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https://www.readbyqxmd.com/read/28645279/diabetes-care-in-a-complex-humanitarian-emergency-setting-a-qualitative-evaluation
#1
Adrianna Murphy, Michel Biringanine, Bayard Roberts, Beverley Stringer, Pablo Perel, Kiran Jobanputra
BACKGROUND: Evidence is urgently needed from complex emergency settings to support efforts to respond to the increasing burden of diabetes mellitus (DM). We conducted a qualitative study of a new model of DM health care (Integrated Diabetic Clinic within an Outpatient Department [IDC-OPD]) implemented by Médecins Sans Frontières (MSF) in Mweso Hospital in eastern Democratic Republic of Congo (DRC). We aimed to explore patient and provider perspectives on the model in order to identify factors that may support or impede it...
June 23, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28638377/a-novel-bromodomain-inhibitor-reverses-hiv-1-latency-through-specific-binding-with-brd4-to-promote-tat-and-p-tefb-association
#2
Huachao Huang, Shuai Liu, Maxime Jean, Sydney Simpson, He Huang, Mark Merkley, Tsuyoshi Hayashi, Weili Kong, Irene Rodríguez-Sánchez, Xiaofeng Zhang, Hailemichael O Yosief, Hongyu Miao, Jianwen Que, James J Kobie, James Bradner, Netty G Santoso, Wei Zhang, Jian Zhu
While combinatory antiretroviral therapy (cART) can effectively reduce HIV-1 viremia, it cannot eliminate HIV-1 infection. In the presence of cART, viral reservoirs remain latent, impeding the cure of HIV-1/AIDS. Recently, latency-reversing agents (LRAs) have been developed with the intent of purging latent HIV-1, providing an intriguing strategy for the eradication of the residual viral reservoirs. Our earlier studies show that the first-generation, methyl-triazolo bromodomain, and extra-terminal domain inhibitor (BETi), JQ1, facilitates the reversal of HIV-1 latency...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28638104/anti-proliferative-therapy-for-hiv-cure-a-compound-interest-approach
#3
Daniel B Reeves, Elizabeth R Duke, Sean M Hughes, Martin Prlic, Florian Hladik, Joshua T Schiffer
In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4(+) T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633331/does-timing-of-antiretroviral-treatment-influence-treatment-outcomes-of-visceral-leishmaniasis-in-northwest-ethiopia
#4
Endashaw M Aderie, Ermias Diro, Rony Zachariah, Marcio Silveira da Fonseca, Charles Abongomera, Bethabile L Dolamo, Koert Ritmeijer
Background: Visceral leishmaniasis (VL) patients with HIV co-infection should receive antiretroviral treatment (ART). However, the best timing for initiation of ART is not known. Among such individuals, we assessed the influence of ART timing on VL outcomes. Methods: A retrospective cohort study was conducted in Northwest Ethiopia among VL patients starting ART between 2008 and 2015. VL outcomes were assessed by the twelfth month of starting ART, within 4 weeks of VL diagnosis or thereafter...
March 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28632974/hcv-positive-donor-organs-in-solid-organ-transplantation-mind-the-gap
#5
EDITORIAL
J A Fishman, X Forns
The shortage of organs for transplantation is a major impediment to access to life-saving therapy. The availability of antiviral therapies that control hepatitis B (HBV) and HIV, or cure hepatitis C (HCV), have changed traditional equations in transplantation, allowing infected individuals access to transplantation without unimpeded viral replication during immunosuppression. The availability of these therapies also permits use of organs from donors actively or potentially infected with these viruses. This article is protected by copyright...
June 20, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28632482/staff-associate-specialist-and-specialty-doctors-national-audit-on-the-management-of-gonorrhoea-in-the-united-kingdom-2015
#6
Helen Mullan, Jane Richards, John Lee
The British Association for Sexual Health and HIV (BASHH) revised United Kingdom national guideline for the management of gonorrhoea in adults, 2011, identified five auditable outcome measures, namely, that all patients should receive first-line treatment, be screened or treated for chlamydial infection, have a test of cure (TOC), be offered written information and have partner notification carried out. The UK National Guideline for Gonorrhoea Testing, Clinical Effectiveness Group, BASHH, 2012, recommended in addition that all reactive nucleic acid amplification tests (NAATs) from pharynx and rectum should be confirmed by supplementary testing, using a second NAAT which detects a different nucleic acid target, all those with a positive NAAT for gonorrhoea should have culture and antimicrobial susceptibility testing and that TOC should be done by two weeks...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28628632/increasing-procaspase-8-expression-using-repurposed-drugs-to-induce-hiv-infected-cell-death-in-ex-vivo-patient-cells
#7
Rahul Sampath, Nathan W Cummins, Sekar Natesampillai, Gary D Bren, Thomas D Chung, Jason Baker, Keith Henry, Amélie Pagliuzza, Andrew D Badley
HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8...
