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https://www.readbyqxmd.com/read/28344011/the-epidemiology-pathogenesis-transmission-diagnosis-and-management-of-multidrug-resistant-extensively-drug-resistant-and-incurable-tuberculosis
#1
REVIEW
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis)...
March 15, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28342375/nanozyme-based-bio-barcode-assay-for-high-sensitive-and-logic-controlled-specific-detection-of-multiple-dnas
#2
Xiaodong Lin, Yaqing Liu, Zhanhui Tao, Jinting Gao, Jiankang Deng, Jinjin Yin, Shuo Wang
Since HCV and HIV share a common transmission path, high sensitive detection of HIV and HCV gene is of significant importance to improve diagnosis accuracy and cure rate at early stage for HIV virus-infected patients. In our investigation, a novel nanozyme-based bio-barcode fluorescence amplified assay is successfully developed for simultaneous detection of HIV and HCV DNAs with excellent sensitivity in an enzyme-free and label-free condition. Here, bimetallic nanoparticles, PtAuNPs, present outstanding peroxidase-like activity and act as barcode to catalyze oxidation of nonfluorescent substrate of amplex red (AR) into fluorescent resorufin generating stable and sensitive "Turn On" fluorescent output signal, which is for the first time to be integrated with bio-barcode strategy for fluorescence detection DNA...
January 5, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28341641/proliferation-of-latently-infected-cd4-t-cells-carrying-replication-competent-hiv-1-potential-role-in-latent-reservoir-dynamics
#3
Nina N Hosmane, Kyungyoon J Kwon, Katherine M Bruner, Adam A Capoferri, Subul Beg, Daniel I S Rosenbloom, Brandon F Keele, Ya-Chi Ho, Janet D Siliciano, Robert F Siliciano
A latent reservoir for HIV-1 in resting CD4(+) T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus...
March 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28331083/maintenance-of-the-hiv-reservoir-is-antagonized-by-selective-bcl2-inhibition
#4
Nathan W Cummins, Amy M Sainski-Nguyen, Sekar Natesampillai, Fatma Aboulnasr, Scott Kaufmann, Andrew D Badley
Decay of the HIV reservoir is slowed over time in part by expansion of the pool of HIV infected cells. This expansion reflects homeostatic proliferation of infected cells by IL-7 or antigenic stimulation, as well as new rounds of infection of susceptible target cells. As novel therapies are being developed to accelerate the decay of the latent HIV reservoir, it will be important to identify interventions that prevent expansion and/or repopulation of the latent HIV reservoir. Our previous studies showed that HIV protease cleaves the host protein procaspase 8 to generate Casp8p41, which can bind and activate BAK to induce apoptosis of infected cells...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28328934/proviruses-with-identical-sequences-comprise-a-large-fraction-of-the-replication-competent-hiv-reservoir
#5
John K Bui, Michele D Sobolewski, Brandon F Keele, Jonathan Spindler, Andrew Musick, Ann Wiegand, Brian T Luke, Wei Shao, Stephen H Hughes, John M Coffin, Mary F Kearney, John W Mellors
The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication-competent proviruses has been controversial. Here, we used single-genome sequencing to probe for identical HIV sequence matches among viruses recovered in different viral outgrowth cultures and between the sequences of outgrowth viruses and proviral or intracellular HIV RNA sequences in uncultured blood mononuclear cells from eight donors on suppressive ART with diverse proviral populations...
March 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28297712/cd32a-is-a-marker-of-a-cd4-t-cell-hiv-reservoir-harbouring-replication-competent-proviruses
#6
Benjamin Descours, Gaël Petitjean, José-Luis López-Zaragoza, Timothée Bruel, Raoul Raffel, Christina Psomas, Jacques Reynes, Christine Lacabaratz, Yves Levy, Olivier Schwartz, Jean Daniel Lelievre, Monsef Benkirane
The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells...
March 15, 2017: Nature
https://www.readbyqxmd.com/read/28287204/-biliary-and-kidney-lithiasis-during-treatment-with-daclatasvir-sofosbuvir-ribavirin-and-atazanavir-ritonavir-abacavir-lamivudine-in-an-hiv-hcv-genotype-4-infected-patient-a-case-report
#7
Andrea Vavassori, Paola Lanza, Ilaria Izzo, Salvatore Casari, Silvia Odolini, Serena Zaltron, Elena Festa, Francesco Castelli
New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin...
