The term chemsex refers to the intentional use of psychoactive substances with the aim of intensifying and/or prolonging sexual experiences [1]. Although documented in diverse populations, the phenomenon is particularly frequent among men who have sex with men (MSM) [2], with elevated and heterogeneous prevalence rates reported in Brazil [3]. Review studies [4] indicate that, among MSM samples, chemsex prevalence ranges from 27% to 69.9%, varying according to substance profiles and recruitment contexts [5]. These data position chemsex as a public health challenge and justify the development of contextually informed and socially grounded care responses.

At the international level, reviews [6,7] underscore that the specific mix of drugs involved in chemsex is not static but depends on local scenes and markets. Nonetheless, crystal methamphetamine, gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL), and mephedrone constitute the core most frequently described in European studies [7]. These patterns are associated with high-risk sexual behaviors [8] (eg, condomless sex with multiple partners and prolonged encounters), a higher burden of sexually transmitted infections (STIs) [7,8], and cooccurrence with events such as the mpox outbreak [9], as well as mental health harms, anxiety, depression, substance-induced psychotic symptoms, and social vulnerabilities [10,11].

In Brazil, understanding chemsex requires attention to specific market dynamics and local cultures of use. In addition to the “classic” trio described in European settings, cocaine powder, crack, ketamine, 3-, 4-methylenedioxymethamphetamine, cannabinoids, poppers (alkyl nitrites), and the adjuvant use of pharmaceuticals such as sildenafil/tadalafil, often combined with alcohol and other substances in party circuits and app-mediated encounters, are relevant [12,13]. Brazilian studies point to widespread availability and use of cocaine/crack and polysubstance use patterns that shape the sexualization of substance use among urban segments, including MSM, but not limited to them [5,14,15]. This drug ecology, which is more diverse than that depicted in the “classic” chemsex literature, reinforces the need for care pathways (CPs) that integrate harm reduction, mental health, and clinical emergency management (eg, GHB/GBL intoxication and stimulant-associated cardiovascular events).

It is also important to recognize that the sexualization of substance use is not limited to MSM. Studies have estimated the pooled prevalence of sexualized substance use (SSU) and chemsex in the general population at around 19.9%, with variations by sex and context, suggesting that sexualized use practices occur across different groups and settings [16]. Although Brazil lacks robust population-based estimates for SSU, the international evidence broadens the scope of surveillance and planning of interventions, including for populations not classified as “key” yet potentially exposed to biomedical and psychosocial risks.

From a service perspective, the research problem arises from the convergence of three gaps: (1) informational—fragmented data on prevalence, polysubstance use patterns, and therapeutic itineraries; (2) care-related—the absence of standardized screening and care flows for early detection, clinical/psychosocial management, and continuous linkage; and (3) organizational—limited integration across points of care (primary care, specialized services, mental health, emergency care, and harm reduction), with consequences for continuity and coordination of care [17,18]. These gaps are exacerbated by stigma and perceived confidentiality barriers, which inhibit disclosure of use and hinder engagement [5,7,10]. In parallel, the intervention literature suggests that multicomponent strategies, such as structured screening, brief counseling, peer educators, digital technologies, and care navigation, are promising for reducing harms and improving outcomes [19].

Brazil has a normative framework capable of guiding integrated responses through the Unified Health System (SUS)/Health Care Network (HCN), established to overcome care fragmentation and organize thematic CPs (eg, HIV/AIDS, viral hepatitis, STIs, mental health, psychosocial care, and harm reduction), with primary health care serving as the coordinator of care [20]. Within this framework, the articulation between surveillance and care, including through regional surveillance groups and bodies, is designed to ensure timely access, longitudinality, comprehensiveness, and effective communication among network points [21]. Despite this, specific CPs for chemsex have not yet been consolidated, creating gaps in STI prevention, management of intoxications and related harms, and the provision of mental health support and psychosocial rehabilitation [19,20].

Thus, the development of a CP for chemsex adapted to the SUS/HCN is justified by (1) high prevalence among MSM and evidence of SSU in the general population; (2) local drug compositions that amplify clinical risks (stimulants, central nervous system depressants, and drug interactions) and psychosocial vulnerabilities; (3) gaps in screening, management, and linkage; and (4) the opportunity to integrate knowledge and practices (clinical care, harm reduction, mental health, testing, and combination STI prevention) into a clear care trajectory with process and outcome indicators [5,17]. Such a CP should include identification tools (screening questions and warning signs), person-centered care packages (including self-testing and linkage), protocols for toxicological emergencies (eg, GHB/GBL), psychosocial support and relapse prevention, and care navigation to reduce losses along the care continuum.

