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Viruses
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HIV and Drugs of Abuse, 3rd Edition
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HIV and Drugs of Abuse, 3rd Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 9191

Special Issue Editors

Dr. Maria Cecilia Garibaldi Marcondes

E-Mail Website
Guest Editor
San Diego Biomedical Research Institute (SDBRI), 3525 John Hopkins Ct., San Diego, CA 92121, USA
Interests: neuroinflammation; neuro-immunemodulation; chronic inflammation; brain pathogenesis; HIV associated neurological disorders; drugs of abuse; innate immune response
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marcus Kaul

E-Mail Website
Guest Editor
Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA 92521, USA
Interests: neuroinflammation; neurodegenerative disease; host-pathogen interactions; HIV-1; drug abuse; innate immunity; microglia/macrophages; neuroprotection; stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Substance use disorders and HIV infection are long-standing public health concerns and frequent comorbidities. HIV continues to cause neurocognitive deficits despite highly effective anti-retroviral therapies that lead to viral suppression. Combined with the neurobehavioral factors underlying substance use and the neurological consequences of addictive drugs, HIV-associated neurological disorders present a range of distinctive characteristics, and there is still no treatment available. The modulation of immune functions by the actions of neurotransmitters released under the influence of such drugs may be one reason for the aggravating effects of addiction on HIV-associated disorders in the central nervous system. Among the addictive drugs, methamphetamine and other stimulants are highly detrimental due to the associated risky behaviors, and due to their effects on neurotransmitters interfering with cellular responses. Given that innate and adaptive immune cells express neurotransmitter receptors, HIV target cells in the context of substance use respond differently than in non-users, particularly in the brain. Polysubstance use is highly prevalent among individuals with addictive behaviors, further complicating the picture. In this Special Issue of Viruses, we aim at integrating information derived from research with humans and animal models, as well as in cells of the immune system, thus providing a unique multidimentional and translational perspective of the clinical and mechanistic interactions between HIV and drugs of abuse that contribute to neurological disorders. Original work performed by interdisciplinary teams will be showcased.

Dr. Maria Cecilia Garibaldi Marcondes
Prof. Dr. Marcus Kaul
Guest Editors

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Keywords

  • substance use disorders
  • HIV
  • HAND
  • methamphetamine

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Published Papers (5 papers)

