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https://www.readbyqxmd.com/read/29346431/sensitivity-and-specificity-of-two-dried-blood-spot-methods-for-hiv-1-viral-load-monitoring-among-patients-in-hanoi-vietnam
#1
Todd M Pollack, Hao T Duong, Phuong T Truong, Thuy T Pham, Cuong D Do, Donn Colby
The use of dried blood spot (DBS) specimens for HIV viral load (VL) monitoring is recommended to support the roll-out of routine VL monitoring in low and middle income countries (LMICs). To better understand the use of DBS for VL monitoring, we evaluated two DBS testing methods, Roche TaqMan® Free Virus Evolution protocol (DBS-FVE) and Roche TaqMan® SPEX protocol (DBS-SPEX)) in patients receiving ART at an HIV clinic in Hanoi, Vietnam. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each DBS testing method at the thresholds of 1000 and 5000 copies/ml compared to plasma VL...
2018: PloS One
https://www.readbyqxmd.com/read/29346413/genetic-diversity-and-potential-routes-of-transmission-of-mycobacterium-bovis-in-mozambique
#2
Adelina Machado, Teresa Rito, Solomon Ghebremichael, Nuelma Muhate, Gabriel Maxhuza, Custodia Macuamule, Ivania Moiane, Baltazar Macucule, Angelica Suzana Marranangumbe, Jorge Baptista, Joaquim Manguele, Tuija Koivula, Elizabeth Maria Streicher, Robin Mark Warren, Gunilla Kallenius, Paul van Helden, Margarida Correia-Neves
Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29346270/resistance-to-hiv-integrase-inhibitors-about-r263k-and-e157q-mutations
#3
REVIEW
Charlotte Charpentier, Diane Descamps
The use of integrase inhibitors (INI) is increasing in antiretroviral therapies (ART) and INI are not all equal regarding genetic barrier to resistance. The aim of this manuscript was to review main in vivo and in vitro knowledge about two particular integrase resistance-associated mutations: R263K and E157Q. The R263K mutation was the first mutation rarely found selected at time of virological failure in patients failing a first-line dolutegravir-based treatment. Further in vitro studies on R263K mutants showed a moderate increase in phenotypic resistance level and a drastic reduction in viral replicative capacity...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29343575/high-resolution-sequencing-of-viral-populations-during-early-siv-infection-reveals-evolutionary-strategies-for-rapid-escape-from-emerging-env-specific-antibody-responses
#4
Sergio Ita, Alison K Hill, Evan C Lam, Fay J Dufort, Xiao Yang, Ruchi Newman, Sivan Leviyang, Ismael B Fofana, Welkin E Johnson
Primate lentiviruses, including the human and simian immunodeficiency viruses (HIV and SIV), produce infections marked by persistent, ongoing viral replication. This occurs despite the presence of virus-specific adaptive immune responses, including antibodies targeting the viral envelope glycoprotein (Env), and evolution of antibody-escape variants is a well-documented feature of lentiviral infection. Here, we examined the evolutionary dynamics of the SIV env gene during early infection (≤ 29 weeks post-infection) in a cohort of four SIVmac251-infected rhesus macaques...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29338056/context-dependent-autoprocessing-of-human-immunodeficiency-virus-type-1-protease-precursors
#5
ChihFeng Tien, Liangqun Huang, Susan M Watanabe, Jordan T Speidel, Carol A Carter, Chaoping Chen
HIV-1 protease autoprocessing is responsible for liberation of free mature protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system was previously developed to examine the autoprocessing mechanism of fusion precursors carrying the p6*-PR miniprecursor sandwiched between various proteins or epitopes. We here report that precursor autoprocessing is context-dependent as its activity and outcomes can be modulated by sequences upstream of p6*-PR. This was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP) when placed at the N-terminus of a fusion precursor...
2018: PloS One
https://www.readbyqxmd.com/read/29329426/a-practical-guide-to-estimating-the-heritability-of-pathogen-traits
#6
Venelin Mitov, Tanja Stadler
Pathogen traits, such as the virulence of an infection, can vary significantly between patients. A major challenge is to measure the extent to which genetic differences between infecting strains explain the observed variation of the trait. This is quantified by the trait's broad-sense heritability, H2. A recent discrepancy between estimates of the heritability of HIV-virulence has opened a debate on the estimators' accuracy. Here, we show that the discrepancy originates from model limitations and important lifecycle differences between sexually reproducing organisms and transmittable pathogens...
January 9, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29328787/immune-responses-to-retroviruses
#7
Asier Saez-Cirion, Nicolas Manel
Retroviruses are genome invaders that have shared a long history of coevolution with vertebrates and their immune system. Found endogenously in genomes as traces of past invasions, retroviruses are also considerable threats to human health when they exist as exogenous viruses such as HIV. The immune response to retroviruses is engaged by germline-encoded sensors of innate immunity that recognize viral components and damage induced by the infection. This response develops with the induction of antiviral effectors and launching of the clonal adaptive immune response, which can contribute to protective immunity...
