Beyond the Syndemic of Opioid Use Disorders and HIV: The Impact of Opioids on Viral Reservoirs

Trunfio, Mattia; Chaillon, Antoine; Beliakova-Bethell, Nadejda; Deiss, Robert; Letendre, Scott; Riggs, Patricia K.; Higgins, Noelle; Gianella, Sara

doi:10.3390/v15081712

Cited by 2 publications

(1 citation statement)

References 79 publications

(160 reference statements)

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“…Accelerated brain aging has also been observed with substance (e.g., opioid) use and HIV syndemic (reviewed in [158,159]. Besides the exacerbating impact of opioids on neuroinflammation, neuropathology, and immune modulation, opioids can worsen HIV infection through immunosuppression and facilitate viral seeding of the CNS by damaging the BBB integrity, increasing recruitment and activation of myeloid cells, via the release of chemo-attractants from astrocytes, enhancing CCR5 and CXCR4 expression (reviewed in [160]). With an ongoing opioid crisis and the synergic effects of HIV and opioids syndemic, it is key to establish a cohort of PWH with substance use histories for future HIV-persistence investigations.…”

Section: Discussionmentioning

confidence: 99%

Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

Mohammadzadeh,

Chomont,

Estaquier

et al. 2023

Viruses

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There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4+ T-cell counts, reverses immunodeficiency, and increases life expectancy. Despite these substantial advances, ART is a lifelong treatment for people with HIV (PWH) and upon cessation or interruption, the virus quickly rebounds in plasma and anatomic sites, including the central nervous system (CNS), resulting in disease progression. With recent advances in quantifying viral burden, detection of genetically intact viral genomes, and isolation of replication-competent virus from brain tissues of PWH receiving ART, it has become apparent that the CNS viral reservoir (largely comprised of macrophage type cells) poses a substantial challenge for HIV cure strategies. Other obstacles impacting the curing of HIV include ageing populations, substance use, comorbidities, limited antiretroviral drug efficacy in CNS cells, and ART-associated neurotoxicity. Herein, we review recent findings, including studies of the proviral integration sites, reservoir decay rates, and new treatment/prevention strategies in the context of the CNS, together with highlighting the next steps for investigations of the CNS as a viral reservoir.

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Section: Discussionmentioning

confidence: 99%

Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

Mohammadzadeh,

Chomont,

Estaquier

et al. 2023

Viruses

View full text Add to dashboard Cite

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Shared and unique 3D genomic features of substance use disorders across multiple cell types

Trang,

Chesi,

Toikumo

et al. 2024

Preprint

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Recent genome-wide association studies (GWAS) have revealed shared genetic components among alcohol, opioid, tobacco and cannabis use disorders. However, the extent of the underlying shared causal variants and effector genes, along with their cellular context, remain unclear. We leveraged our existing 3D genomic datasets comprising high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq and RNA-seq across >50 diverse human cell types to focus on genomic regions that coincide with GWAS loci. Using stratified LD regression, we determined the proportion of genome-wide SNP heritability attributable to the features assayed across our cell types by integrating recent GWAS summary statistics for the relevant traits: alcohol use disorder (AUD), tobacco use disorder (TUD), opioid use disorder (OUD) and cannabis use disorder (CanUD). Statistically significant enrichments (P<0.05) were observed in 14 specific cell types, with heritability reaching 9.2-fold for iPSC-derived cortical neurons and neural progenitors, confirming that they are crucial cell types for further functional exploration. Additionally, several pancreatic cell types, notably pancreatic beta cells, showed enrichment for TUD, with heritability enrichments up to 4.8-fold, suggesting genomic overlap with metabolic processes. Further investigation revealed significant positive genetic correlations between T2D with both TUD and CanUD (FDR<0.05) and a significant negative genetic correlation with AUD. Interestingly, after partitioning the heritability for each cell type's cis-regulatory elements, the correlation between T2D and TUD for pancreatic beta cells was greater (r=0.2) than the global genetic correlation value. Our study provides new genomic insights into substance use disorders and implicates cell types where functional follow-up studies could reveal causal variant-gene mechanisms underpinning these disorders.

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Beyond the Syndemic of Opioid Use Disorders and HIV: The Impact of Opioids on Viral Reservoirs

Cited by 2 publications

References 79 publications

Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

Shared and unique 3D genomic features of substance use disorders across multiple cell types

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