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HIV gene therapy

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https://www.readbyqxmd.com/read/28099434/mlst-based-population-genetic-analysis-in-a-global-context-reveals-clonality-amongst-cryptococcus-neoformans-var-grubii-vni-isolates-from-hiv-patients-in-southeastern-brazil
#1
Kennio Ferreira-Paim, Leonardo Andrade-Silva, Fernanda M Fonseca, Thatiana B Ferreira, Delio J Mora, Juliana Andrade-Silva, Aziza Khan, Aiken Dao, Eduardo C Reis, Margarete T G Almeida, Andre Maltos, Virmondes R Junior, Luciana Trilles, Volker Rickerts, Ariya Chindamporn, Jane E Sykes, Massimo Cogliati, Kirsten Nielsen, Teun Boekhout, Matthew Fisher, June Kwon-Chung, David M Engelthaler, Marcia Lazéra, Wieland Meyer, Mario L Silva-Vergara
Cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with HIV. In Brazil, despite the free availability of antiretroviral therapy (ART) in the public health system, the mortality rate due to Cryptococcus neoformans meningitis is still high. To obtain a more detailed picture of the population genetic structure of this species in southeast Brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. Among the patients, 59% had a fatal outcome mainly in HIV-positive male patients...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28099408/multiphenotype-association-study-of-patients-randomized-to-initiate-antiretroviral-regimens-in-aids-clinical-trials-group-protocol-a5202
#2
Anurag Verma, Yuki Bradford, Shefali S Verma, Sarah A Pendergrass, Eric S Daar, Charles Venuto, Gene D Morse, Marylyn D Ritchie, David W Haas
BACKGROUND: High-throughput approaches are increasingly being used to identify genetic associations across multiple phenotypes simultaneously. Here, we describe a pilot analysis that considered multiple on-treatment laboratory phenotypes from antiretroviral therapy-naive patients who were randomized to initiate antiretroviral regimens in a prospective clinical trial, AIDS Clinical Trials Group protocol A5202. PARTICIPANTS AND METHODS: From among 5 9545 294 polymorphisms imputed genome-wide, we analyzed 2544, including 2124 annotated in the PharmGKB, and 420 previously associated with traits in the GWAS Catalog...
January 5, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28094770/rapamycin-mediated-mtor-inhibition-uncouples-hiv-1-latency-reversal-from-cytokine-associated-toxicity
#3
Alyssa R Martin, Ross A Pollack, Adam Capoferri, Richard F Ambinder, Christine M Durand, Robert F Siliciano
Current strategies for HIV-1 eradication require the reactivation of latent HIV-1 in resting CD4+ T cells (rCD4s). Global T cell activation is a well-characterized means of inducing HIV-1 transcription, but is considered too toxic for clinical applications. Here, we have explored a strategy that involves a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. In purified rCD4s from HIV-1-infected individuals on antiretroviral therapy, rapamycin treatment downregulated markers of toxicity, including proinflammatory cytokine release and cellular proliferation that were induced after potent T cell activation using αCD3/αCD28 antibodies...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28091937/ocular-mycobacteriosis-dual-infection-of-m-tuberculosis-complex-with-m-fortuitum-and-m-bovis
#4
Kusum Sharma, Natasha Gautam, Megha Sharma, Mohit Dogra, Priya Bajgai, Basavaraj Tigari, Aman Sharma, Vishali Gupta, Surya Prakash Sharma, Ramandeep Singh
BACKGROUND: We report unfavorable outcome in a patient with subretinal granuloma caused by dual infection of Mycobacterium tuberculosis complex with Mycobacterium fortuitum and Mycobacterium bovis in an immunosuppressed, non-HIV patient. We did a systematic review of literature on dual infection due to M. tuberculosis and M. fortuitum via MEDLINE and PUBMED and could not find any case reported of causing this kind of dual infection in the eye. RESULTS: A 38-year-old Indian male patient presented with decreased vision in the left eye for 3 months, diagnosed as tubercular choroidal granuloma with associated retinal angiomatosis proliferans (RAP) lesion...
