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HIV cure

Madhukar Pai, Mark P Nicol, Catharina C Boehme
Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement...
October 2016: Microbiology Spectrum
Kenichi Morikawa, Tomoe Shimazaki, Rei Takeda, Takaaki Izumi, Machiko Umumura, Naoya Sakamoto
Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus...
September 2016: Annals of Translational Medicine
Héloïse M Delagrèverie, Constance Delaugerre, Sharon R Lewin, Steven G Deeks, Jonathan Z Li
In chronic human immunodeficiency virus (HIV)-1 infection, long-lived latently infected cells are the major barrier to virus eradication and functional cure. Several therapeutic strategies to perturb, eliminate, and/or control this reservoir are now being pursued in the clinic. These strategies include latency reversal agents (LRAs) designed to reactivate HIV-1 ribonucleic acid transcription and virus production and a variety of immune-modifying drugs designed to reverse latency, block homeostatic proliferation, and replenish the viral reservoir, eliminate virus-producing cells, and/or control HIV replication after cessation of antiretroviral therapy...
October 2016: Open Forum Infectious Diseases
Sara Gianella, Jeff Taylor, Timothy R Brown, Andy Kaytes, Cristian L Achim, David J Moore, Susan J Little, Ron J Ellis, Davey M Smith
Despite extensive investigations, we still do not fully understand the dynamics of the total body HIV reservoir and how sub-reservoirs in various compartments relate to one another. Studies using macaque models are enlightening but eradication strategies will still need to be tested in humans. To take the next steps in understanding and eradicating HIV reservoirs throughout the body, we propose to develop a "peri-mortem translational research model" of HIV-infected individuals (called 'The Last Gift'), which is similar to existing models in cancer research...
October 14, 2016: AIDS
Bingjie Shi, Juan Li, Xuanling Shi, Wenxu Jia, Yi Wen, Xiongbing Hu, Fengfeng Zhuang, Jianzhong Xi, Linqi Zhang
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity and low cytotoxicity. We report here systematic design and characterization of twenty eight novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity and lower cytotoxicity compared to zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials...
October 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Céline Marban, Faezeh Forouzanfar, Amina Ait-Ammar, Faiza Fahmi, Hala El Mekdad, Fadoua Daouad, Olivier Rohr, Christian Schwartz
One of the top research priorities of the international AIDS society by the action "Towards an HIV Cure" is the purge or the decrease of the pool of all latently infected cells. This strategy is based on reactivation of latently reservoirs (the shock) followed by an intensifying combination antiretroviral therapy (cART) to kill them (the kill). The central nervous system (CNS) has potential latently infected cells, i.e., perivascular macrophages, microglial cells, and astrocytes that will need to be eliminated...
2016: Frontiers in Immunology
Jianbin Wang, Michael C Holmes
The battle with human immunodeficiency virus (HIV) has been ongoing for more than 30 years, and although progress has been made, there are still significant challenges remaining. A few unique features render HIV to be one of the toughest viruses to conquer in the modern medicine era, such as the ability to target the host immune system, persist by integrating into the host genome and adapt to a hostile environment such as a single anti-HIV medication by continuously evolving. The finding of combination anti-retroviral therapy (cART) about 2 decades ago has transformed the treatment options for HIV-infected patients and significantly improved patient outcomes...
November 2016: Cytotherapy
Jon Cohen
No abstract text is available yet for this article.
October 14, 2016: Science
Xiaotang Hu
Since 2012, the CRISPR-Cas9 system has been quickly and successfully tested in a broad range of organisms and cells including hematopoietic cells. The application of CRISPR-Cas9 in human hematopoietic cells mainly involves the genes responsible for HIV infection, β-thalassemia and sickle cell disease (SCD). The successful disruption of CCR5 and CXCR4 genes in T cells by CRISPR-Cas9 promotes the prospect of the technology in the functional cure of HIV. More recently, eliminating CCR5 and CXCR4 in induced pluripotent stem cells (iPSCs) derived from patients and targeting the HIV genome have been successfully carried out in several laboratories...
October 2, 2016: Blood Cells, Molecules & Diseases
Guido Ferrari, Barton F Haynes, Scott Koenig, Jeffrey L Nordstrom, David M Margolis, Georgia D Tomaras
HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope (HIV-1 Env) glycoproteins are expressed on the cell surface, transforming latently infected cells into targets for HIV-1 Env-specific monoclonal antibodies (mAbs), which can engage immune effector cells to kill productively infected CD4(+) T cells and thus limit the spread of progeny virus...
October 7, 2016: Nature Reviews. Drug Discovery
Aschalew Tamiru, Bethlehem Tigabu, Sisay Yifru, Ermias Diro, Asrat Hailu
BACKGROUND: Visceral leishmaniasis (VL) is a protozoan disease that is invariably fatal if left untreated. The disease is found in 70 countries with incidence of 0.2 - 0.4 million cases. The mainstay of treatment in resource limited countries like Ethiopia is antimonials, while use of liposomal amphotericin B is reserved for treatment of complicated VL cases. The aim of this study was to assess the safety and efficacy of liposomal amphotericin B in HIV negative VL patients diagnosed with complications...
