54.1%). A total of 16.8% of participants also reported unprotected anal sex with casual partners in the last six months (n=96), while 6.7% (n=38) reported testing positive for an STI in the past six months.
Association between substance use class membership and sexual health outcomes Association between substance use class membership and mental health outcomes

Discussion
This study sought to identify classes of YMSM based on the substances that they had ever used in sexualized contexts. We explored the sociodemographic and substance use patterns across each of the different classes, and how these classes differed based on their associations with a variety of sexual and mental health outcomes, speci cally recent unprotected anal sex with casual partners and STI diagnoses, as well as depression severity and ever contemplating suicide. This study is noteworthy in that, to our knowledge, no prior study has sought to delineate classes of substance use speci cally in younger samples of MSM, which allows us to better understand the risk factors that may be associated with substance use initiation. Furthermore, no other study had ever sought to investigate such patterns of substance use among GBMSM in Singapore.
Results of latent class analysis revealed three classes of YMSM based on the substances that they had ever used in sexualized contexts, which we labelled post hoc as 'substance-naïve', 'substance novice', and 'chemsex'. Those in the substance-naïve group had only ever used alcohol, while the substance-novice group were primarily poppers users with a small proportion who reported using drugs typically associated with chemsex, including meth, GHB/GBL, as well as erectile dysfunction drugs (13,36). The chemsex group comprised individuals who had mostly used such drugs. This nding aligns with that of other studies, which identi ed classes of GBMSM characterized by those who were negligible or non-users of recreational substances excluding alcohol, those who were 'soft' drug users, and those who were 'hard' drug or polydrug users (25). Several studies have also found nd greater nuances in such patterns of use, separating those who are polydrug users without meth or mephedrone, and those who do (14,37).
Controlling for potential confounders, we found that being in the substance-novice or chemsex classes were associated with poorer sexual and mental health outcomes, compared to those who were in the substance-naïve class. Given that those in the chemsex class reported both historical and recent indicators of poorer mental health, we believe that this may underpin certain mechanisms that lead to both sexual risk and substance use risk-related behaviors. This corroborates the ndings of other studies (38, 39). As we are not able to establish causation due to the study design, an alternative explanation would be that substance use itself may be a factor that may cause poorer mental health, and disinhibition associated with sexual risk-related behaviors, which corroborate the ndings of other studies as well (40). These two may mechanisms may also be working in tandem to exacerbate poorer sexual and mental health outcomes in the chemsex class, compared to the substance-naïve class of YMSM. We remain mindful that we cannot draw a direct association between substance use and some of these outcomes as the time frame assessed for both differ.
Our study has several strengths. As it was conducted among self-identi ed HIV-negative YMSM aged 18 to 25 years old, we may be identifying certain risk factors and substance use patterns that may place them at risk of HIV and other STI acquisition. We may also draw conclusions around factors that may be associated with substance use initiation without stronger confounds of age, as GBMSM are more likely to be exposed to various substances throughout their life course due to its cumulative availability via sexual and social networks (41).
We are mindful of several limitations in our study. As only HIV-negative YMSM were recruited in this study, we may have missed out on HIV-positive YMSM whom may exhibit higher levels of substance use, which would be consistent with the ndings of the other studies (42,43). Furthermore, as drug use carries with it severe penalties in Singapore, participants may not be entirely honest with their answers around drug use, which may have led to an underreporting of substance use in the present sample. This form of non-differential misclassi cation would have biased our results towards the null, when in fact the associations between substance use and the outcomes of interest would have been stronger.
We have several recommendations for health promotion and policy interventions. Overall, such health promotion efforts and interventions should acknowledge that substance use-related support needs among YMSM and GBMSM may be heterogenous, and would require a combination of upstream interventions that promote literacy around the risks associated with substance use, and downstream ones that mitigate such risks or promote the well-being of those who require long-term support. Findings of this study indicate that efforts for early intervention and education for YMSM should focus on addressing suicide and depression, which may be associated with future HIV and other STI acquisition risk and other risks associated with substance use. Ethics approval and consent to participate: Ethics approval was provided by the National University of Singapore Institutional Review Board (Reference Code S-19-007). Participants provided written informed consent to participate.

Consent for publication:
Prior to data collection, participants were given a copy of the participant information sheet and subsequently provided written informed consent by clicking on a link.
Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests:
The authors declare that they have no competing interests Funding: