Chemsex, HIV, and Psychiatric Diagnosis in Gay or Bisexual Men in Hong Kong

Abstract Background: Psychotropic substance use, for chemsex in particular, is common in gay or bisexual men (GBM) with HIV infection. This case-control study examined the association between Axis I psychiatric disorders and active psychotropic substance use, and identified factors affecting the prevalence of psychiatric disorders in HIV-infected GBM. Methods: Participants were 62 HIV-infected self-identified GBM who reported psychotropic substance use in the past 1 year (cases), and 55 HIV-infected self-identified GBM without psychotropic substance use in the past 1 year and had negative toxicology tests at recruitment (controls). The Chinese-bilingual Structured Clinical Interview for DSM-IV (Axis I, Patient version) was followed to establish the psychiatric diagnoses. Socio-demographic data, level of social support, HIV-related data, and pattern of psychotropic substance use were collected. Results: Cases had lower level of social support, more depressive disorders (AOR 3.4, 95% CI 1.3-8.7, p=0.01) and psychotic disorders (AOR 7.2, 95% CI 1.2-41, p=0.03) but not anxiety disorders. Significant difference in the prevalence of psychiatric disorders was only evident for disorders with onset after HIV diagnosis. Methamphetamine dependence, weekly methamphetamine use for 2 years or more, using methamphetamine beyond chemsex, duration of HIV diagnosis were significant predictors for psychiatric disorders in the cases. Conclusion: Active psychotropic substance use in HIV-infected gay or bisexual men was associated with an overall 3-fold increase in Axis I psychiatric disorders. Coordinated efforts from HIV, psychiatric and substance use services are needed to prevent harms arising from chemsex and to identify those in need and facilitate treatment access.


Introduction
Psychotropic substance (PS) use is highly common in gay or bisexual men (GBM) with HIV infection with reported prevalence up to 60% over 1-year period. (Daskalopoulou et al., 2014;Wei et al., 2012). The pattern of PS use has shifted from with the predominate use of 'club drugs' , like ketamine for dancing and socializing (Halkitis & Palamar, 2008;Halkitis & Parsons, 2002) to methamphetamine and g-hydroxybutyrate (GHB) for enhancing their sexual experiences (Hurley & Prestage, 2009;Ross et al., 2003), a phenomenon now commonly known as 'chemsex' (Bourne et al., 2015) that popularized with the use of mobile applications for sexual networking among GBM. Methamphetamine, in particular the crystalline form, is a highly addictive and neurotoxic stimulant. Previous studies showed that up to a third of methamphetamine users experienced transient mood or psychotic symptoms and almost half of those with dependence features met criteria for any psychiatric disorders like depression or psychosis (McKetin et al., 2016;McKetin et al., 2006;Salo et al., 2011). The pattern of PS use in chemsex is unique because these substances are used before or during sexual activities that take place at a variable frequency and variable duration. How this pattern of PS use evolves and relates to the pattern of psychiatric disorders are uncertain.
Moreover, sexual minority and HIV infection both increased the risks for psychiatric disorders (Ciesla & Roberts, 2001;Jallow et al., 2017;King et al., 2008;Meyer, 2003). The minority stress model conceptualizes the range of stresses arising from the social and institutionalized discrimination and stigma faced by the sexual minority group and the processes that lead to the excess burden of health issues, including substance use and psychiatric disorders (Meyer, 2003). A higher level of psychiatric morbidities was observed in people living with HIV (PLHIV) with symptomatic infections (Gaynes et al., 2008;Gonzalez et al., 2011;Gutiérrez et al., 2014;Helleberg et al., 2015), absence or non-adherence of antiretroviral treatment (ART), low nadir CD4 (Anagnostopoulos et al., 2015) and co-occurring HCV infection (Anagnostopoulos et al., 2015;Atkinson et al., 2008). HIV infection was related to psychiatric disorders because the diagnosis and the associated physical symptoms of the infection act as psychological stressors that precipitated or perpetuated the psychiatric conditions, or the psychiatric condition be the effect of HIV on the brain functions, or both HIV and the psychiatric condition were the consequences of the same behavior like substance use or non-consensual sex.
