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https://www.readbyqxmd.com/read/28453836/commonly-transmitted-hiv-1-drug-resistance-mutations-in-reverse-transcriptase-and-protease-in-antiretroviral-treatment-naive-patients-and-response-to-regimens-containing-tenofovir-disoproxil-fumarate-or-tenofovir-alafenamide
#1
Nicolas A Margot, Pamela Wong, Rima Kulkarni, Kirsten White, Danielle Porter, Michael E Abram, Christian Callebaut, Michael D Miller
Background.: The presence of transmitted drug resistance mutations (TDRMs) in antiretroviral treatment (ART)-naive patients can adversely affect the outcome of ART. Methods.: Resistance testing was conducted in 6704 ART-naive subjects predominantly from the United States and Europe in 9 clinical studies conducted by Gilead Sciences from 2000 to 2013. Results.: The presence of TDRMs increased during this period (from 5.2% to 11.4%), primarily driven by an increase in nonnucleoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations (from 0...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28453835/herpes-simplex-virus-type-2-acquisition-among-hiv-1-infected-adults-treated-with-tenofovir-disoproxyl-fumarate-as-part-of-combination-antiretroviral-therapy-results-from-the-actg-a5175-pearls-study
#2
Connie Celum, Ting Hong, Anne Cent, Deborah Donnell, Rhoda Morrow, Jared M Baeten, Cynthia Firnhaber, Beatriz Grinsztejn, Mina C Hosseinipour, Umesh Lalloo, Mulinda Nyirenda, Cynthia Riviere, Jorge Sanchez, Breno Santos, Khuanchai Supparatpinyo, James Hakim, N Kumarasamy, Thomas B Campbell
Objective.: Tenofovir disoproxyl fumarate (TDF) disoproxyl fumarate (TDF) has in vitro activity against herpes simplex virus type 2 (HSV-2) and reduced HSV-2 acquisition as preexposure prophylaxis. Whether TDF-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Design.: Secondary analysis of AIDS Clinical Trials Group A5175, a randomized, open-label study of 3 ART regimens among 1571 participants. Methods.: HSV-2 serostatus was assessed at baseline, at study exit, and before a change in ART regimen...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28453589/-effects-of-prebiotics-and-probiotics-on-gastrointestinal-tract-lymphoid-tissue-in-hiv-infected-patients
#3
Manuel G Feria, Natalia A Taborda, Juan C Hernandez, María T Rugeles
HIV infection induces alterations in almost all immune cell populations, mainly in CD4+ T cells, leading to the development of opportunistic infections. The gut-associated lymphoid tissue (GALT) constitutes the most important site for viral replication, because the main target cells, memory T-cells, reside in this tissue. It is currently known that alterations in GALT are critical during the course of the infection, as HIV-1 induces loss of tissue integrity and promotes translocation of microbial products from the intestinal lumen to the systemic circulation, leading to a persistent immune activation state and immune exhaustion...
February 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/28449096/two-ribosome-recruitment-sites-direct-multiple-translation-events-within-hiv1-gag-open-reading-frame
#4
Jules Deforges, Sylvain de Breyne, Melissa Ameur, Nathalie Ulryck, Nathalie Chamond, Afaf Saadi, Yann Ponty, Theophile Ohlmann, Bruno Sargueil
In the late phase of the HIV virus cycle, the unspliced genomic RNA is exported to the cytoplasm for the necessary translation of the Gag and Gag-pol polyproteins. Three distinct translation initiation mechanisms ensuring Gag production have been described with little rationale for their multiplicity. The Gag-IRES has the singularity to be located within Gag ORF and to directly interact with ribosomal 40S. Aiming at elucidating the specificity and the relevance of this interaction, we probed HIV-1 Gag-IRES structure and developed an innovative integrative modelling strategy to take into account all the gathered information...
April 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28449051/viral-kinetics-in-semen-with-different-antiretroviral-families-in-treatment-na%C3%A3-ve-hiv-infected-patients-a-randomized-trial
#5
Alicia Gutierrez-Valencia, Omar J Benmarzouk-Hidalgo, Inmaculada Rivas-Jeremías, Nuria Espinosa, María Trujillo-Rodríguez, Tamara Fernandez-Magdaleno, Pompeyo Viciana, Luis F López-Cortés
Background: There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of HIV-RNA decay in semen. Objective: To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma of treatment-naïve HIV-infected patients. Methods: Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-DF plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv)...
