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https://www.readbyqxmd.com/read/29789664/the-bet-bromodomain-inhibitor-apabetalone-induces-apoptosis-of-latent-hiv-1-reservoir-cells-following-viral-reactivation
#1
Xuan-Xuan Zhang, Jian Lin, Tai-Zhen Liang, Heng Duan, Xing-Hua Tan, Bao-Min Xi, Lin Li, Shu-Wen Liu
The persistence of latent HIV-1 reservoirs throughout combination antiretroviral therapy (cART) is a major barrier on the path to achieving a cure for AIDS. It has been shown that bromodomain and extra-terminal (BET) inhibitors could reactivate HIV-1 latency, but restrained from clinical application due to their toxicity and side effects. Thus, identifying a new type of BET inhibitor with high degrees of selectivity and safety is urgently needed. Apabetalone is a small-molecule selective BET inhibitor specific for second bromodomains, and has been evaluated in phase III clinical trials that enrolled patients with high-risk cardiovascular disorders, dyslipidemia, and low HDL cholesterol...
May 22, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29781356/combating-the-hiv-reservoirs
#2
Guido van Marle, Deirdre L Church, Frank van der Meer, M John Gill
Impressive advances have been made in the treatment and management of HIV-1 infected individuals. Combination antiretroviral therapy (cART) has turned HIV-1 infection from an almost invariable deadly infectious disease, to a lifelong manageable infectious disease. However, a cure or vaccine has not been forthcoming. A major problem in HIV-1 infection is the persistent and latently infected cellular and tissue reservoirs. One of these reservoirs is the Gut Associated Lymphoid tissue (GALT), which has been the research focus of our group...
May 21, 2018: Biotechnology & Genetic Engineering Reviews
https://www.readbyqxmd.com/read/29778137/deciphering-natural-control-of-hiv-1-a-valuable-strategy-to-achieve-antiretroviral-therapy-termination
#3
REVIEW
Hamza Loucif, Steven Gouard, Xavier Dagenais-Lussier, Armstrong Murira, Simona Stäger, Cécile Tremblay, Julien Van Grevenynghe
Antiretroviral therapy (ART) has dramatically reduced HIV-1-associated morbidity and mortality, and has transformed HIV-1 infection into a manageable chronic condition by suppressing viral replication. However, despite recent patient care improvements, ART still fails to cure HIV-1 infection due to the inability to counteract immune defects and metabolic disturbances that are associated with residual inflammation alongside viral persistence. Life-long drug administration also results in multiple side-effects in patients including lipodystrophy and insulin resistance...
April 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29773895/crispr-cas9-system-targeting-regulatory-genes-of-hiv-1-inhibits-viral-replication-in-infected-t-cell-cultures
#4
Youdiil Ophinni, Mari Inoue, Tomohiro Kotaki, Masanori Kameoka
The CRISPR/Cas9 system provides a novel and promising tool for editing the HIV-1 proviral genome. We designed RNA-guided CRISPR/Cas9 targeting the HIV-1 regulatory genes tat and rev with guide RNAs (gRNA) selected from each gene based on CRISPR specificity and sequence conservation across six major HIV-1 subtypes. Each gRNA was cloned into lentiCRISPRv2 before co-transfection to create a lentiviral vector and transduction into target cells. CRISPR/Cas9 transduction into 293 T and HeLa cells stably expressing Tat and Rev proteins successfully abolished the expression of each protein relative to that in non-transduced and gRNA-absent vector-transduced cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769442/distinct-biomarker-signatures-in-hiv-acute-infection-associate-with-viral-dynamics-and-reservoir-size
#5
Jeffrey E Teigler, Louise Leyre, Nicolas Chomont, Bonnie Slike, Ningbo Jian, Michael A Eller, Nittaya Phanuphak, Eugène Kroon, Suteeraporn Pinyakorn, Leigh Anne Eller, Merlin L Robb, Jintanat Ananworanich, Nelson L Michael, Hendrik Streeck, Shelly J Krebs
