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HIV viral dynamics

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https://www.readbyqxmd.com/read/29317618/development-of-an-oral-once-weekly-drug-delivery-system-for-hiv-antiretroviral-therapy
#1
Ameya R Kirtane, Omar Abouzid, Daniel Minahan, Taylor Bensel, Alison L Hill, Christian Selinger, Anna Bershteyn, Morgan Craig, Shirley S Mo, Hormoz Mazdiyasni, Cody Cleveland, Jaimie Rogner, Young-Ah Lucy Lee, Lucas Booth, Farhad Javid, Sarah J Wu, Tyler Grant, Andrew M Bellinger, Boris Nikolic, Alison Hayward, Lowell Wood, Philip A Eckhoff, Martin A Nowak, Robert Langer, Giovanni Traverso
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316955/single-molecule-techniques-to-quantify-and-genetically-characterise-persistent-hiv
#2
REVIEW
Xiao Qian Wang, Sarah Palmer
Antiretroviral therapy effectively suppresses, but does not eradicate HIV-1 infection. Persistent low-level HIV-1 can still be detected in plasma and cellular reservoirs even after years of effective therapy, and cessation of current treatments invariably results in resumption of viral replication. Efforts to eradicate persistent HIV-1 require a comprehensive examination of the quantity and genetic composition of HIV-1 within the plasma and infected cells located in the peripheral blood and tissues throughout the body...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29304821/impact-of-the-hiv-1-genetic-background-and-hiv-1-population-size-on-the-evolution-of-raltegravir-resistance
#3
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/29283955/effects-of-reaching-national-goals-on-hiv-incidence-by-race-and-ethnicity-in-the-united-states
#4
Evin Uzun Jacobson, Katherine A Hicks, Emily L Tucker, Paul G Farnham, Stephanie L Sansom
CONTEXT: Human immunodeficiency virus (HIV) incidence and prevalence in the United States are characterized by significant disparities by race/ethnicity. National HIV care goals, such as boosting to 90% the proportion of persons whose HIV is diagnosed and increasing to 80% the proportion of persons living with diagnosed HIV who are virally suppressed, will likely reduce HIV incidence, but their effects on HIV-related disparities are uncertain. OBJECTIVE: We sought to understand by race/ethnicity how current HIV care varies, the level of effort required to achieve national HIV care goals, and the effects of reaching those goals on HIV incidence and disparities...
December 27, 2017: Journal of Public Health Management and Practice: JPHMP
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
#5
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
https://www.readbyqxmd.com/read/29275329/amino-acid-residues-in-hiv-2-reverse-transcriptase-that-restrict-the-development-of-nucleoside-analogue-resistance-through-the-excision-pathway
#6
Mar Álvarez, Maria Nevot, Jesus Mendieta, Miguel A Martinez, Luis Menéndez-Arias
Nucleoside reverse transcriptase (RT) inhibitors (NRTIs) are the backbone of current antiretroviral treatments. However, emergence of viral resistance against NRTIs is a major threat to their therapeutic effectiveness. In HIV-1, NRTI resistance-associated mutations either reduce RT-mediated incorporation of NRTI triphosphates (discrimination mechanism) or confer an ATPmediated nucleotide excision activity that removes the inhibitor from the 3'-terminus of DNA primers, enabling further primer elongation (excision mechanism)...
December 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29246070/propensity-of-a-single-walled-carbon-nanotube-peptide-to-mimic-a-kk10-peptide-in-an-hla-tcr-complex
#7
Mei Feng, David R Bell, Ruhong Zhou
The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter...
December 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29244809/hiv-1-viraemia-and-drug-resistance-amongst-female-sex-workers-in-soweto-south-africa-a-cross-sectional-study
#8
Jenny Coetzee, Gillian Hunt, Maya Jaffer, Kennedy Otwombe, Lesley Scott, Asiashu Bongwe, Johanna Ledwaba, Sephonono Molema, Rachel Jewkes, Glenda E Gray
BACKGROUND: HIV drug resistance (HIVDR) poses a threat to future antiretroviral therapy success. Monitoring HIVDR patterns is of particular importance in populations such as sex workers (SWs), where documented HIV prevalence is between 34-89%, and in countries with limited therapeutic options. Currently in South Africa, there is a dearth in evidence and no ongoing surveillance of HIVDR amongst sex work populations. This study aims to describe the prevalence of HIVDR amongst a sample of female sex workers (FSWs) from Soweto, South Africa...
