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https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#1
Antu K Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K Sharma, Anna-Janina Behrens, Eden P Go, Thomas J Ketas, Anila Yasmeen, Per J Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A Wilson, Rogier W Sanders, Thomas Hassell, Andrew Ward, John P Moore
We describe the properties of BG505 SOSIP.664 HIV-1 envelope glycoprotein trimers produced under current Good Manufacturing Practice (cGMP) conditions. These proteins are the first of a new generation of native-like trimers that are the basis for many structure-guided immunogen development programs aimed at devising how to induce broadly neutralizing antibodies (bNAbs) to HIV-1 by vaccination. The successful translation of this prototype demonstrates the feasibility of producing similar immunogens on an appropriate scale and of an acceptable quality for Phase I experimental medicine clinical trials...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150360/changes-in-the-epidemiology-and-distribution-of-the-hepatitis-c-virus-genotypes-in-north-eastern-spain-over-the-last-35-years
#2
Doroteo Acero Fernández, María José Ferri Iglesias, María Buxó Pujolràs, Carmen López Nuñez, Isabel Serra Matamala, Xavier Queralt Molés, Xavier Aldeguer Manté
BACKGROUND: Genotypic distribution and epidemiology of HCV infection in Western Europe countries has changed over the last decades. AIM: To establish the local genotypic profile and characterize the associated demographic variables. MATERIAL AND METHOD: All the genotyping from 1988 to 2015 were considered. Associated demographic variables were included in logistic regression models. Genotyping was carried out with updated commercial kits. RESULTS: Genotype 1b was the most prevalent (42...
November 14, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/29149197/sieve-analysis-of-breakthrough-hiv-1-sequences-in-hvtn-505-identifies-vaccine-pressure-targeting-the-cd4-binding-site-of-env-gp120
#3
Allan C deCamp, Morgane Rolland, Paul T Edlefsen, Eric Sanders-Buell, Breana Hall, Craig A Magaret, Andrew J Fiore-Gartland, Michal Juraska, Lindsay N Carpp, Shelly T Karuna, Meera Bose, Steven LePore, Shana Miller, Annemarie O'Sullivan, Kultida Poltavee, Hongjun Bai, Kalpana Dommaraju, Hong Zhao, Kim Wong, Lennie Chen, Hasan Ahmed, Derrick Goodman, Matthew Z Tay, Raphael Gottardo, Richard A Koup, Robert Bailer, John R Mascola, Barney S Graham, Mario Roederer, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Elizabeth Adams, Patricia D'Souza, James Kublin, Lawrence Corey, Daniel E Geraghty, Nicole Frahm, Georgia D Tomaras, M Juliana McElrath, Lisa Frenkel, Sheila Styrchak, Sodsai Tovanabutra, Magdalena E Sobieszczyk, Scott M Hammer, Jerome H Kim, James I Mullins, Peter B Gilbert
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120)...
2017: PloS One
https://www.readbyqxmd.com/read/29148108/human-pegivirus-hpgv-infection-in-sub-saharan-africa-a-call-for-a-renewed-research-agenda
#4
REVIEW
Shivank Singh, Jason T Blackard
The human pegivirus (HPgV)-formerly GB virus C-has a beneficial impact on HIV disease progression that has been described in multiple studies. Given the high prevalence of HIV in sub-Saharan Africa and the continuing need to suppress HIV replication, this review provides a comprehensive overview of the existing data on HPgV infection in sub-Saharan Africa, with a particular focus on studies of prevalence and the circulating HPgV genotypes. This review also highlights the need for additional studies of HPgV conducted on the African continent and proposes a research agenda for evaluation of HPgV...
November 17, 2017: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29143565/hiv-1-resistance-rarely-observed-in-subjects-using-darunavir-once-daily-regimens-across-clinical-studies
#5
Erkki Lathouwers, Eric Y Wong, Donghan Luo, Sareh Seyedkazemi, Sandra De Meyer, Kimberley Brown
BACKGROUND: Darunavir 800 mg once daily (QD) is indicated for HIV-1-infected treatment-naïve and treatment-experienced (without darunavir resistance-associated mutations [RAMs]) individuals, and has been evaluated in phase 2/3 studies with durations between 48 and 192 weeks. OBJECTIVE: To summarize the development (or identification) of post-baseline resistance (RAMs and antiretroviral phenotypic susceptibility) among subjects receiving darunavir QD dosing. METHODS: Seven phase 2/3 studies with available genotypes/phenotypes for subjects treated with ritonavir- or cobicistat-boosted darunavir 800 mg QD regimens were assessed: ARTEMIS (NCT00258557; n = 343), GS-US-299-0102 (NCT01565850; n = 153), GS-US-216-0130 (NCT01440569; n = 313), ODIN (NCT00524368; n = 294), INROADS (NCT01199939; n = 54), MONET (NCT00458302; n = 256), and PROTEA (NCT01448707; n = 273)...