April 25, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28448594/novel-in-natural-infection-subdominant-hiv-1-cd8-t-cell-epitopes-revealed-in-human-recipients-of-conserved-region-t-cell-vaccines
#6
Nicola Borthwick, Zhansong Lin, Tomohiro Akahoshi, Anuska Llano, Sandra Silva-Arrieta, Tina Ahmed, Lucy Dorrell, Christian Brander, Hayato Murakoshi, Masafumi Takiguchi, Tomáš Hanke
BACKGROUND: Fine definition of targeted CD8+ T-cell epitopes and their human leucocyte antigen (HLA) class I restriction informs iterative improvements of HIV-1 T-cell vaccine designs and may predict early vaccine success or failure. Here, lymphocytes from volunteers, who had received candidate HIVconsv vaccines expressing conserved sub-protein regions of HIV-1, were used to define the optimum-length target epitopes and their HLA restriction. In HIV-1-positive patients, CD8+ T-cell responses predominantly recognize immunodominant, but hypervariable and therefore less protective epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28448574/fusion-expression-of-occludin-extracellular-loops-and-an-%C3%AE-helical-bundle-a-new-research-model-for-tight-junction
#7
Xiaojing Chi, Xia Zhao, Wei Wang, Yuqiang Niu, Min Cheng, Xiuying Liu, Sheng Cui, Wei Yang
Tight junctions (TJs) are the outermost structures of intercellular junctions and are highly specialized membrane domains involved in many important cellular processes. However, most TJ proteins are four-time transmembrane proteins and are difficult to express in their correct soluble form, which limits their functional study and therapeutic application. Human occludin (OCLN) is a major component of TJs and an essential co-receptor for hepatitis C virus (HCV) cell entry. To explore expression strategy for recombinant TJ proteins possessing integrated and functional extracellular loops, OCLN was here used as a model molecule, and several prokaryotic fusion constructs were designed by docking OCLN extracellular loops (ECLs) to HIV-1 gp41 NHR and CHR six-helical bundle (6HV1); then their biophysical features and anti-HCV activity were evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28448121/hiv-1-frameshift-rna-targeted-triazoles-inhibit-propagation-of-replication-competent-and-multi-drug-resistant-hiv-in-human-cells
#8
Thomas A Hilimire, Jeffrey M Chamberlain, Viktoriya Anokhina, Ryan P Bennett, Oliver Swart, Jason R Myers, John M Ashton, Ryan A Stewart, Aaron L Featherston, Kathleen Gates, Eric D Helms, Harold C Smith, Stephen Dewhurst, Benjamin L Miller
The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus' life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multi-drug-resistant strain...
April 27, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28447585/metabolic-profiles-of-individuals-switched-to-second-line-antiretroviral-therapy-after-failing-standard-first-line-therapy-for-treatment-of-hiv-1-infection-in-a-randomized-controlled-trial
#9
Amanda H Yao, Cecilia L Moore, Poh Lian Lim, Jean-Michel Molina, Juan Sierra Madero, Stephen Kerr, Paddy Wg Mallon, Sean Emery, David A Cooper, Mark A Boyd
BACKGROUND: To investigate metabolic changes associated with second-line antiretroviral therapy (ART) following virological failure of first-line ART. METHODS: SECOND-LINE was an open-label randomized controlled trial. Participants were randomized 1:1 to receive ritonavir-boosted lopinavir (LPV/r) with 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI-group) or raltegravir (RAL-group) Two hundred and ten participants had a dual energy X-ray absorptiometry (DXA)-scan at baseline, week 48 and 96...
April 27, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28447329/immune-response-against-salmonella-enteritidis-is-unsettled-by-hiv-infection
#10
Maira Costa Cacemiro, Milena Sobral Espíndola, Leonardo Judson Galvão-Lima, Luana Silva Soares, Caroline Fontanari, Marco Aurélio Prata, Fábio Campioni, Juliana Pfrimer Falcão, Valdes Roberto Bollela, Fabiani Gai Frantz
The human immunodeficiency virus (HIV) is responsible for more than 2 million new infections per year and opportunistic infections such as Salmonella spp. Gastroenteritis is an important cause of mortality and morbidity in developing countries. Monocytes and macrophages play a critical role in the innate immune response against bacterial infections. However during HIV infection the virus can infect these cells and although they are more resistant to the cytopathic effects, they represent an important viral reservoir in these patients...