2017: PloS One
https://www.readbyqxmd.com/read/29244129/dolutegravir-reshapes-the-genetic-diversity-of-hiv-1-reservoirs
#9
Pierre Gantner, Guinevere Q Lee, David Rey, Thibault Mesplede, Marialuisa Partisani, Christine Cheneau, Geneviève Beck-Wirth, Jean-Pierre Faller, Mahsa Mohseni-Zadeh, Martin Martinot, Mark A Wainberg, Samira Fafi-Kremer
Objectives: Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen. Methods: Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5)...
December 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29239894/temporal-variation-in-hiv-specific-igg-subclass-abs-during-acute-infection-differentiates-spontaneous-controllers-from-chronic-progressors
#10
Saheli Sadanand, Jishnu Das, Amy W Chung, Matthew K Schoen, Sophie Lane, Todd J Suscovich, Hendrik Streeck, Davey Smith, Susan Little, Douglas A Lauffenburger, Douglas Richman, Galit Alter
OBJECTIVE: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between subjects who ultimately became controllers versus those who became progressors. METHODS: IgG was purified from plasma from nine acutely infected subjects who subsequently controlled HIV spontaneously (controllers) and ten acutely infected individuals who did not control viremia (progressors)...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29237328/modeling-the-full-length-hiv-1-gag-polyprotein-reveals-the-role-of-its-p6-subunit-in-viral-maturation-and-the-effect-of-non-cleavage-site-mutations-in-protease-drug-resistance
#11
Chinh Tran-To Su, Chee-Keong Kwoh, Chandra Shekhar Verma, Samuel Ken-En Gan
HIV polyprotein Gag is increasingly found to contribute to protease inhibitor resistance. Despite its role in viral maturation and in developing drug resistance, there remain gaps in the knowledge of the role of certain Gag subunits (e.g. p6), and that of non-cleavage mutations in drug resistance. As p6 is flexible, it poses a problem for structural experiments, and is hence often omitted in experimental Gag structural studies. Nonetheless, as p6 is an indispensable component for viral assembly and maturation, we have modeled the full length Gag structure based on several experimentally determined constraints and studied its structural dynamics...
December 13, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29234320/increasing-the-clinical-potential-and-applications-of-anti-hiv-antibodies
#12
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
https://www.readbyqxmd.com/read/29234103/an-exhaustive-search-algorithm-to-aid-nmr-based-structure-determination-of-rotationally-symmetric-transmembrane-oligomers
#13
Jing Yang, Alessandro Piai, Hong-Bin Shen, James J Chou
Nuclear magnetic resonance (NMR) has been an important source of structural restraints for solving structures of oligomeric transmembrane domains (TMDs) of cell surface receptors and viral membrane proteins. In NMR studies, oligomers are assembled using inter-protomer distance restraints. But, for oligomers that are higher than dimer, these distance restraints all have two-fold directional ambiguity, and resolving such ambiguity often requires time-consuming trial-and-error calculations using restrained molecular dynamics (MD) with simulated annealing (SA)...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29230242/families-living-with-blood-borne-viruses-the-case-for-extending-the-concept-of-serodiscordance
#14
REVIEW
Asha Persson, Christy E Newman, Myra Hamilton, Joanne Bryant, Jack Wallace, Kylie Valentine
The concept of "serodiscordance" (mixed infection status) is primarily associated with epidemiological concerns about HIV transmission risk in couples. We make the case for extending this concept to include families with mixed HIV and viral hepatitis status. Social research on couples with mixed HIV and hepatitis C status has laid an important foundation for illuminating how experiences of serodiscordance within intimate partnerships are much broader than concerns about risk. This body of work attests to serodiscordance holding promise as a valuable concept for understanding viral infections as socially situated and intensely relational phenomena...
