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https://www.readbyqxmd.com/read/29142136/size-composition-and-evolution-of-hiv-dna-populations-during-early-antiretroviral-therapy-and-intensification-with-maraviroc
#1
Antoine Chaillon, Sara Gianella, Steven M Lada, Josué Perez-Santiago, Parris Jordan, Caroline Ignacio, Maile Karris, Douglas Richman, Sanjay R Mehta, Susan J Little, Joel O Wertheim, Davey M Smith
Residual viremia is common during antiretroviral therapy (ART), and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART Intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial, and followed for a median of 107 weeks. Participants started ART with (n=9) or without (n=9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142124/truncating-the-gp41-cytoplasmic-tail-of-siv-decreases-sensitivity-to-neutralizing-antibodies-without-increasing-envelope-content-of-virions
#2
Ellen White, Fan Wu, Elena Chertova, Julian Bess, James D Roser, Jeffrey D Lifson, Vanessa M Hirsch
An incomplete understanding of native HIV and SIV envelope glycoprotein (Env) impedes the development of structural models of Env and vaccine design. This shortcoming is due in part to the low number of Env trimers on virus particles. For SIV, this low expression can be counteracted by truncating the cytoplasmic tail (CT) of Env. CT truncation has been shown to increase Env incorporation into the virion and is commonly used in vaccine and imaging studies, but its effects on viral antigenicity have not been fully elucidated...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29141348/-molecular-epidemiology-and-transmission-of-hiv-1-infection-in-zhejiang-province-2015
#3
J Z Yang, W J Chen, W J Zhang, L He, J F Zhang, X H Pan
Objective: To understand the distribution of HIV-1 subtype diversity and its transmission characteristics in Zhejiang province. Methods: A total of 302 newly diagnosed HIV-1 positive patients were selected through stratified random sampling in Zhejiang in 2015. HIV-1 pol genes were sequenced successfully with reverse transcription PCR/nested PCR and phylogenetic analysis was conducted for 276 patients. Then a molecular epidemiologic study was performed combined with field epidemiological investigation. Results: Of 276 sequence samples analyzed, 122 CRF07_BC strains (44...
November 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/29140932/characteristics-of-treatment-experienced-hiv-infected-african-children-and-adolescents-initiating-darunavir-and-or-etravirine-based-antiretroviral-treatment
#4
Bethany Corrigan, Irene Mukui, Lloyd Mulenga, Nobuhle Mthethwa, Mosilinyane Letsie, Stephanie Bruno, Natella Rakhmanina
BACKGROUND: Data are limited on the selection and sequencing of second and third-line pediatric antiretroviral treatment (ART) in resource-limited settings. This study aimed to evaluate characteristics of African pediatric patients initiated on darunavir (DRV) and/or etravirine (ETR) through a specific drug donation program. METHODS: This was a cross-sectional study of baseline immunologic, virologic and demographic characteristics of children and adolescents initiating DRV- and/or ETR-based ART...
November 14, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29137637/molecular-evolution-of-hiv-1-integrase-during-the-20%C3%A2-years-prior-to-the-first-approval-of-integrase-inhibitors
#5
Karolin Meixenberger, Kaveh Pouran Yousef, Maureen Rebecca Smith, Sybille Somogyi, Stefan Fiedler, Barbara Bartmeyer, Osamah Hamouda, Norbert Bannert, Max von Kleist, Claudia Kücherer
BACKGROUND: Detailed knowledge of the evolutionary potential of polymorphic sites in a viral protein is important for understanding the development of drug resistance in the presence of an inhibitor. We therefore set out to analyse the molecular evolution of the HIV-1 subtype B integrase at the inter-patient level in Germany during a 20-year period prior to the first introduction of integrase strand inhibitors (INSTIs). METHODS: We determined 337 HIV-1 integrase subtype B sequences (amino acids 1-278) from stored plasma samples of antiretroviral treatment-naïve individuals newly diagnosed with HIV-1 between 1986 and 2006...
