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https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#1
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329153/hiv-1-dna-decay-dynamics-with-early-long-term-virologic-control-of-perinatal-infection
#2
Priyanka Uprety, Kunjal Patel, Brad Karalius, Carrie Ziemniak, Ya Hui Chen, Sean S Brummel, Suzanne Siminski, Russell B Van Dyke, George R Seage, Deborah Persaud
Background: Early antiretroviral treatment (ART) limits proviral reservoirs, a goal for HIV-1 remission strategies. Whether this is an immediate or long-term effect of virologic suppression (VS) in perinatal infection is unknown. Methods: We quantified HIV-1 DNA longitudinally for up to 14 years in peripheral blood mononuclear cells (PBMCs) among 61 perinatally HIV-1-infected youth in the Pediatric HIV/AIDS Cohort Study who achieved VS at different ages. Group 1 (N=13) were < 1 year of age and group 2 (N=48) were between 1-5 years of age at VS...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328934/proviruses-with-identical-sequences-comprise-a-large-fraction-of-the-replication-competent-hiv-reservoir
#3
John K Bui, Michele D Sobolewski, Brandon F Keele, Jonathan Spindler, Andrew Musick, Ann Wiegand, Brian T Luke, Wei Shao, Stephen H Hughes, John M Coffin, Mary F Kearney, John W Mellors
The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication-competent proviruses has been controversial. Here, we used single-genome sequencing to probe for identical HIV sequence matches among viruses recovered in different viral outgrowth cultures and between the sequences of outgrowth viruses and proviral or intracellular HIV RNA sequences in uncultured blood mononuclear cells from eight donors on suppressive ART with diverse proviral populations...
March 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28316071/chlamydia-trachomatis-and-hpv-co-infections-in-hiv-negative-men-from-a-multi-ethnic-area-of-northern-italy-at-high-prevalence-of-cervical-malignancies
#4
Manola Comar, Silva Seraceni, Claudia Colli, Viviana Luska, Sara Morassut, Libera Clemente, Marina Drabeni, Gianmichele Moise, Francesco Fontana, Lorenzo Monasta, Barbara Suligoi
Chlamydia trachomatis and HPV coinfections in the male population are often a disregarded issue. We performed a study to evaluate the prevalence of such infections in heterosexual HIV negative men from a Northern Italy multi-ethnic area at high prevalence for cervical malignancies. Urethral swabs (US) or first-voided urine were evaluated retrospectively from 1317 patients attending Sexually Transmitted Infections (STI) clinic and from 3388 outpatients attending private clinics. Informations about participants' demographic characteristics and attributes of Chlamydia trachomatis, including chronic infection, and HPV genotypes testing, were collected...
March 18, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28297712/cd32a-is-a-marker-of-a-cd4-t-cell-hiv-reservoir-harbouring-replication-competent-proviruses
#5
Benjamin Descours, Gaël Petitjean, José-Luis López-Zaragoza, Timothée Bruel, Raoul Raffel, Christina Psomas, Jacques Reynes, Christine Lacabaratz, Yves Levy, Olivier Schwartz, Jean Daniel Lelievre, Monsef Benkirane
The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells...
March 15, 2017: Nature
https://www.readbyqxmd.com/read/28287825/quantification-of-residual-germinal-center-activity-and-hiv-1-dna-and-rna-levels-using-fine-needle-biopsies-of-lymph-nodes-during-antiretroviral-therapy
#6
William J Hey-Nguyen, Yin Xu, Chester F Pearson, Michelle Bailey, Kazuo Suzuki, Robyn Tantau, Solange Obeid, Brad Milner, Andrew Field, Andrew Carr, Mark Bloch, David A Cooper, Anthony D Kelleher, John J Zaunders, Kersten K Koelsch
HIV-1 reservoirs are most often studied in peripheral blood (PB), but not all lymphocytes recirculate, particularly T follicular helper (Tfh) CD4(+) T cells, as well as germinal center (GC) B cells, in lymph nodes (LNs). Ultrasound-guided fine needle biopsies (FNBs) from inguinal LNs and PB samples were obtained from 10 healthy controls (HCs) and 21 HIV-1-infected subjects [11 antiretroviral therapy (ART) naive and 10 on ART]. Tfh cells and GC B cells were enumerated by flow cytometry. HIV-1 DNA and cell-associated (CA) RNA levels in LNs and PB were quantified by real-time polymerase chain reaction...
