Mitochondrial dysfunctions in HIV infection and antiviral drug treatment

Ganta, Krishna Kumar; Chaubey, Binay

doi:10.1080/17425255.2019.1692814

Cited by 12 publications

(9 citation statements)

References 111 publications

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Section: Discussionmentioning

confidence: 99%

“…14,15 With the decrease of CD4+ T lymphocytes, the incidence of opportunistic infections will increase, threatening the function of blood-retinal barrier 12,13 and finally lead to HIV retinopathy. [16][17][18] HAART has been demonstrated to be the most effective treatment for HIV infection. According to our results, the CD4+ T lymphocyte counts of the patients significantly increased from 451.37±2.10 to 563.34±2.56 cells/μL, and the plasma viral load of HIV-1 decreased significantly from 4794 to 0 copy/mL (P=0.000) after effective HAART treatment.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Highly Active Antiretroviral Therapy on Fundus Images and Retinal Microvessel Diameter in HIV/AIDS Patients

Li¹,

Chen²,

Ye³

et al. 2023

HIV

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Introduction We aimed to investigate whether there were changes in fundus picture and retinal microvascularity of patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who were treated with highly active antiretroviral therapy (HAART). Methods From July 2015 to November 2016, 130 HIV/AIDS patients were collected by the Yunnan Institute of Traditional Chinese Medicine, including 63 treatment-naïve patients and 67 that received HAART for 12 months. Fundus picture lesions, retinal microvascular diameters, CD4+ T lymphocyte count and HIV-1 plasma viral loads were compared between the two groups. The recruited patients were mainly young and middle-aged, with more males than females. There were no significant differences in smoking history, comorbidities and opportunistic infections between the two groups. Results According to the analysis results from SPSS 20.0 software, the number of CD4+ T lymphocytes in the treated patients (563.34±2.56 cells/μL) increased significantly (P=0.009) as compared with untreated patients (451.37±2.10 cells/μL), and the HIV-1 plasma viral load reduced considerably (4794 vs 0 copy/mL, P=0.000). No significant differences were observed from the fundus picture of patients after effective HAART therapy, including the retinal artery diameter, venous diameter and arteriovenous diameter ratio.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Highly Active Antiretroviral Therapy on Fundus Images and Retinal Microvessel Diameter in HIV/AIDS Patients

Li¹,

Chen²,

Ye³

et al. 2023

HIV

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“…Tenofovir is still widely used ( 6 ). PIs directly inhibit cell metabolism through decreasing the mitochondrial membrane potential which is pivotal in ATP production, but this effect may vary with cell type ( 59 , 60 ). Efavirenz, like HIV infection, inhibits CI in the human ETC whilst murine studies have shown that Efavirenz inhibits CIV resulting in decreased ATP production and increased ROS production ( 61 ).…”

Section: Mitochondria Are Regulatory Hubs For Cell Metabolism and Fun...mentioning

confidence: 99%

Human immunodeficiency virus and antiretroviral therapy-mediated immune cell metabolic dysregulation in children born to HIV-infected women: potential clinical implications

2023

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Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+) has dramatically improved the health of HIV-infected women and their children, with the majority being of HIV-exposed children born uninfected (HEU). This success has led to an increasing population of HIV-infected women receiving ART during pregnancy and children exposed to ART in utero. Nonetheless, a small proportion of children are still infected with HIV (HEI) each year. HEI children suffer from reduced immunocompetence and host-defence, due to CD4+ T lymphocyte depletion, but also dysregulation of other immune cells including CD8+ T lymphocytes, natural killer (NK) cells, macrophages including B lymphocytes. Furthermore, although HEU children are uninfected, altered immune responses are observed and associated with increased vulnerability to infections. The mechanisms underlying immune dysregulation in HEU children remain poorly described. Building on early studies, emerging data suggests that HIV/ART exposure early in life affects cell metabolic function of HEU children. Prenatal HIV/ART exposure has been associated with dysregulation of mitochondria, including impaired DNA polymerase activity. Furthermore, dysregulation of oxidative phosphorylation (OXPHOS) causes a decreased generation of adenosine triphosphate (ATP) and increased production of reactive oxygen species (ROS), resulting in oxidative stress. These altered metabolic processes can affect immune cell viability and immune responses. Recent studies have indicated that immune-metabolic dysregulation may contribute to HIV-associated pathogenesis and clinical observations associated with HIV and ART exposure in HEU/HEI children. Given the critical role metabolic processes in immune cell functioning, immune-metabolic dysregulation in HEU and HEI children may have implications in effective host-defence responses against pathogens, as well as efficacy of standard ART regimens and future novel HIV cure approaches in HEI children. At the same time, targeting metabolic pathways of immune cells may provide safer and novel approaches for HIV cure strategies. Here, we review the current literature investigating immune-metabolic dysregulation in paediatric HIV pathogenesis.

