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https://www.readbyqxmd.com/read/29342281/phenotypic-analysis-of-hiv-1-e157q-integrase-polymorphism-and-impact-on-virological-outcome-in-patients-initiating-an-integrase-inhibitor-based-regimen
#1
Charlotte Charpentier, Isabelle Malet, Elisabeth Andre-Garnier, Alexandre Storto, Laurence Bocket, Corinne Amiel, Laurence Morand-Joubert, Camille Tumiotto, Thuy Nguyen, Anne Maillard, Audrey Rodallec, Marie Leoz, Brigitte Montes, Véronique Schneider, Jean-Christophe Plantier, Julia Dina, Coralie Pallier, Audrey Mirand, Catherine Roussel, Anne Signori-Schmuck, Stéphanie Raymond, Vincent Calvez, Constance Delaugerre, Anne-Geneviève Marcelin, Diane Descamps
Objectives: To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen. Methods: This was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay. Results: Prevalence of the E157Q polymorphism was 2...
January 12, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29339801/cardiac-glycoside-aglycones-inhibit-hiv-1-gene-expression-by-a-mechanism-requiring-mek1-2-erk1-2-signaling
#2
Raymond W Wong, Clifford A Lingwood, Mario A Ostrowski, Tyler Cabral, Alan Cochrane
The capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing-a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations used in patients with heart conditions...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29338735/mental-health-service-utilization-is-associated-with-retention-in-care-among-persons-living-with-hiv-at-a-university-affiliated-hiv-clinic
#3
Lauren A Saag, Ashutosh R Tamhane, D Scott Batey, Michael J Mugavero, Ellen F Eaton
BACKGROUND: Mental health (MH) comorbidities reduce retention in care for persons living with HIV (PLWH) and are associated with poor health outcomes. Optimizing retention in primary care is vital, as poor retention is associated with delayed receipt of antiretroviral (ARV) therapy, ARV non-adherence, and poor health outcomes, including failure to suppress viral load, decreased CD4 counts, and clinically significant ARV drug resistance. We hypothesized that MH service utilization would be associated with improved retention in care for patients with HIV and MH comorbidities...
January 16, 2018: AIDS Research and Therapy
https://www.readbyqxmd.com/read/29332597/synthesis-of-a-novel-class-of-1-3-oxathiolane-nucleoside-derivatives-of-t-705-and-evaluation-of-their-anti-influenza-a-virus-and-anti-hiv-activity
#4
Mingming Han, Xu Zhao, Xuedong Wu, Wei Huang, Xingzhou Li, Fang Yu
Backgroud: T-705 (Favipiravir) is a broad spectrum antiviral agent approved for stockpiling in Japan and currently in Phase 3 testing in the United States. Against influenza acts as a prodrug, converted intracellularly to selectively inhibit viral RNA-dependent RNA polymerase or similar enzymes. This is regarded as a novel antiviral mechanism of action, reducing cross-resistance to other existing anti-influenza drugs. OBJECTIVE: To develop new analogs, a class of 1,3-oxathiolane nucleoside derivatives of T-705 were designed and synthesized in this work...
January 11, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29330726/ultra-deep-genomic-sequencing-of-hcv-ns5a-resistance-associated-substitutions-in-hcv-hiv-coinfected-patients
#5
Enass A Abdel-Hameed, Susan D Rouster, Ceejay L Boyce, Xiang Zhang, Jacek Biesiada, Mario Medvedovic, Kenneth E Sherman
BACKGROUND AND AIMS: The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing methodologies are applied. METHODS: HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias...
January 12, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29330384/detection-of-apparent-cell-free-m-tuberculosis-dna-from-plasma
#6
E S Click, W Murithi, G S Ouma, K McCarthy, M Willby, S Musau, H Alexander, E Pevzner, J Posey, K P Cain
New diagnostics are needed to improve clinicians' ability to detect tuberculosis (TB) disease in key populations such as children and persons living with HIV and to rapidly detect drug resistance. Circulating cell-free DNA (ccfDNA) in plasma is a diagnostic target in new obstetric and oncologic applications, but its utility for diagnosing TB is not known. Here we show that Mycobacterium tuberculosis complex DNA can be detected in plasma of persons with sputum smear-positive TB, even in the absence of mycobacteremia...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329553/inhibitors-of-the-integrase-transportin-sr2-interaction-block-hiv-nuclear-import
#7
Jonas Demeulemeester, Jolien Blokken, Stéphanie De Houwer, Lieve Dirix, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Frauke Christ, Zeger Debyser
BACKGROUND: Combination antiretroviral therapy efficiently suppresses HIV replication in infected patients, transforming HIV/AIDS into a chronic disease. Viral resistance does develop however, especially under suboptimal treatment conditions such as poor adherence. As a consequence, continued exploration of novel targets is paramount to identify novel antivirals that do not suffer from cross-resistance with existing drugs. One new promising class of targets are HIV protein-cofactor interactions...
