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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
#1
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/29141704/human-competence-to-transmit-leishmania-infantum-to-lutzomyia-longipalpis-and-the-influence-of-human-immunodeficiency-virus-infection
#2
Gabriel Reis Ferreira, José Carlos Castelo Branco Ribeiro, Antônio Meneses Filho, Teresinha de Jesus Cardoso Farias Pereira, Daniela Moura Parente, Humberto Feitosa Pereira, Jailthon Carlos da Silva, Danielle Alves Zacarias, Letiano Vieira da Silva, Symonara Karina Medeiros Faustino, Walfrido Salmito Almeida Neto, Dorcas Lamounier Costa, Ivete Lopes de Mendonça, Carlos Henrique Nery Costa
Visceral leishmaniasis (VL) caused by Leishmania infantum is a lethal disease transmitted by sand flies. Although, considered a zoonosis with dogs held as the main reservoirs, humans are also sources of infection. Therefore, control policies currently focused on dog culling may need to consider that VL and human immunodeficiency virus (HIV)/VL patients may also be infectious, contributing to transmission. Reservoir competence of patients with VL without and with HIV infection and of persons asymptomatically infected with Leishmania was assessed by xenodiagnosis with the vector Lutzomyia longipalpis...
November 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29140109/host-methyltransferases-and-demethylases-potential-new-epigenetic-targets-for-hiv-cure-strategies-and-beyond
#3
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
#4
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/29135580/wake-me-up-before-you-go-a-strategy-to-reduce-the-latent-hiv-reservoir
#5
Nicolas Chomont, Afam A Okoye, David Favre, Lydie Trautmann
: In the quest to eliminate or reduce the HIV reservoir, shock and kill strategies require the combined administration of a latency reversing agent (LRA) to reactivate the latent reservoir and an intervention to boost effector functions to clear this reservoir. Both parts of this strategy are quite inefficient when LRAs are administered to HIV-infected individuals on suppressive ART for several years, possibly due to low levels of induced antigen expression, negative impact of LRAs on clearance mechanisms, and very low number of effective cytotoxic T cells (CTLs)...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29135490/the-microbiome-and-hiv-persistence-implications-for-viral-remission-and-cure
#6
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/29127275/allogeneic-stem-cell-transplantation-in-fully-mhc-matched-mauritian-cynomolgus-macaques-recapitulates-diverse-human-clinical-outcomes
#7
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/29126877/chidamide-a-histone-deacetylase-inhibitor-based-anticancer-drug-effectively-reactivates-latent-hiv-1-provirus
#8
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/29119608/synthetic-aav-crispr-vectors-for-blocking-hiv-1-expression-in-persistently-infected-astrocytes
#9
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/29112956/hiv-1-persistence-following-extremely-early-initiation-of-antiretroviral-therapy-art-during-acute-hiv-1-infection-an-observational-study
#10
Timothy J Henrich, Hiroyu Hatano, Oliver Bacon, Louise E Hogan, Rachel Rutishauser, Alison Hill, Mary F Kearney, Elizabeth M Anderson, Susan P Buchbinder, Stephanie E Cohen, Mohamed Abdel-Mohsen, Christopher W Pohlmeyer, Remi Fromentin, Rebecca Hoh, Albert Y Liu, Joseph M McCune, Jonathan Spindler, Kelly Metcalf-Pate, Kristen S Hobbs, Cassandra Thanh, Erica A Gibson, Daniel R Kuritzkes, Robert F Siliciano, Richard W Price, Douglas D Richman, Nicolas Chomont, Janet D Siliciano, John W Mellors, Steven A Yukl, Joel N Blankson, Teri Liegler, Steven G Deeks
BACKGROUND: It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29112072/an-advanced-blt-humanized-mouse-model-for-extended-hiv-1-cure-studies
#11
Kerry J Lavender, Craig Pace, Kathrin Sutter, Ronald J Messer, Dakota L Pouncey, Nathan W Cummins, Sekar Natesampillai, Jim Zheng, Joshua Goldsmith, Marek Widera, Erik S Van Dis, Katie Phillips, Brent Race, Ulf Dittmer, George Kukolj, Kim J Hasenkrug
OBJECTIVE: Although BLT-humanized mice provide a robust model for HIV-1 infection and enable evaluation of cure strategies dependent on endogenous immune responses, most mice develop graft versus host disease (GVHD), limiting their utility for extended HIV cure studies. This study aimed to: 1) Evaluate the GVHD-resistant C57BL/6 Rag2γcCD47 triple knockout (TKO)-BLT mouse as a model to establish HIV-1 latency. 2) Determine whether TKO-BLT mice could be maintained on ART for extended periods of time...