2017: PloS One
https://www.readbyqxmd.com/read/28628526/determinants-of-hiv-1-cd4-independent-brain-adaptation
#8
Madina Shakirzyanova, Xiang-Peng Kong, Cecilia Cheng-Mayer
BACKGROUND: HIV-1 is known to adapt to the local environment in its usage of receptors and it can become CD4 independent in the brain where the receptor is scarce. This adaptation is through amino acid variations, but the patterns of such variation are not yet well understood. Given that infection of long-lived CD4-low and CD4-negative cells in anatomic compartments such as the brain expand cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4-independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis, but may guide functional cure strategies as well...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28628041/hiv-persistence-clonal-expansion-of-cells-in-the-latent-reservoir
#9
Kyungyoon J Kwon, Robert F Siliciano
While antiretroviral therapy (ART) can reduce HIV-1 to undetectable levels, the virus generally reappears if treatment is stopped. Resurgence of the virus is due to the reactivation of T cells harboring latent integrated provirus, and recent studies indicate that proliferation of these latently infected cells helps maintain the HIV-1 reservoir. In this issue of the JCI, Lee et al. evaluated CD4+ T cell subsets to determine whether certain populations are more likely to harbor full-length, replication-competent provirus...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28625133/recent-advances-in-targeting-the-hiv-1-tat-tar-complex
#10
Fardokht A Abulwerdi, Stuart F J Le Grice
Following seminal discoveries by Rosen and co-workers in 1985, the HIV-1 TAR has emerged as one of the most extensively studied regulatory elements of the HIV-1 genome. Located adjacent to the long terminal repeat promoter, this cis-acting motif, in conjunction with the viral Tat protein, plays a critical role in viral genomic RNA synthesis via modification of the transcription complex. As such, the Tat/TAR axis has been the subject of intense efforts aimed at developing therapeutic interventions, directed against both the protein and nucleic acid components...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28620380/human-immunodeficiency-virus-playing-hide-and-seek-understanding-the-tfh-cell-reservoir-and-proposing-strategies-to-overcome-the-follicle-sanctuary
#11
REVIEW
Yew Ann Leong, Anurag Atnerkar, Di Yu
Human immunodeficiency virus (HIV) infects millions of people worldwide, and new cases continue to emerge. Once infected, the virus cannot be cleared by the immune system and causes acquired immunodeficiency syndrome. Combination antiretroviral therapeutic regimen effectively suppresses viral replication and halts disease progression. The treatment, however, does not eliminate the virus-infected cells, and interruption of treatment inevitably leads to viral rebound. The rebound virus originates from a group of virus-infected cells referred to as the cellular reservoir of HIV...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28617961/interlaboratory-quality-control-of-total-hiv-1-dna-load-measurement-for-multicenter-reservoir-studies
#12
Pierre Gantner, Adeline Mélard, Florence Damond, Constance Delaugerre, Julia Dina, Marie Gueudin, Anne Maillard, Karine Sauné, Audrey Rodallec, Edouard Tuaillon, Jean-Christophe Plantier, Christine Rouzioux, Véronique Avettand-Fenoel
BACKGROUND: Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. METHODS: Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in 4 samples (QCMD). RESULTS: Good reproducibility was found between laboratories (standard deviation ≤ 0...
June 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28608973/high-hepatitis-c-cure-rates-among-black-and-non-black-hiv-infected-adults-in-an-urban-center
#13
Oluwaseun Falade-Nwulia, Catherine Sutcliffe, Juhi Moon, Geetanjali Chander, Tanyaporn Wansom, Jeanne Keruly, Jennifer Katzianer, Amy Nathanson, Jillian Marks, Shruti Mehta, David Thomas, Richard Moore, Mark Sulkowski
Background Hepatitis C virus (HCV) cure rates have been similar in patients with and without HIV co-infection; however, in the ION-4 study, black patients treated with ledipasvir/sofosbuvir were significantly less likely to achieve cure (90%) compared to non-black patients (99%). There are limited real world data on the effectiveness of oral direct acting antivirals (DAAs) in predominantly minority HIV/HCV co-infected populations. Methods We analyzed HCV treatment outcomes among 255 HCV co-infected patients initiating DAAs between February 2014 and March 2016 in an urban clinic in Baltimore, Maryland...
June 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28606284/-efficacy-of-clindamycin-primaquine-as-the-salvage-treatment-for-pneumocystis-pneumonia-in-non-hiv-infected-patients
#14
X Wang, G F Wang, Z Jin, J J Huang, X D Mu, W Zhang
Objective: To evaluate the efficacy of clindamycin-primaquine as the salvage treatment for pneumocystis pneumonia (PCP) in non-HIV-infected patients. Methods: Clinical data of non-HIV-infected patients with PCP who were treated with clindamycin-primaquine as the salvage treatment in Peking University First Hospital from Jan 2010 to May 2016 were collected and reviewed in this retrospective study. Clinical outcomes were analyzed to evaluate the efficacy of clindamycin-primaquine as a salvage treatment. Results: A total of 19 non-HIV-infected patients with PCP were included...
