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https://www.readbyqxmd.com/read/29157060/mycobacterium-genavense-infections-in-non-hiv-immunocompromised-hosts-a-systematic-review
#1
Maryam Mahmood, Saira Ajmal, Omar M Abu Saleh, Alexandra Bryson, Jasmine R Marcelin, John W Wilson
BACKGROUND: Mycobacterium genavense is a non-tuberculous mycobacterium which can rarely cause disease in non-HIV immunocompromised hosts. We describe our experience with this unusual infection and perform a systematic review of the literature to describe the features of M. genavense infection in non-HIV immunocompromised hosts. METHODS: All cases of Mycobacterium genavense infection in non-HIV patients at our institution were reviewed. In addition, we conducted a systematic review of the literature to identify previously published cases of M...
November 20, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/29151636/bedaquiline-fallible-hope-against-drug-resistant-tuberculosis
#2
REVIEW
Priya Singh, Rashmi Kumari, Rup Lal
Tuberculosis (TB) is a deadly bacterial infectious disease caused by intra-cellular pathogen Mycobacterium tuberculosis (Mtb). There were an estimated 1.4 million TB deaths in 2015 and an additional 0.4 million deaths resulting from TB among individuals with HIV. Drug-discovery for its cure is very slow in comparison with the causative organism's fast pace of mutations conferring drug resistance. Moreover, the field of drug-discovery of anti-TB drugs is constantly being challenged by the drug resistant strains of Mtb...
December 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/29149917/treatment-outcome-with-a-short-multidrug-resistant-tuberculosis-regimen-in-nine-african-countries
#3
A Trébucq, V Schwoebel, Z Kashongwe, A Bakayoko, C Kuaban, J Noeske, S Hassane, B Souleymane, A Piubello, F Ciza, V Fikouma, M Gasana, M Ouedraogo, M Gninafon, A Van Deun, D M Cirillo, K G Koura, H L Rieder
<h2>SETTING:</h2>Nine countries in West and Central Africa.<h2>OBJECTIVE:</h2>To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs.<h2>DESIGN:</h2>Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months...
November 17, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29149399/overcoming-hiv-stigma-a-qualitative-analysis-of-hiv-cure-research-and-stigma-among-men-who-have-sex-with-men-living-with-hiv
#4
Feng Wu, Alice Zhang, Andrew Babbitt, Qingyan Ma, Nir Eyal, Xin Pan, Weiping Cai, Fengyu Hu, Yu Cheng, Joseph D Tucker
Despite global progress in HIV stigma reduction, persistent HIV stigma thwarts effective HIV service delivery. Advances in HIV biomedical research toward a cure may shift perceptions of people living with HIV and HIV stigma. The purpose of this study was to examine how men who have sex with men (MSM) living with HIV in Guangzhou, China perceive HIV cure research and its potential impact on MSM and HIV stigma. We conducted in-depth interviews with 26 MSM living with HIV about their perceptions of HIV cure research and the potential impact of an HIV cure on their lives...
November 17, 2017: Archives of Sexual Behavior
https://www.readbyqxmd.com/read/29145733/harnessing-novel-imaging-approaches-to-guide-hiv-prevention-and-cure-discoveries-a-national-institutes-of-health-and-global-hiv-vaccine-enterprise-2017-meeting-report
#5
Brigitte Elisabeth Sanders-Beer, Yegor Voronin, David McDonald, Anjali Singh
Advances in imaging technologies have greatly increased our understanding of cellular and molecular interactions in humans and their corresponding animal models of infectious diseases. In the HIV/SIV field, imaging has provided key insights into mucosal viral transmission, local and systemic virus spread, host-virus dynamics, and chronic inflammation/immune activation and the resultant immunopathology. Recent developments in imaging applications are yielding physical, spatial, and temporal measurements to enhance insight into biological functions and disease processes, while retaining important cellular, microenvironmental, organ and intact organism contextual details...
November 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29143620/optimising-diagnosis-of-viraemic-hepatitis-c-infection-the-development-of-a-target-product-profile
#6
Elena Ivanova Reipold, Philippa Easterbrook, Alessandra Trianni, Nivedha Panneer, Douglas Krakower, Stefano Ongarello, Teri Roberts, Veronica Miller, Claudia Denkinger
BACKGROUND: The current low access to virological testing to confirm chronic viraemic HCV infection in low- and middle-income countries (LMIC) is limiting the rollout of hepatitis C (HCV) care. Existing tests are complex, costly and require sophisticated laboratory infrastructure. Diagnostic manufacturers need guidance on the optimal characteristics a virological test needs to have to ensure the greatest impact on HCV diagnosis and treatment in LMIC. Our objective was to develop a target product profile (TPP) for diagnosis of HCV viraemia using a global stakeholder consensus-based approach...
