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HIV gene therapy

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https://www.readbyqxmd.com/read/28738474/-hiv-1-drug-resistance-transmission-threshold-survey-in-dehong-prefecture-of-yunnan-province-2015
#1
M Chen, J B Wang, H Xing, Y L Ma, J Yang, H C Chen, S T Yao, H B Luo, X Duan, Y K Wang, S Duan, M H Jia
Objective: To study the HIV-1 drug resistance transmission level in HIV infected persons receiving no antiviral therapy in Dehong prefecture of Yunnan province in 2015. Methods: A total of 72 plasma samples were collected from recently reported HIV-infected persons aged 16-25 years in Dehong from January to July 2015 for drug resistance gene detection. Results: Forty eight samples were successfully sequenced and analyzed. Among them, 31.2% (15/48) were from Chinese, and 68.8% (33/48) were from Burmese. Based on pol sequences, HIV genotypes included URF (52...
July 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28729655/a-crispr-cas9-guidance-rna-screen-platform-for-hiv-provirus-disruption-and-hiv-aids-gene-therapy-in-astrocytes
#2
Zaohua Huang, Madahavan Nair
HIV/AIDS remains a major health threat despite significant advances in the prevention and treatment of HIV infection. The major reason is the inability of existing treatments to eradicate the multiple HIV reservoirs in the human body, including astrocytes in the human brain. CRISPR/Cas9 system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV provirus in HIV reservoir cells, which may lead to a complete cure of HIV/AIDS. The key components of CRISPR/Cas9 are guide RNAs (gRNAs) which determine specific sequence targeting of DNAs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728523/structural-insights-into-the-binding-of-small-ligand-molecules-to-a-g-quadruplex-dna-located-in-the-hiv-1-promoter
#3
Petar M Mitrasinovic
Targeting guanine (G)-rich DNA sequences, folded into non-canonical G-quadruplex (G4) structures, by small ligand molecules is a promising strategy for gene therapy of various diseases. There is experimental proposal that, among eight studied ligands, nitidine chloride - NC and a benzo phenanthridine derivative - BPD have the highest binding affinities for such a sequence (5'-T(1)G(2)G(3)C(4)C(5)T(6)G(7)G(8)G(9)C(10)G(11)G(12)G(13)A(14)C(15)T(16)G(17)G(18)G(19)-3') in the HIV-1 promoter, indicating that an anti-HIV-1 prodrug may regulate the expression of the promoter...
July 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28718515/impact-of-single-nucleotide-polymorphisms-on-plasma-concentrations-of-efavirenz-and-lopinavir-ritonavir-in-chinese-children-infected-with-the-human-immunodeficiency-virus
#4
Xia Liu, Qing Ma, Yan Zhao, Weiwei Mu, Xin Sun, Yuewu Cheng, Huiping Zhang, Ye Ma, Fujie Zhang
Single-nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. While primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and solute carrier organic (SLCO) anion transporter, respectively OBJECTIVE: To investigate the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV) METHODS: Genotyping was performed on CYP2B6 516G→T, -1459C→T, and -983T→C, ABCB1 3435C→T, and SLCO1B1 521T→C in 229 HIV-infected Chinese pediatric patients with an age range from 4...
July 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28717861/patient-perspectives-on-gene-transfer-therapy-for-sickle-cell-disease
#5
Heather Strong, Monica J Mitchell, Alana Goldstein-Leever, Lisa Shook, Punam Malik, Lori E Crosby
INTRODUCTION: Sickle cell disease (SCD) is a chronic genetic disease with high morbidity and early mortality; it affects nearly 100,000 individuals in the USA. Bone marrow transplantation, the only curative treatment, is available to less than 20% of patients because of a number of access barriers. Gene transfer therapy (GTT) has been shown to be curative in animal models and is approved for use in humans for early-phase studies at a few centers. GTT would offer a more accessible treatment option available to all patients...
July 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28705213/the-therapeutic-landscape-of-hiv-1-via-genome-editing
#6
REVIEW
Alexander Kwarteng, Samuel Terkper Ahuno, Godwin Kwakye-Nuako
Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR-Cas9) are transforming the therapeutic landscape of HIV-1...