November 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/29137167/transmission-dynamics-of-hiv-1-drug-resistance-among-treatment-na%C3%A3-ve-individuals-in-greece-the-added-value-of-molecular-epidemiology-to-public-health
#6
Dimitrios Paraskevis, Evangelia Kostaki, Panagiotis Gargalianos, Georgios Xylomenos, Marios Lazanas, Maria Chini, Athanasios Skoutelis, Vasileios Papastamopoulos, Dimitra Paraskeva, Anastasia Antoniadou, Antonios Papadopoulos, Mina Psichogiou, Georgios L Daikos, Georgios Chrysos, Vasileios Paparizos, Sofia Kourkounti, Helen Sambatakou, Nikolaos V Sipsas, Malvina Lada, Periklis Panagopoulos, Efstratios Maltezos, Stylianos Drimis, Angelos Hatzakis
The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance...
November 13, 2017: Genes
https://www.readbyqxmd.com/read/29136743/-drug-resistance-mutations-and-its-associated-factors-among-579-hiv-aids-patients-experiencing-failure-of-antiretroviral-therapy-in-jiangsu-province-china
#7
P P Xiao, J Lu, H Y Hu, X Q Xu, P Ding, G F Fu, X P Huan, Y Zhou, H T Yang
Objective: To understand the incidence and related factors of HIV-1 drug resistance among HIV/AIDS patients experiencing treatment failure in Jiangsu province, China. Methods: The HIV/AIDS integrated prevention and control data information management system of China were used to collect the basic data of patients, blood specimens were collected from patients who had antiretroviral therapy (ART) failure with ≥12 months and older than 18 years in 2016 in Jiangsu, excluding cases with missing information, 713 cases were enrolled in this study...
November 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29134258/novel-full-length-major-histocompatibility-complex-class-i-allele-discovery-and-haplotype-definition-in-pig-tailed-macaques
#8
Matthew R Semler, Roger W Wiseman, Julie A Karl, Michael E Graham, Samantha M Gieger, David H O'Connor
Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques...
November 13, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29133803/microbial-diversity-of-genital-ulcers-of-hsv-2-seropositive-women
#9
Supriya D Mehta, Ashish K Pradhan, Stefan J Green, Ankur Naqib, Elijah Odoyo-June, Charlotte A Gaydos, Sheila Barry, Alan Landay, Robert C Bailey
We measured the microbial community structure of genital ulcers in women. Swabs from clinically detected ulcers were tested for HSV-2 and Treponema pallidum by polymerase chain reaction (PCR). HSV-2 and T. pallidum were detected by serum antibody testing. Microbial community structure was characterized by high-throughput 16 s rRNA gene amplicon sequencing. Multiple group testing and Elastic net and Lasso regressions identified taxa associated with differences in factors of interest. Among 49 ulcer specimens from 49 HSV-2 seropositive women, by PCR HSV-2 was recovered from 28 (57%) specimens and T...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132303/prevalence-of-naturally-occurring-ns5a-resistance-associated-substitutions-in-patients-infected-with-hepatitis-c-virus-subtype-1a-1b-and-3a-co-infected-or-not-with-hiv-in-brazil
#10
Fernanda Malta, Karine Vieira Gaspareto, Gaspar Lisboa-Neto, Flair José Carrilho, Maria Cássia Mendes-Correa, João Renato Rebello Pinho
BACKGROUND: Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown...
November 13, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29131878/association-of-brain-structure-changes-and-cognitive-function-with-combination-antiretroviral-therapy-in-hiv-positive-individuals
#11
Ryan Sanford, Lesley K Fellows, Beau M Ances, D Louis Collins
Importance: Despite the introduction of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders continue to be a problem for treated HIV-positive individuals. The cause of this impairment remains unclear. Objective: To determine if detectable brain changes occur during a 2-year period in HIV-positive individuals who were aviremic and treated with cART. Design, Setting, and Participants: In this longitudinal case-control study, participants underwent neuroimaging and neuropsychological assessment approximately 2 years apart...
