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https://www.readbyqxmd.com/read/28729655/a-crispr-cas9-guidance-rna-screen-platform-for-hiv-provirus-disruption-and-hiv-aids-gene-therapy-in-astrocytes
#1
Zaohua Huang, Madahavan Nair
HIV/AIDS remains a major health threat despite significant advances in the prevention and treatment of HIV infection. The major reason is the inability of existing treatments to eradicate the multiple HIV reservoirs in the human body, including astrocytes in the human brain. CRISPR/Cas9 system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV provirus in HIV reservoir cells, which may lead to a complete cure of HIV/AIDS. The key components of CRISPR/Cas9 are guide RNAs (gRNAs) which determine specific sequence targeting of DNAs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719012/the-impact-of-immunoglobulin-in-acute-hiv-infection-on-the-hiv-reservoir-a-randomized-controlled-trial
#2
J Tiraboschi, S Ray, K Patel, A Teague, M Pace, P Phalora, N Robinson, E Hopkins, J Meyerowitz, Y Wang, J Cason, S Kaye, J Sanderson, P Klenerman, S Fidler, J Frater, J Fox
OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19)...
July 18, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28717763/burkitt-s-lymphoma-and-b-cell-lymphoma-unclassifiable-with-features-intermediate-between-diffuse-large-b-cell-lymphoma-and-burkitt-s-lymphoma-in-patients-with-hiv-outcomes-in-a-south-african-public-hospital
#3
Gerhard Sissolak, Matthew Seftel, Thomas S Uldrick, Tonya M Esterhuizen, Nooroudien Mohamed, Danie Kotze
PURPOSE: Burkitt's lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. METHODS: We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28698211/extra-rectal-lymphogranuloma-venereum-in-france-a-clinical-and-molecular-study
#4
Arnaud Desclaux, Arabella Touati, Didier Neau, Cécile Laurier-Nadalié, Cécile Bébéar, Bertille de Barbeyrac, Charles Cazanave
OBJECTIVES: To describe a series of extrarectal lymphogranuloma venereum (LGV) cases diagnosed in France. METHODS: Consecutive LGV cases confirmed at the French Reference Centre for chlamydiae with an extrarectal sample from January 2010 to December 2015 were included. The first part of the study consisted of a retrospective case note review and analysis. In a second part, the complete ompA gene sequence of our samples was determined. RESULTS: There were 56 cases overall: 50 cases of genital LGV and six cases of pharyngeal LGV...
July 11, 2017: Sexually Transmitted Infections
https://www.readbyqxmd.com/read/28693508/unsuccessful-tb-treatment-outcomes-with-a-focus-on-hiv-co-infected-cases-a-cross-sectional-retrospective-record-review-in-a-high-burdened-province-of-south-africa
#5
M C Engelbrecht, N G Kigozi, P Chikobvu, S Botha, H C J van Rensburg
BACKGROUND: South Africa did not meet the MDG targets to reduce TB prevalence and mortality by 50% by 2015, and the TB cure rate remains below the WHO target of 85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co-infected patients are more likely to have unsuccessful TB treatment outcomes. This paper analyses the demographic and clinical characteristics of new TB patients with unsuccessful treatment outcomes, as well as factors associated with unsuccessful treatment outcomes for HIV co-infected patients...
July 10, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28692539/hiv-hepatitis-b-virus-co-infection-epidemiology-pathogenesis-and-treatment
#6
Kasha P Singh, Megan Crane, Jennifer Audsley, Sharon R Lewin
: HIV infection has a significant impact on the natural history of chronic hepatitis B virus (HBV) infection, with increased levels of HBV DNA, accelerated progression of liver disease, and increased liver-associated mortality compared with HBV monoinfection. Widespread uptake and early initiation of HBV-active antiretroviral therapy has substantially improved the natural history of HIV-HBV coinfection but the prevalence of liver disease remains elevated in this population. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease and seroconversion in HIV-HBV coinfection in the era of HBV-active antiretroviral therapy and the effects of HIV directly on liver disease...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28692305/fight-fire-with-fire-gene-therapy-strategies-to-cure-hiv
#7
Jon Huyghe, Sips Magdalena, Linos Vandekerckhove
Human Immunodeficiency Virus (HIV) to date remains one of the most notorious viruses mankind has ever faced. Despite enormous investments in HIV research for more than 30 years an effective cure for HIV has been elusive. Areas covered: Combination antiretroviral therapy (cART) suppresses active viral replication, but is not able to eliminate the virus completely due to stable integration of HIV inside the host genome of infected cells and the establishment of a latent reservoir, that is insensitive to cART...