January 12, 2018: Retrovirology
https://www.readbyqxmd.com/read/29329299/multi-drug-resistant-non-typhoidal-salmonella-associated-with-invasive-disease-in-western-kenya
#8
Adam Akullian, Joel M Montgomery, Grace John-Stewart, Samuel I Miller, Hillary S Hayden, Matthew C Radey, Kyle R Hager, Jennifer R Verani, John Benjamin Ochieng, Jane Juma, Jim Katieno, Barry Fields, Godfrey Bigogo, Allan Audi, Judd Walson
Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in Africa, but the various contributions of host susceptibility versus unique pathogen virulence factors are unclear. We used data from a population-based surveillance platform (population ~25,000) between 2007-2014 and NTS genome-sequencing to compare host and pathogen-specific factors between individuals presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates...
January 12, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29324969/apobec-mutagenesis-in-drug-resistance-and-immune-escape-in-hiv-and-cancer-evolution
#9
S Venkatesan, R Rosenthal, N Kanu, N McGranahan, J Bartek, S A Quezada, J Hare, R S Harris, C Swanton
The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants...
January 8, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29324842/effect-of-analytical-treatment-interruption-and-reinitiation-of-antiretroviral-therapy-on-hiv-reservoirs-and-immunologic-parameters-in-infected-individuals
#10
Katherine E Clarridge, Jana Blazkova, Kevin Einkauf, Mary Petrone, Eric W Refsland, J Shawn Justement, Victoria Shi, Erin D Huiting, Catherine A Seamon, Guinevere Q Lee, Xu G Yu, Susan Moir, Michael C Sneller, Mathias Lichterfeld, Tae-Wook Chun
Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29321334/mechanism-of-hiv-1-resistance-to-an-electronically-constrained-%C3%AE-helical-peptide-membrane-fusion-inhibitor
#11
Xiyuan Wu, Zixuan Liu, Xiaohui Ding, Danwei Yu, Huamian Wei, Bo Qin, Yuanmei Zhu, Huihui Chong, Sheng Cui, Yuxian He
SC29EK is an electronically constrained α-helical peptide HIV-1 fusion inhibitor highly effective against both wild-type and enfuvirtide (T20)-resistant viruses. In this study, we focused on investigating the mechanism of HIV-1 resistance to SC29EK by two approaches. First, SC29EK-escaping HIV-1 variants were selected and characterized. Three mutant viruses, which possessed two (E43K/E49A) or three (Q39R/N43K/N126K, N43K/E49A/N126K) amino acid substitutions in the N- and C-terminal repeat regions of gp41 were identified as conferring high resistance to SC29EK and cross-resistance to the first-generation (T20, C34) and newly-designed (sifuvirtide, MT-SC29EK, 2P23) fusion inhibitors...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29315303/genome-wide-comparison-of-ethiopian-leishmania-donovani-strains-reveals-differences-potentially-related-to-parasite-survival
#12
Arie Zackay, James A Cotton, Mandy Sanders, Asrat Hailu, Abedelmajeed Nasereddin, Alon Warburg, Charles L Jaffe
Leishmania donovani is the main cause of visceral leishmaniasis (VL) in East Africa. Differences between northern Ethiopia/Sudan (NE) and southern Ethiopia (SE) in ecology, vectors, and patient sensitivity to drug treatment have been described, however the relationship between differences in parasite genotype between these two foci and phenotype is unknown. Whole genomic sequencing (WGS) was carried out for 41 L. donovani strains and clones from VL and VL/HIV co-infected patients in NE (n = 28) and SE (n = 13)...
January 9, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29304821/impact-of-the-hiv-1-genetic-background-and-hiv-1-population-size-on-the-evolution-of-raltegravir-resistance
#13
Axel Fun, Thomas Leitner, Linos Vandekerckhove, Martin Däumer, Alexander Thielen, Bernd Buchholz, Andy I M Hoepelman, Elizabeth H Gisolf, Pauline J Schipper, Annemarie M J Wensing, Monique Nijhuis
BACKGROUND: Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive selection of a specific pathway are still poorly understood. We investigated the impact of the HIV-1 genetic background and population dynamics on the emergence of raltegravir resistance...