November 2, 2017: AIDS
https://www.readbyqxmd.com/read/29100529/vaccine-related-poliovirus-shedding-in-trivalent-polio-vaccine-and-human-immunodeficiency-virus-status-analysis-from-under-five-children
#12
Joanne Hassan, Laura Wangai, Peter Borus, Christopher Khayeka-Wandabwa, Lucy Wanja Karani, Mercy Kithinji, Michael Kiptoo
BACKGROUND: Poliomyelitis is an acute viral infection caused by poliovirus and transmitted via the fecal-oral route. The causative agent is one of the three serotypes of poliovirus (serotypes 1, 2, 3) that differ slightly in capsid protein. Prolonged vaccine-related poliovirus shedding in human immunodeficiency virus (HIV) positive individuals has been linked to possible reservoir for reintroduction of polioviruses after eradication. The study therefore aimed at estimating the duration for vaccine-related poliovirus shedding among potentially and HIV-infected persons...
November 3, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29099677/novel-latency-reversal-agents-for-hiv-1-cure
#13
Adam M Spivak, Vicente Planelles
Antiretroviral therapy (ART) has rendered HIV-1 infection a treatable illness; however, ART is not curative owing to the persistence of replication-competent, latent proviruses in long-lived restingTcells. Strategies that target these latently infected cells and allow immune recognition and clearance of this reservoir will be necessary to eradicate HIV-1 in infected individuals. This review describes current pharmacologic approaches to reactivate the latent reservoir so that infected cells can be recognized and targeted, with the ultimate goal of achieving an HIV-1 cure...
November 3, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29098898/the-pharmacological-treatment-of-acute-hiv-infections-in-neonates
#14
Louise Kuhn, Stephanie Shiau
Recent goals of antiretroviral treatment of neonates have expanded from reducing morbidity and mortality to also aiming to facilitate HIV remission. Areas covered: In this review, we present and discuss the rationale and evidence-bases for each of these distinct goals. Next we discuss the challenges of how to identify HIV-infected neonates. Finally, we discuss the specific antiretroviral drugs that are preferred for this group, making distinctions between the use of these agents in prevention and treatment...
November 3, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29098230/rna-mediated-tilda-for-improved-cell-capacity-and-enhanced-detection-of-multiply-spliced-hiv-rna
#15
Hannah M Pezzi, Scott M Berry, David J Beebe, Rob Striker
Quantification of the HIV viral reservoir is critical to understanding HIV latency, advancing patient care and ultimately achieving a cure. To quantify the reservoir, a new metric was recently introduced, which quantified cells carrying multiply spliced HIV RNA. The developed assay, Tat/rev Induced Limiting Dilution Assay (TILDA), enables quantification of cells containing multiply-spliced HIV RNA events as an indicator of reservoir size. Due to TILDA's reliance on a limiting dilution format paired with the rarity of target events, numerous individual reactions are required to obtain a single endpoint...
