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https://www.readbyqxmd.com/read/28447075/sofosbuvir-velpatasvir-fixed-dose-combination-for-the-treatment-of-chronic-hepatitis-c-virus-infection
#1
V Nehra, S A Rizza, Z Temesgen
The fixed-dose combination of sofosbuvir, a nucleotide analogue NS5B polymerase inhibitor, and velpatasvir, a second-generation NS5A inhibitor, has been approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection. This combination, administered over 12 weeks as a single-tablet regimen, has resulted in high cure rates in all 6 HCV genotypes and in a variety of patient populations, including patients without cirrhosis, patients with compensated cirrhosis and patients with HIV coinfection...
March 2017: Drugs of Today
https://www.readbyqxmd.com/read/28446770/instability-of-8e5-calibration-standard-revealed-by-digital-pcr-risks-inaccurate-quantification-of-hiv-dna-in-clinical-samples-by-qpcr
#2
Eloise Busby, Alexandra S Whale, R Bridget Ferns, Paul R Grant, Gary Morley, Jonathan Campbell, Carole A Foy, Eleni Nastouli, Jim F Huggett, Jeremy A Garson
Establishing a cure for HIV is hindered by the persistence of latently infected cells which constitute the viral reservoir. Real-time qPCR, used for quantification of this reservoir by measuring HIV DNA, requires external calibration; a common choice of calibrator is the 8E5 cell line, which is assumed to be stable and to contain one HIV provirus per cell. In contrast, digital PCR requires no external calibration and potentially provides 'absolute' quantification. We compared the performance of qPCR and dPCR in quantifying HIV DNA in 18 patient samples...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439936/hiv-positive-men-who-have-sex-with-men-are-at-high-risk-of-development-of-significant-liver-fibrosis-after-an-episode-of-acute-hepatitis-c
#3
K Steininger, A Boyd, S Dupke, I Krznaric, A Carganico, M Munteanu, S Neifer, M Schuetze, M Obermeier, K Arasteh, A Baumgarten, P Ingiliz
Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct-acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single-centre cohort of HIV-positive MSM with acute HCV infection...
April 25, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28437703/antiviral-treatment-strategies-based-on-gene-silencing-and-genome-editing
#4
REVIEW
Roger Badia, Ester Ballana, José A Esté, Eva Riveira-Muñoz
The ability of some viruses to establish latently infected chronic reservoirs that escape to immune control becomes a major roadblock that impedes the cure of these infections. Therefore, new alternatives are needed to pursuit the eradication of viral persistent infections. Gene silencing technologies are in constant evolution and provide an outstanding sequence specificity that allows targeting any coding sequence of interest. Here we provide an overview of the development of gene silencing technologies ranging from initially RNA interference to the recently developed CRISPR/Cas9 and their potential as new antiviral strategies focusing on the eradication of HIV...
April 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28435691/interrupting-antiretroviral-treatment-in-hiv-cure-research-scientific-and-ethical-considerations
#5
EDITORIAL
Samual A Garner, Stuart Rennie, Jintanat Ananworanich, Karine Dube, David M Margolis, Jeremy Sugarman, Randall Tressler, Adam Gilbertson, Liza Dawson
Over the past several years there has been intense activity directed at the possibility of achieving remission or eradication of HIV infection. Current assays for the measurement of latent HIV are insufficient to demonstrate complete clearance of replication-competent HIV. Therefore, the ultimate test for assessing whether investigational interventions have resulted in HIV remission or eradication is to interrupt standard antiretroviral therapy (ART) in a carefully controlled clinical trial setting. These procedures, known as analytic treatment interruptions (ATIs), raise important scientific and ethical questions...
April 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28434128/aspects-on-the-history-of-transmission-and-favor-of-distribution-of-viruses-by-iatrogenic-action-perhaps-an-example-of-a-paradigm-of-the-worldwide-spread-of-hiv
#6
REVIEW
Lutz G Gürtler, Josef Eberle
Transmission of infectious agents might be associated with iatrogenic actions of charitable help in health care. An example is the vaccination against yellow fever in USA that transmitted hepatitis B virus. Another example is injections of praziquantel for treatment and cure of schistosomiasis in Central and Northern Africa, with a focus in Egypt that has spread hepatitis C virus. There is no indication that human T-lymphotropic virus type 1 was spread by injection treatment for African trypanosomiasis, syphilis and treponematosis, but these treatments might have contributed to the early spread of human immunodeficiency virus type 1 (HIV-1) in Central Africa...
