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Hiv cure trial

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https://www.readbyqxmd.com/read/28219694/lenalidomide-maintenance-in-patients-with-relapsed-diffuse-large-b-cell-lymphoma-who-are-not-eligible-for-autologous-stem-cell-transplantation-an-open-label-single-arm-multicentre-phase-2-trial
#1
Andrés J M Ferreri, Marianna Sassone, Francesco Zaja, Alessandro Re, Michele Spina, Alice Di Rocco, Alberto Fabbri, Caterina Stelitano, Maurizio Frezzato, Chiara Rusconi, Renato Zambello, Suzana Couto, Yan Ren, Annalisa Arcari, Giovanni Bertoldero, Alessandro Nonis, Lydia Scarfò, Teresa Calimeri, Caterina Cecchetti, Marianna Chiozzotto, Silvia Govi, Maurilio Ponzoni
BACKGROUND: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) not eligible for autologous stem cell transplantation (ASCT) or having relapse after ASCT have a low likelihood of cure. Single-drug maintenance after salvage therapy might be an attractive strategy to prolong survival in these patients. Lenalidomide is a suitable candidate for long-lasting maintenance as it is an oral drug, active against DLBCL that can be taken for years with an acceptable toxicity profile. We designed a study to investigate safety and efficacy of lenalidomide maintenance in patients with chemosensitive relapse of DLBCL not eligible for ASCT or having relapse after ASCT...
February 16, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28133794/hiv-antibodies-for-treatment-of-hiv-infection
#2
REVIEW
David M Margolis, Richard A Koup, Guido Ferrari
The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28088870/fatal-relapse-of-myelodysplastic-syndrome-in-a-patient-with-hiv-hepatitis-c-coinfection-treated-with-simeprevir-sofosbuvir
#3
Efemena Michael Diejomaoh, Joseph Clayton Gathe, Carl Craig Mayberry, John Benjamin Clemmons, Bernie Miguel, Alan Glombicki, Benjamin Daquioag
Registrational studies and observational cohorts clearly suggest sustained virologic response (SVR) rates in HIV-/hepatitis C-coinfected patients are similar to monoinfected patients when utilizing interferon-free regimens, and this can be accomplished with agents that are well tolerated with minimal adverse events. These randomized trials that led to the approval of several of our new direct-acting antiviral agents, however, specifically excluded patients who had significant comorbidities and none to our knowledge accepted patients with a history of cancer...
January 1, 2017: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/28060545/safety-and-immunogenicity-of-adenovirus-35-tb-vaccine-candidate-in-adults-with-active-or-previous-tb-a-randomized-trial
#4
Richard N van Zyl-Smit, Aliasgar Esmail, Mary E Bateman, Rodney Dawson, Jonathan Goldin, Eva van Rikxoort, Macaya Douoguih, Maria Grazia Pau, Jerald C Sadoff, J Bruce McClain, Margaret Ann Snowden, Jacqueline Benko, David A Hokey, Kathryn Tucker Rutkowski, Andrew Graves, Barbara Shepherd, Sadritdin Ishmukhamedov, Benjamin M N Kagina, Brian Abel, Willem A Hanekom, Thomas J Scriba, Eric D Bateman
RATIONALE: Administration of tuberculosis vaccines in participants with previous or current pulmonary tuberculosis may have the potential for causing harmful post-vaccination immunological (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored tuberculosis candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary tuberculosis...
January 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28060012/post-treatment-control-or-treated-controllers-viral-remission-in-treated-and-untreated-primary-hiv-infection
#5
Genevieve E Martin, Morgane Gossez, James P Williams, Wolfgang Stöhr, Jodi Meyerowitz, Ellen M Leitman, Philip Goulder, Kholoud Porter, Sarah Fidler, John Frater
OBJECTIVE(S): An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterization of both natural viral control and the effect of ART on viral control after treatment interruption. DESIGN: Analysis of transient viral control in recent seroconverters in the Short Pulse AntiRetroviral Therapy at Acute Seroconversion trial. METHODS: We compared untreated and treated HIV seroconverters (n = 292) and identified periods of control (plasma HIV RNA < 400 copies/ml for ≥16 weeks off therapy) in 7...
February 20, 2017: AIDS
https://www.readbyqxmd.com/read/28056752/inhibiting-the-secretion-of-hepatitis-b-surface-antigen-hbsag-to-treat-hepatitis-b-infection-a-review
#6
Simon D Baugh
Chronic Hepatitis B is a major global health issue, and has no known cure. Currently there are over 240 million people infected with the disease, and it leads to the death of over 686,000 people each year. A total of seven treatments which help to control the disease are currently available: interferon-based treatments (pegasys, and interferon alpha), and nucleoside and nucleotide analogs (Viread, Baraclude, Tyzeka, Hepsera, Epivir-HBV), but all require continuing treatment to maintain control of the disease...
