Preplanned Studies: Psychoactive Substance Use and the Impact on the AIDS Epidemic Among the MSM Population: a Meta-Analysis — Worldwide, 2014–2023

The prevalence of human immunodeficiency virus (HIV) among men who have sex with men (MSM) has surged in recent decades, drawing substantial public health attention (1). Research indicates that the MSM population has a 28-fold higher risk of HIV infection than the general adult male population. In China, 7,762 cases of HIV transmission via homosexual contact constituted 25% of all new HIV infections in the second quarter of 2023 among individuals living with HIV/acquired immune deficiency syndrome (AIDS), as indicated by a 2023 report from the China CDC (2-3).

Designer drugs, or psychoactive substances, have posed a significant challenge to global public health since their inception (4). Numerous studies have demonstrated their potential to cause escalating harm worldwide through neurotoxicity and psychiatric symptoms (5). In recent years, there’s been increased attention on the impact of psychoactive substance abuse within MSM communities, particularly on HIV prevalence. Research indicates that psychoactive substance use can increase the risk of HIV infection among MSM by promoting unsafe sexual practices and compromising immune systems (6-7).

Although experimental studies have begun to investigate the link between psychoactive substance use and HIV prevalence among MSM cohorts, findings remain inconclusive. Therefore, this meta-analysis aims to synthesize high-quality research to determine the impact of psychoactive substance use on HIV prevalence in MSM communities.

We conducted a comprehensive search for relevant studies published from January 1, 2014 to December 31, 2023, across 4 Chinese databases (CNKI, WanFang, CQVIP, and SinoMed) and four English databases (PubMed, Web of Science, the Cochrane Library, and Embase). Our search strategy involved using both subject headings and keywords related to HIV, MSM, and psychoactive substances (such as amphetamines, ecstasy, ketamine, Rush, capsule 0, etc.). Please refer to Supplementary Material for details on inclusion and exclusion criteria, data extraction, and assessment of study quality.

Statistical analyses were performed using Stata (version 17.0; Computer Resource Center, Chicago, US), with “metan,” “metaninf,” “metabias,” and “metareg” commands. Results were depicted via forest plots, combining odd ratio (OR) values using the “Random [Mantel-Haenszel (M-H) heterogeneity]” method. Heterogeneity was assessed using I², where values <25% indicate low heterogeneity, 25% to 75% moderate heterogeneity, and >75% high heterogeneity. Publication bias was evaluated using funnel plots and Egger’s test. Subgroup analyses explored sources of heterogeneity, considering region, study type, psychoactive substance type, and year of data collection. Statistical significance was set at P<0.05 (2-tailed), with combinatorial stability assessed through dropout-by-dropout sensitivity analysis.

A total of 1,606 records were identified through literature search, from which 31 studies were screened for inclusion by the researcher, as depicted in Supplementary Figure S1. Detailed search steps are presented in Supplementary Table S1. Sensitivity analyses, following the sequential exclusion of individual studies, demonstrated no significant changes. The results were corroborated by Egger’s test, which yielded a P value of 0.639, and the symmetry of the funnel plots, both of which suggest an absence of significant publication bias in the literature. These findings are graphically represented in Supplementary Figures S2 and S3.

Supplementary Table S2 provides an overview of the characteristics of all included studies. The 31 studies encompassed 88,181 samples, yielding 8,437 HIV-positive patients. Among them, 29 studies were cross-sectional, while 2 were cohort studies. Statistics on the prevalence of individual psychoactive substance use in MSM populations were reported in 17 publications that incorporated multiple psychoactive substances. Figure 1 depicts the percentage of psychoactive substance use among the entire MSM population, within China, and across other regions and nations. Within the overall MSM population, rush poppers and amphetamine derivatives exhibited the highest rates of use, constituting 10.91% and 9.97%, respectively. Notably, in China, the utilization rate of rush poppers among MSM surpassed that of the entire MSM population, reaching 47.26%. Furthermore, in other regions and countries, amphetamine derivatives (12.86%), rush poppers (3.62%), and GHB (3.34%) exhibited high rates of utilization, ranking as the top 3 substances among psychoactive substances used within the MSM population.

Figure 1. 

Percentage of psychoactive substance use in the full MSM population, China and other regions and countries.(A) All; (B) China; (C) Other regions and countries.

Note: All: All literature included in the study, from both China and other regions. China: All literature from China. Other regions and countries: Literature from regions and countries other than China..

Pooling data from the 31 studies involving 18,025 MSM populations using psychoactive substances revealed a prevalence of 17% [95% confidence interval (CI): 14%, 20%]. The I² index was 97.6%, with a Cochran Q-test significance of P<0.001, utilizing a random-effects model, as illustrated in Figure 2. In China, the prevalence was 16% (95% CI: 13%, 19%), while in other regions and countries, it was 19% (95% CI: 12%, 26%).

Figure 2. 

Forest plots for HIV prevalence among MSM using psychoactive substances.

Note: Weights and between-subgroup heterogeneity test are from random-effects model.

Figure 3 presents the subgroup analysis results, depicting the impact of psychoactive substances on HIV prevalence in the MSM population by region. The analysis revealed a significant difference in the effect of psychoactive substances between China and other countries/regions, with an OR of 1.57 (95% CI: 1.42, 1.74) in China and 2.16 (95% CI: 1.72, 2.71) elsewhere. Furthermore, the effect of psychoactive substances on HIV prevalence in MSM populations by study type was examined. Although the difference in effect between study types was not significant, subgroups were delineated based on the use of rush poppers alone, amphetamine derivatives alone, and psychoactive substances (including various substances beyond rush poppers and amphetamine derivatives). Notably, significant differences were observed in the impact of psychoactive substance type on HIV prevalence, with an OR of 1.76 (95% CI: 1.53, 2.02) for the psychoactive substances group, 1.51 (95% CI: 1.23, 1.84) for the rush poppers group, and 3.06 (95% CI: 2.38, 3.93) for the amphetamine derivative group. In an effort to juxtapose data gathered in the last decade with earlier data, we encountered a challenge. Given that the majority of the research data spanned an extensive timeframe, and considering the collection dates of the included papers, we delineated the data into two cohorts: before 2015 and 2016 onward.

Figure 3. 

Forest plots for impact of psychoactive substances on HIV prevalence in the MSM population (A) by region (B) by design (C) by drugs (D) by data.

Note: Psychoactive Substance: Both rush poppers and amphetamine derivatives were used in the study. Weights and between-subgroup heterogeneity test are from random-effects model.