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
#7
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/29140110/il-21-therapy-controls-immune-activation-and-maintains-antiviral-cd8-t-cell-responses-in-acute-simian-immunodeficiency-virus-infection
#8
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/29140109/host-methyltransferases-and-demethylases-potential-new-epigenetic-targets-for-hiv-cure-strategies-and-beyond
#9
Daniela Boehm, Melanie Ott
A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29140108/cytomegalovirus-and-hiv-persistence-pouring-gas-on-the-fire
#10
Aaron Christensen-Quick, Christophe Vanpouille, Andrea Lisco, Sara Gianella
The inherent stability of a small population of T cells that are latently infected with HIV despite antiretroviral therapy (ART) remains a stubborn obstacle to an HIV cure. By exploiting the memory compartment of our immune system, HIV maintains persistence in a small subset of quiescent cells with varying phenotypes, thus evading immune surveillance and clinical detection. Understanding the molecular and immunological mechanisms that maintain the latent reservoir will be critical to the success of HIV eradication strategies...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29137626/treatment-outcomes-of-mdr-tuberculosis-patients-in-brazil-a-retrospective-cohort-analysis
#11
Mayara Lisboa Bastos, Lorrayne Beliqui Cosme, Geisa Fregona, Thiago Nascimento do Prado, Adelmo Inácio Bertolde, Eliana Zandonade, Mauro N Sanchez, Margareth Pretti Dalcolmo, Afrânio Kritski, Anete Trajman, Ethel Leonor Noia Maciel
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a threat for the global TB epidemic control. Despite existing evidence that individualized treatment of MDR-TB is superior to standardized regimens, the latter are recommended in Brazil, mainly because drug-susceptibility tests (DST) are often restricted to first-line drugs in public laboratories. We compared treatment outcomes of MDR-TB patients using standardized versus individualized regimens in Brazil, a high TB-burden, low resistance setting...
November 14, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29135490/the-microbiome-and-hiv-persistence-implications-for-viral-remission-and-cure
#12
Wei Li A Koay, Lilly V Siems, Deborah Persaud
PURPOSE OF REVIEW: This article discusses the interaction between HIV infection, the gut microbiome, inflammation and immune activation, and HIV reservoirs, along with interventions to target the microbiome and their implications for HIV remission and cure. RECENT FINDINGS: Most studies show that HIV-infected adults have a gut microbiome associated with decreased bacterial richness and diversity, and associated systemic inflammation and immune activation. A unique set of individuals, elite controllers, who spontaneously control HIV replication, have a similar microbiome to HIV-uninfected individuals...
November 10, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29132303/prevalence-of-naturally-occurring-ns5a-resistance-associated-substitutions-in-patients-infected-with-hepatitis-c-virus-subtype-1a-1b-and-3a-co-infected-or-not-with-hiv-in-brazil
#13
Fernanda Malta, Karine Vieira Gaspareto, Gaspar Lisboa-Neto, Flair José Carrilho, Maria Cássia Mendes-Correa, João Renato Rebello Pinho
BACKGROUND: Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown...
November 13, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29127275/allogeneic-stem-cell-transplantation-in-fully-mhc-matched-mauritian-cynomolgus-macaques-recapitulates-diverse-human-clinical-outcomes
#14
Benjamin J Burwitz, Helen L Wu, Shaheed Abdulhaqq, Christine Shriver-Munsch, Tonya Swanson, Alfred W Legasse, Katherine B Hammond, Stephanie L Junell, Jason S Reed, Benjamin N Bimber, Justin M Greene, Gabriela M Webb, Mina Northrup, Wolfram Laub, Paul Kievit, Rhonda MacAllister, Michael K Axthelm, Rebecca Ducore, Anne Lewis, Lois M A Colgin, Theodore Hobbs, Lauren D Martin, Betsy Ferguson, Charles R Thomas, Angela Panoskaltsis-Mortari, Gabrielle Meyers, Jeffrey J Stanton, Richard T Maziarz, Jonah B Sacha
Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.-tumor immunity are hampered by the lack of a physiologically relevant, preclinical model of allogeneic HSCT. Here we show a spectrum of diverse clinical HSCT outcomes including primary and secondary graft failure, lethal GvHD, and stable, disease-free full donor engraftment using reduced intensity conditioning and mobilized peripheral blood HSCT in unrelated, fully MHC-matched Mauritian-origin cynomolgus macaques...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29127137/ethics-of-treatment-interruption-trials-in-hiv-cure-research-addressing-the-conundrum-of-risk-benefit-assessment
#15
Gail E Henderson, Holly L Peay, Eugene Kroon, Rosemary Jean Cadigan, Karen Meagher, Thidarat Jupimai, Adam Gilbertson, Jill Fisher, Nuchanart Q Ormsby, Nitiya Chomchey, Nittaya Phanuphak, Jintanat Ananworanich, Stuart Rennie
Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption (ATI), involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally...