January 4, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28039275/qualitative-and-quantitative-hiv-antibodies-and-viral-reservoir-size-characterization-in-vertically-infected-children-with-virological-suppression
#7
Josephine Brice, Mariam Sylla, Sophie Sayon, Fatoumata Telly, Djeneba Bocar-Fofana, Robert Murphy, Sidonie Lambert-Niclot, Eve Todesco, Maxime Grude, Francis Barin, Souleymane Diallo, Deenan Pillay, Anne Derache, Vincent Calvez, Anne-Geneviève Marcelin, Almoustapha Issiaka Maiga
BACKGROUND: Absence of detectable viraemia after treatment cessation in some vertically HIV-infected (VHIV) children suggests that early initiation of HAART could lead to functional cure. OBJECTIVES: We described the factors associated with HIV antibody levels and the viral reservoir size in HAART-treated VHIV children. METHODS: Study included 97 VHIV children with virological suppression, in Bamako, Mali. The anti-gp41 antibody activities and HIV serostatus were assessed...
December 30, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27941595/achieving-hiv-1-control-through-rna-directed-gene-regulation
#8
REVIEW
Vera Klemm, Jye Mitchell, Christina Cortez-Jugo, Francesca Cavalieri, Geoff Symonds, Frank Caruso, Anthony Dominic Kelleher, Chantelle Ahlenstiel
HIV-1 infection has been transformed by combined anti-retroviral therapy (ART), changing a universally fatal infection into a controllable infection. However, major obstacles for an HIV-1 cure exist. The HIV latent reservoir, which exists in resting CD4+ T cells, is not impacted by ART, and can reactivate when ART is interrupted or ceased. Additionally, multi-drug resistance can arise. One alternate approach to conventional HIV-1 drug treatment that is being explored involves gene therapies utilizing RNA-directed gene regulation...
December 7, 2016: Genes
https://www.readbyqxmd.com/read/27905840/combining-cell-and-gene-therapy-in-an-effort-to-eradicate-hiv
#9
Thor A Wagner
More than 30 million people are infected with HIV, and HIV remains the fifth leading cause of disability-adjusted life years worldwide. Antiretroviral therapy (ART) dramatically decreases mortality rate, but there are side effects, long-term toxicities, expenses, stigmas, and inconveniences associated with chronic treatment, and HIV-infected individuals on ART have an increased risk of malignancies, cardiovascular disease, neurologic disease, and shortened life expectancy. Therefore, a cure for HIV remains an important goal...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27898045/dendritic-cell-based-immunotherapies-to-fight-hiv-how-far-from-a-success-story-a-systematic-review-and-meta-analysis
#10
REVIEW
Antonio Victor Campos Coelho, Ronald Rodrigues de Moura, Anselmo Jiro Kamada, Ronaldo Celerino da Silva, Rafael Lima Guimarães, Lucas André Cavalcanti Brandão, Luiz Cláudio Arraes de Alencar, Sergio Crovella
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27881659/glycosylphosphatidylinositol-anchored-anti-hiv-scfv-efficiently-protects-cd4-t-cells-from-hiv-1-infection-and-deletion-in-hu-pbl-mice
#11
Chaobaihui Ye, Weiming Wang, Liang Cheng, Guangming Li, Michael Wen, Qi Wang, Qing Zhang, Dan Li, Paul Zhou, Lishan Su
: Despite success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of the HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from a homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance in permissive cells...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27869733/antiviral-therapy-by-hiv-1-broadly-neutralizing-and-inhibitory-antibodies
#12
REVIEW
Zhiqing Zhang, Shaowei Li, Ying Gu, Ningshao Xia
Human immunodeficiency virus type 1 (HIV-1) infection causes acquired immune deficiency syndrome (AIDS), a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART) but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1...
November 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27854119/clinical-applications-of-genome-editing-to-hiv-cure
#13
Cathy X Wang, Paula M Cannon
Despite significant advances in HIV drug treatment regimens, which grant near-normal life expectancies to infected individuals who have good virological control, HIV infection itself remains incurable. In recent years, novel gene- and cell-based therapies have gained increasing attention due to their potential to provide a functional or even sterilizing cure for HIV infection with a one-shot treatment. A functional cure would keep the infection in check and prevent progression to AIDS, while a sterilizing cure would eradicate all HIV viruses from the patient...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27801499/six-month-therapy-for-abdominal-tuberculosis
#14
REVIEW
Sophie Jullien, Siddharth Jain, Hannah Ryan, Vineet Ahuja
BACKGROUND: Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six-month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six-month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers...
