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Sample records for hiv meets gene

  1. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  2. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Arun K. Nalla

    2016-03-01

    Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

  3. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Science.gov (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  4. Technology evaluation: HIV ribozyme gene therapy, Gene Shears Pty Ltd.

    Science.gov (United States)

    de Feyter, R; Li, P

    2000-06-01

    Ribozymes (catalytic RNAs) can be made to specifically cleave target RNAs that are involved in disease conditions and therefore have potential as therapeutic agents. Gene Shears Pty Ltd is developing hammerhead ribozyme technology for therapy against HIV infection, targeting either the tat gene or the RNA packaging sequence (Psi) of HIV. These ribozymes have been expressed from constructs that were introduced into hematopoietic cells in culture, thereby protecting the cells against viral infection. Two phase I clinical trials are underway to test the safety and feasibility of the approach with the anti-tat ribozyme in human subjects.

  5. CD25 Preselective Anti-HIV Vectors for Improved HIV Gene Therapy

    OpenAIRE

    Kalomoiris, Stefanos; Lawson, Je'Tai; Chen, Rachel X.; Bauer, Gerhard; Nolta, Jan A; Anderson, Joseph S.

    2012-01-01

    As HIV continues to be a global public health problem with no effective vaccine available, new and innovative therapies, including HIV gene therapies, need to be developed. Due to low transduction efficiencies that lead to low in vivo gene marking, therapeutically relevant efficacy of HIV gene therapy has been difficult to achieve in a clinical setting. Methods to improve the transplantation of enriched populations of anti-HIV vector-transduced cells may greatly increase the in vivo efficacy ...

  6. Newer Gene Editing Technologies toward HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Premlata Shankar

    2013-11-01

    Full Text Available Despite the great success of highly active antiretroviral therapy (HAART in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.

  7. CD25 preselective anti-HIV vectors for improved HIV gene therapy.

    Science.gov (United States)

    Kalomoiris, Stefanos; Lawson, Je'tai; Chen, Rachel X; Bauer, Gerhard; Nolta, Jan A; Anderson, Joseph S

    2012-12-01

    As HIV continues to be a global public health problem with no effective vaccine available, new and innovative therapies, including HIV gene therapies, need to be developed. Due to low transduction efficiencies that lead to low in vivo gene marking, therapeutically relevant efficacy of HIV gene therapy has been difficult to achieve in a clinical setting. Methods to improve the transplantation of enriched populations of anti-HIV vector-transduced cells may greatly increase the in vivo efficacy of HIV gene therapies. Here we describe the development of preselective anti-HIV lentiviral vectors that allow for the purification of vector-transduced cells to achieve an enriched population of HIV-resistant cells. A selectable protein, human CD25, not normally found on CD34+ hematopoietic progenitor cells (HPCs), was incorporated into a triple combination anti-HIV lentiviral vector. Upon purification of cells transduced with the preselective anti-HIV vector, safety was demonstrated in CD34+ HPCs and in HPC-derived macrophages in vitro. Upon challenge with HIV-1, improved efficacy was observed in purified preselective anti-HIV vector-transduced macrophages compared to unpurified cells. These proof-of-concept results highlight the potential use of this method to improve HIV stem cell gene therapy for future clinical applications.

  8. 76 FR 30942 - Meeting of the Presidential Advisory Council on HIV/AIDS; Correction

    Science.gov (United States)

    2011-05-27

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS; Correction AGENCY: Office of... Advisory Council on HIV/AIDS; Phone: (202) 690-5560. More detailed information about PACHA can be obtained.... Christopher H. Bates, Executive Director, Presidential Advisory Council on HIV/AIDS. BILLING CODE 4150-43-M ...

  9. 78 FR 49516 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2013-08-14

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS AGENCY: Office of the Assistant... Service (DHHS) is hereby giving notice that the Presidential Advisory Council on HIV/AIDS (PACHA) will... HIV/AIDS, Department of Health and Human Services, 200 Independence Avenue SW., Room 443H, Hubert H...

  10. 77 FR 74017 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2012-12-12

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS AGENCY: Office of the Assistant... Services (DHHS) is hereby giving notice that the Presidential Advisory Council on HIV/AIDS (PACHA) will... Health Assistant, Presidential Advisory Council on HIV/AIDS, Department of Health and Human Services, 200...

  11. 78 FR 19710 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2013-04-02

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS AGENCY: Department of Health and... Service (DHHS) is hereby giving notice that the Presidential Advisory Council on HIV/AIDS (PACHA) will..., Public Health Assistant, Presidential Advisory Council on HIV/AIDS, Department of Health and Human...

  12. 75 FR 19403 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2010-04-14

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS AGENCY: Department of Health and... (DHHS) is hereby giving notice that the Presidential Advisory Council on HIV/AIDS (PACHA) will hold a... Council on HIV/AIDS, Department of Health and Human Services, 200 Independence Avenue, SW., Room 443H...

  13. 77 FR 59196 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2012-09-26

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS AGENCY: Department of Health and... Service (DHHS) is hereby giving notice that the Presidential Advisory Council on HIV/AIDS (PACHA) will.... Caroline Talev, Public Health Assistant, Presidential Advisory Council on HIV/AIDS, Department of Health...

  14. 77 FR 74016 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2012-12-12

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS AGENCY: Office of the Assistant... Service (DHHS) is hereby giving notice that the Presidential Advisory Council on HIV/AIDS (PACHA) will... HIV/AIDS, Department of Health and Human Services, 200 Independence Avenue SW., Room 443H, Washington...

  15. 75 FR 2546 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2010-01-15

    ... HUMAN SERVICES Meeting of the Presidential Advisory Council on HIV/AIDS AGENCY: Department of Health and... (DHHS) is hereby giving notice that the Presidential Advisory Council on HIV/AIDS (PACHA) will hold a...: Mr. Melvin Joppy, Committee Manager, Presidential Advisory Council on HIV/AIDS, Department of Health...

  16. Gene therapy: a possible future standard for HIV care.

    Science.gov (United States)

    Abou-El-Enein, Mohamed; Bauer, Gerhard; Reinke, Petra

    2015-07-01

    Despite undeniable accomplishments in developing cell and gene therapeutic strategies to combat HIV infection, key social, economic, and policy-related challenges still need to be overcome for any future commercialization efforts of these novel therapies to be successful. Here, we address these challenges and structure a framework for eradicating HIV/AIDS using gene therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Stem cell based anti-HIV Gene therapy

    Science.gov (United States)

    Kitchen, Scott G.; Shimizu, Saki; An, Dong Sung

    2011-01-01

    Human stem cell-based therapeutic intervention strategies for treating HIV infection have recently undergone a renaissance as a major focus of investigation. Unlike most conventional antiviral therapies, genetically engineered hematopoietic stem cells possess the capacity for prolonged self-renewal that would continuously produce protected immune cells to fight against HIV. A successful strategy therefore has the potential to stably control and ultimately eradicate HIV from patients by a single or minimal treatment. Recent progress in the development of new technologies and clinical trials sets the stage for the current generation of gene therapy approaches to combat HIV infection. In this review, we will discuss two major approaches that are currently underway in the development of stem cell-based gene therapy to target HIV: One that focuses on the protection of cells from productive infection with HIV, and the other that focuses on targeting immune cells to directly combat HIV infection. PMID:21247612

  18. Achieving HIV-1 Control through RNA-Directed Gene Regulation

    Directory of Open Access Journals (Sweden)

    Vera Klemm

    2016-12-01

    Full Text Available HIV-1 infection has been transformed by combined anti-retroviral therapy (ART, changing a universally fatal infection into a controllable infection. However, major obstacles for an HIV-1 cure exist. The HIV latent reservoir, which exists in resting CD4+ T cells, is not impacted by ART, and can reactivate when ART is interrupted or ceased. Additionally, multi-drug resistance can arise. One alternate approach to conventional HIV-1 drug treatment that is being explored involves gene therapies utilizing RNA-directed gene regulation. Commonly known as RNA interference (RNAi, short interfering RNA (siRNA induce gene silencing in conserved biological pathways, which require a high degree of sequence specificity. This review will provide an overview of the silencing pathways, the current RNAi technologies being developed for HIV-1 gene therapy, current clinical trials, and the challenges faced in progressing these treatments into clinical trials.

