Abstract
The use of stimulants such as methamphetamine may accelerate HIV disease progression, but scant research has examined stimulant-associated pathophysiologic alterations in treated HIV. In a sample of 55 HIV-positive, methamphetamine-using sexual minority men with a viral load less than 200 copies/mL, 27 participants with a urine sample that was reactive for recent stimulant use (Stimulant Tox+) were compared to 28 who tested negative in urine for stimulants (Stimulant Tox−). Analyses employed the false discovery rate (FDR) under the Benjamini-Hochberg procedure with a 10% cut-off. Stimulant Tox+ participants did not differ from those who were Stimulant Tox− on demographic and clinical characteristics. However, Stimulant Tox+ participants reported more days using methamphetamine in the past 30 days (10.7 versus 4.0; p < 0.01). RNA sequencing provided evidence for differential expression of 32 genes and perturbation of 168 pathways in recent stimulant users. Most notably, we observe upregulation single genes linked to HIV latency (i.e., CD274 and FCGR2A) in Stimulant Tox+ participants. Pathway analyses indicated that recent stimulant use was associated with two-directional perturbation of gene sets governing HIV latency, immune activation, inflammation, neuroendocrine hormone regulation, and neurotransmitter synthesis. Stimulant Tox+ participants also displayed significantly higher log10 TNF-alpha plasma levels (Mean = 1.74 versus 1.63; p = 0.023). Further research is needed to examine these mechanisms whereby stimulant use may contribute to HIV persistence and disease progression.
