Structural Determinants of Health and Markers of Immune Activation and Systemic Inflammation in Sexual Minority Men With and Without HIV.

Among sexual minority men (SMM), HIV and use of stimulants such as methamphetamine are linked with immune activation and systemic inflammation. Throughout the COVID-19 pandemic, SMM encountered financial challenges and structural obstacles that might have uniquely contributed to immune dysregulation and systemic inflammation, beyond the impacts of HIV and stimulant use. Between August 2020 and February 2022, 72 SMM with and without HIV residing in South Florida enrolled in a COVID-19 prospective cohort study. Multiple linear regression analyses examined unemployment, homelessness, and history of arrest as structural correlates of soluble markers of immune activation (i.e., sCD14 and sCD163) and inflammation (i.e., sTNF-α receptors I and II) at baseline after adjusting for HIV status, stimulant use, and recent SARS-CoV-2 infection. Enrolled participants were predominantly Latino (59%), gay-identified (85%), and with a mean age of 38 (SD, 12) years with approximately one-third (38%) of participants living with HIV. After adjusting for HIV status, SARS-CoV-2 infection, and recent stimulant use, unemployment independently predicted higher levels of sCD163 (ß = 0.24, p = 0.04) and sTNF-α receptor I (ß = 0.26, p = 0.02). Homelessness (ß = 0.25, p = 0.02) and history of arrest (ß = 0.24, p = 0.04) independently predicted higher levels of sCD14 after adjusting for HIV status, SARS-CoV-2 infection, and recent stimulant use. Independent associations exist between structural barriers and immune activation and systemic inflammation in SMM with and without HIV. Future longitudinal research should further elucidate complex bio-behavioral mechanisms linking structural factors with immune activation and inflammation.

Patient Attitudes Toward Self- or Partner-, Friend-, or Family-Administered Long-acting Injectable Antiretroviral Therapy: A Mixed-Methods Study Across 3 Urban Human Immunodeficiency Virus Clinics.

Background: Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) offers a novel drug delivery option for persons with human immunodeficiency virus (PWH) but requires administration every 4 or 8 weeks by a medical professional. Methods: To facilitate LAI antiretroviral therapy (ART) scale-up, we evaluated patient interest in alternative administration approaches via a mixed-methods, serial cross-sectional study across 3 US HIV clinics. We surveyed PWH (December 2021 to May 2022) on appeal of self- or partner/friend/family-administered LAI-CAB/RPV; multivariable ordinal logistic regression explored associated characteristics. To contextualize survey results, we thematically analyzed semi-structured interview data collected from PWH (August 2020 to July 2021) on attitudes toward out-of-clinic LAI-ART administration. Results: Among 370 surveyed PWH (median age, 46 years; 26% cisgender female, 59% Black, 56% sexual minority, 34% housing instability), self-administering LAI-CAB/RPV appealed to 67%. PWH who were White (adjusted odds ratio [aOR], 3.30 [95% confidence interval {CI}, 1.42-7.64]), stably housed (aOR, 2.16 [95% CI, 1.30-3.59]), or gay/bisexual (aOR, 1.81 [1.14-2.89]) were more likely to endorse self-administration. Fewer PWH (60%) reported partner/friend/family administration as appealing; adjusted models revealed similar sociodemographic preferences for this outcome. In 72 interviews, PWH noted that acceptability of out-of-clinic LAI-ART administration was qualified by convenience, prior injection experience, and potential fear of self-inflicted pain, dependence on others, and/or HIV disclosure. Conclusions: In a multisite sample of PWH, self- and, to a lesser extent, partner/friend/family-administration of LAI-CAB/RPV appealed to most; however, was less appealing among populations more impacted by health disparities. Innovative LAI-ART delivery options could free up in-clinic resources to focus scale-up among marginalized populations.

A positive affect intervention alters leukocyte DNA methylation in sexual minority men with HIV who use methamphetamine.