January 12, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29324969/apobec-mutagenesis-in-drug-resistance-and-immune-escape-in-hiv-and-cancer-evolution
#8
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/29324755/hiv-1-co-receptor-tropism-and-liver-fibrosis-in-hiv-infected-patients
#9
Annalisa Saracino, Alessandro Cozzi-Lepri, Milensu Shanyinde, Francesca Ceccherini Silberstein, Silvia Nozza, Antonio Di Biagio, Giovanni Cassola, Giuseppe Bruno, Maria Capobianchi, Massimo Puoti, Laura Monno, Antonella d'Arminio Monforte
BACKGROUND: In vitro, gp120 of both X4 and R5 HIV-1 strains activates human hepatic stellate cells, but if it can promote liver fibrosis in vivo is unknown. We aimed to evaluate if patients carrying X4 or R5 strains have a different liver fibrosis (LF) progression over time. METHODS: A total of 1,137 HIV-infected patients in ICONA cohort (21% females, 7% HCV co-infected) with an available determination of HIV-1 co-receptor tropism (CRT), a Fibrosis-4 Index for Liver Fibrosis (FIB-4) <3...
2018: PloS One
https://www.readbyqxmd.com/read/29321964/introduction-of-h2c2-type-zinc-binding-residues-into-hiv-2-vpr-increases-its-expression-level
#10
Ryoko Koga, Minami Yamamoto, Halil Ibrahim Ciftci, Masami Otsuka, Mikako Fujita
Human immunodeficiency virus type 2 has two structurally similar proteins, Vpx and Vpr. Vpx degrades the host anti-viral protein SAMHD1 and is expressed at high levels, while Vpr is responsible for cell cycle arrest and is expressed at much lower levels. We constructed a Vpr mutant with a high level of expression by replacing the amino acids HHCR/HHCH with a putative H2C2-type zinc-binding site that is carried by Vpx. Our finding suggests that during the evolution of Vpr and Vpx, zinc-binding likely became a mechanism for regulating their expression levels...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29316828/hodgkin-s-lymphoma-and-its-association-with-ebv-and-hiv-infection
#11
Ravnit Grewal, Alexandra Irimie, Nasheen Naidoo, Nooroudien Mohamed, Bobe Petrushev, Manogari Chetty, Ciprian Tomuleasa, Emmanuel-Akinola Abayomi
Hodgkin's lymphoma (HL) constitutes a clonal expansion of what appears to be malignant B cells. Viruses are involved in its pathogenesis, such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Since these viral infections have been shown to play key roles in the pathogenesis of HL, countries with a prevalence of HIV and EBV represent interesting population targets to study the pathogenesis of HL, linking the evolution of the disease with viral infections. Usually, patients present with late stage disease often involving the bone marrow at the time of diagnosis...
January 9, 2018: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/29314658/comparative-assessment-of-five-trials-of-universal-hiv-testing-and-treatment-in-sub-saharan-africa
#12
REVIEW
Delphine Perriat, Laura Balzer, Richard Hayes, Shahin Lockman, Fiona Walsh, Helen Ayles, Sian Floyd, Diane Havlir, Moses Kamya, Refeletswe Lebelonyane, Lisa A Mills, Velephi Okello, Maya Petersen, Deenan Pillay, Kalpana Sabapathy, Kathleen Wirth, Joanna Orne-Gliemann, François Dabis
DESIGN: Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa...
January 2018: Journal of the International AIDS Society
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/29275182/the-impact-of-hiv-1-within-host-evolution-on-transmission-dynamics
#14
REVIEW
Kristof Theys, Pieter Libin, Andrea-Clemencia Pineda-Peña, Ann Nowé, Anne-Mieke Vandamme, Ana B Abecasis
The adaptive potential of HIV-1 is a vital mechanism to evade host immune responses and antiviral treatment. However, high evolutionary rates during persistent infection can impair transmission efficiency and alter disease progression in the new host, resulting in a delicate trade-off between within-host virulence and between-host infectiousness. This trade-off is visible in the disparity in evolutionary rates at within-host and between-host levels, and preferential transmission of ancestral donor viruses. Understanding the impact of within-host evolution for epidemiological studies is essential for the design of preventive and therapeutic measures...
December 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/29259927/gelatinous-transformation-of-bone-marrow-rare-or-underdiagnosed
#15
REVIEW
Khushdeep Kaur Shergill, Gagandeep Singh Shergill, Hari Janardanan Pillai
Gelatinous transformation of the bone marrow (GTBM) is a rare hematologic entity, which was first described by Paul Michael in 1930. GTBM is mostly associated with caloric intake/anorexia nervosa, although it also has been described accompanying other pathologic conditions, such as malignancy, systemic lupus erythematosus, HIV infections. Even though the diagnostic features of the hematopoietic tissue, such as hypoplasia, adipose cell atrophy, and deposition of a gelatinous substance in the bone marrow (which stains with Alcian blue at pH 2...
