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Hiv cure trial

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https://www.readbyqxmd.com/read/29324227/getting-the-kill-into-shock-and-kill-strategies-to-eliminate-latent-hiv
#1
REVIEW
Youry Kim, Jenny L Anderson, Sharon R Lewin
Despite the success of antiretroviral therapy (ART), there is currently no HIV cure and treatment is life long. HIV persists during ART due to long-lived and proliferating latently infected CD4+ T cells. One strategy to eliminate latency is to activate virus production using latency reversing agents (LRAs) with the goal of triggering cell death through virus-induced cytolysis or immune-mediated clearance. However, multiple studies have demonstrated that activation of viral transcription alone is insufficient to induce cell death and some LRAs may counteract cell death by promoting cell survival...
January 10, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29305405/real-world-treatment-of-hepatitis-c-with-second-generation-direct-acting-antivirals-initial-results-from-a-multicentre-canadian-retrospective-cohort-of-diverse-patients
#2
Alex I Aspinall, Abdel A Shaheen, Golasa S Kochaksaraei, Breean Haslam, Samuel S Lee, Gisela Macphail, Jeff Kapler, Oscar E Larios, Kelly W Burak, Mark G Swain, Meredith A Borman, Carla S Coffin
BACKGROUND: High hepatitis C cure rates have been observed in registration trials with second-generation direct-acting antivirals. Real-world data also indicate high sustained viral response (SVR) rates. Our objective was to determine real-world SVR rates for patients infected with hepatitis C virus (HCV) who were treated with second-generation direct-acting antivirals in the first 18 months of their availability in Canada. METHODS: Four centres in Calgary contributed their treatment data for a diverse patient population including those who had or had not undergone liver transplantation, those coinfected with HIV and vulnerable populations...
January 5, 2018: CMAJ Open
https://www.readbyqxmd.com/read/29280961/rna-interference-therapies-for-an-hiv-1-functional-cure
#3
REVIEW
Robert J Scarborough, Anne Gatignol
HIV-1 drug therapies can prevent disease progression but cannot eliminate HIV-1 viruses from an infected individual. While there is hope that elimination of HIV-1 can be achieved, several approaches to reach a functional cure (control of HIV-1 replication in the absence of drug therapy) are also under investigation. One of these approaches is the transplant of HIV-1 resistant cells expressing anti-HIV-1 RNAs, proteins or peptides. Small RNAs that use RNA interference pathways to target HIV-1 replication have emerged as competitive candidates for cell transplant therapy and have been included in all gene combinations that have so far entered clinical trials...
December 27, 2017: Viruses
https://www.readbyqxmd.com/read/29243498/-cart-intensification-by-the-hiv-1-tat-b-clade-vaccine-progress-to-phase-iii-efficacy-studies
#4
Aurelio Cafaro, Cecilia Sgadari, Orietta Picconi, Antonella Tripiciano, Sonia Moretti, Vittorio Francavilla, Maria Rosaria Pavone Cossut, Stefano Buttò, Giovanni Cozzone, Fabrizio Ensoli, Paolo Monini, Barbara Ensoli
In spite of its success at suppressing HIV replication, combination antiretroviral therapy (cART) only partially reduces immune dysregulation and loss of immune functions. These cART-unmet needs appear to be due to persistent virus replication and cell-to-cell transmission in reservoirs, and are causes of increased patients' morbidity and mortality. Up to now, therapeutic interventions aimed at cART-intensification by attacking the virus reservoir have failed. Areas covered: We briefly review the rationale and clinical development of Tat therapeutic vaccine in cART-treated subjects in Italy and South Africa (SA)...
December 15, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29237332/traditional-complementary-and-alternative-medical-cures-for-hiv-rationale-and-implications-for-hiv-cure-research
#5
Xin Pan, Alice Zhang, Gail E Henderson, Stuart Rennie, Chuncheng Liu, Weiping Cai, Feng Wu, Joseph D Tucker
Traditional, complementary, and alternative medicine (TCAM) has been used by some people living with HIV (PLHIV) in an attempt to cure HIV. This article reviews the main factors influencing their decision to choose TCAM to cure HIV and discusses implications for HIV cure research. Those who decide to pursue traditional, complementary, and alternative medical cures may be influenced by the health system, cultural, and social dynamics, and their own individual beliefs and preferences. These same factors may impact participation in HIV cure research...
December 13, 2017: Global Public Health
https://www.readbyqxmd.com/read/29226307/macrolides-for-treatment-of-haemophilus-ducreyi-infection-in-sexually-active-adults
#6
REVIEW
Laura Romero, Cesar Huerfano, Carlos F Grillo-Ardila
BACKGROUND: Chancroid is a genital ulcerative disease caused by Haemophilus ducreyi. This microorganism is endemic in Africa, where it can cause up to 10% of genital ulcers. Macrolides may be an effective alternative to treat chancroid and, based on their oral administration and duration of therapy, could be considered as first line therapy. OBJECTIVES: To assess the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults...
