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.

Blue Monday: Co-occurring Stimulant Use and HIV Persistence Predict Dysregulated Catecholamine Synthesis.

BACKGROUND: This longitudinal study examined whether co-occurring stimulant use and HIV disease processes predicted greater risk for depression via dysregulated metabolism of amino acid precursors for neurotransmitters. METHODS: In total, 110 sexual minority men (ie, gay, bisexual, and other men who have sex with men) living with HIV who had biologically confirmed recent methamphetamine use were enrolled in a randomized controlled trial. The kynurenine/tryptophan (K/T) and phenylalanine/tyrosine (P/T) ratios were measured over 15 months to index dysregulated metabolism of amino acid precursors for serotonin and catecholamines. Markers of gut-immune dysregulation such as lipopolysaccharide binding protein and soluble CD14 (sCD14), HIV persistence in immune cells (ie, proviral HIV DNA), and stimulant use were examined as predictors. These bio-behavioral measures, including the K/T and P/T ratios, were also examined as predictors of greater risk for depression over 15 months. RESULTS: Higher time-varying sCD14 levels (ß = 0.13; P = 0.04) and time-varying detectable viral loads (ß = 0.71; P < 0.001) were independent predictors of a higher K/T ratio. Time-varying reactive urine toxicology results for stimulants (ß = 0.53; P < 0.001) and greater proviral HIV DNA at baseline (ß = 0.34; P < 0.001) independently predicted an increased P/T ratio. Greater time-varying, self-reported methamphetamine use uniquely predicted higher odds of screening positive for depression (Adjusted Odds Ratio = 1.08; 95% confidence interval: 1.01 to 1.17). CONCLUSIONS: Ongoing stimulant use and HIV persistence independently predict dysregulated metabolism of amino acid precursors for catecholamines, but this did not explain amplified risk for depression.

Getting to the point: Methamphetamine injection is associated with biomarkers relevant to HIV pathogenesis.

BACKGROUND: People living with HIV who use stimulants, such as methamphetamine, display greater immune dysregulation and experience faster clinical HIV progression. However, it remains unclear if the extent of immune dysregulation differs between methamphetamine users who engage in injection drug use (Meth IDU) and methamphetamine users who do not. METHODS: This cross-sectional study enrolled 86 sexual minority men living with HIV who had an undetectable viral load (< 40 copies/mL) and recent, biologically confirmed methamphetamine use. Meth IDU participants were compared to methamphetamine users who did not report IDU with respect to microbial translocation, immune activation, and inflammation plasma biomarkers. Multiple linear regression models were adjusted for age, antiretroviral therapy regimen, CD4 + T-cell count, and reactive urine toxicology results (Tox+) for stimulants. RESULTS: The Meth IDU participants were significantly more likely to be homeless and Tox + for stimulants. In adjusted analyses, those reporting Meth IDU displayed elevated plasma levels of lipopolysaccharide binding protein (LBP), soluble CD163 (sCD163), interleukin-6 (IL-6), and soluble tumor necrosis factor - alpha receptor I (sTNF-αRI). DISCUSSION: Even among methamphetamine users with treated HIV, those who engage in Meth IDU display exacerbations in key pathophysiologic processes that are linked to faster clinical HIV progression. These findings highlight the importance of screening for Meth IDU, discussing safer injection practices, and providing linkages to needle exchanges to reduce the harms of Meth IDU. Those who are not ready, willing, or able to abstain from methamphetamine use could also derive important health benefits from avoiding Meth IDU.

Substance-associated elevations in monocyte activation among methamphetamine users with treated HIV infection.

OBJECTIVE: Microbial translocation and monocyte activation predict mortality in treated HIV. We examined whether substance use independently contributes to these pathophysiologic processes. DESIGN: Cross-sectional study at baseline for a randomized controlled trial. METHODS: HIV-positive, methamphetamine-using MSM with undetectable HIV viral load (less than 40 copies/ml) were enrolled. We examined if plasma biomarkers of monocyte activation and intestinal barrier integrity were associated with the following: reactive urine toxicology results (Tox+) for stimulants (i.e., methamphetamine or cocaine) and substance use severity measured by the Addiction Severity Index. Multiple linear regression models adjusted for age, antiretroviral therapy regimen, CD4 T-cell count, interleukin-6, and alcohol use severity. RESULTS: The sample of 84 virally suppressed MSM had a median CD4 T-cell count of 645 cells/µl. Those who were Tox+ for stimulants displayed higher soluble CD14 (sCD14) levels (2087 versus 1801 ng/ml; P = 0.009), and this difference remained significant after adjusting for covariates (standardized beta = 0.23, P = 0.026). Greater substance use severity was also independently associated with higher sCD14 after adjusting for covariates (standardized beta = 0.29, P = 0.013). Being Tox+ for stimulants and substance use severity were not associated with soluble CD163 (sCD163) or intestinal fatty acid binding protein (iFABP) levels (P > 0.05). CONCLUSIONS: Monocyte activation is one plausible mechanism by which stimulant use may increase clinical HIV progression.