December 2017: Journal of Ophthalmic Inflammation and Infection
https://www.readbyqxmd.com/read/28086981/does-antiretroviral-treatment-change-hiv-1-codon-usage-patterns-in-its-genes-a-preliminary-bioinformatics-study
#5
Navaneethan Palanisamy, Nathan Osman, Frédéric Ohnona, Hong-Tao Xu, Bluma Brenner, Thibault Mesplède, Mark A Wainberg
BACKGROUND: Codon usage bias has been described for various organisms and is thought to contribute to the regulation of numerous biological processes including viral infections. HIV-1 codon usage has been previously shown to be different from that of other viruses and man. It is evident that the antiretroviral drugs used to restrict HIV-1 replication also select for resistance variants. We wanted to test whether codon frequencies in HIV-1 sequences from treatment-experienced patients differ from those of treatment-naive individuals due to drug pressure affecting codon usage bias...
January 7, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28049128/immune-reconstitution-inflammatory-syndrome-associated-with-pulmonary-pathogens
#6
REVIEW
Radha Gopal, Rekha R Rapaka, Jay K Kolls
Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated immune response to a variety of pathogens in response to antiretroviral therapy-mediated recovery of the immune system in HIV-infected patients. Although IRIS can occur in many organs, pulmonary IRIS, associated with opportunistic infections such as Mycobacterium tuberculosis and Pneumocystis jirovecii, is particularly associated with high morbidity and mortality. The pathology of IRIS is associated with a variety of innate and adaptive immune factors, including CD4(+) T-cells, CD8(+) T-cells, γδ T-cells, natural killer cells, macrophages, the complement system and surfactant proteins, Toll-like receptors and pro-inflammatory cytokines and chemokines...
January 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28046052/integrative-analysis-of-immunological-data-to-explore-chronic-immune-t-cell-activation-in-successfully-treated-hiv-patients
#7
Marie-Quitterie Picat, Isabelle Pellegrin, Juliette Bitard, Linda Wittkop, Cécile Proust-Lima, Benoît Liquet, Jean-François Moreau, Fabrice Bonnet, Patrick Blanco, Rodolphe Thiébaut
OBJECTIVES: To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. DESIGN: Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. METHODS: Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years...
2017: PloS One
https://www.readbyqxmd.com/read/28025070/a-recombinant-vesicular-stomatitis-virus-encoding-ccr5-tropic-hiv-1-receptors-targets-hiv-1-infected-cells-and-controls-hiv-1-infection
#8
Kazu Okuma, Koji Fukagawa, Takuya Kohma, Youichi Takahama, Yukio Hamaguchi, Mamoru Ito, Yuetsu Tanaka, Linda Buonocore, John K Rose, Isao Hamaguchi
Anti-retroviral therapy is useful to treat human immunodeficiency virus type 1 (HIV-1)-infected individuals, but has some major problems, such as the generation of multidrug-resistant viruses. To develop a novel supplemental or alternative therapeutic for CCR5-tropic (R5) HIV-1 infection, we generated a recombinant vesicular stomatitis virus (rVSV) in which the gene encoding its envelope glycoprotein (G) was replaced with the genes encoding R5 HIV-1 receptors (human CD4 and CCR5), designated VSVΔG-CC5. Our present data demonstrate that this rVSV specifically infects cells that are transiently expressing R5 HIV-1 envelope glycoproteins, but does not infect those expressing CXCR4-tropic HIV-1 envelope glycoproteins...
