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https://www.readbyqxmd.com/read/30119633/selective-resistance-profiles-emerging-in-patient-derived-clinical-isolates-with-cabotegravir-bictegravir-dolutegravir-and-elvitegravir
#1
Maureen Oliveira, Ruxandra-Ilinca Ibanescu, Kaitlin Anstett, Thibault Mésplède, Jean-Pierre Routy, Marjorie A Robbins, Bluma G Brenner
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended for first-line HIV therapy based on their relatively high genetic barrier to resistance. Although raltegravir (RAL) and elvitegravir (EVG) resistance profiles are well-characterized, resistance patterns for dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) remain largely unknown. Here, in vitro drug selections compared the development of resistance to DTG, BIC, CAB, EVG and RAL using clinical isolates from treatment-naïve primary HIV infection (PHI) cohort participants (n = 12), and pNL4...
August 17, 2018: Retrovirology
https://www.readbyqxmd.com/read/30116231/structural-implications-of-genotypic-variations-in-hiv-1-integrase-from-diverse-subtypes
#2
Leonard Rogers, Adetayo E Obasa, Graeme B Jacobs, Stefan G Sarafianos, Anders Sönnerborg, Ujjwal Neogi, Kamalendra Singh
Human immunodeficiency virus type 1 (HIV-1) integrase (IN) integrates viral DNA into the host genome using its 3'-end processing and strand-transfer activities. Due to the importance of HIV-1 IN, it is targeted by the newest class of approved drugs known as integrase strand transfer inhibitors (INSTIs). INSTIs are efficient in maintaining low viral load; however, as with other approved antivirals, resistance mutations emerge in patients receiving INSTI-containing therapy. As INSTIs are becoming increasingly accessible worldwide, it is important to understand the mechanism(s) of INSTI susceptibility...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30115986/prevalence-of-transmitted-hiv-drug-resistance-in-antiretroviral-treatment-na%C3%A3-ve-newly-diagnosed-individuals-in-china
#3
Shuai Zhao, Yi Feng, Jing Hu, Yang Li, Zhongbao Zuo, Jing Yan, Jing Zhang, Pi Cao, Wei Xu, Fan Li, Yuxueyun Li, Lingjie Liao, Yuhua Ruan, Yiming Shao, Hui Xing
To investigate the prevalence and temporal trend of transmitted drug resistance (TDR), a nationwide cross-sectional survey was conducted among 5627 ART naïve newly diagnosed HIV-infected individuals in 2015 in China. Totally 4704 partial pol sequences were obtained. Among them, the most common HIV-1 circulating recombinant form (CRF) or subtype was CRF01_AE (39.0%), followed by CRF07_BC (35.6%), CRF08_BC (8.9%), and subtype B (5.5%). TDR mutations were found in 3.6% of the cases, with 1.1% harboring TDR to protease inhibitors (PIs), 1...
August 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30114999/treatment-of-disseminated-histoplasmosis-in-advanced-hiv-using-itraconazole-with-increased-bioavailability
#4
Rekha P Mangalore, Michael A Moso, Katie Cronin, Katrina Young, James H McMahon
Disseminated histoplasmosis (DH), an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, is a life-threatening infection in immunocompromised hosts. A patient with newly-diagnosed human immunodeficiency virus (HIV) infection presented with a violaceous, raised, indurated, pruritic rash over the face, arms and trunk on a background of significant weight loss, fevers with sweats, diarrhoea and worsening shortness of breath. His CD4+ T cell count was 14 cells/µl (12%). Histoplasmosis was diagnosed from histology, fungal stain and culture of skin biopsy...
August 16, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/30112315/epidemiological-profile-of-multidrug-resistant-tuberculosis-patients-in-gorakhpur-division-uttar-pradesh-india
#5
U Venkatesh, D K Srivastava, A K Srivastava, H C Tiwari
Introduction: Multidrug-resistant tuberculosis (MDR-TB) poses a major threat to control of TB worldwide. Adequate information on socioepidemiological factors and their interaction is required for its control. The aim was to study the social and epidemiological profile of MDR-TB patient in Gorakhpur division. Methodology: A cross-sectional study of 157 MDR-TB patients from Gorakhpur division admitted at DR-TB Center of a tertiary care center were interviewed during initiation of MDR-TB treatment using structured questionnaire and collected data were described using descriptive statistics...
