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https://www.readbyqxmd.com/read/29142136/size-composition-and-evolution-of-hiv-dna-populations-during-early-antiretroviral-therapy-and-intensification-with-maraviroc
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28851229/the-california-hiv-aids-research-program-history-impact-and-hiv-cure-initiative
#13
Lisa Loeb Stanga, Anwer Mujeeb, Laura Packel, Tyler Martz, George Lemp
This Special Issue of AIDS Research and Human Retroviruses features results from the HIV Cure Initiative, funded by the California HIV/AIDS Research Program (CHRP). As a publicly-funded grant maker, CHRP has served for more than three decades as a unique resource for innovative researchers in California whose work seeks to address all aspects of the HIV epidemic and the communities affected by it. Early initiatives at CHRP pioneered what would become enduring cornerstones of HIV science: isolation of the virus; efficacy and toxicities of the first HIV treatments; the emergence of drug resistance; the first biospecimen banks for HIV-related research; the first community-based laboratory service for HIV diagnostic serology; and the first population-based longitudinal cohort study of persons living with HIV - The Gay Men's Health Study...
August 29, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28835533/a-phase-ii-clinical-study-to-assess-the-feasibility-of-self-and-partner-anal-examinations-to-detect-anal-canal-abnormalities-including-anal-cancer
#14
Alan G Nyitray, Joseph T Hicks, Lu-Yu Hwang, Sarah Baraniuk, Margaret White, Stefanos Millas, Nkechi Onwuka, Xiaotao Zhang, Eric L Brown, Michael W Ross, Elizabeth Y Chiao
OBJECTIVE: Anal cancer is a common cancer among men who have sex with men (MSM); however, there is no standard screening protocol for anal cancer. We conducted a phase II clinical trial to assess the feasibility of teaching MSM to recognise palpable masses in the anal canal which is a common sign of anal cancer in men. METHODS: A clinician skilled in performing digital anorectal examinations (DARE) used a pelvic manikin to train 200 MSM, aged 27-78 years, how to do a self-anal examination (SAE) for singles or a partner anal examination (PAE) for couples...
August 23, 2017: Sexually Transmitted Infections
https://www.readbyqxmd.com/read/28782474/the-relevance-of-post-transcriptional-mechanisms-in-hiv-latency-reversal
#15
Ambra Sarracino, Alessandro Marcello
BACKGROUND: Infection by the human immunodeficiency virus has become a curable disease, which could not be cured because the virus persists in the face of an efficacious drug treatment. Current efforts for the rescue of replication-competent virus from cellular reservoirs are limited to drugs targeting transcriptional reactivation of the dormant virus and clinical trials so far are disappointing. One explanation could be that post-transcriptional pathways are not optimal thus impeding full reactivation of the virus, which is required for purging the cellular reservoirs...
August 3, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28755872/new-approaches-for-the-enhancement-of-chimeric-antigen-receptors-for-the-treatment-of-hiv
#16
REVIEW
Mayra A Carrillo, Anjie Zhen, Jerome A Zack, Scott G Kitchen
HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28751153/ccr5-edited-gene-therapies-for-hiv-cure-closing-the-door-to-viral-entry
#17
REVIEW
Kevin G Haworth, Christopher W Peterson, Hans-Peter Kiem
Human immunodeficiency virus (HIV) was first reported and characterized more than three decades ago. Once thought of as a death sentence, HIV infection has become a chronically manageable disease. However, it is estimated that a staggering 0.8% of the world's population is infected with HIV, with more than 1 million deaths reported in 2015 alone. Despite the development of effective anti-retroviral drugs, a permanent cure has only been documented in one patient to date. In 2007, an HIV-positive patient received a bone marrow transplant to treat his leukemia from an individual who was homozygous for a mutation in the CCR5 gene...
July 24, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28719012/the-impact-of-immunoglobulin-in-acute-hiv-infection-on-the-hiv-reservoir-a-randomized-controlled-trial
#18
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)...
November 2017: HIV Medicine
https://www.readbyqxmd.com/read/28689442/drug-interactions-in-hiv-infected-patients-treated-for-hepatitis-c
#19
REVIEW
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)...
August 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
#20
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
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