2017: Interdisciplinary Perspectives on Infectious Diseases
https://www.readbyqxmd.com/read/29227356/novel-advances-on-tissue-immune-dynamics-in-hiv-simian-immunodeficiency-virus-lessons-from-imaging-studies
#15
Eirini Moysi, Kartika Padhan, Giulia Fabozzi, Constantinos Petrovas
PURPOSE OF REVIEW: To describe recent findings on the effect of HIV/SIV infection on lymph node viral and T-cell dynamics using imaging-based methodologies. RECENT FINDINGS: Chronic infection, particularly HIV/SIV, alters dramatically the microenvironment, immune cell frequency, distribution, function and tissue organization of secondary lymphoid tissues. These changes are not always reversible. Over the past few years, the implementation of advanced imaging protocols on human lymph node biopsies as well as on longitudinal lymphoid tissues samples from nonhuman primates (NHP) have provided a wealth of information on how local immune responses evolve over time in response to a persisting retroviral pathogen...
December 8, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29223580/modeling-hiv-disease-progression-and-transmission-at-population-level-the-potential-impact-of-modifying-disease-progression-in-hiv-treatment-programs
#16
Jennifer M Ross, Roger Ying, Connie L Celum, Jared M Baeten, Katherine K Thomas, Pamela M Murnane, Heidi van Rooyen, James P Hughes, Ruanne V Barnabas
INTRODUCTION: Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated...
December 5, 2017: Epidemics
https://www.readbyqxmd.com/read/29214223/novel-elvitegravir-nanoformulation-approach-to-suppress-the-viral-load-in-hiv-infected-macrophages
#17
Yuqing Gong, Pallabita Chowdhury, Narasimha M Midde, Mohammad A Rahman, Murali M Yallapu, Santosh Kumar
Purpose: Monocytes serve as sanctuary sites for HIV-1 from which virus is difficult to be eliminated. Therefore, an effective viral suppression in monocytes is critical for effective antiretroviral therapy (ART). This study focuses on a new strategy using nanoformulation to optimize the efficacy of ART drugs in HIV-infected monocytes. Methods: Poly(lactic-co-glycolic acid) (PLGA)-based elvitegravir nanoparticles (PLGA-EVG) were prepared by nano-precipitation technique...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29202020/computational-model-and-dynamics-of-monomeric-full-length-apobec3g
#18
Suresh Gorle, Yangang Pan, Zhiqiang Sun, Luda S Shlyakhtenko, Reuben S Harris, Yuri L Lyubchenko, Lela Vuković
APOBEC3G (A3G) is a restriction factor that provides innate immunity against HIV-1 in the absence of viral infectivity factor (Vif) protein. However, structural information about A3G, which can aid in unraveling the mechanisms that govern its interactions and define its antiviral activity, remains unknown. Here, we built a computer model of a full-length A3G using docking approaches and molecular dynamics simulations, based on the available X-ray and NMR structural data for the two protein domains. The model revealed a large-scale dynamics of the A3G monomer, as the two A3G domains can assume compact forms or extended dumbbell type forms with domains visibly separated from each other...
November 22, 2017: ACS Central Science
https://www.readbyqxmd.com/read/29191733/trna-dynamics-between-the-nucleus-cytoplasm-and-mitochondrial-surface-location-location-location
#19
REVIEW
Kunal Chatterjee, Regina T Nostramo, Yao Wan, Anita K Hopper
Although tRNAs participate in the essential function of protein translation in the cytoplasm, tRNA transcription and numerous processing steps occur in the nucleus. This subcellular separation between tRNA biogenesis and function requires that tRNAs be efficiently delivered to the cytoplasm in a step termed "primary tRNA nuclear export". Surprisingly, tRNA nuclear-cytoplasmic traffic is not unidirectional, but, rather, movement is bidirectional. Cytoplasmic tRNAs are imported back to the nucleus by the "tRNA retrograde nuclear import" step which is conserved from budding yeast to vertebrate cells and has been hijacked by viruses, such as HIV, for nuclear import of the viral reverse transcription complex in human cells...
November 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29179726/modulation-of-the-functional-association-between-the-hiv-1-intasome-and-the-nucleosome-by-histone-amino-terminal-tails
#20
Mohamed S Benleulmi, Julien Matysiak, Xavier Robert, Csaba Miskey, Eric Mauro, Delphine Lapaillerie, Paul Lesbats, Stéphane Chaignepain, Daniel R Henriquez, Christina Calmels, Oyindamola Oladosu, Eloïse Thierry, Oscar Leon, Marc Lavigne, Marie-Line Andreola, Olivier Delelis, Zoltán Ivics, Marc Ruff, Patrice Gouet, Vincent Parissi
BACKGROUND: Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process...
November 28, 2017: Retrovirology
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