November 10, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/29126877/chidamide-a-histone-deacetylase-inhibitor-based-anticancer-drug-effectively-reactivates-latent-hiv-1-provirus
#16
Wenqian Yang, Zhiwu Sun, Chen Hua, Qian Wang, Wei Xu, Qiwen Deng, Yanbin Pan, Lu Lu, Shibo Jiang
Although combination antiretroviral therapy (cART) is highly effective in suppressing human immunodeficiency virus type 1 (HIV-1) replication, it fails to eradicate the virus from HIV-1-infected individuals because HIV-1 integrates into the resting CD4(+) T cells, establishing latently infected reservoirs. Histone deacetylation is a key element in regulating HIV-1 latent infection. Chidamide, a new anticancer drug, is a novel type of selective histone deacetylase inhibitor. Here we showed that chidamide effectively reactivated HIV-1 latent provirus in different latently infected cell lines in a dose- and time-dependent manner...
November 8, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29124683/the-21st-century-cures-act-implications-for-the-reduction-of-racial-health-disparities-in-the-us-criminal-justice-system-a-public-health-approach
#17
Donna M Cole, Dawna Marie Thomas, Kelsi Field, Amelia Wool, Taryn Lipiner, Natalie Massenberg, Barbara J Guthrie
Past drug epidemics have disproportionately criminalized drug addiction among African Americans, leading to disparate health outcomes, increased rates of HIV/AIDS, and mass incarceration. Conversely, the current opioid addiction crisis in the USA focuses primarily on white communities and is being addressed as a public health problem. The 21st Century Cures Act has the potential to reduce racial health disparities in the criminal justice system through the Act's public health approach to addiction and mental health issues...
November 9, 2017: Journal of Racial and Ethnic Health Disparities
https://www.readbyqxmd.com/read/29120617/live-visualization-of-hiv-1-proviral-dna-using-a-dual-color-labeled-crispr-system
#18
Yingxin Ma, Mingxiu Wang, Wei Li, Zhi-Ping Zhang, Xiaowei Zhang, Tianwei Tan, Zongqiang Cui, Xian-En Zhang
HIV latency is one of the major problems in HIV/AIDS cure. Imaging single-copy integrated proviral HIV DNA in host cell has both virology and clinical significance but remains technical challenge. Here, we developed a dual-color labeled CRISPR system to image the HIV-1 integrated proviral DNA in latently infected cells. The pair of CRISPRs was fluorescently labeled with two different color QDs using two alternative bioorthogonal ligation reactions. Integrated HIV-sequences are successfully mapped based on the co-localized signals of QDs in living cells...
November 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29119608/synthetic-aav-crispr-vectors-for-blocking-hiv-1-expression-in-persistently-infected-astrocytes
#19
Christine Kunze, Kathleen Börner, Eike Kienle, Tanja Orschmann, Ejona Rusha, Martha Schneider, Milena Radivojkov-Blagojevic, Micha Drukker, Sabrina Desbordes, Dirk Grimm, Ruth Brack-Werner
Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes...
November 9, 2017: Glia
https://www.readbyqxmd.com/read/29118125/alt-803-transiently-reduces-siv-replication-in-the-absence-of-antiretroviral-treatment
#20
Amy L Ellis-Connell, Alexis J Balgeman, Katie R Zarbock, Gabrielle Barry, Andrea Weiler, Jack O Egan, Emily K Jeng, Thomas Friedrich, Jeffrey S Miller, Ashley T Haase, Timothy W Schacker, Hing C Wong, Eva Rakasz, Shelby L O'Connor
Developing biological interventions to control HIV replication in the absence of antiretroviral therapy (ART) could contribute to the development of a functional cure. As a potential alternative to ART, the IL-15 superagonist ALT-803 has been shown to boost the number and function of HIV-specific CD8(+) T and NK cell populations, in vitro. Four SIV(+) rhesus macaques, three of whom possessed MHC alleles associated with control of SIV, and all of whom had received SIV vaccine vectors that had the potential to elicit CD8(+) T cell responses, were given ALT-803 in three treatment cycles...
November 8, 2017: Journal of Virology
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