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Hiv drug resistance

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https://www.readbyqxmd.com/read/28637235/monotherapy-with-either-dolutegravir-or-raltegravir-fails-to-durably-suppress-hiv-viraemia-in-humanized-mice
#1
Alonso Heredia, Said Hassounah, Sandra Medina-Moreno, Juan C Zapata, Nhut M Le, Yingshan Han, James S Foulke, Charles Davis, Joseph Bryant, Robert R Redfield, Mark A Wainberg
Objectives: To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy. Methods: We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIV BaL . Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture...
June 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28634358/hiv-1-gp41-targeting-fusion-inhibitory-peptides-enhance-the-gp120-targeting-protein-mediated-inactivation-of-hiv-1-virions
#2
Qianqian Qi, Qian Wang, Weizao Chen, Lanying Du, Dimiter S Dimitrov, Lu Lu, Shibo Jiang
Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT)...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28633446/genetic-indicators-of-drug-resistance-in-the-highly-repetitive-genome-of-trichomonas-vaginalis
#3
Martina Bradic, Sally D Warring, Grace E Tooley, Paul Scheid, William E Secor, Kirkwood M Land, Po-Jung Huang, Ting-Wen Chen, Chi-Ching Lee, Petrus Tang, Steven A Sullivan, Jane M Carlton
Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance...
June 19, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28627486/the-association-between-detected-drug-resistance-mutations-and-cd4-t-cell-decline-in-hiv-positive-individuals-maintained-on-a-failing-treatment-regimen
#4
Anna Schultze, Roger Paredes, Caroline Sabin, Andrew N Phillips, Deenan Pillay, Nicola Mackie, Antonella Castagna, David Chadwick, Karolin Falconer, Anna Maria Geretti, Frank A Post, Teresa Hill, Ole Kirk, Anton Pozniak, Mark Nelson, Anna Tostevin, David Dunn, Jens Lundgren, Alessandro Cozzi-Lepri
BACKGROUND: To analyse the effect of drug resistance mutations (DRM) on CD4 cell trends in HIV-positive people maintained on virologically failing antiretroviral therapy (ART). METHODS: Individuals from two large cohorts experiencing virological failure (VF) while maintained on ART with >1 CD4 count and >1 resistance test were included. CD4 cell slopes were estimated using linear mixed models. Principal component analysis (PCA) was used to assess the effect of clusters of mutations, defined using extracted component based scores from the PCA, on CD4 cell decline...
June 19, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28627427/144-week-efficacy-and-safety-of-a-once-daily-single-tablet-regimen-of-tenofovir-lamivudine-and-efavirenz-among-arv-na%C3%A3-ve-and-arv-experienced-hiv-1-infected-thai-adults
#5
Anchalee Avihingsanon, Wirach Maek-A-Nantawat, Sivaporn Gatechompol, Vorapot Sapsirisavat, Wanida Thiansanguankul, Jiratchaya Sophonphan, Narujakorn Thammajaruk, Sasiwimol Ubolyam, David M Burger, Kiat Ruxrungtham
OBJECTIVES: To assess the efficacy and safety of a new single tablet regimen(STR) of tenofovir disoproxil fumarate(TDF) 300mg, lamivudine(3TC) 300mg and efavirenz(EFV) 600mg in HIV-infected Thais. METHODS: This was a 144 week, prospective study among 51 treatment naïve and 49 experienced patients on separated pill of TDF, 3TC and EFV with HIV RNA<50 copies/ml. CD4, HIV RNA, liver, renal functions and lipid profiles were assessed at baseline, weeks 12, 24, 48 and then every 24 weeks...
June 13, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28623781/inhibition-activities-of-catechol-diether-based-non-nucleoside-inhibitors-against-the-hiv-reverse-transcriptase-variants-insights-from-molecular-docking-and-oniom-calculations
#6
Pabitra Narayan Samanta, Kalyan Kumar Das
The therapeutic effectiveness of the catechol diether analogs against both the wild-type and drug-resistant reverse transcriptase (RT) mutants of HIV strains are investigated by performing molecular docking and hybrid ONIOM calculations. The docking protocol has been used to predict the binding modes of the non-nucleoside inhibitors inside the active site cavity of the viral enzymes. For each enzyme-inhibitor adduct, the predicted docked poses are assessed by employing different scoring function based programs...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28622345/the-infection-staging-and-profile-of-genotypic-distribution-and-drug-resistance-mutation-among-the-human-immunodeficiency-virus-1-infected-blood-donors-from-five-chinese-blood-centers-2012-2014
#7
Peibin Zeng, Yu Liu, Miao He, Jingxing Wang, Sheila Keating, Wei Mao, Mei Huang, Hongli Ma, Weilan He, Xinhong Bi, Dan Liao, Michael Busch, Paul Ness, Jing Liu, Hua Shan
The increasing complexity and diversity of the human immunodeficiency virus-1 (HIV-1) infections challenge the disease control and anti-retrovirus treatment in China. The infection stages and molecular characteristics of HIV-1 from infected Chinese blood donors were examined to shed light on the HIV genotype distribution and the status of drug resistance mutations (DRMs) in the changing HIV epidemic in China. Western blot (WB) confirmed HIV-1 positive plasma samples were collected from blood donors at five Chinese blood centers from April 16, 2012, through June 30, 2014...