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“…Studies into HAART and their associated disorders show that individual ARV drugs have different degrees of toxicity that are tissue-specific and time-dependent [ 13 , 14 ]. Oxidative stress and mitochondrial dysfunction are highlighted as key metabolic pathways by which ARV drug-induced toxicity arises [ 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Moringa oleifera Lam Leaf Extract Stimulates NRF2 and Attenuates ARV-Induced Toxicity in Human Liver Cells (HepG2)

Ndlovu

Chuturgoon

Ghazi

2023

Plants

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The World Health Organization (WHO) reported that there are 37 million individuals living with the human immunodeficiency virus (HIV) worldwide, with the majority in South Africa. This chronic disease is managed by the effective use of antiretroviral (ARV) drugs. However, with prolonged use, ARV drug-induced toxicity remains a clinically complex problem. This study investigated the toxicity of ARV drugs on mitochondria and the NRF2 antioxidant pathway and its possible amelioration using Moringa oleifera Lam (MO) leaf extracts. This medicinal plant has a range of functional bioactive compounds. Liver (HepG2) cells were treated with individual ARV drugs: Tenofovir disoproxil fumarate (TDF), Emtricitabine (FTC), and Lamivudine (3TC) for 96 h, followed by MO leaf extracts for 24 h. Intracellular ROS, cytotoxicity, lipid peroxidation, total and reduced glutathione (GSH), ATP, and mitochondrial polarisation were determined. Finally, protein (pNRF2, NRF2, SOD2, CAT, and Sirt3) and mRNA (NRF2, CAT, NQO1 SOD2, Sirt3, and PGC1α) expression were measured using Western blot and qPCR, respectively. TDF, FTC, and 3TC significantly increased intracellular ROS and extracellular levels of both MDA and LDH. ARVs also reduced the GSH and ATP levels and altered the mitochondrial polarization. Further, ARVs reduced the expression of NRF2 SOD2, Sirt3, CAT, NQO1, UCP2 and PGC1α mRNA and consequently pNRF2, NRF2, SOD2, Sirt3 and CAT protein. In contrast, there was a significant reduction in the extracellular MDA and LDH levels post-MO treatment. MO significantly reduced intracellular ROS while significantly increasing GSH, ATP, and mitochondrial membrane polarization. The addition of MO to ARV-treated cells significantly upregulated the expression of NRF2, SOD2, Sirt3, CAT, UCP2, PGC1α, and NQO1 mRNA and pNRF2, NRF2, SOD2, Sirt3 proteins. Thus, MO ameliorates ARV-induced hepatotoxicity by scavenging oxidants by inducing the NRF2 antioxidant pathway. MO shows great therapeutic potential and may be considered a potential supplement to ameliorate ARV drug toxicity.

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Mitochondrial dysfunctions in HIV infection and antiviral drug treatment

Cited by 12 publications

References 111 publications

Effect of Highly Active Antiretroviral Therapy on Fundus Images and Retinal Microvessel Diameter in HIV/AIDS Patients

Effect of Highly Active Antiretroviral Therapy on Fundus Images and Retinal Microvessel Diameter in HIV/AIDS Patients

Human immunodeficiency virus and antiretroviral therapy-mediated immune cell metabolic dysregulation in children born to HIV-infected women: potential clinical implications

Moringa oleifera Lam Leaf Extract Stimulates NRF2 and Attenuates ARV-Induced Toxicity in Human Liver Cells (HepG2)

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