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https://www.readbyqxmd.com/read/28535179/reduced-frequency-of-cells-latently-infected-with-replication-competent-hiv-1-in-virally-suppressed-individuals-living-in-rakai-uganda
#1
Jessica L Prodger, Jun Lai, Steven J Reynolds, Jeanne C Keruly, Richard D Moore, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule, David Serwadda, Martha Nason, Adam A Capoferri, Stephen F Porcella, Robert F Siliciano, Andrew D Redd, Janet D Siliciano, Thomas C Quinn
Background: HIV-1 persists in latently infected resting CD4+ T cells (rCD4), posing a major barrier to curing HIV-1 infection. Previous studies have quantified this pool of latently infected cells in Americans; however, no study has quantified this reservoir in sub-Saharan Africans, who make up the largest population of HIV-1-infected individuals globally. Methods: Peripheral blood was collected from 70 virally suppressed HIV-1-infected individuals from Rakai District, Uganda, who had initiated antiretroviral therapy (ART) during chronic infection...
May 23, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28534887/when-is-early-antiretroviral-therapy-early-enough-for-hiv-remission
#2
Eva Poveda, Manuelo Cresp
Several strategies to reduce and control the HIV reservoir are being evaluating to achieve the great challenge of HIV remission or functional cure. Some of these are based on immune and gene therapy, or in the use of agents with latency reversing properties. Moreover, acute HIV infection and the impact of early antiretroviral treatment (ART) initiation is another key issue of current research. It has been demonstrated that ART initiation during acute HIV infection minimizes the establishment of the latent HIV reservoir...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28530684/tackling-hiv-and-aids-contributions-by-non-human-primate-models
#3
Koen K A Van Rompay
During the past three decades, non-human primate (NHP) models have gained an increasing importance in HIV basic and translational research. In contrast to natural host models, infection of macaques with virulent simian or simian-human immunodeficiency viruses (SIV, SHIV) results in a disease that closely resembles HIV infection and AIDS. Although there is no perfect animal model, and each of the available models has its benefits and limitations, carefully designed NHP studies with selection of experimental variables have unraveled important questions of basic pathogenesis and have provided the tools to explore and screen intervention strategies...
May 22, 2017: Lab Animal
https://www.readbyqxmd.com/read/28530113/refining-current-scientific-priorities-identifying-new-scientific-gaps-in-hiv-related-heart-lung-blood-and-sleep-hlbs-research
#4
Homer L TwiggIII, Ronald Crystal, Judith Currier, Paul M Ridker, Nancy Berliner, Hans-Peter Kiem, George Rutherford, Shimian Zou, Simone Glynn, Renee Wong, Emmanuel Peprah, Michael Engelgau, Tony L Creazzo, Sandra Colombini-Hatch, Elisabet Caler
The National Heart, Lung and Blood Institute (NHLBI) AIDS Program's goal is to provide direction and support for research and training programs in areas of HIV-related heart, lung, blood and sleep (HLBS) diseases. To better define NHLBI current HIV-related scientific priorities and with the goal of identifying new scientific priorities and gaps in HIV-related HLBS research, a wide group of investigators gathered for a scientific NHLBI HIV Working Group on December 14-15, 2015, in Bethesda, MD. The core objectives of the Working Group included discussions on: 1) HIV-related HLBS comorbidities in the antiretroviral era; 2) HIV cure; 3) HIV prevention; and 4) mechanisms to implement new scientific discoveries in an efficient and timely manner so as to have the most impact on people living with HIV (PLWH)...
