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https://www.readbyqxmd.com/read/29143673/the-heptestcontest-a-global-innovation-contest-to-identify-approaches-to-hepatitis-b-and-c-testing
#1
Joseph D Tucker, Kathrine Meyers, John Best, Karyn Kaplan, Razia Pendse, Kevin A Fenton, Isabelle Andrieux-Meyer, Carmen Figueroa, Pedro Goicochea, Charles Gore, Azumi Ishizaki, Giten Khwairakpam, Veronica Miller, Antons Mozalevskis, Michael Ninburg, Ponsiano Ocama, Rosanna Peeling, Nick Walsh, Massimo G Colombo, Philippa Easterbrook
BACKGROUND: Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines...
November 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29142136/size-composition-and-evolution-of-hiv-dna-populations-during-early-antiretroviral-therapy-and-intensification-with-maraviroc
#2
Antoine Chaillon, Sara Gianella, Steven M Lada, Josué Perez-Santiago, Parris Jordan, Caroline Ignacio, Maile Karris, Douglas Richman, Sanjay R Mehta, Susan J Little, Joel O Wertheim, Davey M Smith
Residual viremia is common during antiretroviral therapy (ART), and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART Intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial, and followed for a median of 107 weeks. Participants started ART with (n=9) or without (n=9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29141633/genome-modification-of-cxcr4-by-staphylococcus-aureus-cas9-renders-cells-resistance-to-hiv-1-infection
#3
Qiankun Wang, Shuliang Chen, Qiaoqiao Xiao, Zhepeng Liu, Shuai Liu, Panpan Hou, Li Zhou, Wei Hou, Wenzhe Ho, Chunmei Li, Li Wu, Deyin Guo
BACKGROUND: The CRISPR/Cas9 system has been widely used for genome editing in mammalian cells. CXCR4 is a co-receptor for human immunodeficiency virus type 1 (HIV-1) entry, and loss of CXCR4 function can protect cells from CXCR4 (X4)-tropic HIV-1 infection, making CXCR4 an important target for HIV-1 gene therapy. However, the large size of the CRISPR/SpCas9 system presents an obstacle to its efficient delivery into primary CD4(+) T cells. Recently, a small Staphylococcus aureus Cas9 (SaCas9) has been developed as a genome editing tool can address this question...
November 15, 2017: Retrovirology
https://www.readbyqxmd.com/read/29140110/il-21-therapy-controls-immune-activation-and-maintains-antiviral-cd8-t-cell-responses-in-acute-simian-immunodeficiency-virus-infection
#4
Gema Méndez-Lagares, Ding Lu, David Merriam, Christopher A Baker, François Villinger, Koen K A Van Rompay, Joseph M McCune, Dennis J Hartigan-O'Connor
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replicate during acute infection in lymphocytes of the gastrointestinal tract, before disseminating systemically. Localized replication and associated loss of gut-resident CD4(+) T cells occur regardless of the portal of entry of the virus (e.g., intravenous vs. rectal). Thus, HIV and SIV are tropic for gut tissue, and their pathogenesis requires the special environment of the intestine. T helper 17 (Th17) cells are important contributors to microbial defense in the gut that are vulnerable to HIV infection and whose loss is associated with translocation of microbial products to the systemic circulation, leading to chronic immune activation and disease progression...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29135907/efavirenz-therapeutic-range-in-hiv-1-treatment-naive-participants
#5
Cindy J Bednasz, Charles S Venuto, Qing Ma, Eric S Daar, Paul E Sax, Margaret A Fischl, Ann C Collier, Kimberly Y Smith, Camlin Tierney, Yang Yang, Gregory E Wilding, Gene D Morse
BACKGROUND: Efavirenz is currently suggested as an alternative to recommended antiretroviral (ARV) regimens by the Department of Health and Human Services for the treatment of HIV-1 in ARV-naive patients. A mid-dosing interval therapeutic range between 1000 and 4000 ng/mL for efavirenz has been proposed in the literature, with patients more likely to experience virologic failure below this range and adverse effects above. The current study reports an analysis of virologic outcome between those above, below, or within the reported efavirenz therapeutic range (1000-4000 ng/mL) and within subgroups...
