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HIV variation

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https://www.readbyqxmd.com/read/28797170/analysis-of-clinical-hiv-1-strains-with-resistance-to-maraviroc-reveals-strain-specific-resistance-mutations-variable-degrees-of-resistance-and-minimal-cross-resistance-to-other-ccr5-antagonists
#1
Jacqueline Flynn, Paula Ellenberg, Renee Duncan, Anne Ellett, Jingling Zhou, Jasminka Sterjovski, Kieran Cashin, Katharina Borm, Lachlan Gray, Marilyn Lewis, Becky Jubb, Mike Westby, Benhur Lee, Sharon Ruth Lewin, Melissa Churchill, Michael Roche, Paul Gorry
Maraviroc (MVC) is an allosteric inhibitor of HIV-1 entry, and is the only CCR5 antagonist licensed for use as an anti-HIV-1 therapeutic. It acts by altering the conformation of the CCR5 extracellular loops, rendering CCR5 unrecognizable by the HIV-1 envelope glycoproteins (Env). This study aimed to understand the mechanisms underlying the development of MVC resistance in HIV-1-infected patients. To do this, we obtained longitudinal plasma samples from 8 subjects who experienced treatment failure with phenotypically verified, CCR5-tropic MVC resistance...
August 11, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28796791/evaluating-turnaround-times-for-early-infant-diagnosis-samples-in-kenya-from-2011-2014-a-retrospective-analysis-of-hitsystem-program-data
#2
Catherine Wexler, An-Lin Cheng, Brad Gautney, Sarah Finocchario-Kessler, Kathy Goggin, Samoel Khamadi
Long turnaround times (TAT) for the processing and posting of results of infant HIV DNA PCR samples can hinder the success of early infant diagnosis (EID) programs. The HITSystem is an eHealth intervention that alerts staff when services are overdue or results are delayed. We conducted a retrospective analysis of 3669 HIV-exposed infants enrolled in 15 Kenya hospital EID programs and three laboratories using the HITSystem from 2011-2014. We assessed mean and median TAT from when a sample was: 1) obtained to when it was shipped to the laboratory, 2) shipped to when it was received at the laboratory, 3) received to when a result was posted, and 4) the total time from obtaining the sample (step 1) to posting the result (step 3)...
2017: PloS One
https://www.readbyqxmd.com/read/28791894/decoding-hiv-resistance-from-genotype-to-therapy
#3
Irene T Weber, Robert W Harrison
Genetic variation in HIV poses a major challenge for prevention and treatment of the AIDS pandemic. Resistance occurs by mutations in the target proteins that lower affinity for the drug or alter the protein dynamics, thereby enabling viral replication in the presence of the drug. Due to the prevalence of drug-resistant strains, monitoring the genotype of the infecting virus is recommended. Computational approaches for predicting resistance from genotype data and guiding therapy are discussed. Many prediction methods rely on rules derived from known resistance-associated mutations, however, statistical or machine learning can improve the classification accuracy and assess unknown mutations...
August 9, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28770939/chemical-optimization-of-macrocyclic-hiv-1-inactivators-for-improving-potency-and-increasing-the-structural-diversity-at-the-triazole-ring
#4
Adel A Rashad, Kriti Acharya, Ann Haftl, Rachna Aneja, Alexej Dick, Andrew P Holmes, Irwin Chaiken
HIV-1 entry inhibition remains an urgent need for AIDS drug discovery and development. We previously reported the discovery of cyclic peptide triazoles (cPTs) that retain the HIV-1 irreversible inactivation functions of the parent linear peptides (PTs) and have massively increased proteolytic resistance. Here, in an initial structure-activity relationship investigation, we evaluated the effects of variations in key structural and functional components of the cPT scaffold in order to produce a platform for developing next-generation cPTs...