December 24, 2016: Microbes and Infection
https://www.readbyqxmd.com/read/28008927/immunotherapy-against-cancer-related-viruses
#9
REVIEW
Haruko Tashiro, Malcolm K Brenner
Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28000678/the-effects-of-prebiotics-on-microbial-dysbiosis-butyrate-production-and-immunity-in-hiv-infected-subjects
#10
S Serrano-Villar, J F Vázquez-Castellanos, A Vallejo, A Latorre, T Sainz, S Ferrando-Martínez, D Rojo, J Martínez-Botas, J Del Romero, N Madrid, M Leal, J I Mosele, M J Motilva, C Barbas, M Ferrer, A Moya, S Moreno, M J Gosalbes, V Estrada
Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV(+) viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART(+)) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV(-) controls (HIV(-)), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study...
December 21, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27999036/role-of-gag-mutations-in-pi-resistance-in-the-swiss-hiv-cohort-study-bystanders-or-contributors
#11
K Kletenkov, D Hoffmann, J Böni, S Yerly, V Aubert, F Schöni-Affolter, D Struck, J Verheyen, T Klimkait
BACKGROUND: HIV Gag mutations have been reported to confer PI drug resistance. However, clinical implications are still controversial and most current genotyping algorithms consider solely the protease gene for assessing PI resistance. OBJECTIVES: Our goal was to describe for HIV infections in Switzerland the potential role of the C-terminus of Gag (NC-p6) in PI resistance. We aimed to characterize resistance-relevant mutational patterns in Gag and protease and their possible interactions...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27992346/prediction-of-hiv-drug-resistance-by-combining-sequence-and-structural-properties
#12
Zoya Khalid, Osman Ugur Sezerman
Drug resistance is a major obstacle faced by therapist in treating HIV infected patients. The reason behind these phenomena is either protein mutation or the changes in gene expression level that induces resistance to drug treatments. These mutations affect the drug binding activity, hence resulting in failure of treatment. Therefore, it is necessary to conduct resistance testing in order to carry out HIV effective therapy. This study combines both sequence and structural features for predicting HIV resistance by applying SVM and Random Forests classifiers...
December 13, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/27959928/an-efficient-microarray-based-genotyping-platform-for-the-identification-of-drug-resistance-mutations-in-majority-and-minority-subpopulations-of-hiv-1-quasispecies
#13
Verónica Martín, Celia Perales, María Fernández-Algar, Helena G Dos Santos, Patricia Garrido, María Pernas, Víctor Parro, Miguel Moreno, Javier García-Pérez, José Alcamí, José Luis Torán, David Abia, Esteban Domingo, Carlos Briones
The response of human immunodeficiency virus type 1 (HIV-1) quasispecies to antiretroviral therapy is influenced by the ensemble of mutants that composes the evolving population. Low-abundance subpopulations within HIV-1 quasispecies may determine the viral response to the administered drug combinations. However, routine sequencing assays available to clinical laboratories do not recognize HIV-1 minority variants representing less than 25% of the population. Although several alternative and more sensitive genotyping techniques have been developed, including next-generation sequencing (NGS) methods, they are usually very time consuming, expensive and require highly trained personnel, thus becoming unrealistic approaches in daily clinical practice...
2016: PloS One
https://www.readbyqxmd.com/read/27941949/in-vitro-effects-of-the-small-molecule-protein-kinase-c-agonists-on-hiv-latency-reactivation
#14
Jessica Brogdon, Widade Ziani, Xiaolei Wang, Ronald S Veazey, Huanbin Xu
The persistence of latently HIV-infected cellular reservoirs represents the major obstacle to virus eradication in patients under antiretroviral therapy (ART). Cure strategies to eliminate these reservoirs are thus needed to reactivate proviral gene expression in latently infected cells. In this study, we tested optimal concentrations of PKC agonist candidates (PEP005/Ingenol-3-angelate, prostratin, bryostatin-1, and JQ1) to reactivate HIV latency in vitro, and examined their effects on cell survival, activation and epigenetic histone methylation after treatment alone or in combination in cell line and isolated CD4 T cells from SIV-infected macaques...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27941595/achieving-hiv-1-control-through-rna-directed-gene-regulation
#15
REVIEW
Vera Klemm, Jye Mitchell, Christina Cortez-Jugo, Francesca Cavalieri, Geoff Symonds, Frank Caruso, Anthony Dominic Kelleher, Chantelle Ahlenstiel
HIV-1 infection has been transformed by combined anti-retroviral therapy (ART), changing a universally fatal infection into a controllable infection. However, major obstacles for an HIV-1 cure exist. The HIV latent reservoir, which exists in resting CD4+ T cells, is not impacted by ART, and can reactivate when ART is interrupted or ceased. Additionally, multi-drug resistance can arise. One alternate approach to conventional HIV-1 drug treatment that is being explored involves gene therapies utilizing RNA-directed gene regulation...
