Recent stimulant use and leukocyte gene expression in methamphetamine users with treated HIV infection

Abstract

Stimulant use may accelerate HIV disease progression through biological and behavioral pathways. However, scant research with treated HIV-positive persons has examined stimulant-associated alterations in pathophysiologic processes relevant to HIV pathogenesis. In a sample of 55 HIV-positive, methamphetamine-using sexual minority men with a viral load less than 200 copies/mL, we conducted RNA sequencing to examine patterns of leukocyte gene expression in participants who had a urine sample that was reactive for stimulants (n = 27) as compared to those who tested non-reactive (n = 28). Results indicated differential expression of 32 genes and perturbation of 168 pathways in recent stimulant users. We observed statistically significant differential expression of single genes previously associated with HIV latency, cell cycle regulation, and immune activation in recent stimulant users (false discovery rate p < 0.10). Pathway analyses indicated enrichment for genes associated with inflammation, innate immune activation, neuroendocrine hormone regulation, and neurotransmitter synthesis. Recent stimulant users displayed concurrent elevations in plasma levels of tumor necrosis factor - alpha (TNF-α) but not interleukin 6 (IL-6). Further research is needed to examine the bio-behavioral mechanisms whereby stimulant use may contribute to HIV persistence and disease progression.

Expression of mitochondrial dysfunction-related genes and pathways in paclitaxel-induced peripheral neuropathy in breast cancer survivors

“…58,59 We followed published best practices 60,61 and our previous experience. 34,41 The total sample size is 50 survivors. For this analysis, the overall dispersion and the gene-wise and tag-wise dispersion were estimated using general linear models estimated using the Cox–Reid-adjusted likelihood method.…”

“…RNA-seq alignment, data processing, and quality control (QC) RNA-seq data processing was performed based on best practices 39,40 and our previous experience. 34,41 Illuimina adapters and leading or trailing low-quality bases were removed, and reads with an average quality per base below 15 in a 4-base sliding window or below a minimum length of 36 bases were removed using trimmomatic. 42 Individual samples were inspected with FASTQC 43 and in aggregate with MultiQC.…”

Psychosocial Correlates of Monocyte Activation and HIV Persistence in Methamphetamine Users

“…Although one prior study observed that methamphetamine users displayed higher proviral HIV DNA compared to non-users (Massanella et al, 2015), findings were not significant after adjusting for ART regimen. In another study with treated methamphetamine users, recent stimulant use was associated with the upregulation of genes and pathways relevant to HIV latency and immune activation (Carrico et al, 2018). Further research is needed to examine substanceassociated elevations in measures of HIV persistence.…”

A “Drug-Dependent” Immune System Can Compromise Protection against Infection: The Relationships between Psychostimulants and HIV

“…Since soluble CD14 is involved in TLR4 activation under certain circumstances [ 258 , 259 ], an effect of methamphetamine on soluble CD14 levels due to TLR4 activation could be inferred. In addition, differential expression of genes associated with HIV latency, cell cycle regulation, innate and adaptive immune activation (mainly related to the TNF-α pathway), neuroendocrine regulation and neurotransmitter synthesis (including catecholamines) has been observed in blood from men infected with HIV that recently used methamphetamine [ 260 ]. Regarding cocaine, older adults with a cocaine use disorder had a higher neutrophil to lymphocyte ratio, described as a marker of chronic inflammation [ 261 ].…”