November 13, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29091218/hiv-1-dna-ultra-deep-sequencing-analysis-at-initiation-of-the-dual-therapy-dolutegravir%C3%A2-%C3%A2-lamivudine-in-the-maintenance-dolulam-pilot-study
#16
Charlotte Charpentier, Brigitte Montes, Marine Perrier, Nadia Meftah, Jacques Reynes
Background: The DOLULAM study assessed the efficacy of dolutegravir + lamivudine dual therapy to maintain virological suppression in heavily treatment-experienced HIV-1-infected adults. No virological failure occurred during the first year of the dual therapy. Objectives: A virological substudy was conducted to assess the prevalence of M184I/V mutations at dual therapy initiation using historical DNA/RNA genotypes and baseline DNA genotype obtained by next-generation sequencing (NGS)...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29090031/how-feasible-is-renal-transplantation-in-hiv-infected-patients
#17
Oana Ramayana Ailioaie, Gabriel Mircescu
HIV infection has been considered for a long time an absolute contraindication to transplantation. The introduction of highly active antiretroviral therapy has led to improved immunovirological control and increased survival in HIV-infected patients. Renal transplantation can now be performed if these patients are on stable highly active antiretroviral therapy and achieve undetectable viral load and a sufficient CD4 level, in the absence of untreatable infections and cancers. Highly active antiretroviral therapy and immunosuppressive medication should be maintained for life in these patients, raising the problem of multiple drugdrug interactions...
June 2017: Mædica
https://www.readbyqxmd.com/read/29089933/curaxin-cbl0100-blocks-hiv-1-replication-and-reactivation-through-inhibition-of-viral-transcriptional-elongation
#18
Maxime J Jean, Tsuyoshi Hayashi, Huachao Huang, Justin Brennan, Sydney Simpson, Andrei Purmal, Katerina Gurova, Michael C Keefer, James J Kobie, Netty G Santoso, Jian Zhu
Despite combination antiretroviral therapy (cART), acquired immunodeficiency syndrome (AIDS), predominantly caused by the human immunodeficiency virus type 1 (HIV-1), remains incurable. The barrier to a cure lies in the virus' ability to establish a latent infection in HIV/AIDS patients. Unsurprisingly, efforts for a sterilizing cure have focused on the "shock and kill" strategy using latency-reversing agents (LRAs) to complement cART in order to eliminate these latent reservoirs. However, this method faces numerous challenges...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29082287/flow-cytometric-analysis-of-hiv-1-transcriptional-activity-in-response-to-shrna-knockdown-in-a2-and-a72-j-lat-cell-lines
#19
Daniela Boehm, Melanie Ott
The main obstacle to eradicating HIV-1 from patients is post-integration latency (Finzi et al., 1999). Antiretroviral treatments target only actively replicating virus, while latent infections that have low or no transcriptional activity remain untreated (Sedaghat et al., 2007). To eliminate viral reservoirs, one strategy focuses on reversing HIV-1 latency via 'shock and kill' (Deeks, 2012). The basis of this strategy is to overcome the molecular mechanisms of HIV-1 latency by therapeutically inducing viral gene and protein expression under antiretroviral therapy and to cause selective cell death via the lytic properties of the virus, or the immune system now recognizing the infected cells...
June 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29077766/peripheral-blood-hiv-1-dna-dynamics-in-antiretroviral-treated-hiv-hcv-co-infected-patients-receiving-directly-acting-antivirals
#20
Gabriella Rozera, Gabriele Fabbri, Patrizia Lorenzini, Ilaria Mastrorosa, Laura Timelli, Mauro Zaccarelli, Alessandra Amendola, Alessandra Vergori, Maria Maddalena Plazzi, Stefania Cicalini, Andrea Antinori, Maria Rosaria Capobianchi, Isabella Abbate, Adriana Ammassari
BACKGROUND: Aim was to determine the dynamics of peripheral blood mononuclear cells (PBMC)- associated total HIV-1 DNA in successfully ART-treated HIV/HCV co-infected patients receiving DAA treatment and to explore possible virological hypotheses underlying the phenomenon. METHODS: Longitudinal, single-centre study measuring total HIV-1 DNA before the start of DAA, at the end of treatment (EOT), and 3 months after treatment. Univariable and multivariable analyses were used to assess factors associated with HIV-1 DNA increase ≥0...
2017: PloS One
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