May 2018: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/30112309/analysis-of-tuberculosis-case-report-in-hyderabad-district-of-telangana-state
#6
Snigdha Pattnaik
Background: The estimated incidence of TB in India was approximately 28,00,000 as per the Global TB report 2017. This accounts for a quarter of the world's TB (Tb) cases. National strategic plan, is a programme which aims at the elimination of Tb by 2018. The programme is crafted in line with other health sector strategies and global efforts, such as the draft National Health Policy 2015, World Health Organization's (WHO) End TB Strategy and the Sustainable Development Goals (SDGs) of the United Nations (UN)...
May 2018: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/30111079/tuberculosis-in-poland-in-2016
#7
Maria Korzeniewska-Koseła
AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2016 in Poland and to compare with the situation in the EU/EEA countries. METHODS: Analysis of case- based data on TB patients from National TB Register, data on anti-TB drug susceptibility testing results in cases notified in 2016, data from National Institute of Public Health- National Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, data from Central Statistical Office on deaths from tuberculosis based on death certificates, data from ECDC report „ European Centre for Disease Prevention and Control/WHO Regional Office for Europe...
2018: Przegla̧d Epidemiologiczny
https://www.readbyqxmd.com/read/30110589/phase-3-study-of-ibalizumab-for-multidrug-resistant-hiv-1
#8
Brinda Emu, Jeffrey Fessel, Shannon Schrader, Princy Kumar, Gary Richmond, Sandra Win, Steven Weinheimer, Christian Marsolais, Stanley Lewis
BACKGROUND: Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4. METHODS: In this single-group, open-label, phase 3 study, we enrolled 40 adults with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral therapies had failed. All the patients had a viral load of more than 1000 copies of HIV-1 RNA per milliliter. After a 7-day control period in which patients continued to receive their current therapy, a loading dose of 2000 mg of ibalizumab was infused; the viral load was quantified 7 days later...
August 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/30110580/ibalizumab-in-multidrug-resistant-hiv-accepting-uncertainty
#9
Virginia Sheikh, Jeffrey S Murray, Adam Sherwat
New England Journal of Medicine, Volume 379, Issue 7, Page 605-607, August 2018.
August 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/30109196/retroviral-nucleocapsid-proteins-and-dna-strand-transfers
#10
REVIEW
Brigitte René, Olivier Mauffret, Philippe Fossé
An infectious retroviral particle contains 1000-1500 molecules of the nucleocapsid protein (NC) that cover the diploid RNA genome. NC is a small zinc finger protein that possesses nucleic acid chaperone activity that enables NC to rearrange DNA and RNA molecules into the most thermodynamically stable structures usually those containing the maximum number of base pairs. Thanks to the chaperone activity, NC plays an essential role in reverse transcription of the retroviral genome by facilitating the strand transfer reactions of this process...
December 2018: Biochimie Open
https://www.readbyqxmd.com/read/30109011/generation-of-a-long-acting-fusion-inhibitor-against-hiv-1
#11
Ye Guo, Pan-Pan Zhou, Sen-Yan Zhang, Xiao-Wen Fan, Yu-Wei Dou, Xuan-Ling Shi
AIDS has evolved from a fatal infectious disease to a manageable chronic disease under the treatment of anti-AIDS medications. HIV fusion inhibitors with high activity, low side effects and strong selectivity are promising drugs against HIV. Only one fusion inhibitor is currently approved, thereby highly active long-acting fusion inhibitors need to be developed for long-term AIDS treatment. Here, we synthesised MT-SC22EK (a small HIV fusion inhibitor) derivatives containing 1-2 staples to improve its stability...