December 11, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29192216/bet-inhibitors-rvx-208-and-pfi-1-reactivate-hiv-1-from-latency
#7
Panpan Lu, Yinzhong Shen, He Yang, Yanan Wang, Zhengtao Jiang, Xinyi Yang, Yangcheng Zhong, Hanyu Pan, Jianqing Xu, Hongzhou Lu, Huanzhang Zhu
Persistent latent reservoir in resting CD4+ T cells is a major obstacle in curing HIV-1 infection. Effective strategies for eradication of the HIV-1 reservoir are urgently needed. We report here for the first time that two BET inhibitors, RVX-208, which has entered phase II clinical trials for diverse cardiovascular disorders, and PFI-1, which has been widely studied in oncology, can reactivate HIV-1 from latency. RVX-208 and PFI-1 treatment alone or in combination with other latency reversing agents efficiently reactivated HIV-1 transcription through an up-regulation of P-TEFb by increasing CDK9 Thr-186 phosphorylation in latently infected Jurkat T cells in vitro...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29164341/mathematical-models-of-hiv-latency
#8
Alison L Hill
Viral latency is a major barrier to curing HIV infection with antiretroviral therapy, and consequently, for eliminating the disease globally. The establishment, maintenance, and potential clearance of latent infection are complex dynamic processes and can be best understood and described with the help of mathematical models. Here we review the use of viral dynamics models for HIV, with a focus on applications to the latent reservoir. Such models have been used to explain the multiphasic decay of viral load during antiretroviral therapy, the early seeding of the latent reservoir during acute infection and the limited inflow during treatment, the dynamics of viral blips, and the phenomenon of posttreatment control...
November 22, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29142136/size-composition-and-evolution-of-hiv-dna-populations-during-early-antiretroviral-therapy-and-intensification-with-maraviroc
#9
Antoine Chaillon, Sara Gianella, Steven M Lada, Josué Perez-Santiago, Parris Jordan, Caroline Ignacio, Maile Karris, Douglas Richman, Sanjay R Mehta, Susan J Little, Joel O Wertheim, Davey M Smith
Residual viremia is common during antiretroviral therapy (ART), and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART Intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial, and followed for a median of 107 weeks. Participants started ART with (n=9) or without (n=9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29127137/ethics-of-treatment-interruption-trials-in-hiv-cure-research-addressing-the-conundrum-of-risk-benefit-assessment
#10
Gail E Henderson, Holly L Peay, Eugene Kroon, Rosemary Jean Cadigan, Karen Meagher, Thidarat Jupimai, Adam Gilbertson, Jill Fisher, Nuchanart Q Ormsby, Nitiya Chomchey, Nittaya Phanuphak, Jintanat Ananworanich, Stuart Rennie
Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption (ATI), involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally...
November 10, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/29095883/patterns-of-patient-and-healthcare-provider-viewpoints-regarding-participation-in-hiv-cure-related-clinical-trials-findings-from-a-multicentre-french-survey-using-q-methodology-anrs-apsec
#11
Christel Protière, Bruno Spire, Marion Mora, Isabelle Poizot-Martin, Marie Préau, Marjolaine Doumergue, Philippe Morlat, David Zucman, Cécile Goujard, François Raffi, Olivier Lambotte, Marie Suzan-Monti
CONTEXT: Despite huge advances in the fight against HIV concerning diagnosis, clinical efficacy of antiretroviral treatments (ART), patient survival and quality of life, there is still no cure. Recent developments in HIV cure research have opened the way for clinical trials which could lead to a temporary or definitive end to ART. However, ethical questions exist about related trial-participation risks. The main goal of the ANRS-APSEC survey was, using Q-methodology, to investigate the viewpoints of people living with HIV (PLWH) and HIV healthcare providers (HHP) regarding motivations for and barriers to participation in HIV Cure-related clinical trials (HCRCT)...
2017: PloS One
https://www.readbyqxmd.com/read/29057088/hiv-cure-research-print-and-online-media-reporting-in-australia
#12
EDITORIAL
Jennifer Power, Bianca Fileborn, Gary W Dowsett, Jayne Lucke, Graham Brown, Jeanne Ellard, Sharon R Lewin, Joseph D Tucker, Sean Slavin, Jeremy Sugarman, Sophie Hill
OBJECTIVES: While still in its early stages, recent scientific research towards a cure for HIV has generated widespread media interest. The aim of this paper was to explore the ways in which this research has been represented in Australian print and online media and discuss implications of this. METHODS: A search of databases from four selected media outlets was conducted to identify published articles that directly discussed HIV cure research. Content analysis was used to explore the discursive framing of HIV cure research and identify the presence or absence of people living with HIV in articles...
