Opioids exacerbate inflammation in people with well-controlled HIV

Abstract

IntroductionPeople with HIV (PWH) are known to have underlying inflammation and immune activation despite virologic control. Substance use including opioid dependence is common in this population and is associated with increased morbidity and reduced lifespan. The primary objective of the present study termed opioid immunity study (OPIS), was to investigate the impact of chronic opioids in PWH.MethodsThe study recruited people with and without HIV who had opioid use disorder (OUD). Study participants (n=221) were categorized into four groups: HIV+OP+, n=34; HIV-OP+, n=66; HIV+OP-, n=55 and HIV-OP-, n=62 as controls. PWH were virally suppressed on ART and those with OUD were followed in a syringe exchange program with confirmation of OP use by urine drug screening. A composite cytokine score was developed for 20 plasma cytokines that are linked to inflammation. Cellular markers of immune activation (IA), exhaustion, and senescence were determined in CD4 and CD8 T cells. Regression models were constructed to examine the relationships of HIV status and opioid use, controlling for other confounding factors.ResultsHIV+OP+ participants exhibited highest inflammatory cytokines and cellular IA, followed by HIV-OP+ for inflammation and HIV+OP- for IA. Inflammation was found to be driven more by opioid use than HIV positivity while IA was driven more by HIV than opioid use. In people with OUD, expression of CD38 on CD28-CD57+ senescent-like T cells was elevated and correlated positively with inflammation.DiscussionGiven the association of inflammation with a multitude of adverse health outcomes, our findings merit further investigations to understand the mechanistic pathways involved.

Soluble Plasma Proteins of Tumor Necrosis Factor and Immunoglobulin Superfamilies Reveal New Insights into Immune Regulation in People with HIV and Opioid Use Disorder

“…In OPIS, we hypothesized that PWH who have OUD would have excessive inflammation and IA, more than that caused by HIV or opioids alone. Our recent study investigated 20 cytokines as well as cellular markers of activation and exhaustion [10]. In support of our hypothesis, we found that PWH who had OUD (HIV+OP+) exhibited the highest inflammatory cytokines and cellular IA, greater than that in PWH without OUD (HIV+OP−).…”

“…The participants for the OPIS study were recruited as described [10] by the study recruiters (Supplementary Figure S1). They were divided into four study groups based on their HIV status (HIV+/−) and OUD (OP+/−) status as HIV+OP+, HIV−OP+, HIV+OP−, and HIV−OP−.…”

“…Figure 1 shows a composite heat map for visualization of the expression of the superfamily molecules analyzed in the four groups, showing heterogeneity in their distribution. The present study took a cue from the results of our previous study [10], in which we analyzed 20 soluble plasma cytokines that play a role in inflammation. In that study, TNFR1, TNFR2, and TNF-α were among the top five most elevated molecules identified in the HIV+ and OP+ groups (Supplemental Figure S2, adapted from ref [10].…”

“…The present study took a cue from the results of our previous study [10], in which we analyzed 20 soluble plasma cytokines that play a role in inflammation. In that study, TNFR1, TNFR2, and TNF-α were among the top five most elevated molecules identified in the HIV+ and OP+ groups (Supplemental Figure S2, adapted from ref [10]. We analyzed the scores of all the superfamily molecules for each participant group (Figure 2).…”

“…In support of our hypothesis, we found that PWH who had OUD (HIV+OP+) exhibited the highest inflammatory cytokines and cellular IA, greater than that in PWH without OUD (HIV+OP−). Opioid use was the primary driver of inflammation, while living with HIV promoted IA [10].…”