Recrudescence of Natural Coccidioidomycosis during Combination Antiretroviral Therapy in a Pigtail Macaque Experimentally Infected with Simian Immunodeficiency Virus

2020 ◽  
Author(s):  
Kathryn A Guerriero ◽  
Robert D Murnane ◽  
Thomas B Lewis ◽  
Brieann Brown ◽  
Audrey Baldessari ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Simian Immunodeficiency Virus ◽  
Combination Antiretroviral Therapy ◽  
Pigtail Macaque ◽  
Immunodeficiency Virus

scholarly journals Evaluating the Intactness of Persistent Viral Genomes in Simian Immunodeficiency Virus-Infected Rhesus Macaques after Initiating Antiretroviral Therapy within One Year of Infection

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Samuel Long ◽  
Christine M. Fennessey ◽  
Laura Newman ◽  
Carolyn Reid ◽  
Sean P. O’Brien ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Genome Sequencing ◽  
Real Time Pcr ◽  
Rhesus Macaques ◽  
Viral Reservoir ◽  
Combination Antiretroviral Therapy ◽  
Viral Dna ◽  
Immunodeficiency Virus

ABSTRACT The major obstacle to more-definitive treatment for HIV infection is the early establishment of virus that persists despite long-term combination antiretroviral therapy (cART) and can cause recrudescent viremia if cART is interrupted. Previous studies of HIV DNA that persists despite cART indicated that only a small fraction of persistent viral sequences was intact. Experimental simian immunodeficiency virus (SIV) infections of nonhuman primates (NHPs) are essential models for testing interventions designed to reduce the viral reservoir. We studied the viral genomic integrity of virus that persists during cART under conditions typical of many NHP reservoir studies, specifically with cART started within 1 year postinfection and continued for at least 9 months. The fraction of persistent DNA in SIV-infected NHPs starting cART during acute or chronic infection was assessed with a multiamplicon, real-time PCR assay designed to analyze locations that are regularly spaced across the viral genome to maximize coverage (collectively referred to as “tile assay”) combined with near-full-length (nFL) single-genome sequencing. The tile assay is used to rapidly screen for major deletions, with nFL sequence analysis used to identify additional potentially inactivating mutations. Peripheral blood mononuclear cells (PBMC) from animals started on cART within 1 month of infection, sampled at least 9 months after cART initiation, contained at least 80% intact genomes, whereas those from animals started on cART 1 year postinfection and treated for 1 year contained intact genomes only 47% of the time. The most common defect identified was large deletions, with the remaining defects caused by APOBEC-mediated mutations, frameshift mutations, and inactivating point mutations. Overall, this approach can be used to assess the intactness of persistent viral DNA in NHPs. IMPORTANCE Molecularly defining the viral reservoir that persists despite antiretroviral therapy and that can lead to rebound viremia if antiviral therapy is removed is critical for testing interventions aimed at reducing this reservoir. In HIV infection in humans with delayed treatment initiation and extended treatment duration, persistent viral DNA has been shown to be dominated by nonfunctional genomes. Using multiple real-time PCR assays across the genome combined with near-full-genome sequencing, we defined SIV genetic integrity after 9 to 18 months of combination antiretroviral therapy in rhesus macaques starting therapy within 1 year of infection. In the animals starting therapy within a month of infection, the vast majority of persistent DNA was intact and presumptively functional. Starting therapy within 1 year increased the nonintact fraction of persistent viral DNA. The approach described here allows rapid screening of viral intactness and is a valuable tool for assessing the efficacy of novel reservoir-reducing interventions.

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 Significant Depletion of CD4+T Cells Occurs in the Oral Mucosa during Simian Immunodeficiency Virus Infection with the Infected CD4+T Cell Reservoir Continuing to Persist in the Oral Mucosa during Antiretroviral Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jeffy George ◽  
Wendeline Wagner ◽  
Mark G. Lewis ◽  
Joseph J. Mattapallil
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Simian Immunodeficiency Virus ◽  
Oral Mucosa ◽  
Mucosal Immunity ◽  
Viral Reservoir ◽  
Long Term Outcome ◽  
Immunodeficiency Virus ◽  
A Minor

Human and simian immunodeficiency virus (HIV and SIV) infections are characterized by manifestation of numerous opportunistic infections and inflammatory conditions in the oral mucosa. The loss of CD4+T cells that play a critical role in maintaining mucosal immunity likely contributes to this process. Here we show that CD4+T cells constitute a minor population of T cells in the oral mucosa and display a predominantly central memory phenotype mirroring other mucosal sites such as the rectal mucosa. Chronic SIV infection was associated with a near total depletion of CD4+T cells in the oral mucosa that appear to repopulate during antiretroviral therapy (ART). Repopulating CD4+T cells harbored a large fraction of Th17 cells suggesting that ART potentially reconstitutes oral mucosal immunity. However, a minor fraction of repopulating CD4+T cells harbored SIV DNA suggesting that the viral reservoir continues to persist in the oral mucosa during ART. Therapeutic approaches aimed at obtaining sustainable CD4+T cell repopulation in combination with strategies that can eradicate the latent viral reservoir in the oral mucosa are essential for better oral health and long-term outcome in HIV infected patients.

scholarly journals T-cell subset differentiation and antibody responses following antiretroviral therapy during simian immunodeficiency virus infection

Immunology ◽  
2018 ◽  
Vol 155 (4) ◽  
pp. 458-466
Author(s):  
Mitra Bhattacharyya ◽  
James B. Whitney ◽  
Michael Seaman ◽  
Dan H. Barouch ◽  
Pablo Penaloza-MacMaster
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Cell Subset ◽  
Antibody Responses ◽  
Simian Immunodeficiency Virus Infection ◽  
T Cell Subset ◽  
Immunodeficiency Virus

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.

Human immunodeficiency virus-associated polymyositis during immune restoration with combination antiretroviral therapy

2000 ◽  
Vol 109 (6) ◽  
pp. 510-512 ◽  
Author(s):  
Pierre Sellier ◽  
Jean-Jacques Monsuez ◽  
John Evans ◽  
Catherine Minozzi ◽  
Jean Passeron ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Combination Antiretroviral Therapy ◽  
Immune Restoration ◽  
Immunodeficiency Virus
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