October 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29023549/supraphysiologic-control-over-hiv-1-replication-mediated-by-cd8-t-cells-expressing-a-re-engineered-cd4-based-chimeric-antigen-receptor
#13
Rachel S Leibman, Max W Richardson, Christoph T Ellebrecht, Colby R Maldini, Joshua A Glover, Anthony J Secreto, Irina Kulikovskaya, Simon F Lacey, Sarah R Akkina, Yanjie Yi, Farida Shaheen, Jianbin Wang, Keith A Dufendach, Michael C Holmes, Ronald G Collman, Aimee S Payne, James L Riley
HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29022531/survival-of-patients-with-kaposi-s-sarcoma-in-the-south-african-antiretroviral-treatment-era-a-retrospective-cohort-study
#14
M M Sengayi, D Kielkowski, M Egger, L Dreosti, J Bohlius
BACKGROUND: When South Africa (SA) implemented its antiretroviral therapy (ART) programme in 2004, the model for treating HIV-positive Kaposi's sarcoma (KS) patients shifted from symptomatic palliation to potential cure. OBJECTIVE: To evaluate survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA. METHODS: We conducted a retrospective review of electronic and paper records of KS patients who accessed cancer care between May 2004 and September 2012...
September 22, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/29017282/plasma-cytokine-predictors-of-tuberculosis-recurrence-in-antiretroviral-treated-human-immunodeficiency-virus-infected-individuals-from-durban-south-africa
#15
Aida Sivro, Lyle R McKinnon, Nonhlanhla Yende-Zuma, Santhana Gengiah, Natasha Samsunder, Salim S Abdool Karim, Kogieleum Naidoo
Background: Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure. Methods: Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB...
September 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28947524/elbasvir-grazoprevir-a-new-direct-acting-antiviral-combination-for-hepatitis-c
#16
REVIEW
Lamis R Karaoui, Hanine Mansour, Elias B Chahine
PURPOSE: The chemistry, pharmacology, pharmacodynamics, pharmacokinetics, efficacy, safety, dosage, administration, and role of elbasvir-grazoprevir in the treatment of hepatitis C virus (HCV) infection are reviewed. SUMMARY: Elbasvir-grazoprevir was recently approved by the Food and Drug Administration for the treatment of chronic HCV genotype 1 or 4 infections with or without ribavirin in patients with or without compensated cirrhosis. Elbasvir exhibits antiviral activity against HCV genotypes 1a, 1b, 2a, 3a, and 4a...
October 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28899104/therapeutic-vaccine-against-hiv-viral-variability-cytotoxic-t-lymphocyte-epitopes-and-genetics-of-patients
#17
Herve Fleury, Camille Tumiotto, Pantxika Bellecave, Patricia Recordon-Pinson
The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored including therapeutic vaccination. Viroimmunological studies on primary infection as well as on elite controllers have demonstrated the importance of the cytotoxic CD8 response and have mainly oriented research on vaccine constructs toward this type of response. The results of these trials are clearly not commensurate with the hope placed in them. Might there be one or more uncontrolled variables? The genetics of patients need to be taken into consideration, especially their human lymphocyte antigen (HLA) alleles...
October 12, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28879787/moving-forward-with-treatment-options-for-hiv-infected-children
#18
Jean-Christophe Beghin, Jean Cyr Yombi, Jean Ruelle, Dimitri Van der Linden
Current international guidelines recommend to treat all HIV-1 infected patients regardless of CD4 cell count. Despite the remarkable worldwide progress for universal access to antiretroviral during the last decade, the pediatric population remains fragile due to lack of randomized studies, inappropriate antiretroviral formulations, adherence difficulties, drug toxicity and development of resistance. Areas covered: This review summarizes the latest recommendations and advances for the treatment of HIV-infected children and highlights the potential complications of a lifelong antiretroviral treatment initiated early in life...
September 7, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28873394/systematic-review-of-clinical-trials-assessing-the-therapeutic-efficacy-of-visceral-leishmaniasis-treatments-a-first-step-to-assess-the-feasibility-of-establishing-an-individual-patient-data-sharing-platform
#19
REVIEW
Jacob T Bush, Monique Wasunna, Fabiana Alves, Jorge Alvar, Piero L Olliaro, Michael Otieno, Carol Hopkins Sibley, Nathalie Strub Wourgaft, Philippe J Guerin
BACKGROUND: There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL) annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28851294/landscape-review-of-current-hiv-kick-and-kill-cure-research-some-kicking-not-enough-killing
#20
REVIEW
Kristian Thorlund, Marc S Horwitz, Brian T Fife, Richard Lester, D William Cameron
BACKGROUND: Current antiretroviral therapy (ART) used to treat human immunodeficiency virus (HIV) patients is life-long because it only suppresses de novo infections. Recent efforts to eliminate HIV have tested the ability of a number of agents to reactivate ('Kick') the well-known latent reservoir. This approach is rooted in the assumption that once these cells are reactivated the host's immune system itself will eliminate ('Kill') the virus. While many agents have been shown to reactivate large quantities of the latent reservoir, the impact on the size of the latent reservoir has been negligible...
August 29, 2017: BMC Infectious Diseases
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