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https://www.readbyqxmd.com/read/29329113/therapeutic-hiv-1-vaccine-time-for-immunomodulation-and-combinatorial-strategies
#1
Nabila Seddiki, Yves Lévy
PURPOSE OF REVIEW: The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells...
January 10, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29324842/effect-of-analytical-treatment-interruption-and-reinitiation-of-antiretroviral-therapy-on-hiv-reservoirs-and-immunologic-parameters-in-infected-individuals
#2
Katherine E Clarridge, Jana Blazkova, Kevin Einkauf, Mary Petrone, Eric W Refsland, J Shawn Justement, Victoria Shi, Erin D Huiting, Catherine A Seamon, Guinevere Q Lee, Xu G Yu, Susan Moir, Michael C Sneller, Mathias Lichterfeld, Tae-Wook Chun
Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29316956/next-generation-in-situ-hybridization-approaches-to-define-and-quantify-hiv-and-siv-reservoirs-in-tissue-microenvironments
#3
REVIEW
Claire Deleage, Chi N Chan, Kathleen Busman-Sahay, Jacob D Estes
The development of increasingly safe and effective antiretroviral treatments for human immunodeficiency virus (HIV) over the past several decades has led to vastly improved patient survival when treatment is available and affordable, an outcome that relies on uninterrupted adherence to combination antiretroviral therapy for life. Looking to the future, the discovery of an elusive 'cure' for HIV will necessitate highly sensitive methods for detecting, understanding, and eliminating viral reservoirs. Next-generation, in situ hybridization (ISH) approaches offer unique and complementary insights into viral reservoirs within their native tissue environments with a high degree of specificity and sensitivity...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29316955/single-molecule-techniques-to-quantify-and-genetically-characterise-persistent-hiv
#4
REVIEW
Xiao Qian Wang, Sarah Palmer
Antiretroviral therapy effectively suppresses, but does not eradicate HIV-1 infection. Persistent low-level HIV-1 can still be detected in plasma and cellular reservoirs even after years of effective therapy, and cessation of current treatments invariably results in resumption of viral replication. Efforts to eradicate persistent HIV-1 require a comprehensive examination of the quantity and genetic composition of HIV-1 within the plasma and infected cells located in the peripheral blood and tissues throughout the body...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29298886/class-1-selective-histone-deacetylase-inhibitors-enhance-hiv-latency-reversal-while-preserving-the-activity-of-hdac-isoforms-necessary-for-maximal-hiv-gene-expression
#5
Thomas D Zaikos, Mark M Painter, Nadia T Sebastian, Valeri H Terry, Kathleen L Collins
Combinations of drugs that affect distinct mechanisms of HIV latency aim to induce robust latency reversal leading to cytopathicity and elimination of the persistent HIV reservoir. Thus far, attempts have focused on combinations of PKC agonists and pan-histone deacetylase inhibitors (HDIs) despite the knowledge that HIV gene expression is regulated by class 1 histone deacetylases. We hypothesized that class 1-selective HDIs would promote more robust HIV latency reversal in combination with a PKC agonist than pan-HDIs because they preserve the activity of pro-viral factors regulated by non-class 1 histone deacetylases...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29291350/accessing-chemical-diversity-from-the-uncultivated-symbionts-of-small-marine-animals
#6
Thomas E Smith, Christopher D Pond, Elizabeth Pierce, Zachary P Harmer, Jason Kwan, Malcolm M Zachariah, Mary Kay Harper, Thomas P Wyche, Teatulohi K Matainaho, Tim S Bugni, Louis R Barrows, Chris M Ireland, Eric W Schmidt
Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV compounds from small, marine tunicates from the Eastern Fields of Papua New Guinea. Tunicates are a reservoir for new bioactive chemicals, yet their small size often impedes identification or even detection of the chemicals within...
January 1, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29287987/observations-on-bradyzoite-biology
#7
Vincent Tu, Rama Yakubu, Louis M Weiss
Tachyzoites of the Apicomplexan Toxoplasma gondii cause acute infection, disseminate widely in their host, and eventually differentiates into a latent encysted form called bradyzoites that are found within tissue cysts. During latent infection, whenever transformation to tachyzoites occurs, any tachyzoites that develop are removed by the immune system. In contrast, cysts containing bradyzoites are sequestered from the immune system. In the absence of an effective immune response released organisms that differentiate into tachyzoites cause acute infection...