May 20, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28529952/advancements-in-developing-strategies-for-sterilizing-and-functional-hiv-cures
#5
REVIEW
Wei Xu, Haoyang Li, Qian Wang, Chen Hua, Hanzhen Zhang, Weihua Li, Shibo Jiang, Lu Lu
Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4(+) T cells. Currently, two types of HIV cures are in development: a "sterilizing cure" and a "functional cure." A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529205/effectiveness-and-safety-of-bedaquiline-containing-regimens-in-the-treatment-of-mdr-and-xdr-tb-a-multicentre-study
#6
Sergey E Borisov, Keertan Dheda, Martin Enwerem, Rodolfo Romero Leyet, Lia D'Ambrosio, Rosella Centis, Giovanni Sotgiu, Simon Tiberi, Jan-Willem Alffenaar, Andrey Maryandyshev, Evgeny Belilovski, Shashank Ganatra, Alena Skrahina, Onno Akkerman, Alena Aleksa, Rohit Amale, Janina Artsukevich, Judith Bruchfeld, Jose A Caminero, Isabel Carpena Martinez, Luigi Codecasa, Margareth Dalcolmo, Justin Denholm, Paul Douglas, Raquel Duarte, Aliasgar Esmail, Mohammed Fadul, Alexey Filippov, Lina Davies Forsman, Mina Gaga, Julia-Amaranta Garcia-Fuertes, José-María García-García, Gina Gualano, Jerker Jonsson, Heinke Kunst, Jillian S Lau, Barbara Lazaro Mastrapa, Jorge Lazaro Teran Troya, Selene Manga, Katerina Manika, Pablo González Montaner, Jai Mullerpattan, Suzette Oelofse, Martina Ortelli, Domingo Juan Palmero, Fabrizio Palmieri, Antonella Papalia, Apostolos Papavasileiou, Marie-Christine Payen, Emanuele Pontali, Carlos Robalo Cordeiro, Laura Saderi, Tsetan Dorji Sadutshang, Tatsiana Sanukevich, Varvara Solodovnikova, Antonio Spanevello, Sonam Topgyal, Federica Toscanini, Adrian R Tramontana, Zarir Farokh Udwadia, Pietro Viggiani, Veronica White, Alimuddin Zumla, Giovanni Battista Migliori
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28527722/crispr-cas9-mediated-ccr5-ablation-in-human-hematopoietic-stem-progenitor-cells-confers-hiv-1-resistance-in%C3%A2-vivo
#7
Lei Xu, Huan Yang, Yang Gao, Zeyu Chen, Liangfu Xie, Yulin Liu, Ying Liu, Xiaobao Wang, Hanwei Li, Weifeng Lai, Yuan He, Anzhi Yao, Liying Ma, Yiming Shao, Bin Zhang, Chengyan Wang, Hu Chen, Hongkui Deng
Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4(+) T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34(+) HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdc(scid)/IL-2Rγ(null) mice...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28520970/perspectives-on-human-immunodeficiency-virus-hiv-cure-hiv-persistence-in-tissue
#8
Eli A Boritz, Daniel C Douek
The uneven anatomic distribution of cell subsets that harbor human immunodeficiency virus (HIV) during antiretroviral therapy (ART) complicates investigation of the barriers to HIV cure. Here we propose that while previous studies done largely in blood cells have led to important investigations into HIV latency, other important mechanisms of HIV persistence during ART may not be readily apparent in the bloodstream. We specifically consider as an example the question of ongoing HIV replication during ART. We discuss how growing understanding of key anatomic sanctuaries for the virus can inform future experiments aimed at further clarifying this issue...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520969/cell-mediated-immunity-to-target-the-persistent-human-immunodeficiency-virus-reservoir
#9
James L Riley, Luis J Montaner
Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520968/measuring-the-size-of-the-latent-human-immunodeficiency-virus-reservoir-the-present-and-future-of-evaluating-eradication-strategies
#10
Timothy J Henrich, Steven G Deeks, Satish K Pillai
One of the major barriers to the successful design and implementation of human immunodeficiency virus (HIV) curative strategies is the limited ability to sensitively, specifically, and precisely quantify and characterize the whole-body burden of replication-competent HIV in individuals on effective antiretroviral therapy. Here, we review the development and validation of assays that directly and indirectly measure the size and distribution of the reservoir in blood and tissues. We also discuss the role that treatment interruptions will have in validating these assays and ultimately as a "proof of cure...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520967/in-vivo-models-of-human-immunodeficiency-virus-persistence-and-cure-strategies
#11
Christopher C Nixon, Maud Mavigner, Guido Silvestri, J Victor Garcia
Current HIV therapy is not curative regardless of how soon after infection it is initiated or how long it is administered, and therapy interruption almost invariably results in robust viral rebound. Human immunodeficiency virus persistence is therefore the major obstacle to a cure for AIDS. The testing and implementation of novel yet unproven approaches to HIV eradication that could compromise the health status of HIV-infected individuals might not be ethically warranted. Therefore, adequate in vitro and in vivo evidence of efficacy is needed to facilitate the clinical implementation of promising strategies for an HIV cure...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520966/clonal-expansion-of-human-immunodeficiency-virus-infected-cells-and-human-immunodeficiency-virus-persistence-during-antiretroviral-therapy
#12
James I Mullins, Lisa M Frenkel
The latent HIV-1 reservoir in blood decays very slowly, even during prolonged suppression of viral replication by antiretroviral therapy (ART). Mechanisms for reservoir persistence include replenishment through low-level viral replication, longevity and homeostatic proliferation of memory T cells, and most recently appreciated, clonal expansion of HIV-infected cells. Clonally expanded cells make up a large and increasing fraction of the residual infected cell population on ART, and insertion of HIV proviruses into certain host cellular genes has been associated with this proliferation...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520965/towards-an-hiv-cure-a-view-of-a-developing-field
#13
David M Margolis
No abstract text is available yet for this article.