Estimating the size of the viral reservoir is critical for HIV cure strategies. Biomarkers in peripheral circulation may give insights into the establishment of the viral reservoir in compartments not easily accessible. We therefore measured systemic levels of 84 soluble biomarkers belonging to a broad array of immune pathways in acute HIV infection in both antiretroviral therapy-naive (ART-naive) individuals as well as individuals who began ART upon early detection of HIV infection. These biomarkers were measured longitudinally during acute and chronic infection and their relationship to viral reservoir establishment and persistence was assessed...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29768503/high-uptake-of-antiretroviral-therapy-among-hiv-positive-tb-patients-receiving-co-located-services-in-swaziland
#6
Ishani Pathmanathan, Munyaradzi Pasipamire, Sherri Pals, E Kainne Dokubo, Peter Preko, Trong Ao, Sikhathele Mazibuko, Janet Ongole, Themba Dhlamini, Samson Haumba
BACKGROUND: Swaziland has the highest adult HIV prevalence and second highest rate of TB/HIV coinfection globally. Recently, the Ministry of Health and partners have increased integration and co-location of TB/HIV services, but the timing of antiretroviral therapy (ART) relative to TB treatment-a marker of program quality and predictor of outcomes-is unknown. METHODS: We conducted a retrospective analysis of programmatic data from 11 purposefully-sampled facilities to evaluate timely ART provision for HIV-positive TB patients enrolled on TB treatment between July-November 2014...
2018: PloS One
https://www.readbyqxmd.com/read/29768175/targeting-the-latent-reservoir-for-hiv-1
#7
REVIEW
Srona Sengupta, Robert F Siliciano
Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4+ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort. We describe how the reservoir is established, challenges involved in eliminating it, and pharmacologic and immunologic strategies for targeting this reservoir...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29758076/high-throughput-generation-and-characterization-of-replication-competent-clade-c-transmitter-founder-simian-human-immunodeficiency-viruses
#8
Debashis Dutta, Samuel Johnson, Alisha Dalal, Martin J Deymier, Eric Hunter, Siddappa N Byrareddy
Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV) and simian tropic HIV (stHIV). This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia...
2018: PloS One
https://www.readbyqxmd.com/read/29755454/the-use-of-the-humanized-mouse-model-in-gene-therapy-and-immunotherapy-for-hiv-and-cancer
#9
REVIEW
Mayra A Carrillo, Anjie Zhen, Scott G Kitchen
HIV and cancer remain prevailing sources of morbidity and mortality worldwide. There are current efforts to discover novel therapeutic strategies for the treatment or cure of these diseases. Humanized mouse models provide the investigative tool to study the interaction between HIV or cancer and the human immune system in vivo . These humanized models consist of immunodeficient mice transplanted with human cells, tissues, or hematopoietic stem cells that result in reconstitution with a nearly full human immune system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29753126/23-valent-pneumococcal-polysaccharide-vaccine-elicits-hierarchical-antibody-and-cellular-responses-in-healthy-and-tuberculosis-cured-elderly-and-hiv-1-infected-subjects
#10
Huichang Huang, Xiaohua Qian, Rong Pan, Ling Shen, Shanshan Liang, Feifei Wang, Peng Zhang, Hongbo Shen, Zheng W Chen
The PPV23 immunizes healthy elderly and other high-risk populations against pneumococcal disease. Immune mechanisms whereby these populations differently mount antibody(Ab) and cellular responses to PPV23 vaccination remain unknown. Here, healthy elderly, those elderly with prior tuberculosis-cured history (TB-cured), and HIV-infected humans were vaccinated with PPV23, and assessed for opsonophagocytic Ab responses and potential cellular mechanisms. PPV23 vaccination elicited hierarchical responses of opsonophagocytic Ab...