December 26, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29262326/hiv-specific-cd8-t-cells-exhibit-reduced-and-differentially-regulated-cytolytic-activity-in-lymphoid-tissue
#8
Morgan A Reuter, Perla M Del Rio Estrada, Marcus Buggert, Constantinos Petrovas, Sara Ferrando-Martinez, Son Nguyen, Alberto Sada Japp, Yuria Ablanedo-Terrazas, Amaranta Rivero-Arrieta, Leticia Kuri-Cervantes, Heidi M Gunzelman, Emma Gostick, David A Price, Richard A Koup, Ali Naji, David H Canaday, Gustavo Reyes-Terán, Michael R Betts
Elimination of lymphoid tissue reservoirs is a key component of HIV eradication strategies. CD8+ T cells play a critical role in control of HIV, but their functional attributes in lymph nodes (LNs) remain unclear. Here, we show that memory, follicular CXCR5+, and HIV-specific CD8+ T cells from LNs do not manifest the properties of cytolytic CD8+ T cells. While the frequency of follicular CXCR5+ CD8+ T cells was strongly inversely associated with peripheral viremia, this association was not dependent on cytolytic CXCR5+ CD8+ T cells...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29261623/microglial-activation-on-11c-cb184-pet-in-a-patient-with-cerebellar-ataxia-associated-with-hiv-infection
#9
Kenji Ishibashi, Yoshiharu Miura, Akifumi Imamura, Jun Toyohara, Kenji Ishii
A 63-year-old man complaining of prolonged imbalance underwent C-CB184 PET to assess microglial activation 3 years after being diagnosed with cerebellar ataxia associated with HIV infection. C-CB184 images revealed significant cerebellar uptake where MRI signal abnormalities were observed at disease onset, although these abnormalities had mostly disappeared at the time of C-CB184 PET. Microglia are believed to be a long-term reservoir for HIV infection, causing persistent immune activation (ie, chronic inflammation)...
December 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29259605/role-of-monocyte-macrophages-during-hiv-siv-infection-in-adult-and-pediatric-acquired-immune-deficiency-syndrome
#10
REVIEW
Kristen M Merino, Carolina Allers, Elizabeth S Didier, Marcelo J Kuroda
Monocytes/macrophages are a diverse group of cells that act as first responders in innate immunity and then as mediators for adaptive immunity to help clear infections. In performing these functions, however, the macrophage inflammatory responses can also contribute to pathogenesis. Various monocyte and tissue macrophage subsets have been associated with inflammatory disorders and tissue pathogeneses such as occur during HIV infection. Non-human primate research of simian immunodeficiency virus (SIV) has been invaluable in better understanding the pathogenesis of HIV infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29250325/modern-biotechnology-based-therapeutic-approaches-against-hiv-infection
#11
Muhammad Imran, Yasir Waheed, Ayesha Ghazal, Sajjad Ullah, Sher Zaman Safi, Muhsin Jamal, Muhammad Ali, Muhammad Atif, Muhammad Imran, Farman Ullah
The causative agent of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus (HIV). Since its discovery before 30 years, a number of drugs known as highly active antiretroviral therapy have been developed to suppress the life cycle of the virus at different stages. With the current therapeutic approaches, ending AIDS means providing treatment to 35 million individuals living with HIV for the rest of their lives or until a cure is developed. Additionally, therapy is associated with various other challenges such as potential of drug resistance, toxicity and presence of latent viral reservoir...
December 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29250073/myeloid-cell-interaction-with-hiv-a-complex-relationship
#12
REVIEW
Vasco Rodrigues, Nicolas Ruffin, Mabel San-Roman, Philippe Benaroch
Cells of the myeloid lineage, particularly macrophages, serve as primary hosts for HIV in vivo, along with CD4 T lymphocytes. Macrophages are present in virtually every tissue of the organism, including locations with negligible T cell colonization, such as the brain, where HIV-mediated inflammation may lead to pathological sequelae. Moreover, infected macrophages are present in multiple other tissues. Recent evidence obtained in humanized mice and macaque models highlighted the capacity of macrophages to sustain HIV replication in vivo in the absence of T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29246970/compounds-producing-an-effective-combinatorial-regimen-for-disruption-of-hiv-1-latency
#13
Pargol Hashemi, Kris Barreto, Wendy Bernhard, Adam Lomness, Nicolette Honson, Tom A Pfeifer, P Richard Harrigan, Ivan Sadowski
Highly active antiretroviral therapy (HAART) has improved the outlook for the HIV epidemic, but does not provide a cure. The proposed "shock-and-kill" strategy is directed at inducing latent HIV reservoirs, which may then be purged via boosted immune response or targeting infected cells. We describe five novel compounds that are capable of reversing HIV latency without affecting the general T-cell activation state. The new compounds exhibit synergy for reactivation of latent provirus with other latency-reversing agents (LRAs), in particular ingenol-3-angelate/PEP005...