2017: PloS One
https://www.readbyqxmd.com/read/28614778/the-human-immunodeficiency-virus-hiv1-protease-inhibitor-sanquinavir-activates-autophagy-and-removes-lipids-deposited-in-lipid-droplets
#8
A Polus, M Bociaga-Jasik, U Czech, J Goralska, U Cialowicz, M Chojnacka, M Polus, K Jurowski, A Dembinska-Kiec
Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28613071/potent-inhibitor-of-drug-resistant-hiv-1-strains-identified-from-the-medicinal-plant-justicia-gendarussa
#9
Hong-Jie Zhang, Emily Rumschlag-Booms, Yi-Fu Guan, Dong-Ying Wang, Kang-Lun Liu, Wan-Fei Li, Van H Nguyen, Nguyen M Cuong, Djaja D Soejarto, Harry H S Fong, Lijun Rong
Justicia gendarussa, a medicinal plant collected in Vietnam, was identified as a potent anti-HIV-1 active lead from the evaluation of over 4500 plant extracts. Bioassay-guided separation of the extracts of the stems and roots of this plant led to the isolation of an anti-HIV arylnaphthalene lignan (ANL) glycoside, patentiflorin A (1). Evaluation of the compound against both the M- and T-tropic HIV-1 isolates showed it to possess a significantly higher inhibition effect than the clinically used anti-HIV drug AZT...
June 14, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28607022/pharmacokinetics-of-pyrazinamide-optimising-dosing-regimens-for-drug-sensitive-and-resistant-tuberculosis
#10
Maxwell T Chirehwa, Helen McIlleron, Roxana Rustomjee, Thuli Mthiyane, Philip Onyebujoh, Peter Smith, Paolo Denti
Pyrazinamide is used in the treatment of tuberculosis(TB) because its sterilising effect against tubercle bacilli allows treatment shortening. It is part of standard treatment for drug-susceptible and drug-resistant TB, and it is being considered as a companion drug in novel regimens. The aim of this analysis was to characterize factors contributing to the variability in exposure and to evaluate drug exposures using alternative doses, thus providing evidence to support revised dosing recommendations for drug-susceptible and multi-drug resistant tuberculosis(MDR-TB)...
June 12, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28606053/protein-kinase-inhibitors-as-potential-antimicrobial-drugs-against-tuberculosis-malaria-and-hiv
#11
Yong Cheng, Jeffrey S Schorey, Cheng-Cai Zhang, Xuejuan Tan
Infectious diseases that are caused by pathogenic microbes such as bacteria, viruses, parasites or fungi remain the top major cause of death across the world, particularly in low income countries, and may be transmitted from person to person, or from insects or animals. In general, infectious diseases may be treated with antimicrobial agents including antibiotics, antiviral, antifungal or antiparasitic medications. The therapeutic application of antimicrobial drugs in the 20th century substantially contributed to the global control of infectious diseases worldwide...
June 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28605418/should-we-be-testing-for-baseline-integrase-resistance-in-patients-newly-diagnosed-with-hiv
#12
Yiannis Koullias, Paul E Sax, Naomi F Fields, Rochelle P Walensky, Emily P Hyle
Background: Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR-testing"), although this class of drugs is a component of most recommended first-line regimens. Methods: We compared the 96-week clinical outcomes and cost-effectiveness of two strategies: no IR-testing vs. IR-testing performed at HIV diagnosis...
June 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28605172/pharmacy-refill-data-can-be-used-to-predict-virologic-failure-for-patients-on-antiretroviral-therapy-in-brazil
#13
David Martin, Paula M Luz, Jordan E Lake, Jesse L Clark, Dayse P Campos, Valdilea G Veloso, Ronaldo I Moreira, Sandra W Cardoso, Jeffrey D Klausner, Beatriz Grinsztejn
INTRODUCTION: Pharmacy adherence measures such as pharmacy dispensing ratios (PDRs) have previously been shown to be predictive of virologic outcomes. We aimed to determine the optimal interval of PDR assessment for predicting virologic failure for HIV-infected patients on antiretroviral therapy (ART). METHODS: Using national Brazilian ART pharmacy refill data, we examined PDRs for patients ≥18 years of age with at least one HIV RNA level ≥180 days after ART initiation on or after 1 January 2011...