February 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28279118/insight-into-binding-mechanisms-of-inhibitors-mkp56-mkp73-mkp86-and-mkp97-to-hiv-1-protease-by-using-molecular-dynamics-simulation
#8
Shuhua Shi, Shaolong Zhang, Qinggang Zhang
HIV-1 protease (PR) has been a significant target for design of potent inhibitors curing acquired immunodeficiency syndrome (AIDS). Molecular dynamics (MD) simulations coupled with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method were performed to study interaction modes of four inhibitors MKP56, MKP73, MKP86 and MKP97 with PR. The results suggest that the main force controlling interactions of inhibitors with PR should be contributed by van der Waals interactions between inhibitors and PR...
March 9, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28275462/highlights-from-the-third-biennial-strategies-for-an-hiv-cure-meeting-14-16-november-2016-bethesda-md-usa
#9
EDITORIAL
Diane Lawrence, Lillian Kuo, Elizabeth Church, Betty Poon, Stephen Smiley, Brigitte Sanders-Beer, Liza Dawson, Karl Salzwedel
Since the first Strategies for an HIV Cure Meeting organised by the National Institute of Allergy and Infectious Diseases (NIAID) in 2012, one of the primary purposes of the meeting has been to facilitate communication and foster collaboration across the NIAID-funded Martin Delaney Collaboratories for HIV cure research (MDC), the broader HIV cure-related research field, and industry and community stakeholders. This year's meeting agenda reflected NIAID's increasing investment over the last 5 years in research to identify strategies for eradicating or achieving long-term remission of HIV infection...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28275461/hiv-reservoir-characterization-symposium-19-september-2016-ghent-belgium
#10
EDITORIAL
Eva Malatinkova, Ward De Spiegelaere, Linos Vandekerckhove, Magdalena Sips
The HIV Cure Research Center (HCRC) in Ghent organised the first HIV Reservoir Characterization Symposium, and brought together virologists, molecular biologists, immunologists and clinicians to discuss the most recent developments in HIV reservoir characterisation with a view to achieving an HIV cure. The one-day symposium covered new developments in the field of HIV reservoir and HIV cure research, with the latest news on the European HIV cure trials. This report summarises the major themes discussed during the symposium...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28275457/willingness-to-participate-and-take-risks-in-hiv-cure-research-survey-results-from-400-people-living-with-hiv-in-the-us
#11
EDITORIAL
Karine Dubé, David Evans, Laurie Sylla, Jeff Taylor, Bryan J Weiner, Asheley Skinner, Harsha Thirumurthy, Joseph D Tucker, Stuart Rennie, Sandra B Greene
INTRODUCTION: Participation in early-phase HIV cure studies includes clinical risks with little to no likelihood of clinical benefit. Examining the willingness of people living with HIV to participate is important to guide study design and informed consent. Our study examined the overall willingness of people living with HIV to participate in HIV cure research in the US, focusing on perceived risks and benefits of participation. METHODS: We undertook an online survey of adults living with HIV in the US...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28275453/insight-into-hiv-2-latency-may-disclose-strategies-for-a-cure-for-hiv-1-infection
#12
EDITORIAL
Suha Saleh, Lenard Vranckx, Rik Gijsbers, Frauke Christ, Zeger Debyser
HIV-1 and HIV-2 originate from two distinct zoonotic transmissions of simian immunodeficiency viruses from primate to human. Although both share similar modes of transmission and can result in the development of AIDS with similar clinical manifestations, HIV-2 infection is generally milder and less likely to progress to AIDS. HIV is currently incurable due to the presence of HIV provirus integrated into the host DNA of long-lived memory cells of the immune system without active replication. As such, the latent virus is immunologically inert and remains insensitive to the administered antiviral drugs targeting active viral replication steps...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28260132/imported-talaromycosis-in-oman-in-advanced-hiv-a-diagnostic-challenge-outside-the-endemic-areas
#13
Jalila Mohsin, Sulin Al Khalili, A H G Gerrits van den Ende, Faryal Khamis, Eskild Petersen, G Sybren de Hoog, Jacques F Meis, Abdullah M S Al-Hatmi
A 37-year-old male living in Oman was seen by his physician with complaints of cough, body aches with bilateral lower limb weakness and on and off fever. He was diagnosed with HIV infection and culture from blood and bone marrow grew Talaromyces marneffei. He had travelled to Malaysia on several occasions. Treatment with liposomal amphotericin B resulted in complete cure. This case is reported for its rarity and unusual presentation to alert clinicians and microbiologists to consider T. marneffei as an etiology in high risk individuals...
