Caffeine and MDMA (ecstasy) exacerbate ER stress triggered by hyperthermia

Drugs of abuse can cause local and systemic hyperthermia, a known trigger of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Another trigger of ER stress and UPR is ER calcium depletion which causes ER exodosis, the secretion of ER resident proteins. Club drugs such as 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) can create hyperthermic conditions in the brain and cause toxicity that is affected by the environmental temperature and the presence of other drugs, such as caffeine. Here we examine the secretion of ER resident proteins and activation of the UPR under combined exposure to MDMA and caffeine in a cellular model of hyperthermia. We show that hyperthermia triggers the secretion of normally ER resident proteins and that this aberrant protein secretion is potentiated by the presence of MDMA, caffeine, or a combination of the two drugs. Hyperthermia activates the UPR but the addition of MDMA or caffeine does not alter canonical UPR gene expression despite the drug effects on ER exodosis of UPR-related proteins. One exception was increased BiP/Grp78 mRNA levels in MDMA-treated cells exposed to hyperthermia. These findings suggest that club drug use under hyperthermic conditions exacerbates disruption of ER proteostasis contributing to cellular toxicity.

Prevalence of and Factors Associated with Club Drug Use among Secondary Vocational Students in China

To understand the prevalence of and factors associated with club drug use among Chinese secondary vocational students, a nationally representative survey was conducted. The multistage cluster sampling strategy was employed to select participants. A total of 9469 students from eleven secondary vocational schools in five cities completed self-reported questionnaires, which included information on club drug use, sociodemographic variables, individual factors, as well as peer and family related factors. The data were separately analyzed with Poisson regression models for female and male students. The overall lifetime prevalence of club drug use was 2.7% (258/9469), and male students had higher prevalence than female students (3.5% vs. 1.9%, p < 0.001). Female and male students shared four risk factors (i.e., having ever smoked, perceiving social benefit expectancies, peer drug using and perceiving peer’s approval of drug use) and one protective factor (i.e., having medium or high levels of refusal skills) for club drug use. Moreover, family drug using and having a part-time job were two additionally independent risk factors for club drug use among male students. These findings indicate that the problem of club drug use among Chinese secondary vocational students is worthy of attention. The prevention of club drug use should address multiple risks and protective factors on individual, peer and family levels.

PEP as a potential antecedent to PrEP among an online sample of HIV-negative and unknown status cis- and transgender sexual minority men: A cross-sectional study (Preprint)

BACKGROUND HIV disproportionately affects sexual minority men (SMM) in the U.S. OBJECTIVE We sought to determine past HIV post-exposure prophylaxis (PEP) use and current pre-exposure prophylaxis (PrEP) use among an online sample of cisgender and transgender men who have sex with men. METHODS In 2019, HIV-negative and unknown status SMM (n=63,015) were recruited via geosocial networking apps, social media, and other online venues to participate in a brief eligibility screening survey. Individuals were asked about past PEP and current PrEP use. We examined associations of demographics, socioeconomic indicators, recent club drug use, and current PrEP use on past PEP use using fully-adjusted logistic regression. RESULTS Prior PEP use was relatively uncommon (11.3%), with 2.66 times more men reporting current PrEP use (30.1%). Most (85.9%) past PEP users were current PrEP users, representing 32.2% of all current PrEP users. In multivariable analysis, current PrEP users had 20.1 times higher odds (95%CI: 18.6-21.6) of past PEP use compared to non-PrEP users. Other factors significantly (p<0.001) associated with past PEP use but with smaller effect sizes included: older age (>24 years old) compared to younger age (AOR=1.15); bisexual identity compared to gay (AOR=0.86); Latino, Black, and other/multiracial race/ethnicity compared to white, individually (AORs=1.37-1.52); having health insurance (AOR=0.80); and recent club drug use (AOR=1.19). CONCLUSIONS Prior PEP use was relatively uncommon in our online sample of SMM, but our findings indicate PEP could potentially be a gateway to PrEP. Advertising and prescribing PEP could support efforts to increase PrEP.

Selling and buying sex in the city: men who have sex with men in the Bangkok men who have sex with men Cohort Study

We describe participants in the Bangkok Men who have sex with men Cohort Study (BMCS) who sold or bought sex. Men who have sex with men (MSM) and transgender women aged ≥18 years had HIV testing and behavioral data collected at enrollment and every four months. We evaluated report of receiving money or goods for sex (selling sex) or giving money or goods for sex (buying sex) at enrollment using logistic regression models; we also describe sex work over time, and HIV and syphilis incidence among those who report sex work. At enrollment, 511 (29.3%) of 1744 participants reported buying or selling sex. Factors associated with selling sex were young age, lower education, living alone or living with a friend, being unemployed, higher HIV knowledge, binge drinking and club drug use, a higher number of casual male partners, meeting sex partners at specific venues, having a foreign sex partner, and being HSV-1 seropositive. MSM aged 18–21 years who sold sex had an HIV incidence of 11.1 per 100 person-years (95% CI: 6.7–17.4). Almost one-third of participants from BMCS reported sex work at enrollment. Young men who sold sex had high HIV incidence and HIV prevention interventions are needed for this at-risk population in Bangkok, Thailand.

