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.

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.

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.

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era.

OBJECTIVE: Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiome-gut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system. METHODS: A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH. RESULTS: Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways). CONCLUSIONS: Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiome-gut-brain axis pathways among PWH in the modern antiretroviral therapy era.

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.

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.

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.