October 10, 2016: BMC Infectious Diseases
Rahul Sampath, Nathan W Cummins, Andrew D Badley
HIV cure is now the focus of intense research after Timothy Ray Brown (the Berlin patient) set the precedent of being the first and only person cured. A major barrier to achieving this goal on a meaningful scale is an elimination of the latent reservoir, which is thought to comprise CD4-positive cells that harbor integrated, replication-competent HIV provirus. These cells do not express viral proteins, are indistinguishable from uninfected CD4 cells, and are thought to be responsible for HIV viral rebound-that occurs within weeks of combination anti retroviral therapy (cART) interruption...
2016: Journal of Cell Death
Guan-Han Li, Lisa Henderson, Avindra Nath
If we have any hope of achieving a cure for HIV infection, close attention to the cell types capable of getting infected with HIV is necessary. Of these cell types, astrocytes are the most ideal cell type for the formation of such a reservoir. These are long-lived cells with a very low turnover rate and are found in the brain and the gastrointestinal tract. Although astrocytes are evidently resistant to infection of cell-free HIV in vitro, these cells are efficiently infected via cell-to-cell contact by which immature HIV virions bud off lymphocytes and have ability directly bind to CXCR4 triggering the process of fusion in the absence of CD4...
October 6, 2016: Current HIV Research
Zoë M McLaren, Amanda A Milliken, Amanda J Meyer, Alana R Sharp
BACKGROUND: Tuberculosis (TB) now ranks alongside HIV as the leading infectious disease cause of death worldwide and incurs a global economic burden of over $12 billion annually. Directly observed therapy (DOT) recommends that TB patients complete the course of treatment under direct observation of a treatment supporter who is trained and overseen by health services to ensure that patients take their drugs as scheduled. Though the current WHO End TB Strategy does not mention DOT, only "supportive treatment supervision by treatment partners", many TB programs still use it despite the fact that the has not been demonstrated to be statistically significantly superior to self-administered treatment in ensuring treatment success or cure...
October 4, 2016: BMC Infectious Diseases
Zora Melkova, Prakash Shankaran, Michaela Madlenakova, Josef Bodor
HIV-1 infection cannot be cured as it persists in latently infected cells that are targeted neither by the immune system nor by available therapeutic approaches. Consequently, a lifelong therapy suppressing only the actively replicating virus is necessary. The latent reservoir has been defined and characterized in various experimental models and in human patients, allowing research and development of approaches targeting individual steps critical for HIV-1 latency establishment, maintenance, and reactivation...
October 5, 2016: Folia Microbiologica
Shengbin Li, Joy M Folkvord, Eva G Rakasz, Hadia M Abdelaal, Reece K Wagstaff, Katalin J Kovacs, Hyeon O Kim, Ryoko Sawahata, Samantha MaWhinney, David Masopust, Elizabeth Connick, Pamela J Skinner
: HIV- and simian immunodeficiency virus (SIV)-specific CD8(+) T cells are typically largely excluded from lymphoid B cell follicles where HIV- and SIV-producing cells are most highly concentrated, indicating that B cell follicles are somewhat of an immune privileged site. To gain insights into virus-specific follicular CD8(+) T cells, we determined the location and phenotype of follicular SIV-specific CD8(+) T cells in situ, the local relationship of these cells to Foxp3(+) cells, and effects of CD8 depletion on levels of follicular SIV-producing cells in chronically SIV infected rhesus macaques...
October 5, 2016: Journal of Virology
Anthony D Harries, Amitabh B Suthar, Kudakwashe C Takarinda, Hannock Tweya, Nang Thu Thu Kyaw, Katie Tayler-Smith, Rony Zachariah
The international community has committed to ending the epidemics of HIV/AIDS, tuberculosis, malaria, and neglected tropical infections by 2030, and this bold stance deserves universal support. In this paper, we discuss whether this ambitious goal is achievable for HIV/AIDS and what is needed to further accelerate progress. The joint United Nations Program on HIV/AIDS (UNAIDS) 90-90-90 targets and the related strategy are built upon currently available health technologies that can diagnose HIV infection and suppress viral replication in all people with HIV...
2016: F1000Research
Di Qu, Chuan Li, Feng Sang, Qiang Li, Zhi-Qiang Jiang, Li-Ran Xu, Hui-Jun Guo, Chiyu Zhang, Jian-Hua Wang
The 5' end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles from major endemic Chinese subtypes are not well characterized...
October 4, 2016: Scientific Reports
Xian Li, Hanxian Zeng, Pengfei Wang, Lu Lin, Lin Liu, Panpan Lu, Huanzhang Zhu
BACKGROUND: Current antiretroviral treatment (ART) cannot cure HIV-1 infection due to the presence of latent viral reservoirs. The "shock and kill" strategy is a promising approach to eliminate the viral reservoir. However, there are various limits existing in current latency-reversing agents, searching for new activators are urgently needed. OBJECTIVE: The present study aimed at investigating the ability of hymecromone and scoparone for activating HIV-1 from latent reservoirs...
October 3, 2016: Current HIV Research
K A R Segbedji, K E Djadou, O-B Tchagbele, M Kpegouni, L K Bessi Kama, K D Azoumah, A D Agbèrè
INTRODUCTION: Tuberculosis (TB) remains one of the most lethal communicable diseases in the world, according to the World Health Organization (WHO). New strategies must be implemented to meet targets for 2035. OBJECTIVE: Describe the epidemiological and therapeutic aspects of tuberculosis in children in Togo. MATERIALS AND METHODS: This retrospective, multicenter, descriptive cross-sectional study examined the files of children younger than 15 years who were diagnosed with TB and treatment in the Maritime region from 2008 to 2011...
August 1, 2016: Médecine et Santé Tropicales
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