OBJECTIVE: This epigenomics sub-study embedded within a randomized controlled trial examined whether an evidenced-based behavioral intervention model that decreased stimulant use altered leukocyte DNA methylation (DNAm). METHODS: Sexual minority men with HIV who use methamphetamine were randomized to a five-session positive affect intervention (n = 32) or an attention-control condition (n = 21), both delivered during three months of contingency management for stimulant abstinence. All participants exhibited sustained HIV virologic control - an HIV viral load less than 40 copies/mL at baseline and six months post-randomization. The Illumina EPIC BeadChip measured leukocyte methylation of cytosine-phosphate-guanosine (CpG) sites mapping onto five a priori candidate genes of interest (i.e., ADRB2, BDNF, FKBP5, NR3C1, OXTR). Functional DNAm pathways and soluble markers of immune dysfunction were secondary outcomes. RESULTS: Compared to the attention-control condition, the positive affect intervention significantly decreased methylation of CpG sites on genes that regulate ß2 adrenergic and oxytocin receptors. There was an inconsistent pattern for the direction of the intervention effects on methylation of CpG sites on genes for glucocorticoid receptors and brain-derived neurotrophic factor. Pathway analyses adjusting for the false discovery rate (padj < 0.05) revealed significant intervention-related alterations in DNAm of Reactome pathways corresponding to neural function as well as dopamine, glutamate, and serotonin release. Positive affect intervention effects on DNAm were accompanied by significant reductions in the self-reported frequency of stimulant use. CONCLUSIONS: There is an epigenetic signature of an evidence-based behavioral intervention model that reduced stimulant use, which will guide the identification of biomarkers for treatment responses.

Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era.

BACKGROUND: Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV. METHOD: Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk. RESULTS: Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample (n = 56). SMM with methamphetamine use (t(101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder (t(101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine. CONCLUSION: We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.

Facilitating the recovery of insect communities in restored streams by increasing oviposition habitat.

Recruitment limitation is known to influence species abundances and distributions. Recognition of how and why it occurs both in natural and in designed environments could improve restoration. Aquatic insects, for instance, rarely reestablish in restored streams to levels comparable to reference streams even years after restoration. We experimentally increased oviposition habitat in five out of 10 restored streams in western North Carolina to test whether insect egg-laying habitat was limiting insect populations in restored streams. A main goal was to test whether adding oviposition habitat in the form of rocks that partially protrude above the water surface could be used to increase the abundance and richness of stream insect eggs and larval insects in restored streams. Adding egg-laying habitat enhanced several response variables (e.g., protruding rocks, number of eggs, egg masses, egg morphotype richness, and oviposition habitat stability) to levels similar to those found in reference streams. Following the addition of protruding rocks, egg mass abundance increased by 186% and richness by 77% in restored-treated streams. Densities of larval insects that attached their eggs to protruding rocks showed an overall pattern consistent with treatment effects due to the combination of nonsignificant and significant increases of several taxa and not just one taxon. Our results indicate that these stream insect populations are limited by oviposition habitat and that adding egg-laying habitat alleviated this component of recruitment limitation. However, the weaker larval response indicates that additional post-recruitment factors, such as egg or larval mortality, may still be limiting a full recovery of larval insect abundances in these restored streams. This study shows the importance of integrating information from animal life histories, ecology, and geomorphology into restoration practices to improve the recovery of aquatic insects, which are commonly used to assess water quality and the biological efficacy of stream restoration.

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.

Housing Instability Associated with Return to Stimulant Use among Previously Abstaining Women.

Stimulant use among unstably housed individuals is associated with increased risks of psychiatric co-morbidity, violence, HIV transmission, and overdose. Due to a lack of highly effective treatments, evidence-based policies targeting the prevention of stimulant use disorder are of critical importance. However, little empirical evidence exists on risks associated with initiating or returning to stimulant use among at-risk populations. In a longitudinal cohort of unstably housed women in San Francisco (2016-2019), self-reported data on stimulant use, housing status, and mental health were collected monthly for up to 6 months, and factors associated with initiating stimulants after a period of non-use were identified through logistic regression. Among 245 participants, 42 (17.1%) started using cocaine and 46 (18.8%) started using methamphetamine. In analyses adjusting for demographics and socio-structural exposures over the preceding month, experiencing street homelessness was associated with initiating cocaine use (AOR: 2.10; 95% CI: 1.04, 4.25) and sheltered homelessness with initiating methamphetamine use (AOR: 2.57; 95% CI: 1.37, 4.79). Other factors-including race, income, unmet subsistence needs, mental health, and treatment adherence-did not reach levels of significance, suggesting the paramount importance of policies directed toward improving access to permanent supportive housing to prevent stimulant use among unstably housed women.

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.

Demonstration Project of Long-Acting Antiretroviral Therapy in a Diverse Population of People With HIV.

BACKGROUND: Intramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables. OBJECTIVE: To examine LA-ART in a population of PWH that includes those with viremia. DESIGN: Observational cohort study. SETTING: Urban academic safety-net HIV clinic. PATIENTS: Publicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use. INTERVENTION: Demonstration project of long-acting injectable CAB-RPV. MEASUREMENTS: Descriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data. RESULTS: Between June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks. LIMITATION: Single-site study. CONCLUSION: This project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed. PRIMARY FUNDING SOURCE: National Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.

