Neuroinflammation in HIV-associated depression: evidence and future perspectives

Rakshasa-Loots, Arish Mudra; Whalley, Heather C.; Vera, Jaime H.; Cox, Simon R.

doi:10.1038/s41380-022-01619-2

Cited by 24 publications

(18 citation statements)

References 231 publications

(226 reference statements)

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“…Furthermore, the development of HIV-associated neuroinflammation and cognitive impairment has been directly linked to gut dysbiosis and increased intestinal permeability [ 127 ]. It has been proposed that HIV-induced alterations in the balance of neurotransmitters in the brain contributes to disruption of the gut–brain axis, which can lead to the development of depression and other neuropsychiatric symptoms [ 128 ].…”

Section: Role Of Host Microbiota In Susceptibility To Viral Infection...mentioning

confidence: 99%

The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis

et al. 2023

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The gut microbiome plays a critical role in maintaining overall health and immune function. However, dysbiosis, an imbalance in microbiome composition, can have profound effects on various aspects of human health, including susceptibility to viral infections. Despite numerous studies investigating the influence of viral infections on gut microbiome, the impact of gut dysbiosis on viral infection and pathogenesis remains relatively understudied. The clinical variability observed in SARS-CoV-2 and seasonal influenza infections, and the presence of natural HIV suppressors, suggests that host-intrinsic factors, including the gut microbiome, may contribute to viral pathogenesis. The gut microbiome has been shown to influence the host immune system by regulating intestinal homeostasis through interactions with immune cells. This review aims to enhance our understanding of how viral infections perturb the gut microbiome and mucosal immune cells, affecting host susceptibility and response to viral infections. Specifically, we focus on exploring the interactions between gamma delta (γδ) T cells and gut microbes in the context of inflammatory viral pathogenesis and examine studies highlighting the role of the gut microbiome in viral disease outcomes. Furthermore, we discuss emerging evidence and potential future directions for microbiome modulation therapy in the context of viral pathogenesis.

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Section: Role Of Host Microbiota In Susceptibility To Viral Infection...mentioning

confidence: 99%

The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis

et al. 2023

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“…Other recent work has shown that monocyte-associated cerebrospinal fluid (CSF) biomarkers, such as TNF-α, MCP-1, neopterin, soluble CD14, and neurofilament light chain protein (NFL), are strongly associated with neuronal damage in people both with and without HIV-1 [ 17 , 18 ]. Furthermore, other authors [ 18 , 19 ] have discussed the use of brain tissue, CSF, and blood biopsies to assess glial cell activation or elevated cytokines, as well as the use of tissue samples to indirectly measure neuroinflammation. Indeed, some pro-inflammatory markers present in CSF have been used as indicators of neuroinflammation, given that CSF is directly connected both to the brain [ 19 ], inflammatory cytokines, and interleukin-15 (IL-15) [ 19 ].…”

Section: Important Genes Involved In the Development Of Hiv-associate...mentioning

confidence: 99%

Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review

Borrajo,

Pérez-Rodríguez,

Fernández-Pereira

et al. 2023

IJMS

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HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and the most serious manifestation of the disease, HIV-associated dementia (HAD), are not yet well understood. Evidence suggests that these mechanisms are likely multifactorial, producing neurocognitive complications involving disorders such as neurogenesis, autophagy, neuroinflammation, and mitochondrial dysfunction. Over the years, multiple pharmacological approaches with specific mechanisms of action acting upon distinct targets have been approved. Although these therapies are effective in reducing viral loading to undetectable levels, they also present some disadvantages such as common side effects, the need for administration with a very high frequency, and the possibility of drug resistance. Genetic studies on HANDs provide insights into the biological pathways and mechanisms that contribute to cognitive impairment in people living with HIV-1. Furthermore, they also help identify genetic variants that increase susceptibility to HANDs and can be used to tailor treatment approaches for HIV-1 patients. Identification of the genetic markers associated with disease progression can help clinicians predict which individuals require more aggressive management and by understanding the genetic basis of the disorder, it will be possible to develop targeted therapies to mitigate cognitive impairment. The main goal of this review is to provide details on the epidemiological data currently available and to summarise the genetic (specifically, the genetic makeup of the immune system), transcriptomic, and epigenetic studies available on HANDs to date. In addition, we address the potential pharmacological therapeutic strategies currently being investigated. This will provide valuable information that can guide clinical care, drug development, and our overall understanding of these diseases.

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“…This directly challenges the 95-95-95 goals defined by UNAIDS; 95% of PLWH should know their status, 95% of PLWH who know their status should be on ART treatment, and 95% of PLWH on treatment should be virally suppressed by 2025 [29,30]. The burden of mental health disorders experienced by PLWH can partly be explained by several factors such as discrimination [31,32] and HIV-related inflammation [33][34][35]. Furthermore, some studies suggest that certain ART drugs such as efavirenz may play a role in developing depression, but without uniform evidence [36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Mental Health Disorders and Their Associated Risk Factors Among People Living with HIV in Rwanda: A Cross-Sectional Study

Omann,

Dushimiyimana,

Musoni-Rwililiza

et al. 2024

AIDS Behav

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While life expectancy of people living with HIV is increasing, their burden of non-communicable diseases, including mental health disorders, is growing as well. The aim of this study is to investigate the prevalence and identify the risk factors associated with mental health disorders among this population in Rwanda. This cross-sectional study enrolled people living with HIV from 12 HIV clinics across Rwanda using random sampling. Trained HIV nurses conducted the Mini International Neuropsychiatric Interview to estimate the prevalence of major depressive episode, post-traumatic stress disorder, and generalized anxiety disorder. Sociodemographic, psychosocial, and HIV-related data were also collected. Associated risk factors for being diagnosed with one of the mental health disorders were assessed using modified Poisson regression with robust error variance. Of 428 participants, 70 (16.4%) had at least one mental health disorder with major depressive episode being most prevalent (n = 60, 14.0%). Almost all participants were adherent to antiretroviral therapy (n = 424, 99.1%) and virally suppressed (n = 412, 96.9%). Of those diagnosed with a mental health disorder, only few were aware of (n = 4, 5.7%) or under treatment for this mental health disorder (n = 5, 7.2%). Mental health disorders were associated with experiences of HIV-related stigma and discrimination (aRR = 2.14, 95%CI 1.30–3.53, p = 0.003). The results demonstrate underdiagnosis and undertreatment of mental health disorders among Rwandan People Living with HIV. Using HIV nurses to diagnose mental health disorders could serve as a low-cost strategy for integrating mental health care with existing HIV services and could inspire the implementation in other low-resource settings.

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Neuroinflammation in HIV-associated depression: evidence and future perspectives

Cited by 24 publications

References 231 publications

The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis

The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis

Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review

Prevalence of Mental Health Disorders and Their Associated Risk Factors Among People Living with HIV in Rwanda: A Cross-Sectional Study

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