December 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29118763/induction-of-antihuman-c-c-chemokine-receptor-type-5-antibodies-by-a-bovine-herpesvirus-type-4-based-vector
#6
Andrea Elizabeth Verna, Valentina Franceschi, Giulia Tebaldi, Francesca Macchi, Valentina Menozzi, Claudia Pastori, Lucia Lopalco, Simone Ottonello, Sandro Cavirani, Gaetano Donofrio
Bovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellular expression of recombinant antigens and can thus be considered as a new prototype vaccine formulation system. An interesting, and actively pursued, antigen in the context of human immunodeficiency virus (HIV) infection prophylaxis (and therapy) is the C-C chemokine receptor type 5 (CCR5) co-receptor, whose blockage by specific antibodies has been shown to inhibit both viral entry and cell-to-cell transmission of the virus...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29118121/hiv-1-r5-macrophage-tropic-envelope-glycoprotein-trimers-bind-cd4-with-high-affinity-while-the-cd4-binding-site-on-non-macrophage-tropic-t-tropic-r5-envelopes-is-occluded
#7
Briana Quitadamo, Paul J Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean McCauley, Jeremy Luban, Maria Duenas-Decamp, Maria Paz Gonzalez-Perez, Paul Clapham
HIV-1 R5 viruses exploit CCR5 as a coreceptor to infect both T-cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic R5 viruses predominate in brain tissue and can be detected in cerebral spinal fluid, but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29100708/safety-and-immune-response-after-two-dose-meningococcal-c-conjugate-immunization-in-hiv-infected-children-and-adolescents-in-rio-de-janeiro-brazil
#8
Ana Cristina C Frota, Bianca Ferreira, Lee H Harrison, Gisele S Pereira, Wania Pereira-Manfro, Elizabeth S Machado, Ricardo Hugo de Oliveira, Thalita F Abreu, Lucimar G Milagres, Cristina B Hofer
We aimed to evaluate immunogenicity and adverse events (AEs) after a booster dose of Meningococcal C conjugated (MCC) vaccine in HIV-infected children and adolescents, who had a previous low seroconversion rate after priming with MCC, at a reference HIV-care center in Rio de Janeiro. METHODS: 2-18 years old HIV-infected subjects with CD4+ T-lymphocyte cell (CD4) ≥15%, without active infection or antibiotic use, were enrolled to receive 2 doses of conjugated meningococcal C oligosaccharide-CRM197 12-18 months apart...
October 31, 2017: Vaccine
https://www.readbyqxmd.com/read/29093088/polyploidy-and-mitotic-cell-death-are-two-distinct-hiv-1-vpr-driven-outcomes-in-renal-tubule-epithelial-cells
#9
Emily H Payne, Dhivya Ramalingam, Donald T Fox, Mary E Klotman
Prior studies found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy remained unclear. Here, we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). As in many cell types, we find that Vpr first initiates a G2 cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29090302/carbosilane-dendrons-with-fatty-acids-at-the-core-as-a-new-potential-microbicide-against-hsv-2-hiv-1-co-infection
#10
C Guerrero-Beltrán, R Ceña-Diez, D Sepúlveda-Crespo, J De la Mata, R Gómez, M Leal, M A Muñoz-Fernández, J L Jiménez
Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) represent the two most frequent sexually transmitted infections (STI) worldwide. Epidemiological studies suggest that HSV-2 increases the risk of HIV-1 acquisition approximately 3-fold mainly due to the clinical and immunological manifestations. In the absence of vaccines against both STI, the development of new preventive strategies has become essential for further studies. We performed the screening of six novel polyanionic carbosilane dendrons to elucidate their potential activity against HSV-2/HIV-1 co-infection and their mechanism of action...
