Overamped: Stimulant Use and HIV Pathogenesis.

PURPOSE OF REVIEW: In the era of HIV treatment as prevention (TasP), more clarity is needed regarding whether people with HIV who use stimulants (i.e., methamphetamine, powder cocaine, and crack cocaine) display elevated HIV viral load and greater immune dysregulation. RECENT FINDINGS: Although rates of viral suppression have improved in the TasP era, stimulant use was independently associated with elevated viral load in 23 of 28 studies included in our review. In the 12 studies examining other HIV disease markers, there was preliminary evidence for stimulant-associated alterations in gut-immune dysfunction and cellular immunity despite effective HIV treatment. Studies generally focused on documenting the direct associations of stimulant use with biomarkers of HIV pathogenesis without placing these in the context of social determinants of health. Stimulant use is a key barrier to optimizing the effectiveness of TasP. Elucidating the microbiome-gut-brain axis pathways whereby stimulants alter neuroimmune functioning could identify viable targets for pharmacotherapies for stimulant use disorders. Examining interpersonal, neighborhood, and structural determinants that could modify the associations of stimulant use with biomarkers of HIV pathogenesis is critical to guiding the development of comprehensive, multi-level interventions.

Motivational Enhancement Interventions to Increase Pre-Exposure Prophylaxis Use in Sexual Minority Men Who Use Stimulants: Protocol for a Pilot Sequential Multiple Assignment Randomized Trial.

BACKGROUND: Although pre-exposure prophylaxis (PrEP) could substantially mitigate HIV risk, sexual minority men who use stimulants commonly experience difficulties with engaging in PrEP clinical services. Motivational interviewing (MI) and contingency management (CM) reduce substance use and condomless anal sex (CAS) in this population, but these motivational enhancement interventions require modifications to promote engagement along the PrEP care continuum. OBJECTIVE: PrEP Readiness Interventions for Supporting Motivation (PRISM) is a pilot sequential multiple assignment randomized trial testing the feasibility, acceptability, and preliminary effectiveness of distinct combinations of telehealth MI and CM in 70 cisgender sexual minority men who use stimulants that are not currently taking PrEP. METHODS: A national sample was recruited via social networking applications to complete a baseline assessment and mail-in HIV testing. Those with nonreactive HIV results were randomized to receive either (1) a 2-session MI intervention focusing on PrEP use (session 1) and concomitant stimulant use or CAS (session 2) or (2) a CM intervention with financial incentives for documented evidence of PrEP clinical evaluation by a medical provider (US $50) and filling a PrEP prescription (US $50). At the 3-month follow-up assessment, participants who reported they had not filled a prescription for PrEP were randomized a second time to either (1) switch to a second-stage intervention (ie, MI+CM or CM+MI) or (2) continue with assessments only. Outcomes for both responders and nonresponders were reassessed at a 6-month follow-up. The primary outcome is documented evidence of filling a PrEP prescription over 6 months. Self-reported secondary outcomes include PrEP clinical evaluation by a medical provider, stimulant use, and CAS. Qualitative exit interviews were conducted with a subgroup of responders and nonresponders to characterize their experiences with the MI and CM interventions. RESULTS: Implementation of PRISM underscores challenges in reaching sexual minority men who use stimulants to optimize HIV prevention efforts. Approximately 1 in 10 (104/1060) eligible participants have enrolled. Of the 104 who enrolled, 87 (84%) completed mail-in HIV testing. We delivered 5 preliminary HIV-positive results, including posttest counseling with referrals to confirmatory testing. CONCLUSIONS: Lessons learned from PRISM underscore the central importance of a flexible, participant-centered approach to support the engagement of sexual minority men who use stimulants. Leveraging telehealth platforms to deliver motivational enhancement interventions also expanded their reach and potential public health impact with this high-priority population. Further research is needed to determine the effectiveness of telehealth MI and CM for supporting PrEP use in sexual minority men who use stimulants. TRIAL REGISTRATION: ClinicalTrials.gov NCT04205487; https://clinicaltrials.gov/study/NCT04205487. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48459.

Stimulant use, HIV, and immune dysregulation among sexual minority men.