November 16, 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/29141014/prevalence-and-risk-factors-of-anal-human-papillomavirus-infection-among-hiv-negative-men-who-have-sex-with-men-in-urumqi-city-of-xinjiang-uyghur-autonomous-region-china
#6
Tian Tian, Peierdun Mijiti, Huang Bingxue, Zhang Fadong, Abidan Ainiwaer, Sang Guoyao, Zhang Zhanlin, Yeledan Mahan, Tuo Xiaoqin, Gong Zheng, Dai Jianghong
BACKGROUND: Infection with human papillomavirus (HPV) is the most common sexually transmitted infection among men who have sex with men (MSM). Study on prevalence and risk factors of anal HPV infection among HIV-negative MSM in Northwestern China was rare. METHODS: We performed a cross-sectional study of HPV prevalence using anal swab specimens among HIV-negative MSM in Urumqi city of Xinjiang Uyghur Autonomous Region, China between April 1st and October 30th in 2016...
2017: PloS One
https://www.readbyqxmd.com/read/29140932/characteristics-of-treatment-experienced-hiv-infected-african-children-and-adolescents-initiating-darunavir-and-or-etravirine-based-antiretroviral-treatment
#7
Bethany Corrigan, Irene Mukui, Lloyd Mulenga, Nobuhle Mthethwa, Mosilinyane Letsie, Stephanie Bruno, Natella Rakhmanina
BACKGROUND: Data are limited on the selection and sequencing of second and third-line pediatric antiretroviral treatment (ART) in resource-limited settings. This study aimed to evaluate characteristics of African pediatric patients initiated on darunavir (DRV) and/or etravirine (ETR) through a specific drug donation program. METHODS: This was a cross-sectional study of baseline immunologic, virologic and demographic characteristics of children and adolescents initiating DRV- and/or ETR-based ART...
November 14, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29137637/molecular-evolution-of-hiv-1-integrase-during-the-20%C3%A2-years-prior-to-the-first-approval-of-integrase-inhibitors
#8
Karolin Meixenberger, Kaveh Pouran Yousef, Maureen Rebecca Smith, Sybille Somogyi, Stefan Fiedler, Barbara Bartmeyer, Osamah Hamouda, Norbert Bannert, Max von Kleist, Claudia Kücherer
BACKGROUND: Detailed knowledge of the evolutionary potential of polymorphic sites in a viral protein is important for understanding the development of drug resistance in the presence of an inhibitor. We therefore set out to analyse the molecular evolution of the HIV-1 subtype B integrase at the inter-patient level in Germany during a 20-year period prior to the first introduction of integrase strand inhibitors (INSTIs). METHODS: We determined 337 HIV-1 integrase subtype B sequences (amino acids 1-278) from stored plasma samples of antiretroviral treatment-naïve individuals newly diagnosed with HIV-1 between 1986 and 2006...
November 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/29136032/virological-response-and-resistance-among-hiv-infected-children-receiving-long-term-antiretroviral-therapy-without-virological-monitoring-in-uganda-and-zimbabwe-observational-analyses-within-the-randomised-arrow-trial
#9
Alexander J Szubert, Andrew J Prendergast, Moira J Spyer, Victor Musiime, Philippa Musoke, Mutsa Bwakura-Dangarembizi, Patricia Nahirya-Ntege, Margaret J Thomason, Emmanuel Ndashimye, Immaculate Nkanya, Oscar Senfuma, Boniface Mudenge, Nigel Klein, Diana M Gibb, A Sarah Walker
BACKGROUND: Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring. METHODS AND FINDINGS: In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135773/tree-based-claims-algorithm-for-measuring-pretreatment-quality-of-care-in-medicare-disabled-hepatitis-c-patients
#10
Viktor V Chirikov, Fadia T Shaya, Ebere Onukwugha, C Daniel Mullins, Susan dosReis, Charles D Howell
BACKGROUND: To help broaden the use of machine-learning approaches in health services research, we provide an easy-to-follow framework on the implementation of random forests and apply it to identify quality of care (QC) patterns correlated with treatment receipt among Medicare disabled patients with hepatitis C virus (HCV). METHODS: Using Medicare claims 2006-2009, we identified 1936 patients with 6 months continuous enrollment before HCV diagnosis. We ran a random forest on 14 pretreatment QC indicators, extracted the forest's representative tree, and aggregated its terminal nodes into 4 QC groups predictive of treatment...