April 22, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28432928/a-humanized-mouse-based-hiv-1-viral-outgrowth-assay-with-higher-sensitivity-than-in-vitro-qvoa-in-detecting-latently-infected-cells-from-individuals-on-art-with-undetectable-viral-loads
#7
Paige Charlins, Kimberly Schmitt, Leila Remling-Mulder, Louise E Hogan, Emily Hanhauser, Kristen S Hobbs, Frederick Hecht, Steven G Deeks, Timothy J Henrich, Ramesh Akkina
Assays that can verify full viral eradication are essential in the context of achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays (qVOA) are currently the gold standard for measuring latent HIV-1 but these assays often fail to detect very low levels of replication-competent virus. Here we investigated an alternative in vivo approach for sensitive viral detection using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV subjects on stable ART with undetectable viral loads by RT-PCR were first assayed by in vitro qVOA...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432579/hcv-cure-and-reinfection-among-people-with-hiv-hcv-coinfection-and-people-who-inject-drugs
#8
REVIEW
Marianne Martinello, Behzad Hajarizadeh, Jason Grebely, Gregory J Dore, Gail V Matthews
PURPOSE OF REVIEW: Highly effective, well-tolerated interferon-free direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) therapeutics, with the opportunity for broad treatment scale-up among marginalised or "high-risk" populations, including people who inject drugs (PWID) and people with HIV/HCV coinfection. RECENT FINDINGS: Concern that HCV reinfection may compromise HCV treatment outcomes is sometimes cited as a reason for not offering treatment to current and former PWID...
April 21, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28431490/new-challenges-in-therapeutic-vaccines-against-hiv-infection
#9
Lorna Leal, Constanza Lucero, Josep M Gatell, Teresa Gallart, Montserrat Plana, Felipe García
There is a growing interest in developing curative strategies for HIV infection. Therapeutic vaccines are one of the most promising approaches. We will review the current knowledge and the new challenges in this research field. Areas covered: PubMed and ClinicalTrial.gov databases were searched to review the progress and prospects for clinical development of immunotherapies aimed to cure HIV infection. Dendritic cells (DC)-based vaccines have yielded the best results in the field. However, major immune-virologic barriers may hamper current vaccine strategies...
April 21, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28429679/mycobacterium-avium-complex-disease
#10
Charles L Daley
Despite the ubiqitous nature of Mycobacterium avium complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some degree of susceptibility due to either underlying lung disease or immunosuppression is required. The frequency of pulmonary MAC disease is increasing in many areas, and the exact reasons are unknown. Isolation of MAC from a respiratory specimen does not necessarily mean that treatment is required, as the decision to treatment requires the synthesis of clinical, radiographic, and microbiologic information as well as a weighing of the risks and benefits for the individual patient...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28423333/hunting-down-the-hiv-1-reservoir-a-starring-role-for-antibodies
#11
Hugo Mouquet
The persistence of viruses "hidden" in a reservoir of latently infected CD4(+) T cells under antiretroviral therapy is the major obstacle to an HIV-1 cure. Recently published in Nature, two seminal studies from Descours et al. (2017) and Nishimura et al. (2017) bring hope for tracking and possibly eradicating the HIV-1 reservoir.
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28422792/progress-in-hiv-1-antibody-research-using-humanized-mice
#12
Henning Gruell, Florian Klein
PURPOSE OF REVIEW: Recent discoveries of highly potent broadly HIV-1 neutralizing antibodies provide new opportunities to successfully prevent, treat, and potentially cure HIV-1 infection. To test their activity in vivo, humanized mice have been shown to be a powerful model and were used to investigate antibody-mediated prevention and therapy approaches. In this review, we will summarize recent findings in humanized mice that have informed on the potential use of broadly neutralizing antibodies targeting HIV-1 in humans...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28418987/the-roles-of-behavioral-and-social-science-research-in-the-fight-against-hiv-aids-a-functional-framework
#13
Paul Gaist, Michael J Stirratt
Landmark advances have been made in HIV/AIDS prevention and treatment. These include proof-of-concept and public health implementation of pre-exposure prophylaxis (PrEP) and "treatment as prevention" (TasP) to reduce HIV transmission as well as definitive evidence of the clinical gain from early antiretroviral treatment (ART) initiation. Significant progress has been made in understanding and addressing the social contexts and behavioral factors that impact HIV prevention, care, and treatment interventions...
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28414780/sensitive-quantification-of-the-hiv-1-reservoir-in-gut-associated-lymphoid-tissue
#14
Sara Morón-López, Maria C Puertas, Cristina Gálvez, Jordi Navarro, Anna Carrasco, Maria Esteve, Josep Manyé, Manel Crespo, Maria Salgado, Javier Martinez-Picado
BACKGROUND: The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As reported in the so called "Boston Patients", despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption...