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Research

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32 pages, 7160 KiB  
Article
Chronic, Low-Dose Methamphetamine Reveals Sexual Dimorphism of Memory Performance, Histopathology, and Gene Expression Affected by HIV-1 Tat Protein in a Transgenic Model of NeuroHIV
by Indira S. Harahap-Carrillo, Dominic Fok, Frances Wong, Gabriel Malik, Ricky Maung, Xinru Qiu, Daniel Ojeda-Juárez, Victoria E. Thaney, Ana B. Sanchez, Adam Godzik, Amanda J. Roberts and Marcus Kaul
Viruses 2025, 17(3), 361; https://doi.org/10.3390/v17030361 - 28 Feb 2025
Viewed by 852
Abstract
Methamphetamine (METH) use is frequent among people with HIV (PWH) and appears to increase the risk of neuronal injury and neurocognitive impairment (NCI). This study explored in vivo the effects of a 12 week (long-term), low-dose METH regimen in a transgenic animal model [...] Read more.
Methamphetamine (METH) use is frequent among people with HIV (PWH) and appears to increase the risk of neuronal injury and neurocognitive impairment (NCI). This study explored in vivo the effects of a 12 week (long-term), low-dose METH regimen in a transgenic animal model of neuroHIV with inducible expression of HIV-1 transactivator of transcription (Tat). Seven months after transient Tat induction and five months after METH exposure ended, we detected behavioral changes in the Barnes maze (BM) spatial memory task in the Tat and METH groups but not the combined Tat + METH group. The novel object recognition (NOR) task revealed that Tat extinguished discrimination in female animals with and without METH, although METH alone slightly improved NOR. In contrast, in males, Tat, METH, and Tat + METH all compromised NOR. Neuropathological examination detected sex-dependent and brain region-specific changes of pre-synaptic terminals, neurites, and activation of astrocytes and microglia. RNA-sequencing and quantitative reverse transcription polymerase chain reaction indicated that METH and Tat significantly altered gene expression, including factors linked to Alzheimer’s disease-like NCI. In summary, chronic low-dose METH exerts long-term effects on behavioral function, neuropathology, and mRNA expression, and modulates the effects of Tat, suggesting sex-dependent and -independent mechanisms may converge in HIV brain injury and NCI. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
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27 pages, 7717 KiB  
Article
Cannabis Use and Cannabidiol Modulate HIV-Induced Alterations in TREM2 Expression: Implications for Age-Related Neuropathogenesis
by Bryant Avalos, Jacqueline R. Kulbe, Mary K. Ford, Anna Elizabeth Laird, Kyle Walter, Michael Mante, Jazmin B. Florio, Ali Boustani, Antoine Chaillon, Johannes C. M. Schlachetzki, Erin E. Sundermann, David J. Volsky, Robert A. Rissman, Ronald J. Ellis, Scott L. Letendre, Jennifer Iudicello and Jerel Adam Fields
Viruses 2024, 16(10), 1509; https://doi.org/10.3390/v16101509 - 24 Sep 2024
Cited by 1 | Viewed by 2282
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. [...] Read more.
Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV’s impact on TREM2 and behavior. TREM2 and related gene expressions were examined in monocyte-derived macrophages (MDMs) from PWH (n = 42) and people without HIV (PWoH; n = 19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not in PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed the upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially reversed by CBD. These findings suggest HIV affects TREM2 expression modulated by cannabis and CBD, offering insights for therapeutic strategies. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
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8 pages, 245 KiB  
Article
Reversibility of Neuropsychiatric Adverse Events after Switching to Darunavir/Cobicistat or Doravirine in Men on INSTI-Based Regimen
by José Antonio Mata-Marín, Carina Aurora Juárez-Contreras, Mara Soraya Rodríguez-Evaristo, Olivia Concepción Martínez-Carrizales, Ericka Pompa-Mera, Alberto Chaparro Sánchez, Salma Triana-González, Ana Luz Cano-Díaz and Jesús Enrique Gaytán-Martínez
Viruses 2024, 16(7), 1083; https://doi.org/10.3390/v16071083 - 5 Jul 2024
Cited by 1 | Viewed by 1254
Abstract
Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to [...] Read more.
Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to evaluate the reversibility of NPAEs via the Patient Health Questionnaire (PHQ-9), the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS-A and D) in patients who started antiretroviral therapy with dolutegravir (DTG) or bictegravir (BIC). These patients were switched to DRV/c or DOR. Scales were compared at the moment of the switch and 12 weeks later. Results: We included 1153 treatment-naïve men, 676 (58.7%) with BIC and 477 (41.3%) with DTG. A total of 32 (2.7%) experienced NPAEs that led to discontinuation. Insomnia was found in 20 patients; depression via PHQ-9 in 21 patients, via HADS-D in 5 patients, and anxiety via HADS-A in 12 patients. All of them were evaluated by a psychiatrist at the moment of the symptoms; 7 (21.8%) started psychotropic drugs. After 12 weeks of follow-up, PHQ-9, ISI, HADS-A, and HADS-D decreased, with a p-value ≤ 0.05. Conclusions: NPAEs seem to improve after switching to a DRV/c- or DOR-based regimen after the first 4 and 12 weeks. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
14 pages, 4143 KiB  
Article
HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy
by Uma Maheswari Deshetty, Nivedita Chatterjee, Shilpa Buch and Palsamy Periyasamy
Viruses 2024, 16(6), 903; https://doi.org/10.3390/v16060903 - 3 Jun 2024
Cited by 1 | Viewed by 1460
Abstract
Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating [...] Read more.
Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating senescent traits. This study investigated how ER stress and dysregulated autophagy impact cellular senescence triggered by HIV-1 Tat in the MIO-M1 cell line (human Müller glial cells). Cells exposed to HIV-1 Tat exhibited increased vimentin expression combined with markers of ER stress (BiP, p-eIF2α), autophagy (LC3, Beclin-1, p62), and the senescence marker p21 compared to control cells. Western blotting and staining techniques like SA-β-gal were employed to examine these markers. Additionally, treatments with ER stress inhibitor 4-PBA before HIV-1 Tat exposure led to a decreased expression of ER stress, senescence, and autophagy markers. Conversely, pre-treatment with the autophagy inhibitor 3-MA resulted in reduced autophagy and senescence markers but did not alter ER stress markers compared to control cells. The findings suggest a link between ER stress, dysregulated autophagy, and the initiation of a senescence phenotype in MIO-M1 cells induced by HIV-1 Tat exposure. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
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Review

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29 pages, 408 KiB  
Review
The Impact of Drugs and Substance Abuse on Viral Pathogenesis—A South African Perspective
by Lufuno Ratshisusu, Omphile E. Simani, Jason T. Blackard and Selokela G. Selabe
Viruses 2024, 16(6), 971; https://doi.org/10.3390/v16060971 - 17 Jun 2024
Viewed by 2923
Abstract
Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis [...] Read more.
Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as “Bluetoothing” has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this “Bluetooth” practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
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