Challenges and Opportunities with at-Home Blood Collection for HIV-1 Viral Load Monitoring among Sexual Minoritized Men who use Stimulants.

Sexually minoritized men (SMM) with HIV who use stimulants experience difficulties achieving and maintaining an undetectable viral load (VL). Home-based VL monitoring could augment HIV care by supporting interim, early identification of detectable VL. We describe implementation challenges associated with a home-collection device for laboratory-based VL testing among SMM with HIV who use stimulants. From March-May 2022, cisgender SMM with HIV reporting moderate-to-severe stimulant use disorder and suboptimal (< 90%) past-month antiretroviral therapy (ART) adherence were recruited via a consent-to-contact participant registry. Eligible men completed teleconference-based informed consent and were mailed a HemaSpot-HD blood collection device (volume capacity 160 µL; lower limit of detection 839 copies/mL) with detailed instructions for home blood self-collection and return shipment. Implementation process measures included estimated blood volume and VL quantification. Among 24 participants, 21 (88%) returned specimens with a median duration of 23 days (range: 10-71 days) between sending devices to participants and receiving specimens. Of these, 13/21 (62%) included enough blood (≥ 40 µL) for confidence in detectable/undetectable results; 10/13 (77%) had detectable VL, with 4/10 (40%) were quantifiable at ≥ 839 copies/mL. The remaining 8/21 had low blood volume (< 40 µL), but 3/8 (38%) still had detectable VL, with 1/3 (33%) quantifiable at ≥ 839 copies/mL. Home blood collection of ≥ 40 µL using HemaSpot-HD was feasible among this high-priority population, with > 50% having a VL detected. However, interim VL monitoring using HemaSpot-HD among those experiencing difficulties with ART adherence may be strengthened by building rapport via teleconferencing and providing detailed instructions to achieve adequate sample volume.

Supporting treatment adherence for resilience and thriving (START): protocol for a mHealth randomized controlled trial.

BACKGROUND: Although behavioral interventions show some promise for reducing stimulant use and achieving durable viral suppression in sexual minority men (SMM) with HIV, scalable mHealth applications are needed to optimize their reach and cost-effectiveness. METHODS: Supporting Treatment Adherence for Resilience and Thriving (START) is a randomized controlled trial (RCT) testing the efficacy and cost-effectiveness of a mHealth application that integrates evidence-based positive affect regulation skills with self-monitoring of adherence and mood. The primary outcome is detectable HIV viral load (i.e., > 300 copies/mL) from self-collected dried blood spot (DBS) specimens at 6 months. Secondary outcomes include detectable DBS viral load at 12 months, self-reported stimulant use severity, anti-retroviral therapy (ART) adherence, and positive affect over 12 months. A national sample of up to 250 SMM with HIV who screen positive for stimulant use disorder and reporting suboptimal ART adherence is being recruited via social networking applications through April of 2024. After providing informed consent, participants complete a run-in period (i.e., waiting period) including two baseline assessments with self-report measures and a self-collected DBS sample. Those who complete the run-in period are randomized to either the START mHealth application or access to a website with referrals to HIV care and substance use disorder treatment resources. Participants provide DBS samples at baseline, 6, and 12 months to measure HIV viral load as well as complete self-report measures for secondary outcomes at quarterly follow-up assessments over 12 months. DISCUSSION: To date, we have paid $117,500 to advertise START on social networking applications and reached 1,970 eligible participants ($59.77 per eligible participant). Although we identified this large national sample of potentially eligible SMM with HIV who screen positive for a stimulant use disorder and report suboptimal ART adherence, only one-in-four have enrolled in the RCT. The run-in period has proven to be crucial for maintaining scientific rigor and reproducibility of this RCT, such that only half of consented participants complete the required study enrollment activities and attended a randomization visit. Taken together, findings will guide adequate resource allocation to achieve randomization targets in future mHealth research SMM with HIV who use stimulants. TRIAL REGISTRATION: This protocol was registered on clinicaltrials.gov (NCT05140876) on December 2, 2021.

"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.

Profibrotic IHG-1 complexes with renal disease associated HSPA5 and TRAP1 in mitochondria.

