scholarly journals Microscopic and biochemical changes on liver and kidney of Wistar rats on combination antiretroviral therapy: the impact of naringenin and quercetin

2020 ◽  
Vol 9 (5) ◽  
pp. 601-608
Author(s):  
Edidiong Nnamso Akang ◽  
Olufunke O Dosumu ◽  
Ini-ibehe Essien Okoko ◽  
Oluwatomisin Faniyan ◽  
Ademola A Oremosu ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Wistar Rats ◽  
Combination Antiretroviral Therapy ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus ◽  
Male Wistar Rats ◽  
Liver And Kidney ◽  
Factor Alpha ◽  
Continuous Use ◽  
The Impact

Abstract Combination antiretroviral therapy (cART), which is a lifelong therapy for people living with human immunodeficiency virus, has been associated with nephrotoxicity and hepatotoxicity leading to its discontinuation. This study aimed at investigating the ameliorative potential of naringenin and quercetin on cART-induced hepatotoxicity and nephrotoxicity. Seventy male Wistar rats (225–260 g) were divided into seven groups as control, cART, naringenin, quercetin, dimethyl sulfoxide (DMSO), naringenin/cART (CN) and quercetin/cART (CQ). cART (24 mg/kg), naringenin (50 mg/kg) and quercetin (50 mg/kg) were dissolved in 1% v/v DMSO and administered orally for 56 days. Combination of cART and bioflavonoids had significant increase in superoxide dismutase (P < 0.05), catalase (P < 0.01), reduced glutathione (P < 0.001) and decreased malondialdehyde (P < 0.001) compared to cART only. Tumor necrosis factor Alpha (TNFα) level increased significantly in cART and CQ (P < 0.01) groups, while others showed no significant changes compared to control. TNFα also significantly decreased in CQ level compared to cART (P < 0.001). In addition, significant increase in creatinine level in cART only indicated progressive renal toxicity. Also, progressive pathological changes including congested blood vessels and hepatocellular necrosis were found in the liver, while the kidney had glomerular atrophy, and tubular distortion in cART-only group. Control, naringenin- and quercetin-treated groups showed normal renal and hepatic cytoarchitecture. These findings elucidate that progressive renal and hepatic toxicity is associated with the continuous use of cART; however, a combination of quercetin and naringenin with cART showed possible potential of ameliorating the damages posed by cART.

scholarly journals All-Cause Mortality and Serious Non-AIDS Events in Adults With Low-level Human Immunodeficiency Virus Viremia During Combination Antiretroviral Therapy: Results From a Swedish Nationwide Observational Study

2020 ◽  
Author(s):  
Olof Elvstam ◽  
Gaetano Marrone ◽  
Patrik Medstrand ◽  
Carl Johan Treutiger ◽  
Anders Sönnerborg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Clinical Outcomes ◽  
Virologic Suppression ◽  
Combination Antiretroviral Therapy ◽  
Low Level ◽  
Immunodeficiency Virus ◽  
All Cause Mortality ◽  
The Impact

Abstract Background The impact of low levels of human immunodeficiency virus (HIV) RNA (low-level viremia [LLV]) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAEs). Methods We grouped individuals starting cART 1996–2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load, 50–999 copies/mL), and nonsuppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50–199 and 200–999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes. Results A total of 6956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR], 2.2; 95% confidence interval [CI], 1.3–3.6). This association was also observed for LLV 50–199 copies/mL (aHR, 2.2; 95% CI, 1.3–3.8), but was not statistically significant for LLV 200–999 copies/mL (aHR, 2.1; 95% CI, .96–4.7). LLV 50–999 copies/mL was not linked to increased risk of AIDS or SNAEs, but in subanalysis, LLV 200–999 copies/mL was associated with SNAEs (aHR, 2.0; 95% CI, 1.2–3.6). Conclusions In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.

scholarly journals Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy

2015 ◽  
Vol 60 (3) ◽  
pp. 1560-1572 ◽  
Author(s):  
Gregory Q. Del Prete ◽  
Kelli Oswald ◽  
Abigail Lara ◽  
Rebecca Shoemaker ◽  
Jeremy Smedley ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Rhesus Macaques ◽  
Saline Control ◽  
Combination Antiretroviral Therapy ◽  
Functional Cure ◽  
Eradication Strategy ◽  
Immunodeficiency Virus ◽  
The Impact

Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremiain vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n= 5) or saline (n= 3) starting 31 to 54 weeks after cART initiation.In vivoRMD treatment resulted in significant transient increases in acetylated histone levels in CD4+T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy.

scholarly journals Is ventricular arrhythmias the end for all conditions ?