  19. HIV viral load scale-up: multiple interventions to meet the HIV treatment cascade.

    Science.gov (United States)

    Carmona, Sergio; Peter, Trevor; Berrie, Leigh

    2017-03-01

    In 2015, the WHO urged countries to provide ART to all people living with HIV, irrespective of their CD4 cell count, this new recommendation supports the Joint United Nations Programme on HIV/AIDS elimination targets. However, to meet these aims, urgent scale-up of viral load testing is critical. The multiple interventions in the healthcare system required to support scale-up of viral load testing are reviewed here. It is estimated that 18.2 million individuals are accessing antiretroviral therapy, consequently this will cause significant demand for viral load monitoring; however, at the current rate of implementation, demand will not meet the required target by 2020. To change this trajectory, multiple stakeholders must be involved, communities and key populations need increased treatment literacy to create demand and greater numbers of healthcare workers will require training. In addition, laboratories and point-of-care testing sites will need to be expanded, and adequate monitoring and evaluation tools will need to be put in place to identify gaps in the system, to institute prompt corrective actions and to direct resources where needed. Sufficient scale-up of viral load may well be possible if innovations in mHealth are used to support healthcare workers and patients with regard to the scale-up and effective use of viral load monitoring; new laboratory technologies are implemented, both at a centralized level and point-of-care, to manage higher volumes and improve coverage; and there is careful coordination between implementing partners and funders.

  20. The network structure of sex partner meeting places reported by HIV-infected MSM: Opportunities for HIV targeted control.

    Science.gov (United States)

    Brantley, Meredith; Schumacher, Christina; Fields, Errol L; Perin, Jamie; Safi, Amelia Greiner; Ellen, Jonathan M; Muvva, Ravikiran; Chaulk, Patrick; Jennings, Jacky M

    2017-06-01

    Baltimore, Maryland ranks among U.S. cities with the highest incidence of HIV infection among men who have sex with men (MSM). HIV screening at sex partner meeting places or venues frequented by MSM with new diagnoses and/or high HIV viral load may reduce transmission by identifying and linking infected individuals to care. We investigated venue-based clustering of newly diagnosed MSM to identify high HIV transmission venues. HIV surveillance data from MSM diagnosed between October 2012-June 2014 and reporting ≥1 sex partner meeting place were examined. Venue viral load was defined according to the geometric mean viral load of the cluster of cases that reported the venue and classified as high (>50,000 copies/mL), moderate (1500-50,000 copies/mL), and low (place, accounting for 132 unique venues. Twenty-six venues were reported by > 1 MSM; of these, a tightly connected cluster of six moderate viral load sex partner meeting places emerged, representing 66% of reports. Small, dense networks of moderate to high viral load venues may be important for targeted HIV control among MSM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1.

    Science.gov (United States)

    Khamaikawin, Wannisa; Shimizu, Saki; Kamata, Masakazu; Cortado, Ruth; Jung, Yujin; Lam, Jennifer; Wen, Jing; Kim, Patrick; Xie, Yiming; Kim, Sanggu; Arokium, Hubert; Presson, Angela P; Chen, Irvin S Y; An, Dong Sung

    2018-06-15

    Investigations of anti-HIV-1 human hematopoietic stem/progenitor cell (HSPC)-based gene therapy have been performed by HIV-1 challenge after the engraftment of gene-modified HSPCs in humanized mouse models. However, the clinical application of gene therapy is to treat HIV-1-infected patients. Here, we developed a new method to investigate an anti-HIV-1 HSPC-based gene therapy in humanized mice previously infected with HIV-1. First, humanized mice were infected with HIV-1. When plasma viremia reached >107 copies/mL 3 weeks after HIV-1 infection, the mice were myeloablated with busulfan and transplanted with anti-HIV-1 gene-modified CD34+ HSPCs transduced with a lentiviral vector expressing two short hairpin RNAs (shRNAs) against CCR5 and HIV-1 long terminal repeat (LTR), along with human thymus tissue under the kidney capsule. Anti-HIV-1 vector-modified human CD34+ HSPCs successfully repopulated peripheral blood and lymphoid tissues in HIV-1 previously infected humanized mice. Anti-HIV-1 shRNA vector-modified CD4+ T lymphocytes showed selective advantage in HIV-1 previously infected humanized mice. This new method will be useful for investigations of anti-HIV-1 gene therapy when testing in a more clinically relevant experimental setting.

  2. Bone Marrow Gene Therapy for HIV/AIDS

    Science.gov (United States)

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-01-01

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described. PMID:26193303

  3. Bone Marrow Gene Therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Elena Herrera-Carrillo

    2015-07-01

    Full Text Available Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS caused by human immunodeficiency virus (HIV. This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described.

  4. NF45 and NF90 Bind HIV-1 RNA and Modulate HIV Gene Expression

    Directory of Open Access Journals (Sweden)

    Yan Li

    2016-02-01

    Full Text Available A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45 and nuclear factor 90 (NF90 as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1 replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 and NF90 diminished the enhancement of HIV infection and gene expression. Both proteins were found to interact with the HIV RNA. RNA decay assays demonstrated that NF90, but not NF45, increased the half-life of the HIV RNA. Overall, these studies indicate that both NF45 and NF90 potentiate HIV infection through their RNA binding domains.

  5. Challenges in Meeting HIV/AIDS Counselling Needs in Nigeria

    Science.gov (United States)

    Gesinde, Abiodun M.

    2012-01-01

    The HIV/AIDS pandemic is recognized globally as the greatest health challenge of the present generation. It is widely acknowledged to be the foremost killer disease in Africa. Since the first AIDS case was publicly announced in 1986, the astronomical increase in victims has been a matter of concern. The rates of HIV/AIDS infection indicate that…

  6. HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene.

    Science.gov (United States)

    Pandit, Aridaman; de Boer, Rob J

    2015-12-17

    Highly active antiretroviral therapy (ART) has successfully turned Human immunodeficiency virus type 1 (HIV-1) from a deadly pathogen into a manageable chronic infection. ART is a lifelong therapy which is both expensive and toxic, and HIV can become resistant to it. An alternative to lifelong ART is gene therapy that targets the CCR5 co-receptor and creates a population of genetically modified host cells that are less susceptible to viral infection. With generic mathematical models we show that gene therapy that only targets the CCR5 co-receptor fails to suppress HIV-1 (which is in agreement with current data). We predict that the same gene therapy can be markedly improved if it is combined with a suicide gene that is only expressed upon HIV-1 infection.