1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27757411/ongoing-clinical-trials-of-human-immunodeficiency-virus-latency-reversing-and-immunomodulatory-agents
#15
REVIEW
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
https://www.readbyqxmd.com/read/27749600/talen-mediated-knockout-of-ccr5-confers-protection-against-infection-of-human-immunodeficiency-virus
#16
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
https://www.readbyqxmd.com/read/27716104/does-directly-observed-therapy-improve-tuberculosis-treatment-more-evidence-is-needed-to-guide-tuberculosis-policy
#17
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
https://www.readbyqxmd.com/read/27677161/topical-gentian-violet-compared-with-nystatin-oral-suspension-for-the-treatment-of-oropharyngeal-candidiasis-in-hiv-1-infected-participants
#18
Pranab K Mukherjee, Huichao Chen, Lauren L Patton, Scott Evans, Anthony Lee, Johnstone Kumwenda, James Hakim, Gaerolwe Masheto, Frederick Sawe, Mai T Pho, Kenneth A Freedberg, Caroline H Shiboski, Mahmoud A Ghannoum, Robert A Salata
OBJECTIVE: Compare the safety and efficacy of topical gentian violet with that of nystatin oral suspension (NYS) for the treatment of oropharyngeal candidiasis in HIV-1-infected adults in resource-limited settings. DESIGN: Multicenter, open-label, evaluator-blinded, randomized clinical trial at eight international sites, within the AIDS Clinical Trials Group. STUDY PARTICIPANTS AND INTERVENTION: Adult HIV-infected participants with oropharyngeal candidiasis, stratified by CD4 cell counts and antiretroviral therapy status at study entry, were randomized to receive either gentian violet (0...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27658863/combined-effect-of-vacc-4x-recombinant-human-granulocyte-macrophage-colony-stimulating-factor-vaccination-and-romidepsin-on-the-hiv-1-reservoir-reduc-a-single-arm-phase-1b-2a-trial
#19
Steffen Leth, Mariane H Schleimann, Sara K Nissen, Jesper F Højen, Rikke Olesen, Mette E Graversen, Sofie Jørgensen, Anne Sofie Kjær, Paul W Denton, Alejandra Mørk, Maja A Sommerfelt, Kim Krogsgaard, Lars Østergaard, Thomas A Rasmussen, Martin Tolstrup, Ole Schmeltz Søgaard
BACKGROUND: Immune priming before reversal of latency might be a component of a functional HIV cure. To assess this concept, we assessed if therapeutic HIV immunisation followed by latency reversal would affect measures of viral transcription, plasma viraemia, and reservoir size in patients with HIV on suppressive antiretroviral therapy. METHODS: In this single-arm, phase 1B/2A trial, we recruited adults treated at the Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark (aged ≥18 years) with successfully treated HIV-1 with plasma RNA loads of less than 50 copies per mL for the previous year and CD4 counts of at least 500 cells per μL...
October 2016: Lancet HIV
https://www.readbyqxmd.com/read/27617268/broad-hiv-1-inhibition-in-vitro-by-vaccine-elicited-cd8-t-cells-in-african-adults
#20
Gaudensia Mutua, Bashir Farah, Robert Langat, Jackton Indangasi, Simon Ogola, Brian Onsembe, Jakub T Kopycinski, Peter Hayes, Nicola J Borthwick, Ambreen Ashraf, Len Dally, Burc Barin, Annika Tillander, Jill Gilmour, Jan De Bont, Alison Crook, Drew Hannaman, Josephine H Cox, Omu Anzala, Patricia E Fast, Marie Reilly, Kundai Chinyenze, Walter Jaoko, Tomáš Hanke, The Hiv-Core 004 Study Group
We are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not only epitopes) of the HIV-1 proteome, which are common to most global variants and which, if mutated, cause a replicative fitness loss. Our first clinical trial in low risk HIV-1-negative adults in Oxford demonstrated the principle that naturally mostly subdominant epitopes, when taken out of the context of full-length proteins/virus and delivered by potent regimens involving combinations of simian adenovirus and poxvirus modified vaccinia virus Ankara, can induce robust CD8(+) T cells of broad specificities and functions capable of inhibiting in vitro HIV-1 replication...
2016: Molecular Therapy. Methods & Clinical Development
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