December 7, 2016: Genes
https://www.readbyqxmd.com/read/27941242/the-interferon-paradox-can-inhibiting-an-antiviral-mechanism-advance-an-hiv-cure
#16
Steven G Deeks, Pamela M Odorizzi, Rafick-Pierre Sekaly
While antiretroviral therapy (ART) has improved the quality of life and increased the life span of many HIV-infected individuals, this therapeutic strategy has several limitations, including a lack of efficacy in fully restoring immune function and a requirement for life-long treatment. Two studies in this issue of the JCI use a humanized mouse model and demonstrate that type I interferon (IFN) is induced early during HIV infection and that type I IFN-associated gene signatures persist, even during ART. Importantly, blockade of type I IFN improved immune function, reduced the HIV reservoir, and caused a delay in viral rebound after ART interruption...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27922854/identification-of-hiv-infection-related-dna-methylation-sites-and-advanced-epigenetic-aging-in-hiv-treatment-na%C3%A3-ve-u-s-veterans
#17
Kristin N Nelson, Qin Hui, David Rimland, Ke Xu, Matthew S Freiberg, Amy C Justice, Vincent C Marconi, Yan V Sun
OBJECTIVE: HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNAm age, an aging marker involving multiple age-related CpG sites, among antiretroviral treatment (ART) naïve HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study (VACS)...
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27911718/attacking-hiv-1-rna-versus-dna-by-sequence-specific-approaches-rnai-versus-crispr-cas
#18
REVIEW
Elena Herrera-Carrillo, Ben Berkhout
Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27905841/cell-delivered-entry-inhibitors-for-hiv-1-ccr5-downregulation-and-blocking-virus-membrane-fusion-in-defending-the-host-cell-population
#19
Geoff Symonds, Jeffrey S Bartlett, Hans-Peter Kiem, Marlene Tsie, Louis Breton
HIV-1 infection requires the presence of the CD4 receptor on the target cell surface and a coreceptor, predominantly CC-chemokine receptor 5 (CCR5). It has been shown that individuals who are homozygous for a defective CCR5 gene are protected from HIV-1 infection. A novel self-inactivating lentiviral vector LVsh5/C46 (Cal-1) has been engineered to block HIV-1 infection with two viral entry inhibitors, conferring resistance to HIV-1 infection from both CCR5 and CXCR4 tropic strains. Cal-1 encodes a short hairpin RNA (sh5) to downregulate CCR5 and C46, an HIV-1 fusion inhibitor...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27905840/combining-cell-and-gene-therapy-in-an-effort-to-eradicate-hiv
#20
Thor A Wagner
More than 30 million people are infected with HIV, and HIV remains the fifth leading cause of disability-adjusted life years worldwide. Antiretroviral therapy (ART) dramatically decreases mortality rate, but there are side effects, long-term toxicities, expenses, stigmas, and inconveniences associated with chronic treatment, and HIV-infected individuals on ART have an increased risk of malignancies, cardiovascular disease, neurologic disease, and shortened life expectancy. Therefore, a cure for HIV remains an important goal...
December 2016: AIDS Patient Care and STDs
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