July 14, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28699519/the-tat-p-tefb-protein-protein-interaction-determining-transcriptional-activation-of-hiv
#7
Kaori Asamitsu, Takashi Okamoto
Human immunodeficiency virus type (HIV) transcription is crucial for its life cycle and is primarily involved in the maintenance of viral latency. HIV transcription is regulated by both viral and cellular transcription factors. Numerous epigenetic factors, as well as transcriptional suppressor proteins, play major roles in the maintenance of transcriptional silencing of viral gene expression from the proviral DNA. Once inducible transcription factors such as nuclear factor B are activated through extracellular signaling, viral latency is terminated and transcription from the silenced proviral DNA is initiated...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28698211/extra-rectal-lymphogranuloma-venereum-in-france-a-clinical-and-molecular-study
#8
Arnaud Desclaux, Arabella Touati, Didier Neau, Cécile Laurier-Nadalié, Cécile Bébéar, Bertille de Barbeyrac, Charles Cazanave
OBJECTIVES: To describe a series of extrarectal lymphogranuloma venereum (LGV) cases diagnosed in France. METHODS: Consecutive LGV cases confirmed at the French Reference Centre for chlamydiae with an extrarectal sample from January 2010 to December 2015 were included. The first part of the study consisted of a retrospective case note review and analysis. In a second part, the complete ompA gene sequence of our samples was determined. RESULTS: There were 56 cases overall: 50 cases of genital LGV and six cases of pharyngeal LGV...
July 11, 2017: Sexually Transmitted Infections
https://www.readbyqxmd.com/read/28692305/fight-fire-with-fire-gene-therapy-strategies-to-cure-hiv
#9
Jon Huyghe, Sips Magdalena, Linos Vandekerckhove
Human Immunodeficiency Virus (HIV) to date remains one of the most notorious viruses mankind has ever faced. Despite enormous investments in HIV research for more than 30 years an effective cure for HIV has been elusive. Areas covered: Combination antiretroviral therapy (cART) suppresses active viral replication, but is not able to eliminate the virus completely due to stable integration of HIV inside the host genome of infected cells and the establishment of a latent reservoir, that is insensitive to cART...
July 14, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28692018/the-state-of-gene-therapy-research-in-africa-its-significance-and-implications-for-the-future
#10
REVIEW
P Arbuthnot, M B Maepa, A Ely, M S Pepper
Gene therapy has made impressive recent progress and has potential for treating a wide range of diseases, many of which are important to Africa. However, as a result of lack of direct public funding and skilled personnel, direct research on gene therapy in Africa is currently limited and resources to support the endeavor are modest. A strength of the technology is that it is based on principles of rational design, and the tools of gene therapy are now highly versatile. For example gene silencing and gene editing may be used to disable viral genes for therapeutic purposes...
July 10, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28687465/on-the-way-to-find-a-cure-purging-latent-hiv-1-reservoirs
#11
REVIEW
Christian Schwartz, Sophie Bouchat, Céline Marban, Virginie Gautier, Carine Van Lint, Olivier Rohr, Valentin Le Douce
Introduction of cART in 1996 has drastically increased the life expectancy of people living with HIV-1. However, this treatment has not allowed cure as cessation of cART is associated with a rapid viral rebound. The main barrier to the eradication of the virus is related to the persistence of latent HIV reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might lead to a cure or a remission. The most studied strategy is the so called "shock and kill" therapy. This strategy is based on reactivation of dormant viruses from the latently-infected reservoirs (the shock) followed by the eradication of the reservoirs (the kill)...
July 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28679441/hiv-1-genetic-diversity-and-primary-drug-resistance-mutations-before-large-scale-access-to-antiretroviral-therapy-republic-of-congo
#12
Fabien Roch Niama, Nicole Vidal, Halimatou Diop-Ndiaye, Etienne Nguimbi, Gabriel Ahombo, Philippe Diakabana, Édith Sophie Bayonne Kombo, Pembe Issamou Mayengue, Simon-Charles Kobawila, Henri Joseph Parra, Coumba Toure-Kane
BACKGROUND: In this work, we investigated the genetic diversity of HIV-1 and the presence of mutations conferring antiretroviral drug resistance in 50 drug-naïve infected persons in the Republic of Congo (RoC). Samples were obtained before large-scale access to HAART in 2002 and 2004. METHODS: To assess the HIV-1 genetic recombination, the sequencing of the pol gene encoding a protease and partial reverse transcriptase was performed and analyzed with updated references, including newly characterized CRFs...