October 2017: Autopsy & case reports
https://www.readbyqxmd.com/read/29246084/dolutegravir-plus-rilpivirine-dual-therapy-in-treating-hiv-1-infection
#16
Amedeo F Capetti, Maria V Cossu, Laura Paladini, Giuliano Rizzardini
In industrialized countries, the HIV-infected population is aging and consequently comorbidities and polypharmacological regimens are increasing. This has led researchers to evaluate the efficacy, safety and durability of dual therapies as a switch option in subjects who have achieved stable virologic suppression to reduce toxicity and drug intake. Initially effective dual combinations relied on protease inhibitors but when dolutegravir, the first integrase inhibitor to display a high genetic barrier, became commercially available, many physicians began to use it in a variety of dual regimens even before randomized clinical trials showed non-inferiority of such regimens towards triple therapies...
December 15, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29244833/genomic-characterization-and-molecular-evolution-analysis-of-subtype-b-and-bf-recombinant-hiv-1-strains-among-argentinean-men-who-have-sex-with-men-reveal-a-complex-scenario
#17
Cintia G Cevallos, Leandro R Jones, Maria A Pando, Jean K Carr, Maria M Avila, Jorge Quarleri
Currently, data on HIV-1 circulating strains among men who have sex with men (MSM) in Argentina is scarce. In South America, the distribution and the prevalence of BF recombinants are dissimilar and exhibit an underappreciated heterogeneity of recombinant structures. Here, we studied for the first time the genetic diversity of HIV-1 BF recombinants and their evolution over time through in-depth phylogenetic analysis and multiple recombination detection methods involving 337 HIV-1 nucleotide sequences (25 near full-length (NFL) and 312 partial pol gene) obtained from Argentinean MSM...
2017: PloS One
https://www.readbyqxmd.com/read/29241646/hiv-population-level-adaptation-can-rapidly-diminish-the-impact-of-a-partially-effective-vaccine
#18
Joshua T Herbeck, Kathryn Peebles, Paul T Edlefsen, Morgane Rolland, James T Murphy, Geoffrey S Gottlieb, Neil Abernethy, James I Mullins, John E Mittler, Steven M Goodreau
BACKGROUND: Development of an HIV vaccine might be essential to ending the HIV/AIDS pandemic. However, vaccines can result in the emergence and spread of vaccine-resistant strains. Indeed, analyses of breakthrough infections in the HIV phase 3 vaccine trial RV144 identified HIV genotypes with differential rates of transmission in vaccine and placebo recipients. We hypothesized that, for HIV vaccination programs based on partially effective vaccines similar to RV144, HIV adaptation will rapidly diminish the expected vaccine impact...
December 11, 2017: Vaccine
https://www.readbyqxmd.com/read/29237831/maintenance-of-ap-2-dependent-functional-activities-of-nef-restricts-pathways-of-immune-escape-from-cd8-t-lymphocyte-responses
#19
Blake Schouest, Andrea M Weiler, Sanath Kumar Janaka, T Alix Myers, Arpita Das, Sarah C Wilder, Jessica Furlott, Melody Baddoo, Erik K Flemington, Eva G Rakasz, David T Evans, Thomas C Friedrich, Nicholas J Maness
Nef-specific CD8+ T lymphocytes (CD8TL) are linked to extraordinary control of primate lentiviral replication, but the mechanisms underlying their efficacy remain largely unknown. The immunodominant, Mamu-B*017:01+ restricted Nef195-203MW9 epitope in SIVmac239 partially overlaps a sorting motif important for interactions with host AP-2 proteins and, hence, downmodulation of several host proteins including Tetherin (CD317/BST-2), CD28, CD4, SERINC3, and SERINC5. We reasoned that CD8TL-driven evolution in this epitope might compromise Nef's ability to modulate these important molecules...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29234320/increasing-the-clinical-potential-and-applications-of-anti-hiv-antibodies
#20
REVIEW
Casey K Hua, Margaret E Ackerman
Preclinical and early human clinical studies of broadly neutralizing antibodies (bNAbs) to prevent and treat HIV infection support the clinical utility and potential of bNAbs for prevention, postexposure prophylaxis, and treatment of acute and chronic infection. Observed and potential limitations of bNAbs from these recent studies include the selection of resistant viral populations, immunogenicity resulting in the development of antidrug (Ab) responses, and the potentially toxic elimination of reservoir cells in regeneration-limited tissues...
2017: Frontiers in Immunology
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