January 5, 2018: Retrovirology
https://www.readbyqxmd.com/read/29302148/association-of-risk-factors-and-drug-resistance-pattern-in-tuberculosis-patients-in-north-india
#14
Pallavi Sinha, G N Srivastava, Anamika Gupta, Shampa Anupurba
Context: India is one of the high tuberculosis (TB) burden countries in the world. Improper implementation in the guidelines for the management of TB and high rate of defaults on the part of the patients are most important risk factors for the development of multi-drug resistant TB. Aims: This study examines the drug resistance profile and the effect of demographic, clinical and behavioral risk factors on the prevalence of TB and multidrug resistance (MDR) in north India...
October 2017: Journal of Global Infectious Diseases
https://www.readbyqxmd.com/read/29297443/screening-for-active-tuberculosis-before-isoniazid-preventive-therapy-among-hiv-infected-west-african-adults
#15
R Moh, A Badjé, J-B N'takpé, G M Kouamé, D Gabillard, T Ouassa, E Ouattara, J Le Carrou, F Bohoussou, E Messou, S Eholié, X Anglaret, C Danel
SETTING: TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance...
December 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29297424/household-context-and-psychosocial-impact-of-childhood-multidrug-resistant-tuberculosis-in-kwazulu-natal-south-africa
#16
M Loveday, B Sunkari, I Master, A Daftary, V Mehlomakulu, S Hlangu, B J Marais
SETTING: Referral hospital for drug-resistant tuberculosis (TB) in KwaZulu-Natal, South Africa. OBJECTIVES: We conducted interviews with primary care givers of children admitted with multidrug-resistant TB (MDR-TB) during a 3-month period in 2015 to identify broader household challenges. RESULTS: We interviewed 26 care givers, most of whom were women (85%). Most households had been decimated by TB/MDR-TB and human immunodeficiency virus (HIV) infection, and were dependent upon government grants...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29295939/structure-of-hiv-1-reverse-transcriptase-cleaving-rna-in-an-rna-dna-hybrid
#17
Lan Tian, Min-Sung Kim, Hongzhi Li, Jimin Wang, Wei Yang
HIV-1 reverse transcriptase (RT) contains both DNA polymerase and RNase H activities to convert the viral genomic RNA to dsDNA in infected host cells. Here we report the 2.65-Å resolution structure of HIV-1 RT engaging in cleaving RNA in an RNA/DNA hybrid. A preferred substrate sequence is absolutely required to enable the RNA/DNA hybrid to adopt the distorted conformation needed to interact properly with the RNase H active site in RT. Substituting two nucleotides 4 bp upstream from the cleavage site results in scissile-phosphate displacement by 4 Å...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29294588/-analysis-on-hiv-1-subtypes-and-transmission-clusters-in-newly-reported-hiv-aids-cases-in-yiwu-zhejiang-province-2016
#18
J F Zhang, J M Yao, Q Fan, W J Chen, X H Pan, X B Ding, J Z Yang, T Fu
Objective: To understand the characteristics of distribution on HIV-1 subtypes and the transmission clusters in Yiwu in Zhejiang province. Methods: A cross-sectional study of molecular epidemiology was carried out on newly reported HIV/AIDS cases in Yiwu. RNA was extracted from 168 plasma samples, followed by RT-PCR and nest-PCR for pol gene amplification, sequencing, phylogenetic tree construction used for analyzing the subtypes and transmission clusters. Mutations on drug resistance was analyzed by CPR 6...
December 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/29291225/application-of-viromics-a-new-approach-to-the-understanding-of-viral-infections-in-humans
#19
REVIEW
Mageshbabu Ramamurthy, Sathish Sankar, Rajesh Kannangai, Balaji Nandagopal, Gopalan Sridharan
This review is focused at exploring the strengths of modern technology driven data compiled in the areas of virus gene sequencing, virus protein structures and their implication to viral diagnosis and therapy. The information for virome analysis (viromics) is generated by the study of viral genomes (entire nucleotide sequence) and viral genes (coding for protein). Presently, the study of viral infectious diseases in terms of etiopathogenesis and development of newer therapeutics is undergoing rapid changes...
December 2017: Virusdisease
https://www.readbyqxmd.com/read/29283390/genotypic-and-phylogenetic-insights-on-prevention-of-the-spread-of-hiv-1-and-drug-resistance-in-real-world-settings
#20
REVIEW
Bluma G Brenner, Ruxandra-Ilinca Ibanescu, Isabelle Hardy, Michel Roger
HIV continues to spread among vulnerable heterosexual (HET), Men-having-Sex with Men (MSM) and intravenous drug user (IDU) populations, influenced by a complex array of biological, behavioral and societal factors. Phylogenetics analyses of large sequence datasets from national drug resistance testing programs reveal the evolutionary interrelationships of viral strains implicated in the dynamic spread of HIV in different regional settings. Viral phylogenetics can be combined with demographic and behavioral information to gain insights on epidemiological processes shaping transmission networks at the population-level...
December 28, 2017: Viruses
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