August 3, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28765078/evolution-of-the-prevalence-of-hcv-infection-and-hcv-genotype-distribution-in-hiv-infected-patients-in-italy-between-1997-and-2015
#5
Barbara Rossetti, Francesca Bai, Alessandro Tavelli, Massimo Galli, Andrea Antinori, Francesco Castelli, Giampietro Pellizzer, Alessandro Cozzi-Lepri, Stefano Bonora, Antonella d'Arminio Monforte, Massimo Puoti, Andrea De Luca
OBJECTIVES: Aim of the study was to analyze the variation of HCV prevalence and genotype distribution and their determinants in people living with HIV who entered care between 1997 and 2015. METHODS: HIV-infected patients enrolled in ICONA who were tested for HCV-Antibodies (HCV-Ab) were included. RESULTS: Overall 3,407/12,135 (28.1%) were HCV-Ab+; and 735/12,135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most represented were genotype 1 and 3...
July 29, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28764644/variable-selection-for-disease-progression-models-methods-for-oncogenetic-trees-and-application-to-cancer-and-hiv
#6
Katrin Hainke, Sebastian Szugat, Roland Fried, Jörg Rahnenführer
BACKGROUND: Disease progression models are important for understanding the critical steps during the development of diseases. The models are imbedded in a statistical framework to deal with random variations due to biology and the sampling process when observing only a finite population. Conditional probabilities are used to describe dependencies between events that characterise the critical steps in the disease process. Many different model classes have been proposed in the literature, from simple path models to complex Bayesian networks...
August 1, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28762239/high-performance-liquid-chromatography-tandem-mass-spectrometry-for-simultaneous-determination-of-raltegravir-dolutegravir-and-elvitegravir-concentrations-in-human-plasma-and-cerebrospinal-fluid-samples
#7
Kiyoto Tsuchiya, Mayu Ohuchi, Naoe Yamane, Hiroaki Aikawa, Hiroyuki Gatanaga, Shinichi Oka, Akinobu Hamada
A simple sample treatment procedure and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method were developed for the simultaneous quantification of the concentrations of human immunodeficiency virus-1 (HIV-1) integrase strand transfer inhibitors (INSTIs); raltegravir (RAL), dolutegravir (DTG), and elvitegravir (EVG); in human plasma and cerebrospinal fluid (CSF). Plasma and CSF samples (20 μL each) were deproteinized with acetonitrile. Raltegravir-d3 was used as the internal standard (IS)...
July 31, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28758224/a-method-to-address-between-subject-heterogeneity-for-identification-of-principal-surrogate-markers-in-repeated-low-dose-challenge-hiv-vaccine-studies
#8
Andrew J Spieker, Ying Huang
Repeated low-dose challenge designs in nonhuman primate studies have recently received attention in the literature as a means of evaluating vaccines for HIV prevention and identifying immune surrogates for their protective effects. Existing methods for surrogate identification in this type of study design rely on the assumption of homogeneity across subjects (namely, independent infection risks after each challenge within each subject and conditional on covariates). In practice, random variation across subjects is likely to occur because of unmeasured biologic factors...
July 31, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28747410/a-systematic-review-and-meta-analysis-of-studies-evaluating-the-performance-and-operational-characteristics-of-dual-point-of-care-tests-for-hiv-and-syphilis
#9
REVIEW
Harriet D Gliddon, Rosanna W Peeling, Mary L Kamb, Igor Toskin, Teodora E Wi, Melanie M Taylor
BACKGROUND: Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality. OBJECTIVES: To systematically review, critically appraise and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use. DESIGN: Systematic review and meta-analysis...
July 26, 2017: Sexually Transmitted Infections
https://www.readbyqxmd.com/read/28743606/the-botanical-drug-substance-crofelemer-as-a-model-system-for-comparative-characterization-of-complex-mixture-drugs
#10
Peter A Kleindl, Jian Xiong, Asha Hewarathna, Olivier Mozziconacci, Maulik K Nariya, Adam C Fisher, Eric J Deeds, Sangeeta B Joshi, C Russell Middaugh, Christian Schöneich, David B Volkin, M Laird Forrest
Crofelemer is a botanical polymeric proanthocyanidin that inhibits chloride channel activity and is used clinically for treating HIV-associated secretory diarrhea. Crofelemer lots may exhibit significant physicochemical variation due to the natural source of the raw material. A variety of physical, chemical, and biological assays were utilized to identify potential critical quality attributes (CQAs) of crofelemer, which may be useful in characterizing differently sourced and/or processed drug products. Crofelemer drug substance was extracted from tablets of one commerical drug product lot, fractionated, and subjected to accelerated thermal degradation studies to produce derivative lots with variations in chemical and physical composition potentially representative of manufacturing and raw material variation...