March 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28279508/tuberculosis-elimination-and-the-challenge-of-latent-tuberculosis
#7
Alberto Matteelli, Giorgia Sulis, Susanna Capone, Lia D'Ambrosio, Giovanni Battista Migliori, Haileyesus Getahun
Latent tuberculosis infection (LTBI) affects one third to one fourth of the human population and is the reservoir for a significant proportion of emerging active tuberculosis (TB) cases, especially in low incidence countries. The World Health Organization launched in 2015 the END-TB strategy that aims at TB elimination and promotes, for the first time ever, the management of LTBI. The preventive package, basically consisting of testing and treatment for LTBI in groups at high risk of reactivation, is a mainstay of the first pillar of the strategy, alongside prompt diagnosis and early treatment of both drug-susceptible and drug-resistant TB disease...
March 6, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28279181/a-mature-macrophage-is-a-principal-hiv-1-cellular-reservoir-in-humanized-mice-after-treatment-with-long-acting-antiretroviral-therapy
#8
Mariluz Araínga, Benson Edagwa, R Lee Mosley, Larisa Y Poluektova, Santhi Gorantla, Howard E Gendelman
BACKGROUND: Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1ADA-infected NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl) /SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency...
March 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/28275461/hiv-reservoir-characterization-symposium-19-september-2016-ghent-belgium
#9
EDITORIAL
Eva Malatinkova, Ward De Spiegelaere, Linos Vandekerckhove, Magdalena Sips
The HIV Cure Research Center (HCRC) in Ghent organised the first HIV Reservoir Characterization Symposium, and brought together virologists, molecular biologists, immunologists and clinicians to discuss the most recent developments in HIV reservoir characterisation with a view to achieving an HIV cure. The one-day symposium covered new developments in the field of HIV reservoir and HIV cure research, with the latest news on the European HIV cure trials. This report summarises the major themes discussed during the symposium...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28275460/reactivation-of-hiv-1-proviruses-in-immune-compromised-mice-engrafted-with-human-voa-negative-cd4-t-cells
#10
EDITORIAL
Zhe Yuan, Guobin Kang, Wuxun Lu, Qingsheng Li
BACKGROUND: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses. METHODS: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted into NSG mice...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28265271/cd4-t-follicular-helper-cells-and-hiv-infection-friends-or-enemies
#11
REVIEW
Félicien Moukambi, Vasco Rodrigues, Yasmina Fortier, Henintsoa Rabezanahary, Chloé Borde, Bernard Krust, Guadalupe Andreani, Ricardo Silvestre, Constantinos Petrovas, Mireille Laforge, Jérôme Estaquier
Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28257302/progress-in-hiv-1-antibody-research-using-humanized-mice
#12
Henning Gruell, Florian Klein
PURPOSE OF REVIEW: Recent discoveries of highly potent broadly HIV-1 neutralizing antibodies provide new opportunities to successfully prevent, treat, and potentially cure HIV-1 infection. To test their activity in vivo, humanized mice have been shown to be a powerful model and were used to investigate antibody-mediated prevention and therapy approaches. In this review, we will summarize recent findings in humanized mice that have informed on the potential use of broadly neutralizing antibodies targeting HIV-1 in humans...
March 2, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#13
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28243867/peripheral-blood-lymphocyte-hiv-dna-levels-correlate-with-hiv-associated-neurocognitive-disorders-in-nigeria
#14
Jibreel Jumare, Sara Sunshine, Hayat Ahmed, Samer S El-Kamary, Laurence Magder, Laura Hungerford, Tricia Burdo, Lindsay M Eyzaguirre, Anya Umlauf, Mariana Cherner, Alash'le Abimiku, Man Charurat, Jonathan Z Li, William A Blattner, Walter Royal
Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample...