July 1, 2018: MedChemComm
https://www.readbyqxmd.com/read/30108947/structure-guided-approach-identifies-a-novel-class-of-hiv-1-ribonuclease-h-inhibitors-binding-mode-insights-through-magnesium-complexation-and-site-directed-mutagenesis-studies
#12
Vasanthanathan Poongavanam, Angela Corona, Casper Steinmann, Luigi Scipione, Nicole Grandi, Fabiana Pandolfi, Roberto Di Santo, Roberta Costi, Francesca Esposito, Enzo Tramontano, Jacob Kongsted
Persistent HIV infection requires lifelong treatment and among the 2.1 million new HIV infections that occur every year there is an increased rate of transmitted drug-resistant mutations. This fact requires a constant and timely effort in order to identify and develop new HIV inhibitors with innovative mechanisms. The HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only viral encoded enzyme that still lacks an efficient inhibitor despite the fact that it is a well-validated target whose functional abrogation compromises viral infectivity...
March 1, 2018: MedChemComm
https://www.readbyqxmd.com/read/30107485/high-cure-rates-with-grazoprevir-elbasvir-with-or-without-ribavirin-guided-by-genotypic-resistance-testing-among-human-immunodeficiency-virus-hepatitis-c-virus-coinfected-men-who-have-sex-with-men
#13
Dominique L Braun, Benjamin Hampel, Roger Kouyos, Huyen Nguyen, Cyril Shah, Markus Flepp, Marcel Stöckle, Anna Conen, Charles Béguelin, Patrizia Künzler-Heule, Dunja Nicca, Patrick Schmid, Julie Delaloye, Mathieu Rougemont, Enos Bernasconi, Andri Rauch, Huldrych F Günthard, Jürg Böni, Jan S Fehr
Background: This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial (clinicaltrials.gov NCT02785666). Methods: We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment...
August 13, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/30106660/new-and-improved-21-st-century-cures-act-revisions-to-certificates-of-confidentiality
#14
Leslie E Wolf, Laura M Beskow
Certificates of Confidentiality ("Certificates") are a federal legal tool designed to protect sensitive, identifiable research data from compelled disclosure. Congress first authorized their use in 1970 to facilitate research on illegal drug use. The scope of their use was later expanded to cover mental health research and then again to apply broadly to identifiable, sensitive research data, regardless of topic. Certificates can be critical to enabling conduct of essential research on sensitive topics, such as effective interventions to curb the opioid epidemic or reduce HIV transmission among minority youth...
May 2018: American Journal of Law & Medicine
https://www.readbyqxmd.com/read/30103267/new-resistance-mutations-to-nucleoside-reverse-transcriptase-inhibitors-at-codon-184-of-hiv-1-reverse-transcriptase-m184l-and-m184t
#15
Lydia Pouga, Maria Mercedes Santoro, Charlotte Charpentier, Domenico Di Carlo, Isabella Romeo, Anna Artese, Stefano Alcaro, Andrea Antinori, Marc Wirden, Carlo Federico Perno, Francesca Alessandra Ambrosio, Vincent Calvez, Diane Descamps, Anne-Geneviève Marcelin, Francesca Ceccherini-Silberstein, Sidonie Lambert-Niclot
OBJECTIVES: Mutations at HIV-1 reverse transcriptase (RT) codon 184 such as M184V confer resistance to two nucleos(t)ide RT inhibitors (NRTI), lamivudine (3TC) and emtricitabine (FTC). METHODS: The prevalence of mutations at HIV-1 RT codon 184 was evaluated using three independent RT sequence databases from treatment-experienced (TE) and treatment-naïve (TN) individuals. Data were collected retrospectively from three centers, one in Italy and two in France between 1997 and 2016...