July 22, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28743254/association-between-serotonin-transporter-gene-polymorphisms-and-increased-suicidal-risk-among-hiv-positive-patients-in-uganda
#11
Allan Kalungi, Soraya Seedat, Sian M J Hemmings, Lize van der Merwe, Moses L Joloba, Ann Nanteza, Noeline Nakassujja, Harriet Birabwa, Jennifer Serwanga, Pontiano Kaleebu, Eugene Kinyanda
BACKGROUND: Persons living with HIV/AIDS (PLWHA) are at an increased risk of suicide. Increased suicidal risk is a predictor of future attempted and completed suicides and has been associated with poor quality of life and poor adherence with antiretroviral therapy. Clinical risk factors have low predictive value for suicide, hence the interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. The serotonin transporter gene has previously been implicated in the aetiology of increased suicidal risk in non-HIV infected study populations and its variations may provide a platform for identifying genetic risk for suicidality among PLWHA...
July 25, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28737979/hect-domain-and-rcc1-like-domain-containing-protein-5-herc-5-gene-polymorphisms-in-hiv-1-infected-individuals-a-study-from-india
#12
Nawaj Shaikh, Vandana Saxena, Sudhanshu Pandey, Ajit Patil, Madhuri Thakar
HECT domain and RCC1-like domain-containing protein 5 (HERC-5) is one of the novel host restriction factors that is known to inhibit HIV release in vitro. Polymorphisms in other host restriction factors have been associated with HIV infection and disease progression. However, no report is available on the HERC-5 polymorphism in HIV-infected individuals. We studied the HERC-5 gene polymorphism in HIV-infected individuals and explored whether it is associated with different disease outcomes. Genomic DNA was isolated from 41 HIV-1 progressors, 39 long-term nonprogressors, and 74 HIV seronegative healthy donors for amplification of HERC5 Exon-18 and other regulatory regions followed by sequencing...
July 24, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28733065/severe-maternal-morbidity-associated-with-maternal-birthplace-a-population-based-register-study
#13
Marcelo L Urquia, Susitha Wanigaratne, Joel G Ray, K S Joseph
OBJECTIVE: This study sought to quantify the risk of severe maternal morbidity (SMM) according to maternal country of birth in Canada. METHODS: The study analyzed 1 252 543 in-hospital deliveries of Ontario residents discharged between April 1, 2002, and March 31, 2012. The main outcome measure was a composite indicator of SMM used for surveillance. The top 10 most common component conditions were also evaluated. Maternal country of birth and other immigration characteristics were obtained through linkage with official immigration records...
July 18, 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28732472/genexpert-hiv-1-quant-assay-a-new-tool-for-scale-up-of-viral-load-monitoring-in-the-success-of-art-programme-in-india
#14
Smita Kulkarni, Sushama Jadhav, Priyanka Khopkar, Suvarna Sane, Rajkumar Londhe, Vaishali Chimanpure, Veronica Dhilpe, Manisha Ghate, Rajendra Yelagate, Narayan Panchal, Girish Rahane, Dilip Kadam, Nitin Gaikwad, Bharat Rewari, Raman Gangakhedkar
BACKGROUND: Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. METHODS: A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays...
July 21, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28729474/trilateral-overlap-of-tuberculosis-diabetes-and-hiv-1-in-a-high-burden-african-setting-implications-for-tb-control
#15
Tolu Oni, Natacha Berkowitz, Mmamapudi Kubjane, Rene Goliath, Naomi S Levitt, Robert J Wilkinson
The diabetes mellitus burden is growing in countries where tuberculosis (TB) and HIV-1 remain major challenges, threatening TB control efforts. This study determined the association between TB and diabetes/impaired glucose regulation in the context of HIV-1.A cross-sectional study was conducted at a TB clinic in Cape Town (South Africa). Participants were screened for diabetes and impaired glucose regulation using fasting plasma glucose, oral glucose tolerance test and glycated haemoglobin (HbA1c).414 TB and 438 non-TB participants were enrolled...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28726743/the-effect-of-n-terminal-cyclization-on-the-function-of-the-hiv-entry-inhibitor-5p12-rantes
#16
Anna F Nguyen, Megan S Schill, Mike Jian, Patricia J LiWang
Despite effective treatment for those living with Human Immunodeficiency Virus (HIV), there are still two million new infections each year. Protein-based HIV entry inhibitors, being highly effective and specific, could be used to protect people from initial infection. One of the most promising of these for clinical use is 5P12-RANTES, a variant of the chemokine RANTES/CCL5. The N-terminal amino acid of 5P12-RANTES is glutamine (Gln; called Q0), a residue that is prone to spontaneous cyclization when at the N-terminus of a protein...