  7. Interleukin Gene Polymorphisms and Susceptibility to HIV Infection

    Indian Academy of Sciences (India)

    Chrysa

    analysis. Running head: Interleukin gene polymorphisms and HIV. Chrissa G. Tsiara,1,2 Georgios K. Nikolopoulos,3* Niki L. Dimou,4 Katerina G. Pantavou,3 Pantelis. G. Bagos,4 Benedicta Mensah,5 Michael Talias,6 Georgia G. Braliou,4 Dimitra ...

  8. HIV Pathogenesis: Abstracts from the March 2017 Cleveland Immunopathogenesis Consortium Meeting

    Directory of Open Access Journals (Sweden)

    Michael M. Lederman

    2017-06-01

    Full Text Available The Cleveland Immunopathogenesis Consortium (CLIC was launched in March 2004 by a small group of investigators (Ron Bosch, Jason Brenchley,  Steven Deeks, Danny Douek, Zvi Grossman, Robert Kalayjian, Clifford Harding, Michael Lederman, Leonid Margolis, Miguel Quinones, Benigno Rodriguez, Rafick Sekaly, Scott Sieg, and Guido Silvestri who were increasingly persuaded that immune activation was an important driver of HIV pathogenesis. We met around a chalk board and scribbled our models of pathogenesis, designed some experiments then went back home to do them. We met again soon to review our new and unpublished findings that refined and shaped these models. The data presentations were short, informal and heavy on discussion. The model worked well, the consortium was productive and the meetings catalyzed numerous collaborations and scores of high impact papers. The CLIC (less formally, the Bad Boys of Cleveland [1] has been meeting regularly since then. Consortium membership has expanded to include other investigators (some are listed in the presentations below. Whether the goal is to prevent the morbid complications of HIV infection, to understand the determinants of HIV persistence or the factors that protect from acquisition of infection, a more clear understanding of HIV immunopathogenesis is central. Here in this issue of Pathogens and Immunity is a brief summary of the most recent CLIC//BBC meeting held in Cleveland in March 2017.

  9. European AIDS Clinical Society Standard of Care meeting on HIV and related coinfections

    DEFF Research Database (Denmark)

    Mussini, C; Antinori, A; Bhagani, S

    2016-01-01

    diagnosed multi-drug-resistant cases. Hepatitis C is widespread in selected geographical areas and risk groups. CONCLUSIONS: The key conclusion from the meeting was that a high-priority group of actions could be identified, including: increasing HIV awareness and testing, improving training for health care......OBJECTIVES: The objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future. METHODS: Data-driven presentations were given on specific topics followed...... by interactive panel discussions. RESULTS: In Eastern European countries, the epidemic is largely driven by injecting drug use, in contrast with Western Europe where the infection mainly occurs through heterosexual contact. A high proportion of people living with HIV remain unaware of their infection...

  10. Gene Therapy Strategies for HIV/AIDS: Preclinical Modeling in Humanized Mice

    Science.gov (United States)

    Bennett, Michael S.; Akkina, Ramesh

    2013-01-01

    In the absence of an effective vaccine and lack of a complete cure, gene therapy approaches to control HIV infection offer feasible alternatives. Due to the chronic nature of infection, a wide window of opportunity exists to gene modify the HIV susceptible cells that continuously arise from the bone marrow source. To evaluate promising gene therapy approaches that employ various anti-HIV therapeutic molecules, an ideal animal model is necessary to generate important efficacy and preclinical data. In this regard, the humanized mouse models that harbor human hematopoietic cells susceptible to HIV infection provide a suitable in vivo system. This review summarizes the currently used humanized mouse models and different anti-HIV molecules utilized for conferring HIV resistance. Humanized mouse models are compared for their utility in this context and provide perspectives for new directions. PMID:24351796

  11. Harnessing Novel Imaging Approaches to Guide HIV Prevention and Cure Discoveries-A National Institutes of Health and Global HIV Vaccine Enterprise 2017 Meeting Report.

    Science.gov (United States)

    Sanders-Beer, Brigitte E; Voronin, Yegor; McDonald, David; Singh, Anjali

    2018-01-01

    Advances in imaging technologies have greatly increased our understanding of cellular and molecular interactions in humans and their corresponding animal models of infectious diseases. In the HIV/SIV field, imaging has provided key insights into mucosal viral transmission, local and systemic virus spread, host-virus dynamics, and chronic inflammation/immune activation and the resultant immunopathology. Recent developments in imaging applications are yielding physical, spatial, and temporal measurements to enhance insight into biological functions and disease processes, while retaining important cellular, microenvironmental, organ, and intact organism contextual details. Taking advantage of the latest advancements in imaging technologies may help answer important questions in the HIV field. The Global HIV Vaccine Enterprise in collaboration with the National Institutes of Health (NIH) sponsored a meeting on May 8 and 9, 2017 to provide a platform to review state-of-the-art imaging technologies and to foster multidisciplinary collaborations in HIV/AIDS research. The meeting covered applications of imaging in studies of early events and pathogenesis, reservoirs, and cure, as well as in vaccine development. In addition, presentations and discussions of imaging applications from non-HIV biomedical research areas were included. This report summarizes the presentations and discussions at the meeting.

  12. Codon usage of HIV regulatory genes is not determined by nucleotide composition.

    Science.gov (United States)

    Phakaratsakul, Supinya; Sirihongthong, Thanyaporn; Boonarkart, Chompunuch; Suptawiwat, Ornpreya; Auewarakul, Prasert

    2018-02-01

    Codon usage bias can be a result of either mutational bias or selection for translational efficiency and/or accuracy. Previous data has suggested that nucleotide composition constraint was the main determinant of HIV codon usage, and that nucleotide composition and codon usage were different between the regulatory genes, tat and rev, and other viral genes. It is not clear whether translational selection contributed to the codon usage difference and how nucleotide composition and translational selection interact to determine HIV codon usage. In this study, a model of codon bias due to GC composition with modification for the A-rich third codon position was used to calculate predicted HIV codon frequencies based on its nucleotide composition. The predicted codon usage of each gene was compared with the actual codon frequency. The predicted codon usage based on GC composition matched well with the actual codon frequencies for the structural genes (gag, pol and env). However, the codon usage of the regulatory genes (tat and rev) could not be predicted. Codon usage of the regulatory genes was also relatively unbiased showing the highest effective number of codons (ENC). Moreover, the codon adaptation index (CAI) of the regulatory genes showed better adaptation to human codons when compared to other HIV genes. Therefore, the early expressed genes responsible for regulation of the replication cycle, tat and rev, were more similar to humans in terms of codon usage and GC content than other HIV genes. This may help these genes to be expressed efficiently during the early stages of infection.

  13. Inhibition of HIV-1 Integrase gene expression by 10-23 DNAzyme

    Indian Academy of Sciences (India)

    We have designed three novel DNAzymes, DIN54, DIN116, and DIN152, against HIV-1 Integrase gene using Mfold software and evaluated them for target site cleavage activity on the in vitro transcribed mRNA. All DNAzymes were tested for its inhibition of expression of HIV Integrase protein in the transiently transfected cell ...