In Hong Kong, a special administrative region in the southern part of China, a HIV epidemic in GBM was observed in the past decade (Special Preventive Programme, 2017). The proportion of new attendees with homosexually acquired HIV reported ever methamphetamine use increased from 24% in 2014 to 36% in 2016 (Chan K. Personal Communication. 7 June 2017). The earlier local studies of psychiatric aspect of PLHIV fell short of focusing in this sexual minority group (Au et al., 2008) without examining the relationships between substance use and psychiatric disorders . There has been no published study using standard diagnostic tools on psychiatric and substance use disorders of GBM with HIV infection in this chemsex era.

Materials and methods
A case-control study was conducted to determine the association between Axis I psychiatric disorders and active PS use, and to identify the socio-demographic, HIV-related and substance-related factors affecting the prevalence of Axis I psychiatric disorders in GBM with HIV infection. Subjects were recruited from Integrated Treatment Center (ITC), the largest local HIV clinic, and eight community non-governmental organizations (NGO) that provide services to GBM or PLHIV. Self-identified GBM diagnosed with HIV infection for 1 month or more were included. Cases were those reported any PS use in the previous 1 year and controls were those reported no PS use in the previous 1 year with a negative urine toxicology screening result at the time of recruitment. HIV status was confirmed for those receiving HIV treatment from ITC or having two different HIV antibody tests tested positive. Those could not communicate in Chinese or English, could not provide an informed consent, aged below 16 or did not usually reside locally (<50% time in previous or coming 6 months) were excluded.
The modules on mood disorders, anxiety disorders, psychotic disorders and substance related disorders of the Chinese-Bilingual Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Axis I, Patient version) (CB-SCID-I/P) were followed to establish the current and lifetime psychiatric diagnosis (So et al., 2003(So et al., , 2004. The types and methods of PS use, its use in chemsex or other settings, frequency of use in past 1 year and days of use in the past 1 month were obtained. Socio-demographic data, duration of HIV diagnosis, use of ART and adherence were collected by a survey. Level of social support was measured by the Medical Outcomes Study Social Support Survey (MOS-SSS) (Sherbourne & Stewart, 1991;Yu et al., 2004). The most recent CD4, HIV viral load (VL), hepatitis C (HCV) co-infection, and stage of HIV infection were obtained from the clinical system of ITC or from the blood samples collected at study recruitment. The definitions are shown in Supplementary Table S1.
Convenience sampling was used. The authors, both were practicing psychiatrists for at least 5 years, conducted the interviews in private rooms in ITC or the NGO. Urine toxicology screening was performed by commercially available kits (Wondfo®) for the presence of amphetamines, barbituates, benzodiazepines, cocaine, marijuana, methamphetamine, MDMA, morphine, opiate, ketamine, and synthetic cannabis. Subjects provided their unique clinic number and date of birth for data retrieval from ITC or provided blood samples for laboratory investigations. Subjects were referred to various treatment agencies when appropriate with their consent.
Sample size was estimated assuming a 20% lifetime prevalence of psychiatric disorders in the controls and is 3 times higher in the cases, 80% power and 5% Type I error. Subjects required in each arm was estimated to be 60. Univariate and multivariate analyses were performed using multiple logistic regression. All statistical analyses were performed using SPSS version 24.0 using two-sided tests and a p-value <0.05 was considered statistically significant.

Subjects' description
During September 2017 to May 2018, 195 potential subjects were referred to the research coordinator and 122 (63%) consented and were recruited. Five were excluded because they did not fulfill the inclusion criteria or complete the interviews. Data collected from 117 subjects, including 62 cases and 55 controls, was available for analysis. Their background characteristics are shown in Table 1. The cases scored significantly lower in the total and subscales of MOS-SSS except tangible support subscale. The cases had higher rate of HIV non-suppression after ART than the controls although the difference was statistically insignificant (Fisher exact test, p = 0.06). The cases were comparable to the controls in terms of other demographic variables and stage of HIV infection. The subjects recruited from ITC and NGO were comparable except all non-Chinese subjects came from ITC (Fisher exact test, p = 0.006). Table 2 lists the specific types and number of PS used by the cases and controls. Methamphetamine was the most used PS: 97% of the cases and 13% of the controls reported ever used. One-third of the controls reported previous PS use. Table 3 details the methamphetamine use pattern in the cases. A quarter started methamphetamine use after HIV diagnosis and 55% of those started methamphetamine use before HIV diagnosis did not reduce the frequency of use afterwards. Only 3% reported regular injections. Methamphetamine use for chemsex, was highly common: 87% initiated and 95% ever used methamphetamine at chemsex. Methamphetamine was also the most frequently used PS with 22% using it for more than 14 days in the previous month, a frequency only reported by 2 cases for GHB and none for other substances (Supplementary data Table S2).