December 2017: Medical Care
https://www.readbyqxmd.com/read/29135574/interferon-free-therapy-for-treating-hcv-in-difficult-to-treat-hiv-coinfected-patients-as-implemented-in-routine-medical-practice
#11
Carlos Mínguez, Miguel García-Deltoro, Juan Flores, Maria-José Galindo, Marta Montero, Sergio Reus, Jorge Carmena, Mar Masiá, Concepción Amador, Enrique Ortega
BACKGROUND/AIMS: Data regarding the use of all-oral direct-acting antivirals (DAA) in HIV/HCV-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognised as predictors of treatment failure. METHODS: COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29129578/cryptococcosis-in-an-infectious-diseases-hospital-of-buenos-aires-argentina-revision-of-2041-cases-diagnosis-clinical-features-and-therapeutics
#12
Alicia Arechavala, Ricardo Negroni, Fernando Messina, Mercedes Romero, Emmanuel Marín, Roxana Depardo, Laura Walker, Gabriela Santiso
BACKGROUND: Cryptococcosis is still a life-threatening mycosis that continues to be of serious concern in Latin American countries, especially among HIV+positive population. However, there is not any reliable information about the prevalence of this disease in this region. AIMS: The aim of this study is to report data of 2041 patients with cryptococcosis that were attended at the Infectious Diseases Hospital F. J. Muñiz over a 30 year-period. METHODS: Information about demographic and clinical data, survival time and the applied treatment, was taken from the Mycology Unit database...
November 9, 2017: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/29120906/efficacy-of-ledipasvir-sofosbuvir-plus-ribavirin-for-12-weeks-in-patients-with-chronic-hepatitis-c-genotype-3-and-compensated-liver-disease
#13
Stephan Moser, Karin Kozbial, Hermann Laferl, Angelika Schütz, Thomas Reiberger, Philipp Schwabl, Enisa Gutic, Cornelia Schwanke, Raphael Schubert, Julian Luhn, Tobias Lang, Michael Schleicher, Petra Steindl-Munda, Hans Haltmayer, Peter Ferenci, Michael Gschwantler
INTRODUCTION: In the era of direct-acting antivirals, hepatitis C virus (HCV) genotype (GT) 3 remains as the most difficult-to-treat HCV-GT. Currently, data on the efficacy of ledipasvir/sofosbuvir plus ribavirin (SOF/LDV+RBV) in GT3-infected patients are limited. We investigated the efficacy of this regimen in a real-life cohort from Austria. PATIENTS AND METHODS: A total of 55 patients with HCV-GT3 and compensated liver disease (20% treatment-experienced, 33% with cirrhosis, 7% with HIV coinfection) from four Austrian hepatitis centers received treatment with SOF/LDV+RBV for 12 weeks...
November 8, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29118167/invasive-disease-caused-simultaneously-by-dual-serotypes-of-streptococcus-pneumoniae
#14
Kedibone Ndlangisa, Mignon du Plessis, Mushal Allam, Nicole Wolter, Linda de Gouveia, Keith P Klugman, Cheryl Cohen, Rebecca A Gladstone, Anne von Gottberg
There are at least 98 known pneumococcal serotypes. Invasive pneumococcal (IPD) disease is usually caused by a single serotype, and dual serotype IPD is rare. To assess factors associated with dual serotype IPD, patient information obtained through laboratory-based surveillance for IPD from 2005 through 2014 in South Africa was reviewed. Genomes of isolate pairs from co-infected individuals were sequenced to determine their molecular characteristics. For 30 (91%) of 33 patients with dual serotypes, one or both isolates were a pneumococcal conjugate vaccine (PCV13) serotype...