May 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29744964/peering-into-the-hiv-reservoir
#11
REVIEW
Marcial García, María J Buzón, José M Benito, Norma Rallón
The main obstacle to HIV eradication is the establishment of a long-term persistent HIV reservoir. Although several therapeutic approaches have been developed to reduce and eventually eliminate the HIV reservoir, only a few have achieved promising results. A better knowledge of the mechanisms involved in the establishment and maintenance of HIV reservoir is of utmost relevance for the design of new therapeutic strategies aimed at purging it with the ultimate goal of achieving HIV eradication or alternatively a functional cure...
May 9, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29737455/current-and-future-use-of-chloroquine-and-hydroxychloroquine-in-infectious-immune-neoplastic-and-neurological-diseases-a-mini-review
#12
REVIEW
Domenico Plantone, Tatiana Koudriavtseva
The process of finding new therapeutic indications for currently used drugs, defined as 'repurposing', is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple's disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjögren's syndrome), and other immunological diseases. Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects...
May 8, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29734220/recovery-of-effective-hiv-specific-cd4-t-cell-activity-following-antiretroviral-therapy-in-paediatric-infection-requires-sustained-suppression-of-viraemia
#13
Emily Adland, Luisa Mori, Leana Laker, Anna Csala, Maximilian Muenchhoff, Alice Swordy, Masa Mori, Philippa Matthews, Gareth Tudor-Williams, Pieter Jooste, Philip Goulder
: The success of increasing access to antiretroviral therapy (ART) in paediatric HIV infection prompts the question of the potential for eradication of HIV infection in this age group. 'Shock-and-kill' HIV cure approaches, currently in development, may depend upon an effective antiviral T-cell response to eradicate virus-infected cells. We here investigate the ability of HIV-infected children receiving ART from early childhood (median 24 months' age) to generate effective HIV-specific CD4+ and CD8+ T-cell immune responses that would facilitate future immune-based cure therapies...
May 3, 2018: AIDS
https://www.readbyqxmd.com/read/29732897/shifting-the-hiv-paradigm-from-care-to-cure-proceedings-from-the-caribbean-expert-summit-in-barbados-august-2017
#14
Robert Clive Landis, Emannuel Akinola Abayomi, Brendan Bain, Edward Greene, George Janossy, Patrice Joseph, Deanna Kerrigan, J Philip McCoy, Cesar Antonio Nunez, Maurice O'Gorman, Alexander Pastoors, Bharat Parekh, Kim Quimby, Thomas C Quinn, Kevin Robertson, Rejean Thomas, Eric van Gorp, Sten H Vermund, Valerie Wilson
The CCAS EXPERT SUMMIT convened an array of international experts in Barbados on August 27-31 2017 under the theme "From Care to Cure - Shifting the HIV Paradigm". The Caribbean Cytometry & Analytical Society (CCAS) partnered with the Joint United Nations Programme on HIV/AIDS (UNAIDS) to deliver a program that reviewed the advances in antiretroviral therapy and the public health benefits accruing from treatment as prevention. Particular emphasis was placed on re-examining stigma and discrimination through a critical appraisal of whether public health messaging and advocacy had kept pace with the advances in medicine...
May 5, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29729309/hiv-glycoprotein-gp120-enhances-mesenchymal-stem-cell-migration-by-upregulating-cxcr4-expression
#15
Lei Li, Ryan Z L Lim, Lawrence S U Lee, Nicholas S Y Chew
BACKGROUND: HIV infection and/or the direct pathogenic effects of circulating HIV proteins impairs the physiological function of mesenchymal stem cells (MSCs), and contribute to the pathogenesis of age-related clinical comorbidities in people living with HIV. The SDF-1/CXCR4 pathway is vital for modulating MSC proliferation, migration and differentiation. HIV glycoprotein gp120 inhibits SDF-1 induced chemotaxis by downregulating the expression and function of CXCR4 in monocytes, B and T cells...