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520964/proviral-latency-persistent-human-immunodeficiency-virus-infection-and-the-development-of-latency-reversing-agents
#14
David M Margolis, Nancie M Archin
Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound viremia after ART interruption and is a central obstacle to the cure of HIV infection. The induction of quiescent provirus is the goal of a new class of potential therapeutics, latency reversing agents (LRAs). The discovery, development, and testing of HIV LRAs is a key part of current efforts to develop latency reversal and viral clearance strategies to eradicate established HIV infection...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520749/access-and-response-to-direct-antiviral-agents-daa-in-hiv-hcv-co-infected-patients-in-italy-data-from-the-icona-cohort
#15
Antonella d'Arminio Monforte, Alessandro Cozzi-Lepri, Francesca Ceccherini-Silberstein, Andrea De Luca, Sergio Lo Caputo, Antonella Castagna, Cristina Mussini, Antonella Cingolani, Alessandro Tavelli, Milensu Shanyinde, Andrea Gori, Enrico Girardi, Massimo Andreoni, Andrea Antinori, Massimo Puoti
BACKGROUND: Real-life data on access and response to direct antiviral agents (DAA) in HIV-HCV coinfected individuals are lacking. METHODS: HCV viremic, HIV-positive patients from Icona and Hepaicona cohorts naïve to DAA by January 2013 were included. Access and predictors of starting DAA were evaluated. Switches of antiretroviral drugs at starting DAA were described. We calculated sustained virological response (SVR12) in those reaching 12 weeks after end-of-treatment (EOT), and defined treatment failure (TF) as discontinuation of DAA before EOT or non-SVR12...
2017: PloS One
https://www.readbyqxmd.com/read/28514279/impact-of-alemtuzumab-on-hiv-persistence-in-an-hiv-infected-individual-on-antiretroviral-therapy-with-sezary-syndrome
#16
Thomas Aagaard Rasmussen, James McMahon, J Judy Chang, Jori Symons, Michael Roche, Ashanti Dantanarayana, Afam Okoye, Bonnie Hiener, Sarah Palmer, Wen Shi Lee, Stephen Kent, Carrie Van Der Weyden, H Miles Prince, Paul U Cameron, Sharon R Lewin
OBJECTIVE: To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4+ T-cells DESIGN:: Case report. METHODS: Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and non-malignant cells were quantified by flow cytometry. HIV-DNA in total CD4+ T-cells, in sorted malignant and non-malignant CD4+ T-cells was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing...
May 16, 2017: AIDS
https://www.readbyqxmd.com/read/28513067/interventions-for-cutaneous-molluscum-contagiosum
#17
REVIEW
Johannes C van der Wouden, Renske van der Sande, Emma J Kruithof, Annet Sollie, Lisette Wa van Suijlekom-Smit, Sander Koning
BACKGROUND: Molluscum contagiosum is a common skin infection that is caused by a pox virus and occurs mainly in children. The infection usually resolves within months in people without immune deficiency, but treatment may be preferred for social and cosmetic reasons or to avoid spreading the infection. A clear evidence base supporting the various treatments is lacking.This is an update of a Cochrane Review first published in 2006, and updated previously in 2009. OBJECTIVES: To assess the effects of specific treatments and management strategies, including waiting for natural resolution, for cutaneous, non-genital molluscum contagiosum in people without immune deficiency...
May 17, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28506734/mtor-vegf-pdgfr-and-c-kit-signaling-pathway-activation-in-kaposi-sarcoma
#18
Darcy A Kerr, Satya Vara Prasad Busarla, Devon C Gimbel, Aliyah R Sohani, Rosalynn M Nazarian
Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (n=274), most (90%) associated with human immunodeficiency virus (HIV)...
May 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28498985/hiv-antibodies-detect-hiv-persistence-and-low-level-viral-replication
#19
Sheila M Keating, Christopher D Pilcher, Vivek Jain, Mila Lebedeva, Dylan Hampton, Mohamed Abdel-Mohsen, Xutao Deng, Gary Murphy, Alex Welte, Shelley N Facente, Frederick Hecht, Steven G Deeks, Satish K Pillai, Michael P Busch
BACKGROUND: HIV antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals on antiretroviral therapy (ART). METHODS: HIV antibody measurements were made over time on and off suppressive ART and were compared to measures of HIV reservoir size and expression of anti-viral restriction factors...
May 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28497113/toward-a-cure-does-host-immunity-play-a-role
#20
Jielin Zhang, Clyde S Crumpacker
Three decades of research on human immunodeficiency virus (HIV) and AIDS reveal that the human body has developed through evolution a genome immune system embodying epigenetic regulation against pathogenic nucleic acid invasion. In HIV infection, this epigenetic regulation plays a cardinal role in HIV RNA production that silences HIV transcription at a molecular (RNA) level, controls viral load at a cellular (biological) level, and governs the viremic stage of AIDS at the clinical (patient) level. Even though the human genome is largely similar among humans and HIV is a single viral species, human hosts show significant differences in viral RNA levels, ranging from cell to organ to individual and expressed as elite controllers, posttreatment controllers, and patients with AIDS...
March 2017: MSphere
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