BACKGROUND: Sexual minority men (SMM) report high rates of stimulant use (e.g., crystal methamphetamine, cocaine) and HIV infection. Stimulant use contributes to immune dysfunction, which enhances risk for HIV acquisition and pathogenesis. Research is needed to examine the independent and interactive relationships of stimulant use and HIV infection with systemic immune dysregulation among SMM, especially during the COVID-19 pandemic. METHODS: From 2020-2022, 75 SMM in Miami, Florida with and without HIV completed an online survey and provided biospecimens to assess HIV status and viral load (VL), recent stimulant use, and soluble markers of immune activation and inflammation in plasma, including soluble CD14 (sCD14) and elevated high-sensitivity C-reactive protein (hs-CRP > 1.0mg/L). Sociodemographics and prior SARS-CoV-2 infection were compared across HIV status/stimulant use groups. Moderation models examined the independent and interactive associations of stimulant use and HIV status with sCD14 and elevated hs-CRP. RESULTS: Thirty participants were persons living with HIV (PWH) (50% with stimulant use), and 45 were HIV-negative (44% with stimulant use). SARS-CoV-2 infection was not associated with stimulant use/HIV groups or immune outcomes. HIV-negative SMM without stimulant use had lower sCD14 compared to other SMM, as well as lower odds of elevated hs-CRP compared to PWH who used stimulants. Stimulant use showed independent associations with immune dysregulation that persisted after controlling for HIV status and VL, whereas HIV status was only independently associated with elevated hs-CRP in one model not controlling for VL. CONCLUSIONS: Among SMM, stimulant use was independently associated with elevated immune activation and inflammation.

Randomized Controlled Trial of Motivational Enhancement Interventions to Increase Pre-Exposure Prophylaxis Use in Sexual Minority Men Who Use Stimulants.

Background: Although pre-exposure prophylaxis (PrEP) could substantially mitigate HIV risk, sexual minority men (SMM) who use stimulants commonly experience difficulties with engaging in PrEP clinical services. Motivational interviewing (MI) and contingency management (CM) reduce substance use and condomless anal sex in this population, but these motivational enhancement interventions require adaptation to promote engagement along the PrEP care continuum. Methods: PRISM is a pilot sequential multiple assignment randomized trial (SMART) testing the feasibility, acceptability, and preliminary effectiveness of distinct combinations of telehealth MI and CM in 70 cisgender SMM who use stimulants that are not currently taking PrEP. A national sample was recruited via social networking applications to complete a baseline assessment and mail-in HIV testing. Those with non-reactive HIV results are randomized to receive either: 1) a 2-session MI intervention focusing on PrEP use (session 1) and concomitant stimulant use or condomless anal sex (session 2); or 2) a CM intervention with financial incentives for documented evidence of PrEP clinical evaluation by a medical provider ($50) and filling a PrEP prescription ($50). At the 3-month follow-up assessment, participants who report they have not filled a prescription for PrEP are randomized a second time to either: 1) Switch to a second-stage intervention (i.e., MI + CM or CM + MI); or 2) Continue with assessments only. Outcomes for both responders and non-responders are reassessed at a 6-month follow-up. The primary outcome is documented evidence of filling a PrEP prescription. Self-reported, secondary outcomes include PrEP clinical evaluation by a medical provider, stimulant use, and condomless anal sex. Qualitative exit interviews are conducted with a sub-group of responders and non-responders to characterize their experiences with the MI and CM interventions. Discussion: Implementation of this pilot SMART underscores the challenges in reaching SMM who use stimulants to optimize HIV prevention efforts such that approximately one in ten (104/1,060) eligible participants enrolled. However, 85% (70/82) of enrolled participants with non-reactive HIV results were randomized. Further research is needed to determine the effectiveness of telehealth MI and CM for supporting PrEP use in SMM who use stimulants. Trial Registration: This protocol was registered on clinicaltrials.gov (NCT04205487) on December 19, 2019.

"The familiar taste of poison": a qualitative study of multi-level motivations for stimulant use in sexual minority men living in South Florida.