The highly conserved mitochondrial protein induced in high glucose-1 (IHG-1) functions to maintain mitochondrial quality and is associated with the development of fibrosis in diabetic nephropathy. Towards identifying novel approaches to treating diabetic kidney disease, IHG-1-protein-protein interactions were investigated using epitope-tagged immunoprecipitation analyses followed by mass spectrometry. Here we show that IHG-1 is solely expressed in mitochondria and localised to the inner mitochondrial membrane, the region where mitochondrial reactive oxygen species are generated. Chaperones HSPA5 and TRAP1 and cold shock protein YBX1 were identified as IHG-1 binding partners. All three proteins are important in the cellular response to oxidative stress and play important roles in mitochondrial transcription and DNA repair. Both redox imbalance and IHG-1 stimulate TGF-ß signalling. IHG-1, HSPA5 and YBX1 all show increased expression in diabetic nephropathy, chronic kidney disease and in the Unilateral Ureteral Obstruction model of kidney fibrosis. Increased IHG-1 expression in UUO correlated with loss of TRAP1 expression. IHG-1 may target TRAP1 for degradation. When IHG-1 is no longer localised to mitochondria, it retains the ability to interact with the cold shock protein YBX1, facilitating anti-fibrotic actions in the nucleus. Targeting these proteins may offer alternative treatments for fibrotic kidney disease.

BMP7-induced-Pten inhibits Akt and prevents renal fibrosis.

Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFß1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFß1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300µg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling. In the kidney, collecting duct and tubular epithelial cells respond to BMP-7 via activation of SMAD1/5/8. Phosphorylation of SMAD1/5/8 was reduced in UUO kidneys from vehicle-treated animals yet maintained in UUO kidneys from BMP-7-treated animals, confirming renal bioactivity of exogenous rhBMP-7. BMP-7 inhibited Collagen Iα1 and Collagen IIIα1 gene expression and Collagen I protein accumulation, while increasing expression of Collagen IVα1 in UUO kidneys. Activation of SMAD2, SMAD3, ERK, p38 and PI3K/Akt signaling occurred during fibrogenesis and BMP-7 significantly attenuated SMAD3 and Akt signaling in vivo. Analysis of renal collecting duct (mIMCD) and tubular epithelial (HK-2) cells stimulated with TGFß1 or hypoxia (1% oxygen) to activate Akt provided further evidence that BMP-7 specifically inhibited PI3K/Akt signaling. PTEN is a negative regulator of PI3K and BMP-7 increased PTEN expression in vivo and in vitro. These data demonstrate an important mechanism by which BMP-7 orchestrates renal protection through Akt inhibition and highlights Akt inhibitors as anti-fibrotic therapeutics.

Missed Opportunity or Cause for Concern? Methamphetamine Use Is Associated With Greater Interest in Event-Driven PrEP Among Sexual Minority Men.

Our study assessed the association between methamphetamine (i.e., crystal meth, CM) use and awareness and interest in event-driven (ED) PrEP among HIV-negative and those with unknown serostatus cisgender males and transgender people. We performed log-binomial regression analysis to predict awareness (i.e., having heard of ED PrEP) and being interested in ED PrEP. We found that participants who recently used CM were less likely to know of ED PrEP (aPR = 0.83, 95% CI [0.69, 0.99]) but more interested in ED PrEP (aPR = 1.12, 95% CI [1.01, 1.30]), after accounting for demographic and HIV-related behaviors. Opportunities to expand PrEP uptake and improve adherence among individuals who report CM use are essential to impact the HIV epidemic significantly. Continued research on the needs and best practices to work with this community is needed to ensure a successful rollout and implementation of ED PrEP.

I was like sh*t this is gonna hurt': Implementing Self-Sampling of Dried Blood Spots to Measure HIV Viral Load.