May 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29725333/follicular-dendritic-cells-of-lymph-nodes-as-human-immunodeficiency-virus-simian-immunodeficiency-virus-reservoirs-and-insights-on-cervical-lymph-node
#16
REVIEW
Rajnish S Dave, Pooja Jain, Siddappa N Byrareddy
A hallmark feature of follicular dendritic cells (FDCs) within the lymph nodes (LNs) is their ability to retain antigens and virions for a prolonged duration. FDCs in the cervical lymph nodes (CLNs) are particularly relevant in elucidating human immunodeficiency virus (HIV)-1 infection within the cerebrospinal fluid (CSF) draining LNs of the central nervous system. The FDC viral reservoir in both peripheral LN and CLN, like the other HIV reservoirs, contribute to both low-level viremia and viral resurgence upon cessation or failure of combined antiretroviral therapy (cART)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29725327/lymph-node-cellular-and-viral-dynamics-in-natural-hosts-and-impact-for-hiv-cure-strategies
#17
REVIEW
Nicolas Huot, Steven E Bosinger, Mirko Paiardini, R Keith Reeves, Michaela Müller-Trutwin
Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomical reservoirs, from which the virus generally rebounds soon after cART cessation. One major anatomical reservoir are lymph node (LN) follicles, where HIV persists through replication in follicular helper T cells and is also trapped by follicular dendritic cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29724920/delamanid-for-rifampicin-resistant-tuberculosis-a-retrospective-study-from-south-africa
#18
Erika Mohr, Jennifer Hughes, Anja Reuter, Laura Trivino Duran, Gabriella Ferlazzo, Johnny Daniels, Virginia De Avezedo, Yulene Kock, Sarah Jane Steele, Amir Shroufi, Serge Ade, Natavan Alikhanova, Guido Benedetti, Jeffrey Edwards, Helen Cox, Jennifer Furin, Petros Isaakidis
BACKGROUND: Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety from a programmatic setting in South Africa. METHODS: This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. Twelve-month interim outcomes, sputum culture conversion (SCC) by months-2 and 6, serious adverse events (SAEs), and QTcF data were reported...
May 3, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29724686/hiv-specific-t-cells-generated-from-naive-t-cells-suppress-hiv-in-vitro-and-recognize-wide-epitope-breadths
#19
Shabnum Patel, Elizabeth Chorvinsky, Shuroug Albihani, Conrad Russell Cruz, R Brad Jones, Elizabeth J Shpall, David M Margolis, Richard F Ambinder, Catherine M Bollard
The Berlin Patient represents the first and only functional HIV cure achieved by hematopoietic stem cell transplant (HSCT). In subsequent efforts to replicate this result, HIV rebounded post-HSCT after withdrawal of antiretroviral therapy. Providing HIV-specific immunity through adoptive T cell therapy may prevent HIV rebound post-HSCT by eliminating newly infected cells before they can seed systemic infection. Adoptive T cell therapy has demonstrated success in boosting Epstein-Barr virus and cytomegalovirus-specific immunity post-HSCT, controlling viral reactivation...
April 12, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29723162/hiv-1-replicates-and-persists-in-vaginal-epithelial-dendritic-cells
#20
Victor Pena-Cruz, Luis M Agosto, Hisashi Akiyama, Alex Olson, Yvetane Moreau, Jean-Robert Larrieux, Andrew Henderson, Suryaram Gummuluru, Manish Sagar
HIV-1 acquisition occurs most commonly after sexual contact. To establish infection, HIV-1 must infect cells that support high level replication, namely CD4+ T cells, which are absent from the outermost genital epithelium. Dendritic cells (DCs), present in mucosal epithelia, potentially facilitate HIV-1 acquisition. We show that vaginal epithelial DCs, termed CD1a+ VEDCs, are unlike other blood and tissue derived DCs because they express langerin but not DC-SIGN, and unlike skin-based langerin+ DC subset, Langerhans cells (LC), they do not harbor Birbeck granules...
May 3, 2018: Journal of Clinical Investigation
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