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https://www.readbyqxmd.com/read/27905840/combining-cell-and-gene-therapy-in-an-effort-to-eradicate-hiv
#1
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
#2
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/glycosyl-phosphatidylinositol-gpi-anchored-anti-hiv-scfv-efficiently-protect-cd4-t-cells-from-hiv-1-infection-and-deletion-in-hu-pbl-mice
#3
Chaobaihui Ye, Weiming Wang, Liang Cheng, Guangming Li, Michael Wen, Qi Wang, Qing Zhang, Dan Li, Paul Zhou, Lishan Su
: Despite the 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 HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from 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 of permissive cells...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27869733/antiviral-therapy-by-hiv-1-broadly-neutralizing-and-inhibitory-antibodies
#4
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
#5
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
#6
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...
November 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27607592/cancer-therapies-in-hiv-cure-research
#13
Thomas A Rasmussen, Jenny L Anderson, Fiona Wightman, Sharon R Lewin
PURPOSE OF REVIEW: This article provides an overview of anticancer therapies in various stages of clinical development as potential interventions to target HIV persistence. RECENT FINDINGS: Epigenetic drugs developed for cancer have been investigated in vitro, ex vivo and in clinical trials as interventions aimed at reversing HIV latency and depleting the amount of virus that persists on antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV expression in patients on antiretroviral therapy but did not reduce the frequency of infected cells...
January 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/27590492/contractualist-reasoning-hiv-cure-clinical-trials-and-the-moral-ir-relevance-of-the-risk-benefit-ratio
#14
Rahul Kumar
Institutional review boards (IRB) normally require of a morally defensible clinical trial that any trial participant will benefit from the inquiry, or at least not be exposed to a significant risk of having their prospects worsened by participating. Stage 1 HIV cure trials tend not to meet this requirement. Does that show them to be morally indefensible? Utilitarian thinking about this question supports a negative answer. But one might reasonably expect a Kantian moral theory to support the conclusion that exposing trial participants to a significant risk of their prospects being worsened by their participation to be morally indefensible, on grounds that this would be a clear case of using a person as a mere means...
September 2, 2016: Journal of Medical Ethics
https://www.readbyqxmd.com/read/27581996/six-months-therapy-for-tuberculous-meningitis
#15
Sophie Jullien, Hannah Ryan, Manish Modi, Rohit Bhatia
BACKGROUND: Tuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Most international guidelines recommend longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis disease to prevent relapse. However, longer regimens are associated with poor adherence, which could contribute to increased relapse, development of drug resistance, and increased costs to patients and healthcare systems...
September 1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27559075/total-hiv-1-dna-a-marker-of-viral-reservoir-dynamics-with-clinical-implications
#16
REVIEW
Véronique Avettand-Fènoël, Laurent Hocqueloux, Jade Ghosn, Antoine Cheret, Pierre Frange, Adeline Melard, Jean-Paul Viard, Christine Rouzioux
HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count...
October 2016: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/27458074/inequality-and-ethics-in-paediatric-hiv-remission-research-from-mississippi-to-south-africa-and-back
#17
Johanna T Crane, Theresa M Rossouw
In 2013, physician-researchers announced that a baby in Mississippi had been 'functionally cured' of HIV [Persaud, D., Gay, H., Ziemniak, C. F., Chen, Y. H., Piatak, M., Chun, T.-W., … Luzuriaga, K. (2013b, March). Functional HIV cure after very early ART of an infected infant. Paper presented at the 20th conference on retroviruses and opportunistic infections, Atlanta, GA]. Though the child later developed a detectable viral load, the case remains unprecedented, and trials to build on the findings are planned [National Institute of Allergy and Infectious Diseases...
July 25, 2016: Global Public Health
https://www.readbyqxmd.com/read/27450662/development-of-a-prospective-cohort-of-hiv-exposed-sero-negative-hesn-individuals-in-jos-nigeria
#18
Sophia Osawe, Evaezi Okpokoro, Ruth Datiri, Grace Choji, Felicia Okolo, Pam Datong, Alash'le Abimiku
BACKGROUND: HIV/AIDS continues to be a global health problem. With currently no cure, it is critical to get an effective vaccine to add to the arsenal of prevention and treatment tools. HIV Exposed Sero-Negative (HESN) individuals were enrolled and followed for 2 years. METHODS: A prospective observational cohort study to enroll HESN volunteers and their partners was developed with a 2-year follow up. This was a vaccine preparedness study and designed as a Phase IIb trial...
2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27439433/improving-treatment-and-liver-fibrosis-outcomes-with-metformin-in-hcv-hiv-co-infected-and-hcv-mono-infected-patients-with-insulin-resistance-study-protocol-for-a-randomized-controlled-trial
#19
Mary-Anne Doyle, Joel Singer, Terry Lee, Miriam Muir, Curtis Cooper
BACKGROUND: Approximately 180 million people worldwide, (3 % of the world's population) are infected with hepatitis C (HCV). Insulin resistance (IR) and type 2 diabetes (T2DM) are common extrahepatic manifestations of chronic HCV infection and associated with poor treatment and liver-related outcomes. The presence of these metabolic complications have been associated with poor response to interferon-based HCV antiviral therapy and increased risk of liver-related outcomes. Metformin, an insulin sensitizer is known to improve HCV treatment response and has been associated with a reduced risk of developing hepatocellular carcinoma (HCC)...
July 20, 2016: Trials
https://www.readbyqxmd.com/read/27418860/role-of-ledipasvir-sofosbuvir-combination-for-genotype-1-hepatitis-c-virus-infection
#20
REVIEW
Vinay Sundaram, Kris V Kowdley
Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Among the six HCV genotypes, genotype 1 was significantly more aggressive when utilizing the combination of pegylated interferon and ribavirin, as genotype 1-infected patients had the lowest likelihood of achieving cure (40%-50%) and required twice as long duration of treatment, as compared to genotypes 2 and 3. Recently, however, significant advances have been made with the advent of all-oral direct-acting antiviral agents, which have significantly improved the safety, efficacy, and tolerability of the treatment of HCV genotype 1...
2016: Hepatic Medicine: Evidence and Research
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