Accordingly, this study aims to develop and pilot-validate a CP for people who engage in chemsex within the SUS/HCN, informed by evidence and sensitive to stigma, articulating surveillance, primary care, specialized services, mental health, and harm-reduction strategies, with clearly defined process and outcome indicators. The research questions guiding this study are as follows: (1) What is the prevalence of chemsex, and what factors are associated with it, in priority municipalities (with an emphasis on MSM and comparisons with other groups)? (2) What gaps, barriers/facilitators, and training needs do managers and professionals identify across HCN care points regarding prevention, testing, toxicological emergency management, mental health, and linkage? (3) Which components and implementation strategies (screening, brief counseling, peer educators, digital tools, navigation) are feasible, acceptable, and scalable in the SUS?

To develop a CP for the health of individuals who engage in chemsex, based on the analysis of health needs and the experiences of users, managers, and professionals within the HCN.

The study uses a multimethod design with a sequential approach, structured into three main phases: (1) predevelopment, (2) Knowledge Creation, and (3) the Action Cycle, as proposed by the Knowledge-to-Action (KTA) framework [22]. This model, grounded in evidence-informed change theories from the fields of health, social sciences, education, and management, has been widely used to implement health interventions.

The study will be conducted in the state of São Paulo, focusing on both urban and regional contexts. Specifically, the research involves the general population within São Paulo, particularly individuals with an active sexual life, in order to estimate the prevalence of chemsex and identify associated factors. Additionally, the study targets health care professionals and managers working in public health services within the HCN. This includes key personnel from the epidemiological surveillance groups (ESG) across the state, who are responsible for monitoring epidemiological data and coordinating health interventions, including those related to STIs, HIV/AIDS, and other public health concerns. The diverse settings in São Paulo provide a comprehensive context for understanding chemsex practices and the corresponding health care responses at both individual and systemic levels.

The questionnaires, conducted both in person and online, will be hosted on the REDCap platform (project with HTTPS connection, audit trails, and access controls). The main survey is structured into five sections, with skip logic and input validations:

To ensure data integrity, REDCap will be configured to allow only one response per IP address and will include mandatory fields and logical checks to reduce missing data and inconsistencies. No direct personal identifiers will be collected; geographic variables will be aggregated to avoid reidentification.

Prior to fieldwork, the questionnaire underwent content and face validation conducted by 5 expert judges (topics: chemsex/SSU, STIs/HIV, harm reduction, mental health, and health service organization). Judges evaluated the relevance, clarity, and comprehensiveness of the items; their suggestions informed revisions to wording, ordering, and response options. Subsequently, a pretest was performed with 10 participants from the target audience to assess comprehension, flow, and completion time, following predefined criteria for adjustments (eg, >10% “don’t know”/missing responses on any item or recurrent comprehension problems).

For the general population survey, the primary outcome is the prevalence of chemsex in the past 12 months (yes/no). The sample size was calculated to estimate this proportion with a 95% confidence level and an absolute precision (margin of error) of 3 percentage points, adopting the conservative estimate P=.50, which maximizes sample size when true prevalence is unknown [23-25]. The standard formula for prevalence studies was applied:

where Z_0.95=1.96, P=0.50, d=0.03. Thus,

Considering the virtual recruitment method using snowball sampling and targeted campaigns, a design effect (deff) of 1.4 was adopted to accommodate potential intranetwork/region dependence, resulting in n ≈ 1068 × 1.4 ≈ 1495. To account for losses, ineligible cases, and incomplete questionnaires, an additional 10% was added, yielding n≈1645. Based on this justification and logistical constraints, a target sample of approximately 1600 participants was defined, a value that preserves the desired precision and enables stratified analyses by relevant subgroups for the protocol (eg, MSM vs others) and by macroregions [16].

The calculation was verified in G*Power (version 3.1.9.7; Heinrich Heine Universität Düsseldorf), using conservative scenarios (assumed prevalence of 50%, 95% CI, 3-percentage-point precision) and scenarios comparing proportions (MSM vs non-MSM). It is noteworthy that selecting P=.50 is a recommended practice when local prevalence is uncertain, as it maximizes sample size and safeguards the planned precision [24,25].