March 4, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28258391/underlying-mechanisms-of-hiv-1-latency
#14
REVIEW
Bizhan Romani, Elham Allahbakhshi
Similarly to other retroviruses, HIV-1 integrates its genome into the cellular chromosome. Expression of viral genes from the integrated viral DNA could then be regulated by the host genome. If the infected cell suppresses viral gene expression, the virus will undergo latency. The latently infected cells cannot be detected or cleared by the immune system since they do not express viral antigens. These cells remain undetected for several years, even under antiretroviral treatments. The silenced HIV-1 DNA could be reactivated under certain conditions...
March 3, 2017: Virus Genes
https://www.readbyqxmd.com/read/28257302/progress-in-hiv-1-antibody-research-using-humanized-mice
#15
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...
March 2, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28250686/prevalence-of-tuberculosis-among-children-in-north-sudan-are-we-only-seeing-the-tip-of-the-iceberg
#16
Wadie M Elmadhooun, Elmuntasir Taha Salah, Sufian K Noor, Sarra O Bushara, Ekhlas O Ahmed, Hamdan Mustafa, Amel A Sulaiman, Mohamed H Ahmed
INTRODUCTION: Tuberculosis (TB) is a significant cause of morbidity and mortality among children. The vague symptoms, the uncertain diagnostic tests and lack of adequate awareness among families all contributed in masking the actual prevalence of the disease. The objective of this study was to describe the epidemiology of childhood TB in River Nile State (RNS), North Sudan. METHODS: All registered cases of TB aged 15 years and below, at the 13 management units in RNS during 3 years, 2011-2013 were included...
January 2017: Journal of Natural Science, Biology, and Medicine
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#17
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28243600/systematic-approach-for-the-formulation-and-optimization-of-solid-lipid-nanoparticles-of-efavirenz-by-high-pressure-homogenization-using-design-of-experiments-for-brain-targeting-and-enhanced-bioavailability
#18
Shweta Gupta, Rajesh Kesarla, Narendra Chotai, Ambikanandan Misra, Abdelwahab Omri
The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28231392/from-dendritic-cells-to-b-cells-dysfunctions-during-hiv-1-infection-tfh-at-the-cross-road
#19
REVIEW
Nicolas Ruffin, Lylia Hani, Nabila Seddiki
T follicular helper (Tfh) cells are essential for B cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal center, where they are the main source of replicative HIV-1 and represent a major reservoir. Paradoxically, Tfh numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV-1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure...
February 23, 2017: Immunology
https://www.readbyqxmd.com/read/28219694/lenalidomide-maintenance-in-patients-with-relapsed-diffuse-large-b-cell-lymphoma-who-are-not-eligible-for-autologous-stem-cell-transplantation-an-open-label-single-arm-multicentre-phase-2-trial
#20
Andrés J M Ferreri, Marianna Sassone, Francesco Zaja, Alessandro Re, Michele Spina, Alice Di Rocco, Alberto Fabbri, Caterina Stelitano, Maurizio Frezzato, Chiara Rusconi, Renato Zambello, Suzana Couto, Yan Ren, Annalisa Arcari, Giovanni Bertoldero, Alessandro Nonis, Lydia Scarfò, Teresa Calimeri, Caterina Cecchetti, Marianna Chiozzotto, Silvia Govi, Maurilio Ponzoni
BACKGROUND: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) not eligible for autologous stem cell transplantation (ASCT) or having relapse after ASCT have a low likelihood of cure. Single-drug maintenance after salvage therapy might be an attractive strategy to prolong survival in these patients. Lenalidomide is a suitable candidate for long-lasting maintenance as it is an oral drug, active against DLBCL that can be taken for years with an acceptable toxicity profile. We designed a study to investigate safety and efficacy of lenalidomide maintenance in patients with chemosensitive relapse of DLBCL not eligible for ASCT or having relapse after ASCT...
February 16, 2017: Lancet Haematology
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