A mixed-methods study of relationship stigma and well-being among sexual and gender minority couples.

Research has documented associations between relationship stigma, relationship quality and adverse health outcomes among sexual and gender minority couples. However, this work focused primarily on one aspect of an individual's or a couple's identity rather than understanding the intersections of multiple, stigmatized social identities. As part of a larger project focused on testing the efficacy of a couples-based intervention to improve HIV medication adherence, 144 couples completed measures of relationship stigma, relationship quality, mental health, and substance use. A subset of 25 participants completed in-depth interviews to better understand the phenomenon of relationship stigma and its impact on their relationships. Quantitative results demonstrated that greater relationship stigma was associated with reduced relationship satisfaction and commitment, as well as greater closeness discrepancy and depressive symptoms. Qualitative findings provided nuanced insights into forms of relationship stigma that often intersected with other types of stigma and related forces of social and structural violence. Results also demonstrated the differential impact that relationship stigma had on couples and the ways in which individuals make adjustments to cope with or actively combat societal stigma. Findings illustrate the importance of attending to intersecting forms of stigma in addressing the well-being of sexual and gender minority couples.

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 Brief Human Immunodeficiency Virus (HIV) Index: A Rapid 3-Item Scale to Measure Engagement in HIV Care.

We created a brief version of The Index, a validated patient-reported measure that has potential to quickly identify patients at risk for poor retention. We analyzed Index scores from 2406 patients from 2016 to 2017 in a national cohort of patients in human immunodeficiency virus (HIV) care. Index scores predicted poor retention 12 months after administered.

Socio-ecological Barriers to Viral Suppression Among Transgender Women Living with HIV in San Francisco and Los Angeles, California.

Troubling disparities in viral suppression persist among transgender (trans) women living with HIV in the US. We utilized baseline data from a randomized controlled trial of a behavioral intervention among trans women living with HIV in San Francisco and Los Angeles, to identify the socio-ecological correlates of biologically confirmed viral suppression (< 200 HIV-1 RNA copies/mL). Among 253 participants, the mean age was 43 (SD = 11), 46% identified as Black or African American and 35% were virally non-suppressed. In adjusted Poisson regression models, the following barriers to viral suppression were identified: injection drug use [adjusted risk ratio (aRR) 0.78, 95% CI 0.65-0.93, Z = - 2.64, p = 0.008], methamphetamine use (aRR 0.65, 95% CI 0.51-0.83, Z = - 3.45, p = 0.001), amphetamine use (aRR 0.62, 95% CI 0.44-0.87, Z = - 2.75, p = 0.006), homelessness (aRR 0.79, 95% CI 0.63-0.98, Z = - 2.06, p = 0.039), and sex work (aRR 0.60, 95% CI 0.41-0.86, Z = - 2.77, p = 0.009). These findings underscore the importance of interventions that address the socio-ecological barriers to viral suppression among trans women in urban settings.

RESUMEN: Persisten disparidades preocupantes en la supresión viral entre las mujeres transgénero (trans) que viven con el VIH en los EE. UU. Utilizamos datos de referencia de un ensayo controlado aleatorizado de una intervención conductual entre mujeres trans que viven con el VIH en San Francisco y Los Ángeles, para identificar los correlatos socioecológicos de la supresión viral confirmada biológicamente (< 200 copias/ml de ARN del VIH-1). Entre 253 participantes, la edad media fue de 43 años (DE = 11), el 46% se identificó como negro o afroamericano y el 35% no tenía supresión viral. En modelos de regresión de Poisson ajustados, se identificaron las siguientes barreras para la supresión viral: uso de drogas inyectables [razón de riesgo ajustada (aRR) 0,78, IC del 95% 0,65­0,93, Z = − 2,64, p = 0,008], uso de metanfetamina (aRR 0,65, IC 95% 0,51­0,83, Z = − 3,45, p = 0,001), consumo de anfetaminas (aRR 0,62, IC 95% 0,44­0,87, Z = − 2,75, p = 0,006), falta de vivienda (aRR 0,79, IC 95% 0,63­0,98, Z = − 2,06, p = 0,039), y trabajo sexual (aRR 0,60, IC 95% 0,41­0,86, Z = − 2,77, p = 0,009). Estos hallazgos subrayan la importancia de las intervenciones que abordan las barreras socioecológicas para la supresión viral entre las mujeres trans en entornos urbanos.

Increased Difficulties Managing Chronic Medical Conditions During the COVID-19 Pandemic Are Associated With Increased Alcohol and Cannabis Use Among Unhoused and Unstably Housed Women.

