Background
The US is experiencing a major drug epidemic that is attributed in large part to synthetic opioids such as fentanyl. We previously reported that fentanyl enhanced the replication of several viruses including HIV. Here, we considered how fentanyl use impacted inflammatory markers in persons living with HIV.
Methods
Whole blood was collected from adults living with HIV, HCV, and/or opioid use, as well as non-opioid using controls. Plasma samples were screened for commonly abused drugs, pro-inflammatory cytokines/chemokines (IL-6 ,IL-8, SDF-1a, MIP-1a, MIP-1b, RANTES, TNFa), and the apoptosis marker M30 by Liquid Chromatography Mass Spectrometry, Luminex multiplex cytokine array, and the M30 Apoptosense ELISA, respectively. Median values were compared by HIV or HCV status using the Kruskal-Wallis test. Multiple regression models were used to explore the associations between the log10-transformed cytokine/chemokine/M30 values and other covariates.
Results
37 of 98 (37.8%) individuals had a diagnosis of opioid use disorder (OUD), and 48 (53.9%) had ever injected drugs. Of those ever-having opioids, 95.9% (47/49) had used fentanyl. HIV-positive status indicated higher RANTES levels (363.1 vs. 174.9; p = 0.014) and lower M30 levels (84.4 vs. 114.7; p = 0.009) compared to HIV-negative status. Being HCV positive was linked to higher IL-8 (9.6 vs. 6.3; p = 0.023), MIP-1b (25.7 vs. 18.4; p = 0.029), TNFa (17.3 vs .10.7; p = 0.033), and M30 (105.7 vs. 90.0; p = 0.029) and lower RANTES (210.5 vs. 363.9; p = 0.044), compared to HCV-negative status. After adjusting for other covariates, IL-8 was associated with both HIV status and HCV status, SDF-1a with ever having injected drugs, and MIP-1b with HCV status. There were no significant associations between the number of drugs of abuse detected and cytokine/chemokine/M30 levels after controlling for covariates.
Conclusions
Drugs of abuse may alter the immune system and viral pathogenesis in several ways. Enhanced pro-inflammatory cytokine and chemokine production represent potential mechanisms by which opioids impact viral infection. Future research that antagonize these processes may provide new therapeutic interventions that reduce morbidity/mortality among persons with HIV and HIV/HCV co-infected with OUD.