November 13, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29131825/a-model-based-clustering-method-to-detect-infectious-disease-transmission-outbreaks-from-sequence-variation
#12
Rosemary M McCloskey, Art F Y Poon
Clustering infections by genetic similarity is a popular technique for identifying potential outbreaks of infectious disease, in part because sequences are now routinely collected for clinical management of many infections. A diverse number of nonparametric clustering methods have been developed for this purpose. These methods are generally intuitive, rapid to compute, and readily scale with large data sets. However, we have found that nonparametric clustering methods can be biased towards identifying clusters of diagnosis-where individuals are sampled sooner post-infection-rather than the clusters of rapid transmission that are meant to be potential foci for public health efforts...
November 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29128752/the-roles-of-five-conserved-lentiviral-rna-structures-in-hiv-1-replication
#13
Yang Liu, Jianbo Chen, Olga A Nikolaitchik, Belete A Desimmie, Steven Busan, Vinay K Pathak, Kevin M Weeks, Wei-Shau Hu
The HIV-1 RNA genome contains complex structures with many structural elements playing regulatory roles during viral replication. A recent study has identified multiple RNA structures with unknown functions that are conserved among HIV-1 and two simian immunodeficiency viruses. To explore the roles of these conserved RNA structures, we introduced synonymous mutations into the HIV-1 genome to disrupt each structure. These mutants exhibited similar particle production, viral infectivity, and replication kinetics relative to the parent NL4-3 virus...
November 9, 2017: Virology
https://www.readbyqxmd.com/read/29128646/hiv-drug-resistance-following-a-decade-of-free-antiretroviral-therapy-program-in-india-a-review
#14
REVIEW
Santosh Karade, Devidas N Chaturbhuj, Sourav Sen, Rajneesh K Joshi, Smita S Kulkarni, Subramanian Shankar, Raman R Gangakhedkar
OBJECTIVE: The objective of this review is to assess the burden of HIV drug resistance mutations (DRM) in Indian adults exposed to first-line ART as per national guidelines. METHODS: We performed advanced search for the published literature on HIV drug resistance in India in PubMed and Scopus. From each publication data pertaining to age, sex, CD4 count and viral load, prevalence of NRTI/NNRTI drug resistance mutations (DRM) was extracted. Year-wise Indian HIV-1 reverse transcriptase (RT) sequences were retrieved from Los Alamos HIV database and mutation analyses were performed...
November 8, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29126456/virological-response-hiv-1-drug-resistance-mutations-and-genetic-diversity-among-patients-on-first-line-antiretroviral-therapy-in-n-djamena-chad-findings-from-a-cross-sectional-study
#15
Chatté Adawaye, Joseph Fokam, Erick Kamangu, Hamit Mahamat Alio, Aoudalkarim Moussa Chahad, Fabrice Susin, Ali Mahamat Moussa, Tchombou Hig-Zounet Bertin, Abdelsalam Tidjani, Dolores Vaira, Michel Moutschen
BACKGROUND: The national antiretroviral therapy in the Republic of Chad provides free of charge antiretroviral regimens and therapeutic monitoring for patients receiving antiretroviral therapy nationwide. For a successful programmatic uptake, these efforts merit to be supported by thorough assessments of antiretroviral therapy response and HIV-1 drug resistance surveillance, especially with risks of cross-resistance due to the gradual stavudine phasing out in such national settings. We therefore evaluated the virological response to antiretroviral therapy, HIV-1 drug resistance emergence and circulating HIV-1 clades in a Chad context...
November 10, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29126318/rnase-h-sequence-preferences-influence-antisense-oligonucleotide-efficiency
#16
Lukasz J Kielpinski, Peter H Hagedorn, Morten Lindow, Jeppe Vinther
RNase H cleaves RNA in RNA-DNA duplexes. It is present in all domains of life as well as in multiple viruses and is essential for mammalian development and for human immunodeficiency virus replication. Here, we developed a sequencing-based method to measure the cleavage of thousands of different RNA-DNA duplexes and thereby comprehensively characterized the sequence preferences of HIV-1, human and Escherichia coli RNase H enzymes. We find that the catalytic domains of E. coli and human RNase H have nearly identical sequence preferences, which correlate with the efficiency of RNase H-recruiting antisense oligonucleotides...