  14. Computational analysis of HIV-1 resistance based on gene expression profiles and the virus-host interaction network.

    Directory of Open Access Journals (Sweden)

    Tao Huang

    Full Text Available A very small proportion of people remain negative for HIV infection after repeated HIV-1 viral exposure, which is called HIV-1 resistance. Understanding the mechanism of HIV-1 resistance is important for the development of HIV-1 vaccines and Acquired Immune Deficiency Syndrome (AIDS therapies. In this study, we analyzed the gene expression profiles of CD4+ T cells from HIV-1-resistant individuals and HIV-susceptible individuals. One hundred eighty-five discriminative HIV-1 resistance genes were identified using the Minimum Redundancy-Maximum Relevance (mRMR and Incremental Feature Selection (IFS methods. The virus protein target enrichment analysis of the 185 HIV-1 resistance genes suggested that the HIV-1 protein nef might play an important role in HIV-1 infection. Moreover, we identified 29 infection information exchanger genes from the 185 HIV-1 resistance genes based on a virus-host interaction network analysis. The infection information exchanger genes are located on the shortest paths between virus-targeted proteins and are important for the coordination of virus infection. These proteins may be useful targets for AIDS prevention or therapy, as intervention in these pathways could disrupt communication with virus-targeted proteins and HIV-1 infection.

  15. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection

    National Research Council Canada - National Science Library

    Wenhui Hu; Rafal Kaminski; Fan Yang; Yonggang Zhang; Laura Cosentino; Fang Li; Biao Luo; David Alvarez-Carbonell; Yoelvis Garcia-Mesa; Jonathan Karn; Xianming Mo; Kamel Khalili

    2014-01-01

    .... We identified highly specific targets within the HIV-1 LTR U3 region that were efficiently edited by Cas9/gRNA, inactivating viral gene expression and replication in latently infected microglial...

  16. Performance of ultra-deep pyrosequencing in analysis of HIV-1 pol gene variation

    National Research Council Canada - National Science Library

    Mild, Mattias; Hedskog, Charlotte; Jernberg, Johanna; Albert, Jan

    2011-01-01

    .... In this study the UDPS technology (FLX platform) was evaluated by analyzing a 120 base pair fragment of the HIV-1 pol gene from plasma samples from two patients and artificial mixtures of molecular clones...

  17. Serological detection of attenuated HIV-1 variants with nef gene deletions.

    Science.gov (United States)

    Greenway, A L; Mills, J; Rhodes, D; Deacon, N J; McPhee, D A

    1998-04-16

    To investigate whether members of a transfusion-linked cohort (the Sydney Bloodbank Cohort) infected with a nef-deleted strain of HIV-1 could be differentiated from individuals infected with wild-type strains of HIV-1 by characterizing the Nef antibody response of cohort members. Retrospective and prospective analysis of the nef gene sequence and the antibody response to Nef peptides in HIV-infected subjects. Plasma was obtained from all individuals of the Sydney cohort, and from a variety of HIV-1-infected and uninfected controls. Antibodies recognizing full-length recombinant HIV-1NL43 Nef protein and synthetic peptide analogues were assessed by enzyme-linked immunosorbent assay. All 34 individuals infected with wild-type HIV-1 had antibodies reacting with full-length Nef protein as well as with a series of synthetic peptides (6-23-mers) spanning most of the Nef protein of HIV-1NL43. Although the HIV-1 quasispecies infecting the Sydney cohort had a consensus deletion of the nef gene corresponding to amino-acids 165-206, HIV-1 strains from individual members of the cohort had additional deletions comprising up to 80% of the nef gene. Members of the cohort had antibodies to peptides homologous to all regions of the Nef protein tested, except for a single peptide (amino-acids 162-177) that lies within the consensus nef deletion for the cohort quasispecies. These data show that nef-deleted strains of HIV-1 can be detected serologically. In the Sydney cohort, detection of antibodies to all regions of Nef tested, except that corresponding to amino-acids 162-177, suggests that observed deletions outside this domain occurred after this virus had infected these subjects and stimulated an immune response. A Nef peptide serological assay may be useful for identifying further examples of individuals infected with nef-deleted, attenuated HIV-1 quasispecies and for assessing the evolution of those variants in vivo.

  18. Combinatorial Anti-HIV Gene Therapy: Using a Multi-Pronged Approach to Reach Beyond HAART

    Science.gov (United States)

    Peterson, Christopher W; Younan, Patrick; Jerome, Keith R; Kiem, Hans-Peter

    2013-01-01

    The “Berlin Patient,” who maintains suppressed levels of HIV viremia in the absence of antiretroviral therapy, continues to be a standard bearer in HIV eradication research. However, the unique circumstances surrounding his functional cure are not applicable to most HIV+ patients. To achieve a functional or sterilizing cure in a greater number of infected individuals worldwide, combinatorial treatments, targeting multiple stages of the viral life cycle, will be essential. Several anti-HIV gene therapy approaches have recently been explored, including disruption of the CCR5 and CXCR4 coreceptor loci in CD4+ T-cells and CD34+ hematopoietic stem cells. However, less is known about the efficacy of these strategies in patients and more relevant HIV model systems such as nonhuman primates. Combinatorial approaches, including genetic disruption of integrated provirus, functional enhancement of endogenous restriction factors, and/or the use of pharmacological adjuvants, could amplify the anti-HIV effects of CCR5/CXCR4 gene disruption. Importantly, delivering gene disruption molecules to genetic sites of interest will likely require optimization on a cell type-by-cell type basis. In this review, we highlight the most promising gene therapy approaches to combat HIV infection, methods to deliver these therapies to hematopoietic cells, and emphasize the need to target viral replication pre- and post-entry in order to mount a suitably robust defense against spreading infection. PMID:23364313

  19. Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART.

    Science.gov (United States)

    Peterson, C W; Younan, P; Jerome, K R; Kiem, H-P

    2013-07-01

    The 'Berlin Patient', who maintains suppressed levels of HIV viremia in the absence of antiretroviral therapy, continues to be a standard bearer in HIV eradication research. However, the unique circumstances surrounding his functional cure are not applicable to most HIV(+) patients. To achieve a functional or sterilizing cure in a greater number of infected individuals worldwide, combinatorial treatments, targeting multiple stages of the viral life cycle, will be essential. Several anti-HIV gene therapy approaches have been explored recently, including disruption of the C-C chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) coreceptor loci in CD4(+) T cells and CD34(+) hematopoietic stem cells. However, less is known about the efficacy of these strategies in patients and more relevant HIV model systems such as non-human primates (NHPs). Combinatorial approaches, including genetic disruption of integrated provirus, functional enhancement of endogenous restriction factors and/or the use of pharmacological adjuvants, could amplify the anti-HIV effects of CCR5/CXCR4 gene disruption. Importantly, delivering gene disruption molecules to genetic sites of interest will likely require optimization on a cell type-by-cell type basis. In this review, we highlight the most promising gene therapy approaches to combat HIV infection, methods to deliver these therapies to hematopoietic cells and emphasize the need to target viral replication pre- and post-entry to mount a suitably robust defense against spreading infection.