July 14, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28692209/the-science-of-durban-aids-2016
#8
Chris Beyrer, Olive Shisana, Stefan D Baral, Koleka Milsana, Kenneth H Mayer, Anton Pozniak, Bruce D Walker, Souleman Mboup, Annette H Sohn, David Serwadda, Helen Rees, Sergii Dvoriak, Mitchell Warren, Safiatou Thiam, Wafaa M El-Sadr, Xavier Hospital, Owen Ryan, Nicolas Thomson, Linda-Gail Bekker
INTRODUCTION: The science presented at the 21st International AIDS Conference in Durban, South Africa, in July 2016, addressed the state of the field across basic, clinical, prevention, law and policy and implementation science. METHODS AND RESULTS: The AIDS response has seen remarkable achievements in scientific advances, in translation of those advances into prevention, treatment and care for affected individuals and communities, and in large scale implementation - reaching 18 million people with antiviral therapy by mid-year 2016...
June 30, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28692018/the-state-of-gene-therapy-research-in-africa-its-significance-and-implications-for-the-future
#9
REVIEW
P Arbuthnot, M B Maepa, A Ely, M S Pepper
Gene therapy has made impressive recent progress and has potential for treating a wide range of diseases, many of which are important to Africa. However, as a result of lack of direct public funding and skilled personnel, direct research on gene therapy in Africa is currently limited and resources to support the endeavor are modest. A strength of the technology is that it is based on principles of rational design, and the tools of gene therapy are now highly versatile. For example gene silencing and gene editing may be used to disable viral genes for therapeutic purposes...
July 10, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28691499/eradication-of-hiv-from-tissue-reservoirs-challenges-for-the-cure
#10
Rebecca R Rose, David J Nolan, Ekaterina Maidji, Cheryl Stoddart, Elyse J Singer, Susanna Lamers, Michael McGrath
The persistence of Human Immunodeficiency Virus (HIV) infection, even after lengthy and successful combined anti-retroviral therapy (cART), has precluded an effective cure. The anatomical locations in which and biological mechanisms through which the viral population is maintained remain unknown. Much research has focused nearly exclusively on circulating resting T-cells as the predominant source of persistent HIV, a strategy with limited success in developing an effective cure strategy. Here, we review research supporting the importance of tissues and other immune cells for HIV maintenance and expansion, including the central nervous system, lymph nodes, and macrophages...
July 9, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28691034/the-effects-of-time-lag-and-cure-rate-on-the-global-dynamics-of-hiv-1-model
#11
Nigar Ali, Gul Zaman, Abdullah, Aisha M Alqahtani, Ali Saleh Alshomrani
In this research article, a new mathematical model of delayed differential equations is developed which discusses the interaction among CD4 T cells, human immunodeficiency virus (HIV), and recombinant virus with cure rate. The model has two distributed intracellular delays. These delays denote the time needed for the infection of a cell. The dynamics of the model are completely described by the basic reproduction numbers represented by R0, R1, and R2. It is shown that if R0 < 1, then the infection-free equilibrium is locally as well as globally stable...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28689442/drug-interactions-in-hiv-infected-patients-treated-for-hepatitis-c
#12
Vicente Soriano, Pablo Labarga, José V Fernandez-Montero, Carmen de Mendoza, Laura Benítez-Gutiérrez, José M Peña, Pablo Barreiro
The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations. Areas covered: Clinically significant DDI may be classified as major (when co-administration should be contraindicated) or minor (when they require close monitoring, changes in drug dosage or in timing)...
July 13, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28687550/sofosbuvir-velpatasvir-a-single-tablet-treatment-for-hepatitis-c-infection-of-all-genotypes
#13
REVIEW
Misty M Miller
PURPOSE: The pharmacology, pharmacokinetics, interaction potential, efficacy, and safety of the newest direct-acting antiviral (DAA) medication for the treatment of chronic hepatitis C are reviewed. SUMMARY: Nonstructural proteins 5A (NS5A) and 5B (NS5B) are key drivers of hepatitis C virus (HCV) replication. Velpatasvir, an inhibitor of NS5A, was coformulated with the NS5B inhibitor sofosbuvir to provide a single-tablet combination DAA (Epclusa, Gilead Sciences)...