July 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28723945/haematological-and-cd4-t-cells-reference-ranges-in-healthy-adult-populations-in-gojjam-zones-in-amhara-region-ethiopia
#17
Wondemagegn Mulu, Bayeh Abera, Zewdie Mekonnen, Yesuf Adem, Mulat Yimer, Yohannes Zenebe, Asmare Amuamuta, Wondimu Gebeyehu
INTRODUCTION: Establishing national population haematological and immunological reference ranges are essential for clinical management of patients. However, there is scarcity of information on community based haematological reference ranges established from Ethiopian population. Therefore, this study aimed at determining haematological and CD4+ T cells reference ranges in healthy adults from East and West Gojjam zones, Ethiopia. METHODS: Community based cross-sectional study was conducted from May 2015 to December 2015 in healthy adult residents of Gojjam zone...
2017: PloS One
https://www.readbyqxmd.com/read/28718235/quality-assessment-of-focused-antenatal-care-service-delivery-in-tertiary-care-health-facility
#18
Farah Ashraf, Inayat Hussain Thaver, Faisal Imtiaz, Adil Ayub
BACKGROUND: Regardless of high maternal deaths in Pakistan, only 37% of pregnant women make four or more antenatal care visits during pregnancy. This proportion has further been diverged between urban and rural. About 62% of women visit clinics for WHO recommended sets of antenatal care (ANC) check-ups in urban as compared to 26% women in rural areas. This study was conducted with the aim to assess quality of Focused ANC service delivery in terms of examination, screening, treatment, counselling and to determine variation in service delivery with provider's clinical qualification and expertise...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28712360/resisting-and-tolerating-p-falciparum-in-pregnancy-under-different-malaria-transmission-intensities
#19
Nicaise Tuikue Ndam, Emmanuel Mbuba, Raquel González, Pau Cisteró, Simon Kariuki, Esperança Sevene, María Rupérez, Ana Maria Fonseca, Anifa Vala, Sonia Maculuve, Alfons Jiménez, Llorenç Quintó, Peter Ouma, Michael Ramharter, John J Aponte, Arsenio Nhacolo, Achille Massougbodji, Valerie Briand, Peter G Kremsner, Ghyslain Mombo-Ngoma, Meghna Desai, Eusebio Macete, Michel Cot, Clara Menéndez, Alfredo Mayor
BACKGROUND: Resistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. falciparum infections among African pregnant women under different intensities of malaria transmission. METHODS: P. falciparum at delivery was assessed by microscopy, quantitative PCR (qPCR) and placental histology in 946 HIV-uninfected and 768 HIV-infected pregnant women from Benin, Gabon, Kenya and Mozambique...
July 17, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28704367/correction-viral-genetic-variation-accounts-for-a-third-of-variability-in-hiv-1-set-point-viral-load-in-europe
#20
François Blanquart, Chris Wymant, Marion Cornelissen, Astrid Gall, Margreet Bakker, Daniela Bezemer, Matthew Hall, Mariska Hillebregt, Swee Hoe Ong, Jan Albert, Norbert Bannert, Jacques Fellay, Katrien Fransen, Annabelle J Gourlay, M Kate Grabowski, Barbara Gunsenheimer-Bartmeyer, Huldrych F Günthard, Pia Kivelä, Roger Kouyos, Oliver Laeyendecker, Kirsi Liitsola, Laurence Meyer, Kholoud Porter, Matti Ristola, Ard van Sighem, Guido Vanham, Ben Berkhout, Paul Kellam, Peter Reiss, Christophe Fraser
[This corrects the article DOI: 10.1371/journal.pbio.2001855.].
July 2017: PLoS Biology
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