  20. Sex Partner Meeting Places Over Time Among Newly HIV-Diagnosed Men Who Have Sex With Men in Baltimore, Maryland.

    Science.gov (United States)

    Jennings, Jacky M; Reilly, Meredith L; Perin, Jamie; Schumacher, Christina; Sharma, Megha; Safi, Amelia Greiner; Fields, Errol L; Muvva, Ravikiran; Nganga-Good, Carolyn; Chaulk, Patrick

    2015-10-01

    Sex partner meeting places may be important locales to access men who have sex with men (MSM) and implement targeted HIV control strategies. These locales may change over time, but temporal evaluations have not been performed. The objectives of this study were to describe the frequency of report of MSM sex partner meeting places over time and to compare frequently reported meeting places in the past 5 years and past year among newly HIV-diagnosed MSM in Baltimore City, Maryland. Public health HIV surveillance data including partner services information were obtained for this study from the Baltimore City Health Department from May 2009 to June 2014. A total of 869 sex partner meeting places were reported, including 306 unique places. Bars/clubs (31%) and Internet-based sites (38%) were the most frequently reported meeting place types. Over the 5-year period, the percentage of bars/clubs decreased over time and the percentage of Internet-based sites increased over time. Among bars/clubs, 4 of 5 of those most frequently reported in the past 5 years were also most frequently reported in the most recent year. Among Internet-based sites, 3 of 5 of those most frequently reported in the past 5 years were also in the top 5 most frequently reported in the past year. This study provides a richer understanding of sex partner meeting places reported by MSM over time and information to health departments on types of places to access a population at high risk for HIV transmission.

  1. Sex partner meeting places over time among newly HIV diagnosed men who have sex with men (MSM) in Baltimore, Maryland

    Science.gov (United States)

    Jennings, Jacky M.; Reilly, Meredith L.; Perin, Jamie; Schumacher, Christina; Sharma, Megha; Safi, Amelia Greiner; Fields, Errol L.; Muvva, Ravikiran; Nganga-Good, Carolyn; Chaulk, Patrick

    2015-01-01

    Background Sex partner meeting places may be important locales to access men who have sex with men (MSM) and implement targeted human immunodeficiency virus (HIV) control strategies. These locales may change over time, but temporal evaluations have not been performed. Methods The objectives of this study were to describe the frequency of report of MSM sex partner meeting places over time, and to compare frequently reported meeting places in the past five years and past year among newly HIV diagnosed MSM in Baltimore City, Maryland. Public health HIV surveillance data including partner services information was obtained for this study from the Baltimore City Health Department from May 2009 to June 2014. Results 869 sex partner meeting places were reported, including 306 unique places. Bars/clubs (31%) and internet-based sites (38%) were the most frequently reported meeting place types. Over the five year period, the percentage of bars/clubs decreased over time and the percentage of internet-based sites increased over time. Among bars/clubs, 4/5 of those most frequently reported in the past five years were also most frequently reported in the most recent year. Among internet-based sites, 3/5 of those most frequently reported in the past five years were also in the top five most frequently reported in the past year. Conclusion This study provides a richer understanding of sex partner meeting places reported by MSM over time and information to health departments on types of places to access a population at high risk for HIV transmission. PMID:26372926

  2. Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy

    Science.gov (United States)

    Browning, Diana L.; Trobridge, Grant D.

    2016-01-01

    Retroviral vector gene therapy is a promising approach to treating HIV-1. However, integrated vectors are mutagens with the potential to dysregulate nearby genes and cause severe adverse side effects. Leukemia has already been a documented severe adverse event in gene therapy clinical trials for the treatment of primary immunodeficiencies. These side effects will need to be reduced or avoided if retroviral vectors are to be used clinically for HIV-1 treatment. The addition of chromatin insulators to retroviral vectors is a potential strategy for reducing adverse side effects. Insulators have already been effectively used in retroviral vectors to reduce genotoxicity in pre-clinical studies. Here, we will review how insulators function, genotoxicity in gene therapy clinical trials, the design of insulated retroviral vectors, promising results from insulated retroviral vector studies, and considerations for the development of insulated retroviral treatment vectors for HIV-1 gene therapy. PMID:28424756

  3. 78 FR 79699 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-12-31

    ... No. FDA-2013-N-0001] Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting... the public. Name of Committee: Cellular, Tissue, and Gene Therapies Advisory Committee. General..., Tissue, and Gene Therapies, Center for Biologics Evaluation and Research (CBER), FDA. On February 26...

  4. RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS).

    Science.gov (United States)

    Shendre, Aditi; Irvin, Marguerite R; Aouizerat, Bradley E; Wiener, Howard W; Vazquez, Ana I; Anastos, Kathryn; Lazar, Jason; Liu, Chenglong; Karim, Roksana; Limdi, Nita A; Cohen, Mardge H; Golub, Elizabeth T; Zhi, Degui; Kaplan, Robert C; Shrestha, Sadeep

    2014-04-01

    Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women's Interagency HIV Study (WIHS). CCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel's method and haplotype association analyses were conducted among the three races separately. SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41×10(-5)), rs11856930 among Whites (p=5.62×10(-4)), and rs2572204 among Blacks (p=2.45×10(-3)). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics. Consistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Kristoffersen, Ulrik Sloth; Pedersen, Sune Folke

    2009-01-01

    endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1...... transgenic (HIV-1Tg) rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1...... was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV...

  6. HIV-infection, atherosclerosis and the inflammatory pathway: candidate gene study in a Spanish HIV-infected population.

    Directory of Open Access Journals (Sweden)

    Laura Ibáñez

    Full Text Available BACKGROUND: Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection. METHODS & FINDINGS: In this study we have tested the possible association between genetic variants in several inflammatory genes and asymptomatic cardiovascular disease measured by carotid intima media thickness (cIMT and atherosclerotic plaque presence as dependent variables in 213 HIV-infected individuals. A total of 101 genetic variants in 25 candidate genes have been genotyped. Results were analyzed using Plink and SPSS statistical packages. We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009, ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004, CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015 and CCL5 (rs3817655 p = 0.018 and rs2107538 p = 0.018 associated with atherosclerotic plaque. cIMT mean has been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008, IL1RN (rs380092 p = 0.002 and ALOX5AP (rs3885907 p = 0.02 genetic variants. CONCLUSIONS: In this study we have found modest associations between genetic variants in several inflammatory genes and atherosclerotic plaque or cIMT. Nevertheless, our study adds evidence to the association between inflammatory pathway genetic variants and the atherosclerotic disease in HIV-infected individuals.

  7. Differential effects of hnRNP D/AUF1 isoforms on HIV-1 gene expression

    Science.gov (United States)

    Lund, Nicole; Milev, Miroslav P.; Wong, Raymond; Sanmuganantham, Tharmila; Woolaway, Kathryn; Chabot, Benoit; Abou Elela, Sherif; Mouland, Andrew J.; Cochrane, Alan

    2012-01-01

    Control of RNA processing plays a major role in HIV-1 gene expression. To explore the role of several hnRNP proteins in this process, we carried out a siRNA screen to examine the effect of depletion of hnRNPs A1, A2, D, H, I and K on HIV-1 gene expression. While loss of hnRNPs H, I or K had little effect, depletion of A1 and A2 increased expression of viral structural proteins. In contrast, reduced hnRNP D expression decreased synthesis of HIV-1 Gag and Env. Loss of hnRNP D induced no changes in viral RNA abundance but reduced the accumulation of HIV-1 unspliced and singly spliced RNAs in the cytoplasm. Subsequent analyses determined that hnRNP D underwent relocalization to the cytoplasm upon HIV-1 infection and was associated with Gag protein. Screening of the four isoforms of hnRNP D determined that, upon overexpression, they had differential effects on HIV-1 Gag expression, p45 and p42 isoforms increased viral Gag synthesis while p40 and p37 suppressed it. The differential effect of hnRNP D isoforms on HIV-1 expression suggests that their relative abundance could contribute to the permissiveness of cell types to replicate the virus, a hypothesis subsequently confirmed by selective depletion of p45 and p42. PMID:22187150

  8. HIV and Mass Incarceration: Where Infectious Diseases and Social Justice Meet.

    Science.gov (United States)

    Wohl, David Alain

    2016-01-01

    More than 1% of all adults in the United States are currently in a jail or prison. This mass incarceration, particularly of African American men, fosters conditions that facilitate the spread of HIV in communities where both HIV and incarceration are endemic. Recognition of the role of mass incarceration in the perpetuation of the HIV epidemic is essential to development of effective HIV prevention policies. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

  9. Low concordance and resistance mutation emergence in the HIV protease gene among circulating and cell-associated viruses at viral replication episodes during darunavir/ritonavir monotherapy.