November 8, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29117017/race-ethnicity-difference-in-the-pharmacogenetics-of-bilirubin-related-atazanavir-discontinuation
#15
Paul Leger, Sanika Chirwa, Jacinta N Nwogu, Megan Turner, Danielle M Richardson, Paxton Baker, Michael Leonard, Husamettin Erdem, Lana Olson, David W Haas
BACKGROUND: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity. PATIENTS AND METHODS: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses...
November 6, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29116287/peginterferon-still-has-a-place-in-the-treatment-of-hepatitis-c-caused-by-genotype-3-virus
#16
Aline Vitali Grando, Paulo Roberto Abrão Ferreira, Mário Guimarães Pessôa, Daniel Ferraz de Campos Mazo, Carlos Eduardo Brandão-Mello, Tânia Reuter, Ana de Lourdes Candolo Martinelli, Mário Peribanez Gonzalez, Ana Catharina Seixas-Santos Nastri, Aléia Faustina Campos, Max Igor Banks Ferreira Lopes, José David Urbaez Brito, Maria Cássia Mendes-Corrêa
Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers...
November 6, 2017: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/29115572/talens-mediated-homozygous-ccr5%C3%AE-32-mutations-endow-cd4-u87-cells-with-resistance-against-hiv%C3%A2-1-infection
#17
Ai Qing Yu, Yan Ding, Zhi Yong Lu, Yan Zhe Hao, Zhi Ping Teng, Shi Rong Yan, Dong Sheng Li, Yi Zeng
Since evidence suggests that transplantation of bone marrow stem cells with the C‑C chemokine receptor type 5 (CCR5)Δ32/Δ32 genotype may cure patients infected with human immunodeficiency virus (HIV)‑1, the present study aimed to reproduce the CCR5Δ32 mutation in cluster of differentiation (CD)4+ U87 cells using genome engineering methods. A modified transcription activator‑like effector nucleases (TALENs) technique, combined with homologous recombination for site‑specific, size‑controlled and homozygous DNA deletions, was used to reproduce the homozygous CCR5Δ32 mutation in CD4+ U87 cells...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29112074/toll-like-receptor-tlr-9-polymorphism-is-associated-with-increased-epstein-barr-virus-and-cytomegalovirus-acquisition-in-hiv-exposed-infants
#18
Kristin Beima-Sofie, Dalton Wamalwa, Elizabeth Maleche-Obimbo, Jairam R Lingappa, Romel Mackelprang, Soren Gantt, Grace John-Stewart, Corey Casper, Jennifer A Slyker
Polymorphisms in the Toll-Like Receptor (TLR9) 1635 locus have been associated with HIV-1 acquisition and progression. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) acquisition were compared between Kenyan HIV-exposed infants by 1635 genotype. Having 1 or more copies of the 1635A allele was associated with increased CMV acquisition in HIV-infected infants (42% vs 11%, p = 0.03) and increased risk of EBV acquisition in HIV-exposed uninfected infants (HR = 4.2, p = 0.02) compared to 1635GG. Additionally, 1635A was associated with 0...
November 2, 2017: AIDS
https://www.readbyqxmd.com/read/29110871/prevalence-of-rifampicin-resistant-mycobacterium-tuberculosis-among-human-immunodeficiency-virus-seropositive-patients-and-their-treatment-outcomes
#19
C K Vidyaraj, A Chitra, S Smita, M Muthuraj, S Govindarajan, B Usharani, S Anbazhagi
Multidrug resistant (MDR) and extensively drug resistant tuberculosis (TB) are a threat to the TB control programs in developing countries, and the situation is worsened by the human immunodeficiency virus (HIV) pandemic. This study was performed to correlate treatment outcome with the resistance patterns in HIV-seropositive patients coinfected with pulmonary TB. Sputum specimens were collected from 1643 HIV-seropositive patients and subjected to microscopy and liquid culture for TB. The smear- and culture-positive Mycobacterium tuberculosis isolates were subjected to Genotype MTBDRplus assay version 2...
December 2017: Journal of Epidemiology and Global Health
https://www.readbyqxmd.com/read/29109851/safety-and-efficacy-of-ledipasvir-sofosbuvir-on-hepatitis-c-eradication-in-hepatitis-c-virus-human-immunodeficiency-virus-co-infected-patients
#20
Xiaoping He, Lynne Hopkins, George Everett, Willie M Carter, Cynthia SchroppDyce, Khalid Abusaada, Vincent Hsu
AIM: To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection in an urban HIV clinic. METHODS: A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level...
October 28, 2017: World Journal of Hepatology
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