BACKGROUND: In the US, stimulant use is associated with a 3-6 times greater rate of HIV seroconversion in sexual minority men (SMM) than in those who do not use stimulants. Annually, 1 in 3 SMM who HIV seroconvert will be persistent methamphetamine (meth) users. The primary objective of this qualitative study was to explore experiences of stimulant use in SMM living in South Florida, a high priority region for the Ending the HIV Epidemic initiative. METHODS: The sample included 25 SMM who use stimulants, recruited via targeted ads on social networking apps. Participants completed one-on-one semi-structured qualitative interviews, conducted from July 2019 through February 2020. A general inductive approach was used to identify themes relating to experiences, motivations, and overall relationship with stimulant use. RESULTS: Mean age of participants was 38.8, ranging from 20 to 61 years old. Participants were 44% White, 36% Latino, 16% Black and 4% Asian. Most participants were born in the US, self-identified as gay, and preferred meth as their stimulant of choice. Themes included: (1) stimulants as cognitive enhancements for focus or task completion, including transitioning to meth after first using prescription psychostimulants; (2) unique South Florida environment where participants could be open regarding their sexual minority status while also being influential on their stimulant use; (3) stimulant use as both stigmatizing and a coping mechanism for stigma. Participants anticipated stigma by family and potential sexual partners due to their stimulant use. They also reported using stimulants to cope with feelings of stigma due to their minoritized identities. CONCLUSION: This study is among the first to characterize motivations for stimulant use in SMM living in South Florida. Results highlight both the risk and protective factors of the South Florida environment, psychostimulant misuse as a risk for meth initiation, and the role of anticipated stigma on stimulant use in SMM. Understanding stimulant use motivations can help to shape intervention development. This includes developing interventions that address individual, interpersonal, and cultural factors that drive stimulant use and increase risk of HIV acquisition. Trial registration NCT04205487.

MyTPill: study protocol for a cross-over randomised controlled trial comparing novel strategies to monitor antiretroviral adherence among HIV+ prescription opioid users.

INTRODUCTION: Adherence to HIV antiretroviral therapy (ART) remains the cornerstone of HIV treatment. For individuals with suboptimal adherence, electronic adherence monitoring (EAM) technologies have become an important component of multimodal adherence support strategies. Most EAM technologies detect pillbox opening, and therefore, assume but cannot verify actual ingestion of oral medication. In contrast, a digital pill system (ID-capsule manufactured by etectRX, here named My/Treatment/Pill) measures directly ingestion of medications. Identifying the superior method to measure ART adherence would improve virological suppression by enabling the delivery of real-time interventions to support ART adherence, particularly in high-risk populations. METHODS AND ANALYSIS: Cross-over, randomised trial with 1:1 variable block size randomisation comparing two EAM systems in prescription opioid-using HIV+patient on once daily oral bictegravir, emtricitabine and tenofovir alafenamide regimens and detectable viral load >200 copies/mL within 30 days of screening (n=80). The primary outcome is once daily ART adherence measurement efficacy as assessed by comparing the accuracy of each EAM system as measured by concordance of the respective EAM systems to dried blood spot ART concentrations. Secondary outcomes are the identification of multilevel factors that are prevalent in the target population most closely linked to ART non-adherence and EAM non-adherence. ETHICS AND DISSEMINATION: This protocol was approved by the institutional review boards of participating sites (The Ohio State University, The Fenway Institute and the University of Miami). Data will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03978793.

Running with Scissors: a Systematic Review of Substance Use and the Pre-exposure Prophylaxis Care Continuum Among Sexual Minority Men.

PURPOSE OF REVIEW: Patterns of sexualized drug use, including stimulants (e.g., methamphetamine) and chemsex drugs, are key drivers of HIV incidence among sexual minority men (SMM). Although pre-exposure prophylaxis (PrEP) mitigates HIV risk, there is no consensus regarding the associations of substance use with the PrEP care continuum. RECENT FINDINGS: SMM who use substances are as likely or more likely to use PrEP. Although SMM who use stimulants experience greater difficulties with daily oral PrEP adherence, some evidence shows that SMM who use stimulants or chemsex drugs may achieve better adherence in the context of recent condomless anal sex. Finally, SMM who use substances may experience greater difficulties with PrEP persistence (including retention in PrEP care). SMM who use stimulants and other substances would benefit from more comprehensive efforts to support PrEP re-uptake, adherence, and persistence, including delivering behavioral interventions, considering event-based dosing, and providing injectable PrEP.