    Science.gov (United States)

    Torres-Cornejo, A; Benmarzouk-Hidalgo, O J; Gutierrez-Valencia, A; Ruiz-Valderas, R; Viciana, P; López-Cortés, L F

    2015-01-01

    To assess the changes on the HIV protease gene in plasma and peripheral blood mononuclear cell (PBMC) compartments during viral replication episodes in patients on boosted-darunavir monotherapy (mtDRV/rtv). A prospective study was carried out in which adult HIV-1-infected patients who started mtDRV/rtv after viral suppression for ≥ 6 months with no major darunavir-related resistance mutations were enrolled. Patients with two consecutive plasma HIV RNA measurements >200 HIV-1 RNA copies/mL were considered as having virological failure (VF), while patients with two consecutive plasma HIV RNA measurements >50 copies/mL without meeting the VF criteria were considered to have virological rebound (VR). HIV protease genotypic profiles from plasma and PBMCs were performed at baseline and at VF and VR episodes. One hundred and fifty patients were included in the study, with overall VF and VR rates of 14% (n=21) and 14.7% (n=22), respectively. No major darunavir resistance mutations were observed in the plasma or PBMC samples. Circulating and cell-associated viruses showed a wild-type protease gene sequence in 54% and 23% of patients, respectively while the remainder patients only harboured minor protease inhibitor-associated mutations. Full concordance between plasma RNA and PBMC DNA protease genotypes was found in 23% of the sequences. No darunavir-related mutations were found in patients with VF or VR, either in plasma or in PBMCs; thus, simplification to mtDRV/rtv does not comprise future antiretroviral treatment options. © 2014 British HIV Association.

  10. Different pattern of immunoglobulin gene usage by HIV-1 compared to non-HIV-1 antibodies derived from the same infected subject.

    Science.gov (United States)

    Li, Liuzhe; Wang, Xiao-Hong; Banerjee, Sagarika; Volsky, Barbara; Williams, Constance; Virland, Diana; Nadas, Arthur; Seaman, Michael S; Chen, Xuemin; Spearman, Paul; Zolla-Pazner, Susan; Gorny, Miroslaw K

    2012-01-01

    A biased usage of immunoglobulin (Ig) genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs) resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP) expressing HIV-1 envelope (Env) proteins of JRFL and BaL and control VLPs (without Env) were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis.

  11. Different pattern of immunoglobulin gene usage by HIV-1 compared to non-HIV-1 antibodies derived from the same infected subject.

    Directory of Open Access Journals (Sweden)

    Liuzhe Li

    Full Text Available A biased usage of immunoglobulin (Ig genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP expressing HIV-1 envelope (Env proteins of JRFL and BaL and control VLPs (without Env were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis.

  12. Genetic association of IL-10 gene promoter polymorphism and HIV-1 infection in North Indians.

    Science.gov (United States)

    Chatterjee, Animesh; Rathore, Anurag; Sivarama, P; Yamamoto, Naohiko; Dhole, Tapan N

    2009-01-01

    Cytokines play a significant role in host immune defense. IL-10 is an anti-inflammatory, immunomodulatory cytokine that can both stimulate and suppress the immune response and inhibits HIV-1 replication in vivo. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to investigate the association of IL-10 gene promoter -1082 G/A, -819 C/T, and 592 C/A polymorphism on HIV-1 transmission /progression in North Indian individuals. A total of 180 HIV-1 seropositive (HSP) stratified on the basis of disease severity (stage I, II, and III), 50 HIV-1 exposed seronegative (HES) and 305 HIV-1 seronegative (HSN) individuals were genotyped for IL-10 gene promoter by polymerase chain reaction-restriction fragment length polymorphism. A suggestive evidence of association was obtained for IL-10 592 C/A promoter polymorphism at the level of allele and genotype distribution. The frequency of IL-10 592 A allele and genotype was significantly increased in HSP compared to HSN (p = 0.013; OR = 1.412 and p = 0.034; OR = 1.685 respectively). Further comparison in between different clinical stages of HIV-1 infected patients of IL-10 592 A allele and genotype revealed a significant increase in its frequency in the stage III compared with those together in stage I (p = 0.004, OR = 2.181 and p = 0.002, OR = 4.156, respectively). This study reports for the first time that IL-10 gene promoter 592 C/A polymorphism may be a risk factor for HIV-1 transmission/progression in HIV-1 infected North Indian individuals.

  13. The Envelope Gene of Transmitted HIV-1 Resists a Late Interferon Gamma-Induced Block.

    Science.gov (United States)

    Rihn, Suzannah J; Foster, Toshana L; Busnadiego, Idoia; Aziz, Muhamad Afiq; Hughes, Joseph; Neil, Stuart J D; Wilson, Sam J

    2017-04-01

    Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFN-γ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFN-γ stimulation can induce an antiviral state that can be both distinct from that of type I interferon and can potently inhibit HIV-1 in primary CD4(+) T cells and a number of human cell lines. Strikingly, we find that transmitted/founder (TF) HIV-1 viruses can resist a late block that is induced by type II IFN, and the use of chimeric IFN-γ-sensitive/resistant viruses indicates that interferon resistance maps to the env gene. Simultaneously, in vitro evolution also revealed that just a single amino acid substitution in the envelope can confer substantial resistance to IFN-mediated inhibition. Thus, the env gene of transmitted HIV-1 confers resistance to a late block that is phenotypically distinct from blocks previously described to be resisted by env and is therefore mediated by unknown IFN-γ-stimulated factor(s) in human CD4(+) T cells and cell lines. This important unidentified block could play a key role in constraining HIV-1 transmission.IMPORTANCE The human immune system can hinder invading pathogens through interferon (IFN) signaling. One consequence of this signaling is that cells enter an antiviral state, increasing the levels of hundreds of defenses that can inhibit the replication and spread of viruses. The majority of HIV-1 infections result from a single virus particle (the transmitted/founder) that makes it past these defenses and colonizes the host. Thus, the founder virus is hypothesized to be a relatively interferon-resistant entity. Here, we show that certain HIV-1 envelope genes have the unanticipated ability to resist specific human defenses mediated by different types of interferons. Strikingly, the envelope gene

  14. 78 FR 15726 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-03-12

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and recommendations to...

  15. 76 FR 18768 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-04-05

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue, and Gene Therapies Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Cellular, Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and recommendations to...

  16. 76 FR 42128 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2011-07-18

    ... call meeting is for PACHA members to discuss their ``game changing'' recommendations letter to the... hold a meeting. The meeting will be conducted as a telephone conference call. The meeting will be open to the public through a conference call phone number. DATES: The meeting will be on August 2, 2011...

  17. Copy number variation of KIR genes influences HIV-1 control

    DEFF Research Database (Denmark)

    Pelak, Kimberly; Need, Anna C; Fellay, Jacques

    2011-01-01

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses...... the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3...... amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection....