OBJECTIVES: The COVID-19 pandemic caused dramatic upsurges in stress and anxiety across the United States, as well as increased substance use to cope with pandemic-related stress. Few studies have focused exclusively on extremely disadvantaged individuals who are already at risk for substance use. We sought to understand factors associated with increased alcohol and cannabis use during the first 10 months of the COVID-19 pandemic among unsheltered and unstably housed women. METHODS: Between July and December 2020, we conducted phone surveys with San Francisco unhoused and unstably housed women regarding substance use, health, and health services use since the beginning of the pandemic (March 2020). RESULTS: Among 128 participants, increased use of alcohol and cannabis were reported by 15% and 23%, respectively. The odds of increased use of both substances were 4 times higher in participants who also had increased difficulties managing symptoms of a chronic medical condition during the pandemic. CONCLUSIONS: An intentional and comprehensive approach to managing the health of particularly vulnerable individuals during the COVID pandemic could help alleviate its exacerbating influences. Such an approach should include resources, tools and interventions for managing substance use, as well as chronic, non-COVID medical conditions, which are common and strongly tied to substance use in unhoused and unstably housed women.

First Demonstration Project of Long-Acting Injectable Antiretroviral Therapy for Persons With and Without Detectable Human Immunodeficiency Virus (HIV) Viremia in an Urban HIV Clinic.

BACKGROUND: Long-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naive or experienced people with human immunodeficiency virus (HIV; PWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART. METHODS: Ward 86 is a large HIV clinic in San Francisco that serves publicly insured and underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method. RESULTS: Between June 2021 and April 2022, 51 patients initiated LAI-ART, with 39 receiving at least 2 follow-up injections by database closure (median age, 46 years; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients who initiated injections with viral suppression (median CD4 cell count, 706 cells/mm3), 100% (95% confidence interval [CI], 86%-100%) maintained viral suppression. Of 15 patients who initiated injections with detectable viremia (median CD4 cell count, 99 cells/mm3; mean log10 viral load, 4.67; standard deviation, 1.16), 12 (80%; 95% CI, 55%-93%) achieved viral suppression, and the other 3 had a 2-log viral load decline by a median of 22 days. CONCLUSIONS: This small demonstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.

Sexual Minority Stress and Cellular Aging in Methamphetamine-Using Sexual Minority Men With Treated HIV.

OBJECTIVE: Sexual minority men (e.g., gay, bisexual, and other men who have sex with men) experience stigma and sexual minority stress, which are theorized to drive negative health outcomes. Sexual minority men with treated HIV display persistent immune dysregulation, which could be amplified by sexual minority stress responses to potentiate cellular aging. METHODS: This cross-sectional study included 52 sexual minority men living with HIV who had undetectable viral load (<40 copies/mL) and biologically confirmed recent methamphetamine use. Participants completed measures assessing sexual minority stress and openness about sexual minority status (i.e., outness). DNA methylation-derived outcomes included the following: the extrinsic epigenetic age acceleration clock, telomere length, naive CD4+ T-helper cells, and naive CD8+ T-cytotoxic/suppressor cells. RESULTS: After adjusting for negative affect and recent stimulant use, higher sexual minority stress was associated with a faster extrinsic epigenetic age acceleration clock ( ß = 0.29, p = .030), shorter telomere length ( ß = -0.43, p = .002), and fewer naive CD4+ (ß = -0.57, p < .001) and naive CD8+ T cells ( ß = -0.57, p < .001). Greater outness was associated with higher naive CD4+ ( ß = 0.32, p = .030) and naive CD8+ T cells ( ß = 0.38, p = .008) as well as lower plasma interleukin 6 ( ß = -0.33, p = .027). CONCLUSIONS: Sexual minority stress processes are associated with markers of cellular aging and inflammation in methamphetamine-using sexual minority men living with HIV. Longitudinal research should elucidate biobehavioral mechanisms linking sexual minority stress processes with accelerated cellular aging in those with and without HIV.

Are Patients and Their Providers Talking About Long-Acting Injectable Antiretroviral Therapy? Penetration into Clinical Encounters at Three U.S. Care Sites.

Use of long-acting injectable antiretroviral therapy depends on patient awareness, provider discussion, and patient willingness to use. We conducted a postvisit survey with patients at 3 HIV clinics in San Francisco, Chicago, and Atlanta in May 2021 to assess for inequities in these early implementation phases.

HIV-related drivers of sexual compulsivity and sexuality in sexual minority men who use methamphetamine.