November 16, 2017: Nanoscale
https://www.readbyqxmd.com/read/29083319/hiv-antibody-complexes-enhance-production-of-type-i-interferon-by-plasmacytoid-dendritic-cells
#11
Rebecca T Veenhuis, Zachary T Freeman, Jack Korleski, Laura K Cohen, Guido Massaccesi, Alessandra Tomasi, Austin W Boesch, Margaret E Ackerman, Joseph B Margolick, Joel N Blankson, Michael A Chattergoon, Andrea L Cox
Type I IFN production is essential for innate control of acute viral infection; however, prolonged high-level IFN production is associated with chronic immune activation in HIV-infected individuals. Although plasmacytoid DCs (pDCs) are a primary source of IFN, the mechanisms that regulate IFN levels following the acute phase are unknown. We hypothesized that HIV-specific Ab responses regulate late IFN production. We evaluated the mechanism through which HIV-activated pDCs produce IFN as well as how both monoclonal HIV-specific Abs and Abs produced in natural HIV infection modulated normal pDC sensing of HIV...
October 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29072229/predictors-of-male-condom-utilization-in-plateau-state-nigeria
#12
M P Chingle, P A Odunze, A Mohammed, T T Bitto, O Y Sodipo, A I Zoakah
BACKGROUND: Nigerian men play major roles in the reproductive decision-making process, including issues concerning fertility. Despite efforts made by the government to reduce the incidence of HIV by using condom as a means of dual protection, the utilization of male condom is still relatively low in Nigeria. This study aimed to assess the condom utilization and predictors of condom use among male respondents in Plateau State. METHODOLOGY: An analysis of secondary data of the 2013 Nigeria Demographic Health Survey dataset was done...
September 2017: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/29067995/induction-of-vaginal-resident-hiv-specific-cd8-t-cells-with-mucosal-prime-boost-immunization
#13
H-X Tan, A K Wheatley, R Esterbauer, S Jegaskanda, J J Glass, D Masopust, R De Rose, S J Kent
Tissue-resident memory (TRM) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 TRM cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 TRM cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29066542/mechanisms-of-cns-viral-seeding-by-hiv-cd14-cd16-monocytes-establishment-and-reseeding-of-viral-reservoirs-contributing-to-hiv-associated-neurocognitive-disorders
#14
Mike Veenstra, Rosiris León-Rivera, Ming Li, Lucio Gama, Janice E Clements, Joan W Berman
HIV reservoirs persist despite antiretroviral therapy (ART) and are established within a few days after infection. Infected myeloid cells in the central nervous system (CNS) may contribute to the establishment of a CNS viral reservoir. The mature CD14(+) CD16(+) monocyte subset enters the CNS in response to chemokines, including CCL2. Entry of infected CD14(+) CD16(+) monocytes may lead to infection of other CNS cells, including macrophages or microglia and astrocytes, and to release of neurotoxic early viral proteins and additional cytokines...
October 24, 2017: MBio
https://www.readbyqxmd.com/read/29059541/creation-of-a-nanoformulated-cabotegravir-prodrug-with-improved-antiretroviral-profiles
#15
Tian Zhou, Hang Su, Prasanta Dash, Zhiyi Lin, Bhagya Laxmi Dyavar Shetty, Ted Kocher, Adam Szlachetka, Benjamin Lamberty, Howard S Fox, Larisa Poluektova, Santhi Gorantla, JoEllyn McMillan, Nagsen Gautam, R Lee Mosley, Yazen Alnouti, Benson Edagwa, Howard E Gendelman
Long-acting parenteral (LAP) antiretroviral drugs have generated considerable interest for treatment and prevention of HIV-1 infection. One new LAP is cabotegravir (CAB), a highly potent integrase inhibitor, with a half-life of up to 54 days, allowing for every other month parenteral administrations. Despite this excellent profile, high volume dosing, injection site reactions and low body fluid drug concentrations affect broad use for virus infected and susceptible people. To improve the drug delivery profile, we created a myristoylated CAB prodrug (MCAB)...