  18. Mechanism of Interferon-Stimulated Gene Induction in HIV-1-Infected Macrophages.

    Science.gov (United States)

    Nasr, Najla; Alshehri, Abdullateef A; Wright, Thomas K; Shahid, Maryam; Heiner, Bonnie M; Harman, Andrew N; Botting, Rachel A; Helbig, Karla J; Beard, Michael R; Suzuki, Kazuo; Kelleher, Anthony D; Hertzog, Paul; Cunningham, Anthony L

    2017-10-15

    Viruses manipulate the complex interferon and interferon-stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells, many of which are antiviral. Here, we examine the mechanism of induction of ISGs and show this occurs in two phases. The first phase was transient (0 to 24 h postinfection [hpi]), induced mainly by extracellular vesicles and one of its component proteins, HSP90α, contained within the HIV inoculum. The second, dominant, and persistent phase (>48 hpi) was induced via newly transcribed HIV RNA and sensed via RIGI, as shown by the reduction in ISG expression after the knockdown of the RIGI adaptor, MAVS, by small interfering RNA (siRNA) and the inhibition of both the initiation and elongation of HIV transcription by short hairpin RNA (shRNA) transcriptional silencing. We further define the induction pathway, showing sequential HIV RNA stimulation via Tat, RIGI, MAVS, IRF1, and IRF7, also identified by siRNA knockdown. IRF1 also plays a key role in the first phase. We also show that the ISGs IFIT1 to -3 inhibit HIV production, measured as extracellular infectious virus. All induced antiviral ISGs probably lead to restriction of HIV replication in macrophages, contributing to a persistent, noncytopathic infection, while the inhibition of interferon facilitates spread to adjacent cells. Both may influence the size of macrophage HIV reservoirs in vivo Elucidating the mechanisms of ISG induction may help in devising immunotherapeutic strategies to limit the size of these reservoirs.IMPORTANCE HIV, like other viruses, manipulates the antiviral interferon and interferon-stimulated gene (ISG) system to facilitate its initial infection and establishment of viral reservoirs. HIV specifically inhibits all type I and III interferons in its target cells, including macrophages, dendritic cells, and T cells

  19. Hot News: Gene Therapy with CRISPR/Cas9 Coming to Age for HIV Cure.

    Science.gov (United States)

    Soriano, Vicente

    2017-01-01

    The huge success of current antiretroviral therapy is mediated by a triple effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the risk of transmission to contacts (treatment as prevention); and (iii) minimizing the risk of HIV acquisition treating uninfected persons at risk (pre-exposure prophylaxis). However, UNAIDS has estimated that only 70% of infected people globally are diagnosed, only 53% are treated, and overall 44% have undetectable viral load, which is the necessary request for ensuring any antiretroviral benefit. Thus, with 37 million people currently living with HIV worldwide and more than 2 million new infections per year, the prospects for global HIV eradication are far on the horizon. Over the past couple of years, rapid development has been seen for technologies enabling modification of gene expression, either by direct inhibition by RNA interference (RNAi) or by genomic modification at DNA level. In particular, genome-editing endonucleases have significantly improved our ability to make precise changes in the DNA of eukaryotic cells. Notably, firstgeneration genome-editing technologies (i.e., ZFNs and TALENs) have been replaced by clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), which work with a short guide RNA (gRNA) to hybridize to a target DNA site and recruit the Cas9 endonuclease. Once integrated into the host genome, HIV gene expression is regulated by the LTR promoter. Hypothetically, gene editing of the HIV promoter might have the potential to deactivate viral transcription by the introduction of mutations or fragment excision. HIV gene therapy progressed very slowly until recent breakthroughs in gene-editing methods using CRISPR/Cas9 (Liao et al. Nat Commun 2015;6:6413). Using a shorter version of the Cas9 endonuclease ensembled into an adenoviral vector, critical segments of thAQ!e viral DNA genome spanning between the LTR and gag regions were successfully removed in HIV transgenic mice

  20. HIV-1 infection causes a down-regulation of genes involved in ribosome biogenesis.

    Directory of Open Access Journals (Sweden)

    Claudia L Kleinman

    Full Text Available HIV-1 preferentially infects CD4+ T cells, causing fundamental changes that eventually lead to the release of new viral particles and cell death. To investigate in detail alterations in the transcriptome of the CD4+ T cells upon viral infection, we sequenced polyadenylated RNA isolated from Jurkat cells infected or not with HIV-1. We found a marked global alteration of gene expression following infection, with an overall trend toward induction of genes, indicating widespread modification of the host biology. Annotation and pathway analysis of the most deregulated genes showed that viral infection produces a down-regulation of genes associated with the nucleolus, in particular those implicated in regulating the different steps of ribosome biogenesis, such as ribosomal RNA (rRNA transcription, pre-rRNA processing, and ribosome maturation. The impact of HIV-1 infection on genes involved in ribosome biogenesis was further validated in primary CD4+ T cells. Moreover, we provided evidence by Northern Blot experiments, that host pre-rRNA processing in Jurkat cells might be perturbed during HIV-1 infection, thus strengthening the hypothesis of a crosstalk between nucleolar functions and viral pathogenesis.

  1. RANTES Gene Polymorphisms Associated with HIV-1 Infections in Kenyan Population

    Directory of Open Access Journals (Sweden)

    Shem P. M. Mutuiri

    2016-01-01

    Full Text Available Previous studies have reported that two single nucleotide polymorphisms (SNPs in the RANTES gene promoter region, -403G/A and -28C/G, are associated with a slower rate of decline in CD4+ T cell count. In addition, as a ligand of the major HIV coreceptor CCR5, it is known to block HIV-CCR5 interactions in the course of the HIV infection cycle. This study was carried out with the aim of determining the occurrence of single nucleotide polymorphisms (SNPs -403G > A and -28C > G in the promoter region of RANTES, in a subset of the Kenyan population. Genomic DNA was extracted from peripheral blood monocular cells and used to amplify the RANTES gene region. Restriction fragment length polymorphism was used to determine the genotypes of the RANTES gene. Out of 100 HIV infected individuals, 19% had G1 genotypes (403G/G, 28C/G, 30% (403A/A, 28C/C, and 50% (403G/A, 28C/C, while in healthy blood donors 13% had G4 (403G/A, 28C/C genotypes, 22% (403A/A, 28C/C, and 54% (403G/A, 28C/C. HIV negative blood donors (54% had higher risk of alteration to risk of HIV transmission compared to those who were HIV infected (50%. However, the risk to transmission and distribution differences was not significant (P=0.092. The study showed that RANTES polymorphisms -403 and -28 alleles do exist in the Kenyan population.

  2. Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients

    Directory of Open Access Journals (Sweden)

    M Held

    2017-10-01

    Full Text Available Background. GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. Objectives. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. Methods. A prospective study of patients with suspected musculoskeletal (bone and joint TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. Results. A total of 206 biopsies from 201 patients (23% HIV-infected were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91 and 99.1% (114/115, respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3% v. 76/91 (83.5%, respectively; p=0.069. GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32 v. 89.6% (43/48 in HIV-uninfected patients (p=0.225. Conclusion. GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB.

  3. Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients.

    Science.gov (United States)

    Held, M; Laubscher, M; Workman, L; Zar, H J; Dunn, R

    2017-09-22

    GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225). GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB.