July 5, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28675900/hiv-1-subtype-diversity-and-prevalence-of-primary-drug-resistance-in-a-single-center-pediatric-cohort-in-germany
#13
Jennifer Neubert, Nadja Michalsky, Hans-Jürgen Laws, Arndt Borkhardt, Björn Jensen, Nadine Lübke
OBJECTIVES: Data on drug-resistant mutations (DRMs) in HIV-1-infected therapy-naïve children are scarce. The aim of this study was to determine the HIV-1 subtype distribution and the prevalence of DRMs in therapy-naïve HIV-1-infected children who received routine care at the University Hospital Düsseldorf, Düsseldorf, Germany. METHODS: Records of all HIV-1-infected children who received routine care between January 2005 and December 2015 were analyzed retrospectively...
2016: Intervirology
https://www.readbyqxmd.com/read/28649306/decreasing-prevalence-of-transmitted-drug-resistance-among-art-naive-hiv-1-infected-patients-in-iceland-1996-2012
#14
Malik Sallam, Gülşen Özkaya Şahin, Hlynur Indriðason, Joakim Esbjörnsson, Arthur Löve, Anders Widell, Magnus Gottfreðsson, Patrik Medstrand
Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches...
2017: Infection Ecology & Epidemiology
https://www.readbyqxmd.com/read/28639194/rnaa-induced-by-tata-box-targeting-micrornas
#15
Yijun Zhang, Hui Zhang
Recent studies reveal that some nuclear microRNAs (miRNA) and synthesized siRNAs target gene promoters to activate gene transcription (RNAa). Interestingly, our group identified a novel HIV-1-encoded miRNA, miR-H3, which targets specifically the core promoter TATA box of HIV-1 and activates viral gene expression. Depletion of miR-H3 significantly impaired the replication of HIV-1. miR-H3 mimics could activate viruses from CD4(+) T cells isolated from patients receiving suppressive highly active antiretroviral therapy, which is very intriguing for reducing HIV-1 latent reservoir...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28628034/clonal-expansion-of-genome-intact-hiv-1-in-functionally-polarized-th1-cd4-t-cells
#16
Guinevere Q Lee, Nina Orlova-Fink, Kevin Einkauf, Fatema Z Chowdhury, Xiaoming Sun, Sean Harrington, Hsiao-Hsuan Kuo, Stephane Hua, Hsiao-Rong Chen, Zhengyu Ouyang, Kavidha Reddy, Krista Dong, Thumbi Ndung'u, Bruce D Walker, Eric S Rosenberg, Xu G Yu, Mathias Lichterfeld
HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28624214/further-characterization-of-the-bifunctional-hiv-entry-inhibitor-scd4-fit45
#17
Alexander Falkenhagen, Sadhna Joshi
HIV entry into target cells is a highly sequential and time-sensitive process. In recent years, potent HIV Env-targeting antibodies, such as VRC01, have been identified. However, antibodies bind only to a single epitope, and mutations that confer resistance to antibody-mediated inhibition of HIV entry have been detected. In contrast, HIV cannot escape from binding to soluble CD4 (sCD4) without a fitness disadvantage. sCD4 has the unique ability to induce conformational changes within the HIV envelope glycoproteins (Env) that allow fusion inhibitors to bind...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622951/population-approach-to-efavirenz-therapy
#18
Hélder Duarte, João Paulo Cruz, Natália Aniceto, Ana Clara Ribeiro, Ana Fernandes, Paulo Paixão, Francisco Antunes, José Morais
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor commonly used as first line therapy in the treatment of human immunodeficiency virus, with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady state plasma concentrations, a population pharmacokinetic model was developed form 96 HIV positive individuals, using a nonlinear mixed effect method with Monolix® software...
June 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28619387/evaluation-of-ameliorative-ability-of-silibinin-against-zidovudine-and-isoniazid-induced-hepatotoxicity-and-hyperlipidaemia-in-rats-role-of-silibinin-in-phase-i-and-ii-drug-metabolism
#19
Raghu Ramanathan, Karthikeyan Sivanesan
HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as "Milk thistle" is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH + AZT-induced toxic insults to liver of rats...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28614778/the-human-immunodeficiency-virus-hiv1-protease-inhibitor-sanquinavir-activates-autophagy-and-removes-lipids-deposited-in-lipid-droplets
#20
A Polus, M Bociaga-Jasik, U Czech, J Goralska, U Cialowicz, M Chojnacka, M Polus, K Jurowski, A Dembinska-Kiec
Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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