Pattern of DSM-IV Axis I psychiatric diagnosis
The specific lifetime and current SUD and other psychiatric diagnoses are listed in Supplementary Tables S3-4. Methamphetamine-related SUD was the most common SUD in the cases: 50% (n = 31) fulfilled criteria for DSM-IV lifetime methamphetamine dependence and 8% (n = 5) methamphetamine abuse. Depressive disorders were the most common diagnoses across all subjects, followed by psychotic disorders. Figure 1 illustrates the pattern of co-occurring psychiatric diagnoses in the cases and controls.
After adjustments with age, duration of HIV diagnosis and level of social support, cases were 3.1 times (95% CI 1.28-7.56, p < 0.001) more likely to have lifetime psychiatric diagnosis excluding SUD (Table 4). Specifically, they were 7.2 times (95% CI 1.27-41.65, p = 0.03) more likely to have lifetime psychotic disorders and 3.4 times (95% CI 1.33-8.69, p = 0.01) more likely to have lifetime depressive disorders. After excluding substance-induced depressive episodes, cases were still 2.7 times (95% CI 1.03-6.94, p = 0.04) more likely to have lifetime depressive disorders. The prevalence of lifetime anxiety disorders in the case and controls did not differ significantly (adjusted OR 1.14, 95% CI 0.28-4.67, p = 0.86).
There was no statistical difference observed in the prevalence of psychiatric disorders with onset prior to HIV diagnosis between the cases and controls, but the cases were 6 times (AOR 6.36, 95% CI 1.96-20.65, p = 0.002) more likely to have any psychiatric disorders with onset after HIV diagnosis (Table 5).

Factors affecting the prevalence of DSM-IV Axis I psychiatric diagnosis
Factors affecting the prevalence of lifetime psychiatric disorders in the cases are shown in Table 6. None of the HIV outcomes were associated significantly with psychiatric  disorders in the cases. A series of multivariate analyses excluding highly correlated variables (Supplementary Table  S5) were performed (Table 7). In the first two models, either methamphetamine dependence (AOR 6.63, 95% CI 1.53-28.72, p = 0.01) or SUD (AOR 6.80, 95% CI 1.38-33.62, p = 0.02) and duration of HIV diagnosis remained as significant predictors. In the third model which excluded methamphetamine dependence and SUD from the analysis, methamphetamine use beyond chemsex (AOR 4.76, 95% CI 1.17-19.41, p = 0.03) and duration of HIV diagnosis remained as independent predictors. As methamphetamine use beyond chemsex was moderately correlated with methamphetamine dependence, r(60) = 0.533, p < 0.01 and weakly correlated with duration of weekly methamphetamine use, r(60) = 0.464, p < 0.01, a fourth model was built excluding methamphetamine dependence, methamphetamine use beyond chemsex, and SUD. In this model, having weekly use of methamphetamine for 2 years or more (AOR 18.60, 95% CI 1.26-274.69, p = 0.03) and duration of HIV diagnosis remained as independent predictors. All models showed satisfactory goodness-of-fit.

Discussion
To our knowledge this is the first study that examined chemsex and related PS use and its relationship with psychiatric disorders in GBM with HIV infection using a standard diagnostic tool. A range of socio-demographic, HIV-related and substance-related factors were incorporated in examining psychiatric epidemiology, enabling understanding into the possible inter-relationships among them. Our results showed that active PS use in GBM with HIV infection was associated with a three-fold increase in psychiatric disorders. Acknowledging the difficulty in establishing causality, our study demonstrated that the diagnosis of HIV was associated with a change in the PS use pattern in GBM. This change, primarily the extension of using methamphetamine beyond chemsex was an important factor that underscores its association with psychiatric disorders as observed in this sample of GBM with HIV infection.