Although co-occurring methamphetamine (meth) use and HIV amplify the risk for neuropsychiatric comorbidities, the underlying neuroimmune mechanisms are not well characterized. We examined whether a detectable viral load and dysregulated metabolism of amino acid precursors for neurotransmitters predicted subsequent levels of sexual compulsivity and sexual sensation seeking. This 15-month longitudinal study enrolled 110 sexual minority men (SMM) living with HIV who had biologically confirmed meth use (i.e., reactive urine or hair toxicology results). Peripheral venous blood samples collected at baseline, 6 months, 12 months, and 15 months were used to measure a detectable viral load (> 40 copies/mL), the kynurenine/tryptophan (K/T) ratio, and the phenylalanine/tyrosine (P/T) ratio. The K/T and P/T ratios index dysregulated serotonin and catecholamine (e.g., dopamine) synthesis, respectively. In a cross-lagged panel model, a detectable viral load at 6 months predicted greater sexual compulsivity at 12 months after adjusting for prior levels of sexual compulsivity and recent stimulant use (ß = 0.26, p = 0.046). A greater P/T ratio at baseline predicted decreased sexual sensation seeking at 6 months (ß = - 0.25, p = 0.004) after adjusting for baseline sexual sensation seeking and recent stimulant use. Taken together, HIV replication and dysregulated catecholamine synthesis could potentiate sexual compulsivity while decreasing sexual pleasure in SMM who use meth.

Randomized Controlled Trial of Healthy Divas: A Gender-Affirming, Peer-Delivered Intervention to Improve HIV Care Engagement Among Transgender Women Living With HIV.

BACKGROUND: Transgender women are disproportionately affected by HIV and are less likely to be optimally engaged in care than other groups because of psychosocial challenges. With community collaboration, we developed Healthy Divas, an individual-level intervention to increase healthcare empowerment and gender affirmation to improve engagement in HIV care. Healthy Divas comprises 6 peer-led individual sessions and one group workshop facilitated by a healthcare provider with expertise in HIV care and transgender health. SETTING/METHODS: To test the intervention's efficacy, we conducted a randomized controlled clinical trial in San Francisco and Los Angeles among transgender women living with HIV; control was no intervention. Transgender field staff conducted recruitment. Assessments occurred at baseline and 3, 6, 9, and 12 months postrandomization. The primary outcome was engagement in HIV care, defined as the sum of (1) self-reported HIV care provider visit, past 6 months, (2) knowledge of most recent CD4 count, (3) self-reported antiretroviral therapy adherence ≥90%, and (4) self-reported antiretroviral therapy adherence ≥80%. RESULTS: We enrolled 278 participants; almost half (46%) were African American/Black and one-third (33%) were Hispanic/Latina. At 6 months, participants in the intervention arm had over twice the odds of being in a higher HIV care engagement category than those in the control arm (aOR = 2.17; 95% CI: 1.06 to 4.45; P = 0.04); there were no significant study arm differences in the outcome at the other time points. CONCLUSIONS: This trial demonstrates the short-term efficacy of an urgently needed behavioral intervention to improve engagement in HIV care among transgender women living with HIV; ongoing intervention may be needed to maintain positive impact over time. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03081559.

The shame spiral of addiction: Negative self-conscious emotion and substance use.

BACKGROUND: The bidirectional associations between negative self-conscious emotions such as shame and guilt and substance use are poorly understood. Longitudinal research is needed to examine the causes, consequences, and moderators of negative self-conscious emotions in people who use substances. METHODS: Using parallel process latent growth curve modeling, we assessed bidirectional associations between shame and guilt and substance use (i.e., number of days in the past 30 used stimulants, alcohol to intoxication, other substances, or injected drugs) as well as the moderating role of positive emotion. Emotions were assessed using the Differential Emotions Scale. The sample included 110 sexual minority cisgender men with biologically confirmed recent methamphetamine use, enrolled in a randomized controlled trial in San Francisco, CA. Participants self-reported emotions and recent substance use behaviors over six time points across 15 months. RESULTS: Higher initial levels of shame were associated with slower decreases in stimulant use over time (b = 0.23, p = .041) and guilt was positively associated with stimulant use over time (ß = 0.85, p < .0001). Initial levels of guilt and alcohol use were positively related (b = 0.29, p = .040), but over time, they had a negative relationship (ß = -0.99, p < .0001). Additionally, higher initial levels of other drug use were associated with slower decreases in shame over time (b = 0.02, p = .041). All results were independent of depression, highlighting the specific role of self-conscious emotions. CONCLUSIONS: Shame and guilt are barriers to reducing stimulant use, and expanded efforts are needed to mitigate the deleterious effects of these self-conscious emotions in recovery from a stimulant use disorder.