December 15, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29246197/a-higher-cd4-cd8-ratio-correlates-with-an-ultralow-cell-associated-hiv-1-dna-level-in-chronically-infected-patients-on-antiretroviral-therapy-a-case-control-study
#14
Yongsong Yue, Nidan Wang, Yang Han, Ting Zhu, Jing Xie, Zhifeng Qiu, Xiaojing Song, Yanling Li, Jean-Pierre Routy, Jianhua Wang, Taisheng Li
BACKGROUND: The HIV-1 DNA reservoir is an important marker that reflects viro-immunological status and can be affected by multiple viral or cellular factors. Determining the potential factors associated with the size of the HIV-1 DNA reservoir benefits the surveillance of disease progression and antiretroviral treatments. METHODS: We conducted a case control study to explore the factors that may affect the level of HIV-1 DNA. The level of HIV-1 total DNA in peripheral blood at 5 time points was quantified by quantitative PCR...
December 15, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29244129/dolutegravir-reshapes-the-genetic-diversity-of-hiv-1-reservoirs
#15
Pierre Gantner, Guinevere Q Lee, David Rey, Thibault Mesplede, Marialuisa Partisani, Christine Cheneau, Geneviève Beck-Wirth, Jean-Pierre Faller, Mahsa Mohseni-Zadeh, Martin Martinot, Mark A Wainberg, Samira Fafi-Kremer
Objectives: Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen. Methods: Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5)...
December 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29243498/-cart-intensification-by-the-hiv-1-tat-b-clade-vaccine-progress-to-phase-iii-efficacy-studies
#16
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/29239894/temporal-variation-in-hiv-specific-igg-subclass-abs-during-acute-infection-differentiates-spontaneous-controllers-from-chronic-progressors
#17
Saheli Sadanand, Jishnu Das, Amy W Chung, Matthew K Schoen, Sophie Lane, Todd J Suscovich, Hendrik Streeck, Davey Smith, Susan Little, Douglas A Lauffenburger, Douglas Richman, Galit Alter
OBJECTIVE: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between subjects who ultimately became controllers versus those who became progressors. METHODS: IgG was purified from plasma from nine acutely infected subjects who subsequently controlled HIV spontaneously (controllers) and ten acutely infected individuals who did not control viremia (progressors)...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29234320/increasing-the-clinical-potential-and-applications-of-anti-hiv-antibodies
#18
REVIEW
Casey K Hua, Margaret E Ackerman
Preclinical and early human clinical studies of broadly neutralizing antibodies (bNAbs) to prevent and treat HIV infection support the clinical utility and potential of bNAbs for prevention, postexposure prophylaxis, and treatment of acute and chronic infection. Observed and potential limitations of bNAbs from these recent studies include the selection of resistant viral populations, immunogenicity resulting in the development of antidrug (Ab) responses, and the potentially toxic elimination of reservoir cells in regeneration-limited tissues...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29232209/recent-progress-in-understanding-hiv-reservoirs
#19
Hsiao-Hsuan Kuo, Mathias Lichterfeld
PURPOSE OF REVIEW: Reservoirs of HIV-1-infected cells persist long-term despite highly effective antiretroviral suppression therapy and represent the main barrier against a cure for HIV-1. This review summarizes recent advances in understanding the complexity and diversity of viral reservoir cells. RECENT FINDINGS: Latently infected memory CD4 T cells are the predominant cell compartment responsible for viral persistence, but some studies suggest that myeloid cells, and possibly hematopoietic progenitors, can also serve as long-term viral reservoirs...
December 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29228979/contrasting-effect-of-the-latency-reversing-agents-bryostatin-1-and-jq1-on-astrocyte-mediated-neuroinflammation-and-brain-neutrophil-invasion
#20
Alizé Proust, Corinne Barat, Mathieu Leboeuf, Jean Drouin, Michel J Tremblay
BACKGROUND: Despite effectiveness of the combined antiretroviral therapy, HIV-1 persists in long-lived latently infected cells. Consequently, new therapeutic approaches aimed at eliminating this latent reservoir are currently being developed. A "shock and kill" strategy using latency-reversing agents (LRA) to reactivate HIV-1 has been proposed. However, the impact of LRA on the central nervous system (CNS) remains elusive. METHODS: We used human fetal astrocytes and investigated the effects of several LRA on their functional and secretory activities...
December 11, 2017: Journal of Neuroinflammation
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