June 13, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28603746/preclinical-evaluation-of-a-lentiviral-vector-for-huntingtin-silencing
#15
Karine Cambon, Virginie Zimmer, Sylvain Martineau, Marie-Claude Gaillard, Margot Jarrige, Aurore Bugi, Jana Miniarikova, Maria Rey, Raymonde Hassig, Noelle Dufour, Gwenaelle Auregan, Philippe Hantraye, Anselme L Perrier, Nicole Déglon
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) backbone and removing the original reporter genes...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28599597/simultaneous-knockout-of-i-cxcr4-i-and-i-ccr5-i-genes-in-cd4-t-cells-via-crispr-cas9-confers-resistance-to-both-x4-and-r5-tropic-hiv-1-infection
#16
Songlin Yu, Yongchao Yao, Hongkui Xiao, Jiaojiao Li, Quan Liu, Yijun Yang, Dickson Adah, Junnan Lu, Siting Zhao, Li Qin, Xiaoping Chen
Previous research has proven that disruption of either <i>CCR5</i> or <i>CXCR4</i> gene confers resistance to R5-tropic or X4-tropic HIV-1 infection, respectively. However, the urgent need to ablate both of the coreceptors in individual post-thymic CD4+ T cells for dual protection remains. Here, we have ablated the <i>CCR5</i> and <i>CXCR4</i> genes in human CD4+ cell lines and primary CD4+ T cells, simultaneously, using CRISPR/Cas9, a well-developed, highly efficient genetic engineering tool...
June 9, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28598793/croi-2017-highlights-of-advances-in-viral-hepatitis-and-liver-fibrosis
#17
Anne F Luetkemeyer, David L Wyles
At the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington, hepatitis C virus (HCV) infection was a major focus in the context of HIV-associated liver disease. Well-tolerated direct-acting antiviral (DAA) regimens have enabled effective treatment of the populations that are hardest to cure, including those with decompensated cirrhosis, and many studies examined the impact of HCV cure on hepatitis and extrahepatic outcomes. Scaling up access to DAA, and the impact that their universal availability can have on reducing prevalence were key topics...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28592548/evaluation-of-the-aptima-hiv-1-quant-dx-assay-for-hiv-1-rna-quantitation-in-different-biological-specimen-types
#18
Christina Yek, Marta Massanella, Tashi Peling, Kristen Lednovich, Sangeetha V Nair, Andrew Worlock, Milenka Vargas, Sara Gianella, Ronald J Ellis, Matthew C Strain, Michael P Busch, C Thomas Nugent, Douglas D Richman
Background The search for a cure for HIV infection has highlighted the need for increasingly sensitive and precise assays to measure viral burden in various tissues and body fluids. We describe the application of a standardized assay for HIV-1 RNA in multiple specimen types.Methods The fully automated Aptima HIV-1 Quant Dx assay (Aptima assay) is FDA-cleared for blood plasma HIV-1 RNA quantitation. In this study, the Aptima assay was applied for the quantitation of HIV RNA in peripheral blood mononuclear cells (PBMC; n=72), seminal plasma (n=20), cerebrospinal fluid (CSF; n=36), dried blood spots (DBS; n=104) and dried plasma spots (DPS; n=104)...
June 7, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28592538/identification-of-il-27-il-27ra-as-a-critical-immune-axis-for-in-vivo-hiv-control
#19
M Ruiz-Riol, D Berdnik, A Llano, B Mothe, C Gálvez, S Pérez-Álvarez, B Oriol-Tordera, A Olvera, S Silva-Arrieta, Michael Meulbroek, Ferran Pujol, J Coll, J Martinez-Picado, C Ganoza, J Sanchez, G Gómez, T Wyss-Coray, C Brander
Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray able to measure >600 plasma proteins involved in cell-to-cell communication was used to measure plasma protein profiles in 96 HIV-infected, treatment-naïve individuals with high (>50,000) or low (<10,000 HIV RNA copies/ml) viral loads...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28592534/comprehensive-cross-clade-characterization-of-antibody-mediated-recognition-complement-mediated-lysis-and-cell-mediated-cytotoxicity-of-hiv-1-envelope-specific-antibodies-towards-the-eradication-of-the-hiv-1-reservoir
#20
Shariq Mujib, Jun Liu, A K M Nur-Ur Rahman, Jordan A Schwartz, Phil Bonner, Feng Yun Yue, Mario A Ostrowski
Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. Here, we determined the ability of twelve well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1, belonging to clades A, B, C and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro...
June 7, 2017: Journal of Virology
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