August 13, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/30102262/body-parts-matter-social-behavioral-and-biological-considerations-for-urethral-pharyngeal-and-rectal-gonorrhea-and-chlamydia-screening-among-msm-in-lima-peru
#16
Ryan Colby Passaro, Eddy R Segura, Amaya Perez-Brumer, Jeanne Cabeza, Silvia M Montano, Jordan E Lake, Jorge Sanchez, Javier R Lama, Jesse L Clark
BACKGROUND: Gonorrhea (Neisseria gonorrhoeae [GC]) and chlamydia (Chlamydia trachomatis [CT]) disproportionately affect men who have sex with men (MSM), and public health implications vary by anatomic site and bacterial agent. Urethral and rectal GC and CT can increase risk of HIV transmission, whereas pharyngeal GC may be a reservoir for antimicrobial resistance. To define screening priorities in Latin America, we compare differences in the prevalence and correlates of urethral, pharyngeal, and rectal GC and CT among MSM in Peru...
September 2018: Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/30101539/switching-to-coformulated-rilpivirine-rpv-emtricitabine-ftc-and-tenofovir-alafenamide-from-either-rpv-ftc-and-tenofovir-disoproxil-fumarate-tdf-or-efavirenz-ftc-and-tdf-96-week-results-from-two-randomized-clinical-trials
#17
D Hagins, C Orkin, E S Daar, A Mills, C Brinson, E DeJesus, F A Post, J Morales-Ramirez, M Thompson, O Osiyemi, B Rashbaum, H-J Stellbrink, C Martorell, H Liu, Y-P Liu, D Porter, S E Collins, D SenGupta, M Das
OBJECTIVES: The single-tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV-1-infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. METHODS: We conducted two distinct randomized, double-blind, active-controlled, noninferiority trials in participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160)...
August 12, 2018: HIV Medicine
https://www.readbyqxmd.com/read/30097235/immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-a-tool-to-improve-patients-selection
#18
REVIEW
Giuseppe Luigi Banna, Francesco Passiglia, Francesca Colonese, Stefania Canova, Jessica Menis, Alfredo Addeo, Antonio Russo, Diego Luigi Cortinovis
The identification of reliable predictive biomarkers of efficacy or resistance to immune-oncology (I-O) agents is a major issue for translational research and clinical practice. However, along with PDL1 and molecular features other clinical, radiological and laboratory factors can be considered for the selection of those patients who would not be the best candidate for immune-checkpoint inhibitors (ICPIs). We examined these factors, emerging from the results of currently available studies in non-small cell lung cancer (NSCLC), aiming to provide a useful and manageable tool which can help Oncologists in their everyday clinical practice...
September 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/30096879/sanger-and-next-generation-sequencing-approaches-to-evaluate-hiv-1-virus-in-blood-compartments
#19
Andrea Arias, Pablo López, Raphael Sánchez, Yasuhiro Yamamura, Vanessa Rivera-Amill
The implementation of antiretroviral treatment combined with the monitoring of drug resistance mutations improves the quality of life of HIV-1 positive patients. The drug resistance mutation patterns and viral genotypes are currently analyzed by DNA sequencing of the virus in the plasma of patients. However, the virus compartmentalizes, and different T cell subsets may harbor distinct viral subsets. In this study, we compared the patterns of HIV distribution in cell-free (blood plasma) and cell-associated viruses (peripheral blood mononuclear cells, PBMCs) derived from ART-treated patients by using Sanger sequencing- and Next-Generation sequencing-based HIV assay...
August 9, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/30096076/structural-and-functional-characterization-of-hiv-1-cell-fusion-inhibitor-t20
#20
Xiujuan Zhang, Xiaohui Ding, Yuanmei Zhu, Huihui Chong, Sheng Cui, Jinsheng He, Xinquan Wang, Yuxian He
OBJECTIVE: The peptide drug T20 (enfuvirtide), derived from the C-terminal heptad repeat region of HIV-1 gp41, is the only membrane fusion inhibitor available for treatment of viral infection; however, its mechanism of action remains elusive and its structural basis is lacking. DESIGN: We focused on determining the crystal structure of T20 in complex with N39, a target mimic peptide derived from the N-terminal heptad repeat region of gp41. Based on the structural information, the mechanisms of action of T20 and its resistance were further characterized...
August 8, 2018: AIDS
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