Club drug users had higher odds of reporting a bacterial STI compared with non-club drug users: results from a cross-sectional analysis of gay and bisexual men on HIV pre-exposure prophylaxis

ObjectivesPre-exposure prophylaxis (PrEP) can reduce HIV transmission risk for many gay, bisexual and other men who have sex with men. However, bacterial STI (BSTI) associated with decreasing condom use among HIV PrEP users is a growing concern. Determining the characteristics of current PrEP users at highest BSTI risk fills a critical gap in the literature.MethodsGay and bisexual men (GBM) in New York City on HIV PrEP for 6 or more months (n=65) were asked about chlamydia, gonorrhoea and syphilis diagnoses in the past 6 months. By design, half (51%) of the sample were club drug users. We examined the associations of length of time on PrEP, type of PrEP care provider, PrEP adherence, number of sexual partners, number of condomless anal sex acts and club drug use on self-reported BSTI using multivariable, binary logistic regressions, adjusting for age, race/ethnicity, education and income.ResultsTwenty-six per cent of GBM on HIV PrEP reported a diagnosis of BSTI in the past 6 months. Men who reported club drug use (adjusted OR (AOR)=6.60, p<0.05) and more frequent condomless anal sex in the past 30 days (AOR=1.13, p<0.05) had higher odds of reporting a BSTI. No other variables were significantly associated with self-reported BSTI in the multivariable models.ConclusionsClub drug users could be at a unique BSTI risk, perhaps because of higher risk sexual networks. Findings should be considered preliminary, but suggest the importance of ongoing BSTI screening and risk-reduction counselling for GBM on HIV PrEP.

Willingness to Use Mobile Phone Apps for HIV Prevention Among Men Who Have Sex with Men in London: Web-Based Survey (Preprint)

BACKGROUND Many men who have sex with men (MSM) use apps to connect with and meet other MSM. Given that these apps are often used to arrange sexual encounters, it is possible that apps may be suitable venues for messages and initiatives related to HIV prevention such as those to increase HIV testing rates among this population. OBJECTIVE The purpose of this study was to assess willingness to use a new app for reminders of when to be tested for HIV infection among a sample of MSM in London who use apps to arrange sexual encounters. METHODS Broadcast advertisements targeted users of a popular social-networking app for MSM in London. Advertisements directed users to a Web-based survey of sexual behaviors and sexual health needs. Willingness to use apps for reminders of when to be tested for HIV was assessed. In addition, participants responded to items assessing recent sexual behaviors, substance use, and demographic characteristics. Exploratory analyses were undertaken to examine differences in willingness to use an app by demographic and behavioral characteristics. RESULTS Broadcast advertisements yielded a sample of 169 HIV-negative MSM. Overall, two-thirds (108/169, 63.9%) reported willingness to use an app to remind them when to be tested for HIV. There were no significant differences in willingness to use these apps based on demographic characteristics, but MSM who reported recent binge drinking and recent club drug use more frequently reported willingness to use this app compared to their nonusing counterparts. CONCLUSIONS MSM in this sample are willing to use a new app for HIV testing reminders. Given the high levels of willingness to use them, these types of apps should be developed, evaluated, and made available for this population.

Dual Epidemics of Club Drug Use and Sexually Transmitted Infections among Chinese Female Sex Workers: New Challenges to STI Prevention

Objectives. To evaluate club drug use and its potential association with STI among female sex workers (FSWs) in China. Methods. From November 2008 to January 2009, participants were recruited at sex work venues in five cities for a questionnaire survey. Free testing for syphilis, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) was provided. Logistic regression models were used to assess factors associated with club drug use and its association with STI. Results. A total of 1604 eligible FSWs were included. The overall prevalence of any STI infection and club drug use in the past 12 months was 22.6% and 7.4%, respectively. STI prevalence was significantly higher among club drug users (33.1%) than among nonusers (21.7%, P<0.05). Multivariable logistic regression found that club drug use was associated with younger age (AOR 2.4, 95% CI 1.0, 6.0), higher education, having injected drugs (AOR 24.4, 95% CI 6.2, 96.8), and having had STI symptoms (AOR 2.2, 95% CI 1.4, 3.4). Conclusions. Club drug use and STI were highly prevalent among FSWs in China, especially among young FSWs. Club drug users had more risk behaviors and higher STI rates. A coordinated risk reduction framework is urgently needed to address the dual epidemic of drug use and STI.