Effect of Opioid Use on Immune Activation and HIV Persistence on ART

Azzoni, Livio; Metzger, David S.; Montaner, Luis J.

doi:10.1007/s11481-020-09959-y

Cited by 11 publications

(18 citation statements)

References 136 publications

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“…The purpose of this study was to collect preliminary evidence to address the hypothesis that the continued engagement of the MOR by methadone-based MOUD would sustain immune activation in PLWH receiving suppressive ART when compared with naltrexone-based MOUD treated or non-OUD ART controls; to address this hypothesis, we tested the expression of biomarkers of inflammation, aging, immune activation, and mucosal integrity 52 . Our results indicate that PLWH treated with methadone have higher levels of immune activation and inflammation markers than those who are either receiving naltrexone or not using opioids.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, low doses of the MOR antagonist naltrexone can also block TLR4, 46–48 with documented anti‐inflammatory effects 49–51 . While MOUD has been shown to improve clinical outcomes in PLWH and OUD by increasing ART adherence (and possibly improving other health‐related conditions 40 ), their effects on ART‐mediated immune recovery following viral suppression remains unclear 52 . While direct evidence is lacking, MOR agonists would be expected to sustain opioid‐mediated immune effects, whereas MOR antagonists have the potential to reverse such effects, with naltrexone potentially limiting TLR4‐mediated inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

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Methadone use is associated with increased levels of sCD14, immune activation, and inflammation during suppressed HIV infection

Azzoni

Giron

Vadrevu

et al. 2022

Journal of Leukocyte Biology

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Opioid use has negative effects on immune responses and may impair immune reconstitution in persons living with HIV (PLWH) infection undergoing antiretroviral treatment (ART). The effects of treatment with μ opioid receptor (MOR) agonists (e.g., methadone, MET) and antagonists (e.g., naltrexone, NTX) on immune reconstitution and immune activation in ART‐suppressed PLWH have not been assessed in‐depth. We studied the effects of methadone or naltrexone on measures of immune reconstitution and immune activation in a cross‐sectional community cohort of 30 HIV‐infected individuals receiving suppressive ART and medications for opioid use disorder (MOUD) (12 MET, 8 NTX and 10 controls). Plasma markers of inflammation and immune activation were measured using ELISA, Luminex, or Simoa. Plasma IgG glycosylation was assessed using capillary electrophoresis. Cell subsets and activation were studied using whole blood flow cytometry. Individuals in the MET group, but no in the NTX group, had higher plasma levels of inflammation and immune activation markers than controls. These markers include soluble CD14 (an independent predictor of morbidity and mortality during HIV infection), proinflammatory cytokines, and proinflammatory IgG glycans. This effect was independent of time on treatment. Our results indicate that methadone‐based MOUD regimens may sustain immune activation and inflammation in ART‐treated HIV‐infected individuals. Our pilot study provides the foundation and rationale for future longitudinal functional studies of the impact of MOUD regimens on immune reconstitution and residual activation after ART‐mediated suppression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Methadone use is associated with increased levels of sCD14, immune activation, and inflammation during suppressed HIV infection

Azzoni

Giron

Vadrevu

et al. 2022

Journal of Leukocyte Biology

Self Cite

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“…Previous in vitro studies suggest that opioids suppress T cell activation as well as the activity of transcription factors including NF-κB, AP1, NFAT and CREB which regulate HIV transcription, [ 32 , 33 ]. Similarly, intravenous drug use, including opioids, is associated with increased inflammation and higher microbial translocation, exacerbating immune activation, which may influence latent reservoir establishment and maintenance [ 34 , 35 , 36 ]. The impact of opioids on the reservoir was suggested using an SIV-infected rhesus macaque model where morphine exposure was associated with a reduced latent reservoir in lymph nodes compared to control animals [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal

Basukala

Rossi

Bendiks

et al. 2023

Viruses

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Of the 12 million people who inject drugs worldwide, 13% live with HIV. Whether opioid use impacts HIV pathogenesis and latency is an outstanding question. To gain insight into whether opioid use influences the proviral landscape and latent HIV reservoir, we performed intact proviral DNA assays (IPDA) on peripheral blood mononuclear cells (PBMCs) from antiretroviral therapy (ART)-suppressed people living with HIV (PWH) with or without current opioid use. No differences were observed between PWH with and without opioid use in the frequency of HIV intact and defective proviral genomes. To evaluate the latent reservoir, we activated PBMCs from ART-suppressed PWH with or without opioid use and assessed the induction of HIV RNA. PWH using opioids had diminished responses to ex vivo HIV reactivation, suggesting a smaller reversible reservoir of HIV-1 latently infected cells. However, in vitro studies using primary CD4+ T cells treated with morphine showed no effect of opioids on HIV-1 infection, replication or latency establishment. The discrepancy in our results from in vitro and clinical samples suggests that while opioids may not directly impact HIV replication, latency and reactivation in CD4+ T cells, opioid use may indirectly shape the HIV reservoir in vivo by modulating general immune functions.

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“…Some studies have suggested the potential direct effects of how substance use (methamphetamine, cocaine, opioids, and cannabis) impacts immune activation pathways and facilitates HIV viral replication ( Azzoni et al, 2020 , Buch et al, 2020 , Feldman et al, 2015 , Jiang et al, 2016 , Massanella et al, 2015 , Napuri et al, 2013 , Prasad et al, 2019 , Rasbach et al, 2013 , Saloner et al, 2020 , Tyagi et al, 2016 , Vidot et al, 2019 ). Alcohol use has also been associated with potentially detrimental effects on viral control, independent of medication adherence ( Agudelo et al, 2015 , Amedee et al, 2014 , Bagasra et al, 1989 , Molina et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of drug and hazardous alcohol use on having a detectable HIV viral load: An adherence mediation analysis

Moges

Qin

Bamford

et al. 2023

Addictive Behaviors Reports

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Effect of Opioid Use on Immune Activation and HIV Persistence on ART

Cited by 11 publications

References 136 publications

Methadone use is associated with increased levels of sCD14, immune activation, and inflammation during suppressed HIV infection

Methadone use is associated with increased levels of sCD14, immune activation, and inflammation during suppressed HIV infection

Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal

Effects of drug and hazardous alcohol use on having a detectable HIV viral load: An adherence mediation analysis

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