For the module involving managers and health care professionals within the HCN, sampling will be conducted by convenience, operationalized in partnership with the ESG of the state of São Paulo, with targets of ≥3 respondents per service (multiprofessional composition). Although this is not a probabilistic sample, the target of approximately 135 professionals from 5 key health care sectors (mental health, STI/HIV/AIDS, emergency care, primary care, and social assistance) will be included, with a focus on those working with the population who engage in chemsex, that allows descriptive estimates with reasonable precision. The sample for managers will be selected by convenience and will consist of 54 individuals, including 27 regional STI/HIV/AIDS coordinators and 27 additional managers from selected municipalities based on HIV incidence.

The study is structured according to the KTA framework, a comprehensive model designed to guide the translation of evidence into practice. Although the KTA cycle comprises two overarching and interlinked components (Knowledge Creation and the Action Cycle), this study operationalizes this framework into 3 sequential phases to better organize the development of the Chemsex Care Pathway within Brazil’s HCN. This framework has been widely applied in health, social sciences, and implementation research, drawing on theories of organizational change, knowledge translation, and evidence-based practice [22]. In this protocol, the model is explicitly adapted to support the development, implementation, and evaluation of a CP tailored to chemsex-related needs.

The predevelopment phase lays the groundwork for the study by identifying the problem, engaging stakeholders, and assessing contextual factors relevant to implementation. This preparatory stage ensures that the study is anchored to real-world demands and enables the effective progression of the subsequent phases. The Knowledge Creation phase encompasses primary knowledge investigation, evidence synthesis, and the generation of best-practice tools and products that will inform the CP. Finally, the Action Cycle phase focuses on implementing, monitoring, and sustaining the CP, ensuring that the knowledge generated is systematically contextualized and translated into practical applications within health care settings (Figure 1 [11]).

The predevelopment phase establishes the foundational conditions required for successful implementation. In this study, it begins with a comprehensive process of problem identification and contextual assessment, which includes the review of scientific literature, policy documents, and epidemiological indicators (such as STI rates, mental health outcomes, and emergency care use) alongside preliminary consultations with key stakeholders. This process allows the research team to identify system gaps, stigma-related barriers, service fragmentation, and contextual determinants that may influence the feasibility and effectiveness of the intervention.

In parallel, stakeholders (professionals and chemsex users) are systematically mapped and engaged, including municipal and state health authorities, ESG, primary care managers, psychosocial care teams, emergency services, nongovernmental organizations, and community representatives. Their early involvement supports the definition of shared expectations, roles, and resource requirements, thereby strengthening feasibility and fostering joint ownership of the CP.

During this phase, the study also completes ethical preparation and methodological alignment. All study materials (including surveys, interview guides, review protocols, and data collection instruments) are finalized and submitted for ethical approval. This stage ensures coherence between the study’s objectives, methodological approach, and governance structure, thereby establishing a solid basis for the subsequent phases of Knowledge Creation and the Action Cycle.

The Knowledge Creation phase is structured into 3 progressively refined generations of knowledge production, each designed to address specific methodological requirements of the KTA framework and to provide the level of detail necessary for replication and external evaluation. This phase follows the logic of funneling broad empirical inputs into increasingly targeted and actionable products that will inform the Chemsex Care Pathway.

The first generation (primary knowledge inquiry) consists of a set of methodologically distinct but interrelated cross-sectional investigations targeting 3 key populations: individuals who engage in chemsex, health care managers, and health professionals. For people who engage in chemsex, the survey instrument is designed to capture multiple analytical domains: (1) substance-use characterization, including granular details on substance types, administration routes, polysubstance combinations, temporal sequencing of consumption during sexual encounters, and adverse effects; (2) behavioral and contextual determinants, such as sexual partnering dynamics, motivations, environmental settings, social networks, and indicators of harm (eg, blackouts, nonintentional substance mixing, or emergency care use); (3) biopsychosocial profiling, including mental health indicators, health care use patterns, perceived barriers, and service needs; and (4) biological vulnerability markers, specifically incidence or self-reported history of HIV, STIs, viral hepatitis, syphilis, and mpox.

Surveys for managers and health professionals are structured to address three domains: (1) knowledge, including familiarity with chemsex-related substances, clinical risks, and care protocols; (2) attitudes toward people who engage in chemsex, with measurement of explicit and implicit stigma and discrimination; and (3) practices, including clinical management, referral patterns, institutional barriers, documentation procedures, and training needs. All instruments undergo content validation by experts, followed by cognitive interviews to ensure clarity and construct alignment. Data will be collected via REDCap using both online and in-person recruitment, and statistical analyses will include descriptive modeling, bivariate testing, and regression models to estimate prevalence ratios or odds ratios with 95% CIs.