February 27, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28243600/systematic-approach-for-the-formulation-and-optimization-of-solid-lipid-nanoparticles-of-efavirenz-by-high-pressure-homogenization-using-design-of-experiments-for-brain-targeting-and-enhanced-bioavailability
#15
Shweta Gupta, Rajesh Kesarla, Narendra Chotai, Ambikanandan Misra, Abdelwahab Omri
The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28243243/role-of-maternal-periodontitis-in-preterm-birth
#16
REVIEW
Hongyu Ren, Minquan Du
In the last two decades, many studies have focused on whether periodontitis is a risk factor for preterm birth (PTB). However, both epidemiological investigation and intervention trials have reached contradictory results from different studies. What explains the different findings, and how should future studies be conducted to better assess this risk factor? This article reviews recent epidemiological, animal, and in vitro studies as well as intervention trials that evaluate the link between periodontitis and PTB...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28239658/loss-of-immune-homeostasis-dictates-shiv-rebound-after-stem-cell-transplantation
#17
Christopher W Peterson, Clarisse Benne, Patricia Polacino, Jasbir Kaur, Cristina E McAllister, Abdelali Filali-Mouhim, Willi Obenza, Tiffany A Pecor, Meei-Li Huang, Audrey Baldessari, Robert D Murnane, Ann E Woolfrey, Keith R Jerome, Shiu-Lok Hu, Nichole R Klatt, Stephen DeRosa, Rafick P Sékaly, Hans-Peter Kiem
The conditioning regimen used as part of the Berlin patient's hematopoietic cell transplant likely contributed to his eradication of HIV infection. We studied the impact of conditioning in simian-human immunodeficiency virus-infected (SHIV-infected) macaques suppressed by combination antiretroviral therapy (cART). The conditioning regimen resulted in a dramatic, but incomplete depletion of CD4(+) and CD8(+) T cells and CD20(+) B cells, increased T cell activation and exhaustion, and a significant loss of SHIV-specific Abs...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239657/tissue-resident-macrophages-can-contain-replication-competent-virus-in-antiretroviral-naive-siv-infected-asian-macaques
#18
Sarah R DiNapoli, Alexandra M Ortiz, Fan Wu, Kenta Matsuda, Homer L Twigg, Vanessa M Hirsch, Kenneth Knox, Jason M Brenchley
SIV DNA can be detected in lymphoid tissue-resident macrophages of chronically SIV-infected Asian macaques. These macrophages also contain evidence of recently phagocytosed SIV-infected CD4(+) T cells. Here, we examine whether these macrophages contain replication-competent virus, whether viral DNA can be detected in tissue-resident macrophages from antiretroviral (ARV) therapy-treated animals and humans, and how the viral sequences amplified from macrophages and contemporaneous CD4(+) T cells compare. In ARV-naive animals, we find that lymphoid tissue-resident macrophages contain replication-competent virus if they also contain viral DNA in ARV-naive Asian macaques...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28233807/a-highly-reproducible-quantitative-viral-outgrowth-assay-for-the-measurement-of-the-replication-competent-latent-hiv-1-reservoir
#19
Axel Fun, Hoi Ping Mok, Mark R Wills, Andrew M Lever
Cure of Human Immunodeficiency Virus (HIV) infection remains elusive due to the persistence of HIV in a latent reservoir. Strategies to eradicate latent infection can only be evaluated with robust, sensitive and specific assays to quantitate reactivatable latent virus. We have taken the standard peripheral blood mononuclear cell (PBMC) based viral outgrowth methodology and from it created a logistically simpler and more highly reproducible assay to quantify replication-competent latent HIV in resting CD4(+) T cells, both increasing accuracy and decreasing cost and labour...
February 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28231392/from-dendritic-cells-to-b-cells-dysfunctions-during-hiv-1-infection-tfh-at-the-cross-road
#20
REVIEW
Nicolas Ruffin, Lylia Hani, Nabila Seddiki
T follicular helper (Tfh) cells are essential for B cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal center, where they are the main source of replicative HIV-1 and represent a major reservoir. Paradoxically, Tfh numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV-1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure...
February 23, 2017: Immunology
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