Background: Sexual minority men (SMM) with HIV who use stimulants may experience greater difficulties with antiretroviral therapy adherence which amplifies risk for unsuppressed HIV viral load (VL). Remote monitoring of VL could support efforts to rapidly respond to sub-optimal adherence. Methods: This qualitative study enrolled 24 SMM with HIV who use stimulants to examine experiences with two different dried blood spots (DBS) self-sampling devices (i.e., Tasso-M20 vs. HemaSpot HD) to measure VL. Participants were asked to complete self-sampling of DBS using both devices, and then participated in a 45-minute semi-structured interview. Interviews focused on ease of use, device preference, experiences with receiving and mailing kits, and barriers to participating in research. A thematic analysis was conducted to analyze interviews transcripts. Results: Twenty-two participants (92%) returned the Tasso-M20 and 21 (88%) returned the Hemaspot HD devices. Among the 22 participants that completed qualitative interviews, twenty-three codes were identified and collapsed within seven themes. Preferences for devices were based on convenience, pain and prior experiences with finger-pricking technology. Participants emphasized that clearer instructions with contingency plans for self-sampling of DBS would improve the user experience with self-sampling of DBS. Intersectional stigma (e.g., HIV, sexual minority status, and substance use) was noted as an important consideration in implementing self-sampling of DBS. Promoting decision making, or the option to choose sampling method based on personal preferences, may improve engagement and likelihood of DBS completion. Conclusions: Findings will guide the broader implementation of self-sampling of DBS to optimize VL monitoring in SMM with HIV who use stimulants.

Point-of-care urine tenofovir test predicts future HIV preexposure prophylaxis discontinuation among young users.

BACKGROUND: Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower preexposure prophylaxis (PrEP) adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS). METHODS: YMSM/TGW participants ( n  = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/ml) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days. RESULTS: Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (<4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation [adjusted odds ratio (AOR) 6.1; 95% confidence interval (CI): 1.4-11; P  = 0.005] and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value. CONCLUSIONS: In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability.

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.

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.

Tina's ParTy line: Polysubstance use patterns in sexual minority men living with HIV who use methamphetamine.

INTRODUCTION: This cross-sectional study examined the associations of demographic, structural and psychological factors with distinct typologies of polysubstance use in sexual minority men (SMM) living with HIV who use methamphetamine. METHODS: In total, 161 SMM living with HIV who reported methamphetamine use in the past 3 months were recruited in San Francisco from 2013 to 2017 for a randomised controlled trial. A latent class analysis was conducted by leveraging baseline measures of self-reported use of 15 substances in the past 3 months as well as validated screening measures of hazardous alcohol and cannabis use. Correlates of latent class membership were examined using a three-step categorical latent variable logistic regression. RESULTS: Four typologies of substance use were identified: (i) methamphetamine use only (43%); (ii) methamphetamine and crack-cocaine use (22%); (iii) party and play use-methamphetamine, gamma-hydroxybutyrate and amyl nitrites (i.e. poppers) with erectile dysfunction drugs (31%); and (iv) high polysubstance use (4%). SMM of colour and those with a history of incarceration were more commonly classified as engaging in methamphetamine and crack-cocaine use compared to party and play use. Men with higher sexual compulsivity scores were more commonly classified as engaging in party and play use and polysubstance use. DISCUSSION AND CONCLUSIONS: There is substantial heterogeneity in polysubstance use patterns among SMM living with HIV who use methamphetamine. This will inform the development of tailored substance use interventions addressing the unique needs of SMM of colour and targeting sexual compulsivity as a prominent comorbidity for some men.

Barriers and Facilitators to Pre-exposure Prophylaxis Uptake Among Black Women: A Qualitative Analysis Guided by a Socioecological Model.

ABSTRACT: Black women experience disparities in HIV incidence. Pre-exposure prophylaxis (PrEP) is a once-daily pill that can prevent HIV transmission. To enhance PrEP uptake among Black women, it is essential to examine their perceptions of PrEP. In 2018, 33 Black women in New York City completed interviews about their attitudes, knowledge, and perceived barriers and facilitators to PrEP use. Emergent themes were organized using a socioecological model. Participants identified barriers at the sociocultural level, including stigma, medical mistrust, and health care avoidance. At the community level, health care access issues and limited community knowledge were reported. Partner-level barriers included trust in partners and meaning attributed to PrEP use within the context of monogamy. Individual-level barriers included low perceived risk and concerns about PrEP's safety and efficacy. Our findings can inform future PrEP research with Black women, as well as PrEP implementation efforts aimed at increasing uptake among this population.