2021 ◽  
Author(s):  
Ahmet Goktug Ertem ◽  
Mehmet Akif Erdol ◽  
Koray Demirtas ◽  
Sefa Unal ◽  
Mustafa Karanfil ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Risk Factor ◽  
Antiretroviral Therapy ◽  
Ventricular Arrhythmias ◽  
Combination Antiretroviral Therapy ◽  
T Wave ◽  
Medical Status ◽  
Immunodeficiency Virus ◽  
Duration Of Disease ◽  
Severity Of The Disease

Dear Editor, We read the article entitled “Abnormal Dispersion of Ventricular Repolarization as a Risk Factor in Patients with Human Immunodeficiency Virus: Tp-e Interval, Tp-e/QTc Ratio” by Unal Evren et al. with interest[1]. The authors evaluated the changes in Tp-e interval, Tp-e/QT and Tp-e/corrected QT (QTc) ratios, and traditional electrocardiographic features of electrical dispersion in adults infected with Human Immunodeficiency Virus (HIV) and their study revealed that the cTp-e interval, Tp-e/QT and Tp-e/QTc ratios were prolonged and correlated to the severity of the disease in HIV-infected patients. Previous studies have revealed that the Tp–e interval, the Tpeak-Tend interval (Tpe), the interval from the T-wave peak to the end of the T wave, has been related to arrhythmogenesis, is specified as an index of totaldispersion of repolarization[2]. Prolonged Tp–e interval is predictable for ventricular arrhythmias and mortality [3]. Unal et al. showed that HIV-infected patients receiving combination antiretroviral therapy (cART) were associated withlonger Tp–e interval and Tp–e/QTc ratio and correlated positively with the duration of disease and the electrophysiologicalabnormalities, and negatively with CD4 count[4]. There were no informations about medical status of patients with HIV, duration of the disease and why hsCRP is higher in patients’ group. The patients were in active phases of infection. We think that these are important datas for results of the study. We thank the authors for adding this article to the literature

scholarly journals Human Immunodeficiency Virus Infection Alters Tumor Necrosis Factor Alpha Production via Toll-Like Receptor-Dependent Pathways in Alveolar Macrophages and U1 Cells

2008 ◽  
Vol 82 (16) ◽  
pp. 7790-7798 ◽  
Author(s):  
Marlynne Q. Nicol ◽  
Jean-Marie Mathys ◽  
Albertina Pereira ◽  
Kevin Ollington ◽  
Michael H. Ieong ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Innate Immune ◽  
Hiv Positive ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Human immunodeficiency virus (HIV)-positive persons are predisposed to pulmonary infections, even after receiving effective highly active antiretroviral therapy. The reasons for this are unclear but may involve changes in innate immune function. HIV type 1 infection of macrophages impairs effector functions, including cytokine production. We observed decreased constitutive tumor necrosis factor alpha (TNF-α) concentrations and increased soluble tumor necrosis factor receptor type II (sTNFRII) in bronchoalveolar lavage fluid samples from HIV-positive subjects compared to healthy controls. Moreover, net proinflammatory TNF-α activity, as measured by the TNF-α/sTNFRII ratio, decreased as HIV-related disease progressed, as manifested by decreasing CD4 cell count and increasing HIV RNA (viral load). Since TNF-α is an important component of the innate immune system and is produced upon activation of Toll-like receptor (TLR) pathways, we hypothesized that the mechanism associated with deficient TNF-α production in the lung involved altered TLR expression or a deficit in the TLR signaling cascade. We found decreased Toll-like receptor 1 (TLR1) and TLR4 surface expression in HIV-infected U1 monocytic cells compared to the uninfected parental U937 cell line and decreased TLR message in alveolar macrophages (AMs) from HIV-positive subjects. In addition, stimulation with TLR1/2 ligand (Pam3Cys) or TLR4 ligand (lipopolysaccharide) resulted in decreased intracellular phosphorylated extracellular signal-regulated kinase and subsequent decreased transcription and expression of TNF-α in U1 cells compared to U937 cells. AMs from HIV-positive subjects also showed decreased TNF-α production in response to these TLR2 and TLR4 ligands. We postulate that HIV infection alters expression of TLRs with subsequent changes in mitogen-activated protein kinase signaling and cytokine production that ultimately leads to deficiencies of innate immune responses that predispose HIV-positive subjects to infection.

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