Our sample was characterized by relatively young age, recent HIV diagnosis, low level of virological or immunological failure and a distinct PS use pattern. These were consistent with other local reports (Hong Kong Advisory Council on AIDS, 2017; Kwan et al., 2016; and contrasted with cohorts in the UK and US that often consisted of men of older age with less favorable HIV outcomes (Daskalopoulou et al., 2014;Skeer et al., 2012). Methamphetamine was the most commonly and frequently used substance, similar to Taiwan (Lee et al., 2021) but unlike the more prevalent use of cannabis or cocaine in the UK, US, and Australia. Injection rate was of the lower range compared to these studies (Daskalopoulou et al., 2014; Methamphetamine users in our study had less frequent, less injection, and shorter duration of methamphetamine use compared to other cohorts of methamphetamine users whose sexual orientation or HIV status were unspecified McKetin et al., 2016;McKetin et al., 2006). Active PS users reported a significantly lower level of social support. This was in line with previous studies highlighting that lower social support was associated with PS use and depression (Armoon et al., 2022; Friedman et al., 2017) and that social support reduced the adverse effect of drug use and depression (Mizuno et al., 2003) and promoted positive well-being (Brener et al., 2020). Consistent with literature, depressive disorders were the most common psychiatric diagnosis in our sample. The risk of lifetime depressive disorders in our cases (AOR 3.40, 95% CI 1.33-8.69, p = 0.01) was different from the lack of significant association of depression with methamphetamine use, slightly stronger than that with cocaine use and was comparable to that with drug abuse reported by Skeer et al. (2012). Although comparison of their cross-sectional measures with our lifetime diagnosis is difficult, the difference observed could be related to their use of PHQ-9 which is less specific than the standard diagnosing tool and the inclusion of active users of other PS in the comparison group hence weakening their associations. It may also be explained by the more severe substance use in our sample: 52% of our cases fulfilled DSM-IV dependence criteria, whereas Skeer et al. (2012) reported in their study that 55% of their substance users fulfilled the less restrictive abuse criteria using PHQ.
The rate of lifetime psychotic disorders in our cases was comparable to other studies McKetin et al., 2006) despite different assessment methods were used in samples with heavier and longer methamphetamine use. The proportion of lifetime methamphetamine-induced psychotic disorder among subjects with methamphetamine dependence (32%) resembled previous findings (McKetin et al., 2006;Salo et al., 2011;Shoptaw et al., 2003). The lack of schizophrenia was likely related to our small sample size with less frequent and shorter duration of methamphetamine use, based on the conversion rate reported by Niemi-Pynttari et al. (2013). It could also be due to a sampling bias as those with significant positive or negative symptoms of schizophrenia did not join our study.
The lack of significant association of anxiety disorders with PS use observed in our study was similarly reported by Skeer et al. (2012). The prevalence of anxiety disorders in our study was relatively low compared to the local figures in the general population (Lam et al., 2015) and the known positive association between being non-heterosexual (King et al., 2008) and with HIV infection (Brandt et al., 2017). It might be possible that those with anxiety disorder did not join the study resulting in a selection bias. Tallied with this possibility was the observations that 'concerned about confidentiality' and 'do not want to be interviewed face-to-face' being common reasons for refusal in our study, and that fear and stigma were identified as key barriers to participate in mental health and HIV research (Woodall et al., 2010;Mills et al., 2004). The effect could be even greater for those who faced triple stigma for being sexual minority, HIV-infected, and PS users. Moreover, as homelessness, HIV symptoms and injection predicted the anxiety level in PLHIV (Ibañez et al., 2005;Semple et al., 2011), the absence of homeless participants, few injection users and dependence and duration of methamphetamine use significantly predicted lifetime psychiatric disorders in our cases. The difference in rates of psychotic disorders as reported by McKetin et al. (2006) could be related to different outcome measures. The infrequent and short durations of methamphetamine use in our non-dependent cases could also have inflated our odds ratio. We showed that weekly use of methamphetamine for 2 years or more significantly predicted psychiatric disorders, concurred with previous findings on the positive relationship between frequency and duration of methamphetamine use and psychotic symptoms McKetin et al., 2006).
