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

Abstract

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 (β = 0.29, p = .030), shorter telomere length (β = −0.43, p = .002), and fewer naive CD4+ (β = −0.57, p < .001) and naive CD8+ T cells (β = −0.57, p < .001). Greater outness was associated with higher naive CD4+ (β = 0.32, p = .030) and naive CD8+ T cells (β = 0.38, p = .008) as well as lower plasma interleukin 6 (β = −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.

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review

“…This is consistent with Dr. Wakim-Takaki's biopsychosocial model of comorbid HIV and CUD (HIV+/CUD+), which documents complex relationships between biological, neurocognitive, and social mechanisms underlying poor outcomes in HIV+/CUD+ patients [15]. In the present review, we generalize this model to CUD and MUD since they have similar complex relationships with cellular, neurocognitive, and social mechanisms [7][8][9][10][16][17][18][19][20]. We will add to this model by reviewing evidence within the past 10 years with a central focus on studies that investigated dopamine dysregulation, applied neuroimaging methods, and differentially affected groups.…”

“…Social adversity may exacerbate the epigenetic changes observed in HIV+/MUD+ MSM. Greater experience of stress related to being a sexual minority was associated with accelerated epigenetic aging, evident through telomere shortening and genome-wide DNA methylation patterns in the brain [16]. These results provide evidence for the molecular manifestations of the interactive relationships between social and biological mechanisms underlying HIV+/MUD+, consistent with Dr. Wakim-Takaki's biopsychosocial model.…”

“…Pre-clinical evidence demonstrated sex differences in behavioral and neurological impairments associated with HIV and cocaine or meth exposure [106,116,117,137]; however, the clinical evidence has only evaluated sex differences in HIV and psychostimulant use disorders independently, likely due to limitations in sample sizes. Researchers should investigate sex differences between HIV+/CUD+ and HIV+/MUD+ in a community-based sample, as social adversity exacerbates their effects in a population-specific manner [16,[163][164][165]. Additionally, researchers should evaluate levels of estrogen in women living with HIV and a psychostimulant use disorder, as pre-clinical evidence suggests estrogen may be a biochemical target for mitigating the effects of HIV and psychostimulant exposure on drug sensitization and responsiveness to ROS scavenger treatment [106,116,117].…”

Brief Report: Impact of Methamphetamine Use and Rectal STIs on Systemic and Rectal Mucosal Inflammation

“…MSM who use MA often experience high rates of social adversity, such as homophobia, racial/ethnic discrimination, stigma, and socioeconomic marginalization, [39][40][41][42] which has been associated with epigenetic alterations that are linked to systemic inflammation and cellular aging. [43][44][45][46] As both systemic and mucosal inflammation have been associated with increased risk of HIV/STI transmission, future studies further evaluating the impacts of MA use and rectal GC/CT on immune dysregulation in these different compartments are warranted.…”

The Interaction of HIV With Mental Health in the Modern Antiretroviral Therapy Era

“…There is also some evidence that the use of stimulants (i.e., methamphetamine, powder cocaine, and crack cocaine) could alter biological processes relevant to HIV pathogenesis in those receiving effective ART ( 32 , 33 ). Findings from Ghanooni and colleagues ( 34 ) demonstrate that sexual minority stress processes were associated with measures of accelerated cellular aging (e.g., the extrinsic epigenetic age acceleration clock) derived from measures of DNA methylation in methamphetamine-using sexual minority men with treated HIV. Future longitudinal research is needed to delineate the biobehavioral pathways relevant to cellular aging among PWH.…”