April 27, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28446667/disparate-contributions-of-human-retrovirus-capsid-subdomains-to-gag-gag-oligomerization-virus-morphology-and-particle-biogenesis
#11
Jessica L Martin, Luiza Mendonça, Isaac Angert, Joachim D Mueller, Wei Zhang, Louis M Mansky
The capsid domain (CA) of the retroviral Gag protein is a primary determinant of Gag oligomerization, which is a critical step for immature Gag lattice formation and virus particle budding. Although the human immunodeficiency virus type 1 (HIV-1) CA carboxy-terminal domain (CTD) is essential for CA-CA interactions, the CA CTD has been suggested to be largely dispensable for human T-cell leukemia virus type 1 (HTLV-1) particle biogenesis. To more clearly define the roles of the HTLV-1 CA amino-terminal domain (NTD) and CA CTD in particle biogenesis, we generated and analyzed a panel of Gag proteins with chimeric HIV-1/HTLV-1 CA domains...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446665/dense-array-of-spikes-on-hiv-1-virion-particles
#12
Armando Stano, Daniel P Leaman, Arthur S Kim, Lei Zhang, Ludovic Autin, Jidnyasa Ingale, Syna K Gift, Jared Truong, Richard T Wyatt, Arthur J Olson, Michael B Zwick
HIV-1 is rare among viruses for having a low number of envelope glycoprotein (Env) spikes per virion, i.e. ∼7-14. This exceptional feature has been associated with avoidance of humoral immunity, i.e. B cell activation and antibody neutralization. Virus-like particles (VLPs) with increased density of Env are being pursued for vaccine development; however these typically require protein engineering that alters Env structure. Here, we used instead a strategy that targets the producer cell. We employed fluorescence activated cell sorting (FACS) to sort for cells that are recognized by trimer crossreactive broadly neutralizing antibody (bnAb) and not by non-neutralizing antibodies...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446664/analysis-of-competing-hiv-1-splice-donor-sites-uncovers-a-tight-cluster-of-splicing-regulatory-elements-within-exon-2-2b
#13
Anna-Lena Brillen, Lara Walotka, Frank Hillebrand, Lisa Müller, Marek Widera, Stephan Theiss, Heiner Schaal
The HIV-1 accessory protein Vif is essential for viral replication by counteracting the host restriction factor APOBEC3G (A3G), and balanced levels of both proteins are required for efficient viral replication. Non-coding exons 2/2b contain the Vif start codon between their alternatively used splice donors 2 and 2b (D2 and D2b). For the vif mRNA, intron 1 must be removed, while intron 2 must be retained. Thus, splice acceptor 1 (A1) must be activated by U1 snRNP binding to either D2 or D2b, while splicing at D2 or D2b must be prevented...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446620/how-to-win-the-hiv-1-drug-resistance-hurdle-race-running-faster-or-jumping-higher
#14
REVIEW
Anna Garbelli, Valentina Riva, Emmanuele Crespan, Giovanni Maga
Infections by the human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), are still totaling an appalling 36.7 millions worldwide, with 1.1 million AIDS deaths/year and a similar number of yearly new infections. All this, in spite of the discovery of HIV-1 as the AIDS etiological agent more than 30 years ago and the introduction of an effective combinatorial antiretroviral therapy (cART), able to control disease progression, more than 20 years ago. Although very effective, current cART is plagued by the emergence of drug-resistant viral variants and most of the efforts in the development of novel direct-acting antiviral agents (DAAs) against HIV-1 have been devoted toward the fighting of resistance...