A prominent finding from this study was the positive association between active PS use and psychiatric disorders appeared only for those with onset after HIV diagnosis. Our findings showed that weekly methamphetamine use of more than 2 years, methamphetamine use beyond chemsex and methamphetamine dependence predicted psychiatric disorders, and that all these factors correlated with a report of initiating or increasing methamphetamine use after HIV diagnosis. There was a lack of literature looking into the longitudinal patterns in severity and settings of drug use, including chemsex patterns, in GBM. A survey in the UK showed that chemsex declined significantly over time among GBM who were HIV negative (Sewell et al., 2019) and that the diagnosis of HIV could be a traumatic experience for   GBM Low level of social support could affect the psychological adjustment toward the diagnosis (Armoon et al., 2022). It could be possible that there could be distinct trajectories of drug use and chemsex patterns in GBM that echo different predisposing factors, such that the diagnosis of HIV made a significant impact on the pattern of PS use in a subgroup of GBM like those who lacked social support, poor adjustment to HIV diagnosis or had other predisposing factors for psychiatric disorders. Nonetheless, the characteristics of such relationships such as causality and temporality need further evaluation. This postulation concurred with earlier studies showing methamphetamine use was associated with the purpose to avoid unpleasant emotions in GBM with mixed HIV-status (Halkitis & Shrem, 2006) and to deal with negative emotions associated with HIV (Chartier et al., 2009;Nakamura et al., 2009;Semple et al., 2002) because of its euphoric effect. Low mood was a major reason for PS use in local drug users with HIV infection, majority of whom were MSM . Our findings extended this knowledgebase and illustrated that using methamphetamine at non-sexual settings correlated with methamphetamine dependence and duration of HIV diagnosis and predicted psychiatric disorders. To avoid ongoing HIV transmissions, instead of using methamphetamine in chemsex which commonly took place over weekends, some cases reported using methamphetamine at other situations such as masturbation that could happen more frequently. This shift in the setting of methamphetamine use was probably unique in GBM, as methamphetamine initiation at chemsex was much less common in the heterosexual population (Hobkirk et al., 2016;Liu et al., 2018;Miltz et al., 2021).
The finding that the duration of HIV diagnosis predicated psychiatric diagnosis echoed previous results (Hammond et al., 2016;McGowan et al., 2017) although direct comparison between the lifetime diagnosis and the point prevalence used in the other studies was difficult. The lack of significant association of psychiatric disorders with the stage of HIV infection echoed previous findings (Anagnostopoulos et al., 2015;Bing et al., 2001;Closson et al., 2018).
Our results carried several implications to the practice in caring for GBM who are infected with HIV. These include regularization of screening for substance use and depression in HIV testing and treatment centers and to ensure the accessibility to coordinated services related to the comorbidity of drug use, HIV, and mental health issues. As our results showed that GBM who are infected with HIV and with active PS use had a significantly lower level of emotional, informational, affectionate support, and positive experiences, community workers should be aware of such and incorporate these elements into their care and support programme. The use of case managers for those who have multiple co-morbidities (Nijhawan et al., 2008) or strengthening psychiatric and substance abuse service at HIV clinics should be considered.
This study had several limitations. There was selection bias in non-randomised samples that limited the generalizability of our results. Our cases were largely comparable to the sample reported by  regarding the proportion of viral suppression and living alone, although they were older with lower CD4 level. This could be explained by the discrepancy in case-mix where the hospital-based clinics were more likely providing care for patients with more severe disease, the minority of heterosexual subjects sampled and the lower CD4 observed with aging. The lack of local data on PS use pattern in this population made assessment of the representativeness regarding these aspects difficult. Sampling at the NGOs where free HIV testing services were provided might have resulted in sampling of subjects with relatively short duration of methamphetamine use or the subjects joined the study for treatment leading to over-estimation of the prevalence of psychiatric disorders. It was also possible that those with more severe symptoms did not join the study resulted in an under-estimation. Yet even if these exist, the comparisons between the cases and the controls should still be valid. The results of this study could not indicate any causal relationships between the factors studied. The study had a relatively small sample size and was not powered to detect the differences in specific psychiatric diagnosis. There could be recall bias in substance use patterns, past psychiatric symptoms and ART adherence rendering difficulties in ascertaining any temporal relationships.

Conclusion
Active PS use in GBM with HIV infection was associated with a three-fold increase in psychiatric disorders. The increase was evident only for those with onset after HIV diagnosis and was predicted by the severity, duration, and context of methamphetamine use and duration of HIV diagnosis. The predictors for psychiatric disorders should be further explored as potentially effective harm reduction measures. With the continued HIV epidemic in GBM and the popularity of methamphetamine in Asia, a proportion of these highly stigmatized individuals suffered multiple biopsychosocial disadvantages despite the availability of highly effective HIV treatment. Chemsex, a less described phenomenon in this region, has been the most important context where they explored and continued their methamphetamine use. Coordinated efforts from HIV, psychiatric, and substance use services are needed to prevent harms arising from chemsex and to identify those in need and facilitate treatment access.