2017: PloS One
https://www.readbyqxmd.com/read/28413739/genetic-modulation-therapy-through-stem-cell-transplantation-for-human-immunodeficiency-virus-1-infection
#15
REVIEW
Varshil Mehta, Divya Chandramohan, Shivika Agarwal
Highly active anti-retroviral treatment has changed the dimensions of the outcomes for patients suffering from human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). However, HIV infection is still an ailment which is spreading throughout the world extensively. Given the confinements of the present restorative methodologies and the non-availability of any strategic vaccination against HIV, there is a squeezing need to build a therapeutic treatment. Viral tropism for HIV includes CD4+ cells, macrophages, and microglial cells, and it is through binding with co-receptors C-C chemokine receptor type 5 (CCR5) and C-X-C chemokine receptor type 4 (CXCR4)...
March 13, 2017: Curēus
https://www.readbyqxmd.com/read/28407485/defective-hiv-1-proviruses-are-expressed-and-can-be-recognized-by-cytotoxic-t-lymphocytes-which-shape-the-proviral-landscape
#16
Ross A Pollack, R Brad Jones, Mihaela Pertea, Katherine M Bruner, Alyssa R Martin, Allison S Thomas, Adam A Capoferri, Subul A Beg, Szu-Han Huang, Sara Karandish, Haiping Hao, Eitan Halper-Stromberg, Patrick C Yong, Colin Kovacs, Erika Benko, Robert F Siliciano, Ya-Chi Ho
Despite antiretroviral therapy, HIV-1 persists in memory CD4(+) T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs)...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28406033/the-impact-of-hiv-antiretroviral-treatment-perception-on-risky-sexual-behaviour-in-botswana-a-short-report
#17
Gobopamang Letamo, Mpho Keetile, Kannan Navaneetham
The aim of this article is to investigate the impact of ART perception on risky sexual behaviours in Botswana. Using binary logistic regression analysis controlling for individual characteristics, the results tend to support the hypothesis that ART misconceptions do not necessarily increase risky sexual behaviours. In particular, the study findings suggest the belief that ARVs cure HIV and AIDS and that people on ARVs should not always use condoms do not necessarily lead to increased risky sexual behaviours, particularly among women...
April 13, 2017: AIDS Care
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#18
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28397698/ledipasvir-sofosbuvir-for-6-weeks-to-treat-acute-hepatitis-c-virus-genotype-1-or-4-infection-in-patients-with-hiv-coinfection-an-open-label-single-arm-trial
#19
Jürgen K Rockstroh, Sanjay Bhagani, Robert H Hyland, Chohee Yun, Hadas Dvory-Sobol, Wei Zheng, Diana M Brainard, Patrick Ingiliz, Thomas Lutz, Christoph Boesecke, Mark Nelson
BACKGROUND: The latest European Association for the Study of the Liver (EASL) guidelines now recommend that patients with acute hepatitis C virus (HCV) infection should be treated with a combination of sofosbuvir and an NS5A inhibitor for 8 weeks. However, the ideal duration of treatment with interferon-free regimens, particularly in HIV-coinfected individuals, remains unknown. We assessed the efficacy and safety of 6 weeks of ledipasvir-sofosbuvir for acute genotype 1 or 4 HCV in HIV-1-coinfected patients...
May 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28397100/the-burden-and-epidemiology-of-community-acquired-central-nervous-system-infections-a-multinational-study
#20
H Erdem, A Inan, E Guven, S Hargreaves, L Larsen, G Shehata, E Pernicova, E Khan, L Bastakova, S Namani, A Harxhi, T Roganovic, B Lakatos, S Uysal, O R Sipahi, A Crisan, E Miftode, R Stebel, B Jegorovic, Z Fehér, C Jekkel, N Pandak, A Moravveji, H Yilmaz, A Khalifa, U Musabak, S Yilmaz, A Jouhar, N Oztoprak, X Argemi, M Baldeyrou, G Bellaud, R V Moroti, R Hasbun, L Salazar, R Tekin, A Canestri, L Čalkić, L Praticò, F Yilmaz-Karadag, L Santos, A Pinto, F Kaptan, P Bossi, J Aron, A Duissenova, G Shopayeva, B Utaganov, S Grgic, G Ersoz, A K L Wu, K C Lung, A Bruzsa, L B Radic, H Kahraman, M Momen-Heravi, S Kulzhanova, F Rigo, M Konkayeva, Z Smagulova, T Tang, P Chan, S Ahmetagic, H Porobic-Jahic, F Moradi, S Kaya, Y Cag, A Bohr, C Artuk, I Celik, M Amsilli, H C Gul, A Cascio, M Lanzafame, M Nassar
Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure...
April 10, 2017: European Journal of Clinical Microbiology & Infectious Diseases
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