April 26, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28446609/glycosylation-of-the-core-of-the-hiv-1-envelope-subunit-protein-gp120-is-not-required-for-native-trimer-formation-or-viral-infectivity
#15
Ujjwal Rathore, Piyali Saha, Sannula Kesavardhana, Aditya Arun Kumar, Rohini Datta, Sivasankar Devanarayanan, Raksha Das, John R Mascola, Raghavan Varadarajan
The gp120 subunit of HIV-1 envelope (Env) protein is heavily glycosylated at approximately 25 glycosylation sites, of which ~7-8 are located in the V1/V2 and V3 variable loops and the others in the remaining core gp120 region. Glycans partially shield Env from recognition by the host immune system and also are believed to be indispensable for proper folding of gp120 and for viral infectivity. Previous attempts to alter glycosylation sites in Env typically involved mutating the glycosylated asparagine residues to structurally similar glutamines or to alanines...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446240/molecular-mechanisms-by-which-herv-k-gag-interferes-with-hiv-1-gag-assembly-and-particle-infectivity
#16
Kazuaki Monde, Hiromi Terasawa, Yusuke Nakano, Ferri Soheilian, Kunio Nagashima, Yosuke Maeda, Akira Ono
BACKGROUND: Human endogenous retroviruses (HERVs), the remnants of ancient retroviral infections, constitute approximately 8% of human genomic DNA. Since HERV-K Gag expression is induced by HIV-1 Tat in T cells, induced HERV-K proteins could affect HIV-1 replication. Indeed, previously we showed that HERV-K Gag and HIV-1 Gag coassemble and that this appears to correlate with the effect of HERV-K Gag expression on HIV-1 particle release and its infectivity. We further showed that coassembly requires both MA and NC domains, which presumably serve as scaffolding for Gag via their abilities to bind membrane and RNA, respectively...
April 26, 2017: Retrovirology
https://www.readbyqxmd.com/read/28445881/absence-of-decline-of-kidney-function-in-human-immunodeficiency-virus-infected-patients-under-routine-clinical-management
#17
Julie Boucquemont, Sylvie Lawson-Ayayi, Claire Rigothier, Fabrice Bonnet, Cécile Proust-Lima, Didier Neau, Carine Greib, Ghada Miremont-Salamé, François Dabis, Michel Dupon, Frédéric-Antoine Dauchy
BACKGROUND: Since the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV)-infected patients have a drastically improved prognosis but at the same time they are also more affected by non-HIV related complications, such as chronic kidney disease. The objective of our study was to investigate the effect of proteinuria and tenofovir (TDF)-containing ART regimens on the temporal evolution of estimated glomerular filtration rate (eGFR). METHODS: Between April 2008 and October 2012, we enrolled 395 patients with a complete renal evaluation among patients from the ANRS C03 Aquitaine cohort, a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in southwestern France...
April 26, 2017: Nephron
https://www.readbyqxmd.com/read/28445724/quantification-of-the-impact-of-the-hiv-1-glycan-shield-on-antibody-elicitation
#18
Tongqing Zhou, Nicole A Doria-Rose, Cheng Cheng, Guillaume B E Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D Schmidt, Kai Xu, Lei Chen, Rita E Chen, Mark K Louder, Marie Pancera, Timothy G Wanninger, Baoshan Zhang, Anqi Zheng, S Katie Farney, Kathryn E Foulds, Ivelin S Georgiev, M Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G Scorpio, Lawrence Shapiro, Adrian B McDermott, John R Mascola, Peter D Kwong
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character)...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445718/the-hiv-1-glycan-shield-strategically-placed-kinks-in-the-armor-improve-antigen-design
#19
Christina Beatrice Karsten, Galit Alter
Dense glycosylation on the HIV-1 envelope glycoprotein hampers the induction of broadly neutralizing antibodies against HIV-1. Zhou et al. remove key glycans to unmask sites of vulnerability and enable the induction of neutralizing antibodies.
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28444865/a-high-rate-of-hiv-1-acquisition-post-immigration-among-migrants-in-sweden-determined-by-a-cd4-t-cell-decline-trajectory-model
#20
J Brännström, A Sönnerborg, V Svedhem, U Neogi, G Marrone
OBJECTIVES: There is a lack of knowledge about the extent to which migrants become HIV-1 infected after arrival in European countries. The objective of this study was to assess the extent to which migrants to Sweden become HIV-1 infected post immigration using a CD4 T-cell decline trajectory model. METHODS: All migrants (n = 2268) who were ≥ 15 years old, were diagnosed with HIV-1 infection in the period 1983-2013, had a known year of arrival in Sweden, did not have primary HIV infection and were not infected via mother-to-child transmission were included in the study...
April 26, 2017: HIV Medicine
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