The second generation (knowledge synthesis) consists of a comprehensive scoping review whose protocol has been published separately as “Healthcare Access Among Individuals Who Practice Chemsex in Brazil: A Scoping Review Protocol” [17]. In accordance with this protocol, the review follows the Joanna Briggs Institute methodology [26-28] and Arksey and O’Malley’s [29] foundational framework. The review question was formulated using the population-concept-context structure, and the search strategy was developed in collaboration with a health sciences librarian to ensure precision and reproducibility. Searches will be conducted in the electronic databases PubMed/MEDLINE, Embase, Scopus, SciELO, LILACS, and PsycINFO, as specified in the published protocol, using free-text terms related to chemsex, sexualized drug use, substance use, and health care access. All retrieved records will undergo dual independent screening at the title/abstract and full-text levels using Covidence, with disagreements resolved by a third reviewer. Data extraction will follow a structured form capturing study characteristics, population details, chemsex-related behaviors, health service use, barriers and facilitators to care, and reported outcomes. Evidence will be synthesized using a mixed methods approach, allowing the integration of quantitative and qualitative findings to comprehensively map existing knowledge. Reporting will follow the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist [30], ensuring transparency in search, screening, extraction, and synthesis procedures. As detailed in the published protocol [17], this methodological structure provides a rigorous and reproducible foundation for understanding health care access among populations who engage in chemsex in Brazil.

The third generation (triangulation and concept mapping) provides the analytical integration needed to translate empirically derived and synthesized evidence into a coherent framework for decision-making. Guided by methodological triangulation principles [31,32], data from the cross-sectional studies, qualitative strands, and the scoping review will be integrated to identify convergence, complementarity, and divergence across sources. A reflexive thematic analysis will be conducted following Braun and Clarke’s [33] established 6-phase framework, as well as their more recent methodological guidance emphasizing reflexivity, analytic transparency, and researcher positionality [34]. The analytic process will include familiarization with the dataset, systematic coding, theme construction, theme review, theme definition, and final reporting. Coding will be performed iteratively by multiple researchers, and regular peer-debriefing meetings will be held to compare coding decisions, refine codebooks, and ensure analytic coherence. Analytic memos and reflexive journals will be maintained throughout to document decision-making processes, positionality considerations, and interpretive influences. To enhance credibility, confirmability, dependability, and transferability, the analysis will incorporate triangulation across stakeholder groups, an audit trail documenting analytic decisions, maintenance of a coding consistency log, and the use of thick descriptions to contextualize findings within the operational realities of the HCN. Following thematic analysis, qualitative themes will be systematically integrated with quantitative findings to identify systemic weaknesses, care discontinuities, risk amplifiers, and context-specific barriers. This integration will support the development of a conceptual map using structured concept mapping approaches [35,36], which will visually articulate the relationships among care needs, service gaps, contextual barriers, and organizational levers for change. The resulting conceptual map will function as a transitional knowledge tool bridging the Knowledge Creation and Action Cycle phases, defining both the theoretical and operational foundations of the Chemsex Care Pathway and guiding the selection of implementation strategies [31,32,35,36].

The quantitative analysis will include descriptive statistics to characterize participants and estimate the prevalence of chemsex, as well as logistic regression to identify associated factors (prevalence ratio), 95% CI; P<.05). Analyses will be conducted using SPSS (IBM Corporation) or Stata (Stata Corp) software.

Qualitative data from interviews and focus groups will be subjected to thematic analysis [31], supported by NVivo software (Lumivero). Triangulation will integrate quantitative and qualitative findings, along with results from the scoping review, to inform the development of the CP and educational materials.

During the implementation phase, process and outcome indicators will be monitored using official systems (SINAN, Mortality Information System, SIH/SUS) to evaluate the impact of the CP in pilot municipalities.

The study complies with resolution numbers 466/2012 and 510/2016 of the Brazilian National Health Council. Aligned with the Declaration of Helsinki, it was approved by the research ethics committee of the Ribeirão Preto College of Nursing from the University of São Paulo (85545824.2.0000.5393) and CRT-DST/AIDS-SP (85545824.2.3002.5375) in April 2025 and is set to begin in June 2025. All participants will be informed of the study’s objectives and will sign the ICF.

Participants will sign the ICF, and data will be accessible only to the authorized research team, to be used exclusively for the purposes outlined in the study protocol. All information will be stored securely, with restricted access, and participants’ anonymity will be guaranteed throughout all phases of the research.