November 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29122886/mechanism-of-polypurine-tract-primer-generation-by-hiv-1-reverse-transcriptase
#17
Małgorzata Figiel, Miroslav Krepl, Sangwoo Park, Jarosław Poznański, Krzysztof Skowronek, Agnieszka Gołąb, Taekjip Ha, Jiři Šponer, Marcin Nowotny
HIV-1 reverse transcriptase (HIV-1 RT) possesses both DNA polymerase activity and RNase H activity that act in concert to convert single-stranded RNA of the viral genome to double-stranded DNA that is then integrated into the DNA of the infected cell. Reverse transcriptase-catalyzed reverse transcription critically relies on the proper generation of a polypurine tract (PPT) primer. However, the mechanism of PPT primer generation and the features of the PPT sequence that are critical for its recognition by HIV-1 RT remain unclear...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29122614/a-recombinant-fusion-protein-based-fluorescent-protease-assay-for-high-throughput-compatible-substrate-screening
#18
Beáta Bozóki, Lívia Gazda, Ferenc Tóth, Márió Miczi, János András Mótyán, József Tőzsér
In connection with the intensive investigation of proteases, several methods have been developed for analysis of the substrate specificity. Due to the great number of proteases and the expected target molecules to be analyzed, time- and cost-efficient high-throughput screening (HTS) methods are preferred. Here we describe the development and application of a separation-based HTS-compatible fluorescent protease assay, which is based on the use of recombinant fusion proteins as substrates of proteases. The protein substrates used in this assay consists of N-terminal (hexahistidine and maltose binding protein) fusion tags, cleavage sequences of the tobacco etch virus (TEV) and HIV-1 proteases, and a C-terminal fluorescent protein (mApple or mTurquoise2)...
November 6, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29121951/increasing-the-cpg-dinucleotide-abundance-in-the-hiv-1-genomic-rna-inhibits-viral-replication
#19
Irati Antzin-Anduetza, Charlotte Mahiet, Luke A Granger, Charlotte Odendall, Chad M Swanson
BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) structural protein Gag is necessary and sufficient to form viral particles. In addition to encoding the amino acid sequence for Gag, the underlying RNA sequence could encode cis-acting elements or nucleotide biases that are necessary for viral replication. Furthermore, RNA sequences that inhibit viral replication could be suppressed in gag. However, the functional relevance of RNA elements and nucleotide biases that promote or repress HIV-1 replication remain poorly understood...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29120906/efficacy-of-ledipasvir-sofosbuvir-plus-ribavirin-for-12-weeks-in-patients-with-chronic-hepatitis-c-genotype-3-and-compensated-liver-disease
#20
Stephan Moser, Karin Kozbial, Hermann Laferl, Angelika Schütz, Thomas Reiberger, Philipp Schwabl, Enisa Gutic, Cornelia Schwanke, Raphael Schubert, Julian Luhn, Tobias Lang, Michael Schleicher, Petra Steindl-Munda, Hans Haltmayer, Peter Ferenci, Michael Gschwantler
INTRODUCTION: In the era of direct-acting antivirals, hepatitis C virus (HCV) genotype (GT) 3 remains as the most difficult-to-treat HCV-GT. Currently, data on the efficacy of ledipasvir/sofosbuvir plus ribavirin (SOF/LDV+RBV) in GT3-infected patients are limited. We investigated the efficacy of this regimen in a real-life cohort from Austria. PATIENTS AND METHODS: A total of 55 patients with HCV-GT3 and compensated liver disease (20% treatment-experienced, 33% with cirrhosis, 7% with HIV coinfection) from four Austrian hepatitis centers received treatment with SOF/LDV+RBV for 12 weeks...
November 8, 2017: European Journal of Gastroenterology & Hepatology
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