July 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28687465/on-the-way-to-find-a-cure-purging-latent-hiv-1-reservoirs
#14
REVIEW
Christian Schwartz, Sophie Bouchat, Céline Marban, Virginie Gautier, Carine Van Lint, Olivier Rohr, Valentin Le Douce
Introduction of cART in 1996 has drastically increased the life expectancy of people living with HIV-1. However, this treatment has not allowed cure as cessation of cART is associated with a rapid viral rebound. The main barrier to the eradication of the virus is related to the persistence of latent HIV reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might lead to a cure or a remission. The most studied strategy is the so called "shock and kill" therapy. This strategy is based on reactivation of dormant viruses from the latently-infected reservoirs (the shock) followed by the eradication of the reservoirs (the kill)...
July 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28683982/research-priorities-to-achieve-universal-access-to-hepatitis-c-prevention-management-and-direct-acting-antiviral-treatment-among-people-who-inject-drugs
#15
Jason Grebely, Julie Bruneau, Jeffrey V Lazarus, Olav Dalgard, Philip Bruggmann, Carla Treloar, Matthew Hickman, Margaret Hellard, Teri Roberts, Levinia Crooks, Håvard Midgard, Sarah Larney, Louisa Degenhardt, Hannu Alho, Jude Byrne, John F Dillon, Jordan J Feld, Graham Foster, David Goldberg, Andrew R Lloyd, Jens Reimer, Geert Robaeys, Marta Torrens, Nat Wright, Icro Maremmani, Brianna L Norton, Alain H Litwin, Gregory J Dore
Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%...
July 3, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28680903/setting-performance-standards-for-a-cost-effective-human-immunodeficiency-virus-cure-strategy-in-south-africa
#16
A David Paltiel, Amy Zheng, Milton C Weinstein, Melanie R Gaynes, Robin Wood, Kenneth A Freedberg, Paul E Sax, Rochelle P Walensky
BACKGROUND: Reports of a single case of human immunodeficiency virus (HIV) eradication suggest that elimination of HIV from individuals is possible. Anticipating both increased research funding and the development of effective, durable cure technologies, we describe the circumstances under which a cure might improve survival and be cost-effective in South Africa. METHODS: We adapted a simulation model comparing a hypothetical cure strategy ("Cure") to the standard of care, lifetime antiretroviral therapy ("LifetimeART") among adherent South Africans (58% female; mean age 33...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28677507/the-hiv-1-tat-protein-mechanism-of-action-and-target-for-hiv-1-cure-strategies
#17
Andrew P Rice
The general mechanism involved in Tat activation of RNA Polymerase II (RNAP II) elongation of the integrated HIV-1 was elucidated over 20 years ago. This mechanism involves Tat binding to the TAR RNA element that forms at the 5' end of viral transcripts and recruiting a general RNAP II elongation factor termed as P-TEFb. This elongation factor consists of CDK9 and Cyclin T1, and when recruited by Tat to TAR RNA, CDK9 was proposed to phosphorylate the carboxyl terminal domain of RNAP II and thereby activate elongation...
July 4, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28673572/elimination-of-cancer-stem-cells-and-reactivation-of-latent-hiv-1-via-ampk-activation-common-mechanism-of-action-linking-inhibition-of-tumorigenesis-and-the-potential-eradication-of-hiv-1
#18
Jahahreeh Finley
Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28666874/anti-dengue-virus-activity-of-scytovirin-and-evaluation-of-point-mutation-effects-by-molecular-dynamics-and-binding-free-energy-calculations
#19
Andrei Santos Siqueira, Alex Ranieri Jerônimo Lima, Rafael Conceição de Souza, Alberdan Silva Santos, João Lídio da Silva Gonçalves Vianez Júnior, Evonnildo Costa Gonçalves
The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations...
June 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28662034/efficacy-and-safety-of-available-treatments-for-visceral-leishmaniasis-in-brazil-a-multicenter-randomized-open-label-trial
#20
Gustavo Adolfo Sierra Romero, Dorcas Lamounier Costa, Carlos Henrique Nery Costa, Roque Pacheco de Almeida, Enaldo Viera de Melo, Sílvio Fernando Guimarães de Carvalho, Ana Rabello, Andréa Lucchesi de Carvalho, Anastácio de Queiroz Sousa, Robério Dias Leite, Simone Soares Lima, Thais Alves Amaral, Fabiana Piovesan Alves, Joelle Rode
BACKGROUND: There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. METHODS: A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days)...
June 2017: PLoS Neglected Tropical Diseases
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