June 5, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28604824/decline-in-cd4-t-lymphocytes-with-monotherapy-bridging-strategy-for-non-adherent-adolescents-living-with-hiv-infection-results-of-the-impaact-p1094-randomized-trial
#14
Allison L Agwu, Meredith G Warshaw, Elizabeth J McFarland, George K Siberry, Ann J Melvin, Andrew A Wiznia, Lee Fairlie, Sandra Boyd, Paul Harding, Hans M L Spiegel, Elaine J Abrams, Vincent J Carey
INTRODUCTION: Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs...
2017: PloS One
https://www.readbyqxmd.com/read/28600625/an-intravaginal-ring-that-releases-three-antiviral-agents-and-a-contraceptive-blocks-shiv-rt-infection-reduces-hsv-2-shedding-and-suppresses-hormonal-cycling-in-rhesus-macaques
#15
Nina Derby, Meropi Aravantinou, Jessica Kenney, Shweta R Ugaonkar, Asa Wesenberg, Jolanta Wilk, Larisa Kizima, Aixa Rodriguez, Shimin Zhang, Olga Mizenina, Keith Levendosky, Michael L Cooney, Samantha Seidor, Agegnehu Gettie, Brooke Grasperge, James Blanchard, Michael Piatak, Jeffrey D Lifson, José Fernández-Romero, Thomas M Zydowsky, Melissa Robbiani
Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG)...
June 9, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28596841/targeting-endosomal-acidification-by-chloroquine-analogs-as-a-promising-strategy-for-the-treatment-of-emerging-viral-diseases
#16
REVIEW
Md Abdul Alim Al-Bari
Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine-resistant Plasmodium strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28592547/performance-of-the-abbott-realtime-mtb-and-mtb-rif-inh-assays-in-a-high-tb-and-hiv-coinfection-setting-in-south-africa
#17
Lesley Scott, Anura David, Lara Noble, Matilda Nduna, Pedro Da Silva, Andrew Black, Francois Venter, Wendy Stevens
Background: South Africa is a country with a high incidence of tuberculosis (TB), complicated by coinfection with HIV. The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is used in South Africa as the test for initial diagnosis of TB, and other molecular platforms such as the m2000 (Abbott Molecular, Des Plaines, IL, USA) are widely used for molecular monitoring of HIV viral load. This latter platform is now also equipped with the RealTime MTB and RealTime MTB RIF/INH assays for TB and first line drug resistance screening, but has not been evaluated in settings of HIV and TB coinfection...
June 7, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28591401/an-overview-of-the-molecular-and-epidemiological-features-of-hiv-1-infection-in-two-major-cities-of-bahia-state-brazil
#18
Amanda Gm Amaral, Isabele B Oliveira, Diego C Carneiro, Luiz Cj Alcantara, Joana P Monteiro-Cunha
BACKGROUND: The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. OBJECTIVE: The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. METHODS: DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012...
June 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28590327/pregnancy-incidence-and-outcomes-in-women-with-perinatal-hiv-infection
#19
Laura Byrne, Rebecca Sconza, Caroline Foster, Pat A Tookey, Mario Cortina-Borja, Claire Thorne
OBJECTIVE(S): To estimate the incidence of first pregnancy in women living with perinatally-acquired HIV (PHIV) in the UK and to compare pregnancy management and outcomes with age-matched women with behaviourally-acquired HIV (BHIV). DESIGN: The National Study of HIV in Pregnancy and Childhood (NSHPC) is a comprehensive, population-based surveillance study that collects demographic and clinical data on all pregnant women living with HIV, their children, and all HIV-infected children in the UK & Ireland...
June 5, 2017: AIDS
https://www.readbyqxmd.com/read/28590068/comparison-of-hiv-1-drug-resistance-genotyping-by-ultra-deep-sequencing-and-sanger-sequencing-using-clinical-samples
#20
Mary-Anne Trabaud, Vinca Icard, Christophe Ramière, Jean-Claude Tardy, Caroline Scholtes, Patrice André
Sanger population sequencing (SPS) is the reference technique to monitor HIV-1-infected patients' therapy. Ultra-deep sequencing (UDS), which allows quantitative detection of drug resistance mutations, may be an alternative method. The study aimed to compare reproducibility and predictions of UDS versus SPS in a routine setting. A control containing low-abundance variants was repeatedly tested and clinical plasma samples from 100 patients were prospectively assayed by SPS and UDS using the Roche 454 system...
June 7, 2017: Journal of Medical Virology
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