October 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/29057087/hiv-cure-research-community-engagement-in-north-carolina-a-mixed-methods-evaluation-of-a-crowdsourcing-contest
#16
EDITORIAL
Allison Mathews, Samantha Farley, Meredith Blumberg, Kimberley Knight, Lisa Hightow-Weidman, Kate Muessig, Stuart Rennie, Joseph Tucker
OBJECTIVES: The purpose of this study was to evaluate the feasibility of using a crowdsourcing contest to promote HIV cure research community engagement. METHODS: Crowdsourcing contests are open calls for community participation to achieve a task, in this case to engage local communities about HIV cure research. Our contest solicited images and videos of what HIV cure meant to people. Contestants submitted entries to IdeaScale, an encrypted online contest platform...
October 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29056481/targeting-the-late-stage-of-hiv-1-entry-for-antibody-dependent-cellular-cytotoxicity-structural-basis-for-env-epitopes-in-the-c11-region
#17
William D Tolbert, Neelakshi Gohain, Nirmin Alsahafi, Verna Van, Chiara Orlandi, Shilei Ding, Loïc Martin, Andrés Finzi, George K Lewis, Krishanu Ray, Marzena Pazgier
Antibodies can have an impact on HIV-1 infection in multiple ways, including antibody-dependent cellular cytotoxicity (ADCC), a correlate of protection observed in the RV144 vaccine trial. One of the most potent ADCC-inducing epitopes on HIV-1 Env is recognized by the C11 antibody. Here, we present the crystal structure, at 2.9 Å resolution, of the C11-like antibody N12-i3, in a quaternary complex with the HIV-1 gp120, a CD4-mimicking peptide M48U1, and an A32-like antibody, N5-i5. Antibody N12-i3 recognizes an epitope centered on the N-terminal "eighth strand" of a critical β sandwich, which our analysis indicates to be emblematic of a late-entry state, after the gp120 detachment...
November 7, 2017: Structure
https://www.readbyqxmd.com/read/29056462/the-sars-cov-fusion-peptide-forms-an-extended-bipartite-fusion-platform-that-perturbs-membrane-order-in-a-calcium-dependent-manner
#18
Alex L Lai, Jean K Millet, Susan Daniel, Jack H Freed, Gary R Whittaker
Coronaviruses are a major infectious disease threat, and include the pathogenic human pathogens of zoonotic origin: SARS-CoV and MERS-CoV. Entry of coronaviruses into host cells is mediated by the viral spike (S) protein, which is structurally categorized as a class I viral fusion protein, within the same group as influenza virus and HIV. However, S proteins have two distinct cleavage sites that can be activated by a much wider range of proteases. The exact location of the coronavirus fusion peptide (FP) has been disputed...
October 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29054243/hiv-testing-at-visits-to-physicians-offices-in-the-u-s-2009-2012
#19
D Cal Ham, Shirley Lecher, Roman Gvetadze, Ya-Lin A Huang, Philip Peters, Karen W Hoover
INTRODUCTION: HIV testing serves as an entry point for HIV care services for those who test HIV positive, and prevention services for those who test HIV negative. The Centers for Disease Control and Prevention recommends routine testing of adults and adolescents in healthcare settings. To identify missed opportunities for HIV testing at U.S. physicians' offices, data from the National Ambulatory Care Surveys from 2009 to 2012 were analyzed. METHODS: The mean annual number and percentage of visits with an HIV test among HIV-uninfected nonpregnant females and males aged 15-65 years was estimated using weighted survey data...
November 2017: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/29051495/the-%C3%AE-20-%C3%AE-21-of-gp120-is-a-regulatory-switch-for-hiv-1-env-conformational-transitions
#20
Alon Herschhorn, Christopher Gu, Francesca Moraca, Xiaochu Ma, Mark Farrell, Amos B Smith, Marie Pancera, Peter D Kwong, Arne Schön, Ernesto Freire, Cameron Abrams, Scott C Blanchard, Walther Mothes, Joseph G Sodroski
The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements...
October 19, 2017: Nature Communications
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