  4. A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Gueckel Eva

    2011-01-01

    Full Text Available Abstract Background Regulated expression of suicide genes is a powerful tool to eliminate specific subsets of cells and will find widespread usage in both basic and applied science. A promising example is the specific elimination of human immunodeficiency virus type 1 (HIV-1 infected cells by LTR-driven suicide genes. The success of this approach, however, depends on a fast and effective suicide gene, which is expressed exclusively in HIV-1 infected cells. These preconditions have not yet been completely fulfilled and, thus, success of suicide approaches has been limited so far. We tested truncated Bid (tBid, a human pro-apoptotic protein that induces apoptosis very rapidly and efficiently, as suicide gene for gene therapy against HIV-1 infection. Results When tBid was introduced into the HIV-1 LTR-based, Tat- and Rev-dependent transgene expression vector pLRed(INS2R, very efficient induction of apoptosis was observed within 24 hours, but only in the presence of both HIV-1 regulatory proteins Tat and Rev. Induction of apoptosis was not observed in their absence. Cells containing this vector rapidly died when transfected with plasmids containing full-length viral genomic DNA, completely eliminating the chance for HIV-1 replication. Viral replication was also strongly reduced when cells were infected with HIV-1 particles. Conclusions This suicide vector has the potential to establish a safe and effective gene therapy approach to exclusively eliminate HIV-1 infected cells before infectious virus particles are released.

  5. 76 FR 55912 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2011-09-09

    .... Melvin Joppy, Committee Manager, Presidential Advisory Council on HIV/AIDS, Department of Health and... prominent community leaders with particular expertise in, or knowledge of, matters concerning HIV and AIDS, public health, global health, philanthropy, marketing or business, as well as other national leaders held...

  6. Meeting the challenge of HIV/AIDS: Marrying formal and informal ...

    African Journals Online (AJOL)

    This stance entails the threading together of the elements of language, the human mind and facilitator cognition and training. This is because facilitators' applied competence around HIV/AIDS issues, plays a crucial role in their capacities to effectively link sexual cultural beliefs, practices and knowledge to HIV/AIDS content ...

  7. The impact of unprotected T cells in RNAi-based gene therapy for HIV-AIDS

    NARCIS (Netherlands)

    Herrera-Carrillo, Elena; Liu, Ying Poi; Berkhout, Ben

    2014-01-01

    RNA interference (RNAi) is highly effective in inhibiting human immunodeficiency virus type 1 (HIV-1) replication by the expression of antiviral short hairpin RNA (shRNA) in stably transduced T-cell lines. For the development of a durable gene therapy that prevents viral escape, we proposed to

  8. Meeting

    Indian Academy of Sciences (India)

    At the invitation of the Regional Research laboratory, Hyderabad, the Academy held its 53rd. Annual Meeting at RRl from Saturday 7 November to Monday 9 November 1987. The meeting began with the inaugural function in the RRl Auditorium at 0930 hours on Saturday 7. November. Dr A V Rama Rao, Director, RRL,.

  9. Gene Therapy of T Helper Cells in HIV Infection. Mathematical Model of the Criteria for Clinical Effect

    DEFF Research Database (Denmark)

    Lund, Ole; Lund, Ole søgaard; Gram, Gregers

    1997-01-01

    The paper presents a mathematical model of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. Our main results are that the therapy should be designed to give the transduced cells a significant but not necessarily total protection against HIV-induced cell...... deaths, and to avoid the production of viral mutants that are insensitive to gene therapy. The transduced cells will not survive if the gene therapy only blocks the spread of virus....

  10. Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies

    Science.gov (United States)

    Kepler, Thomas B.; Liao, Hua-Xin; Alam, S. Munir; Bhaskarabhatla, Rekha; Zhang, Ruijun; Stewart, Shelley; Anasti, Kara; Kelsoe, Garnett; Parks, Robert; Lloyd, Krissey E.; Stolarchuk, Christina; Pritchett, Jamie; Solomon, Erika; Friberg, Emma; Morris, Lynn; Karim, Salim S. Abdool; Cohen, Myron S.; Walter, Emmanuel; Moody, M. Anthony; Wu, Xueling; Altae-Tran, Han R.; Georgiev, Ivelin S.; Kwong, Peter D.; Boyd, Scott D.; Fire, Andrew Z.; Mascola, John R.; Haynes, Barton F.

    2014-01-01

    Summary Induction of HIV-1 broad neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development but has remained challenging partially due to unusual traits of bnAbs, including high somatic hypermutation (SHM) frequencies and in-frame insertions and deletions (indels). Here we examined the propensity and functional requirement for indels within HIV-1 bnAbs. High-throughput sequencing of the immunoglobulin (Ig) VHDJH genes in HIV-1 infected and uninfected individuals revealed that the indel frequency was elevated among HIV-1-infected subjects, with no unique properties attributable to bnAb-producing individuals. This increased indel occurrence depended only on the frequency of SHM point-mutations. Indel-encoded regions were generally proximal to antigen binding sites. Additionally, reconstruction of a HIV-1 CD4-binding site bnAb clonal lineage revealed that a large compound VHDJH indel was required for bnAb activity. Thus, vaccine development should focus on designing regimens targeted at sustained activation of bnAb lineages to achieve the required SHM and indel events. PMID:25211073

  11. Intrahost and interhost variability of the HIV type 1 nef gene in Brazilian children.

    Science.gov (United States)

    Cavalieri, Elizabeth; Florido, Camila; Leal, Elcio; Machado, Daisy Maria; Camargo, Michelle; Diaz, Ricardo S; Janini, Luiz Mario

    2009-11-01

    Many aspects of HIV-1 pathogenesis are affected by Nef protein activity, and efforts have been made to study variation in the nef gene and how that variation relates to disease outcome. We studied the genetic diversity of the nef gene in distinct clones obtained from the same patient (intrahost) and in sequences obtained from different hosts (interhost). The set of sequences analyzed was obtained from HIV-1-infected Brazilian children and contained 112 clones from 25 children (intrahost samples), as well as 55 sequences from epidemiologically unlinked children (interhost samples). We found extensive site polymorphisms and amino acid length variations, mainly in the amino terminal region of the nef gene, between the myristoylation motif (MGxxxS) and the MHC-1 downregulation motif (Rxx). Analysis of the sequences deposited in the Los Alamos HIV sequences database ( www.hiv.lanl.gov ) indicated that the most frequent motif at the MHC-1 downregulation site in the subtype B strain is R(86%)A(64%)E(82%) (n = 1040) and R(78%)T(74%)E(56%) in the subtype C strain (n = 549). Conversely, the Brazilian subtype B isolates presented the motif R(81%)T(62%)E(67%) at this site (n = 64). A detailed analysis of selective pressures identified a concentration of codons under strong positive selection in the amino terminal region of the nef gene. We also determined that different sites are under positive selection in the subtype B and subtype C viruses. The amino acid composition in the MHC-1 downregulation motif of the nef gene in our sequences may indicate a distinct adaptive pattern of HIV-1 subtype B to the Brazilian host population.

  12. Copy number variation of KIR genes influences HIV-1 control

    DEFF Research Database (Denmark)

    Pelak, Kimberly; Need, Anna C; Fellay, Jacques

    2011-01-01

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses...... the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3...... individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative...

  13. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

    Directory of Open Access Journals (Sweden)

    Anne Mette Fisker Hag

    Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

  14. HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene

    NARCIS (Netherlands)

    Pandit, Aridaman; de Boer, Rob J

    2015-01-01

    Highly active antiretroviral therapy (ART) has successfully turned Human immunodeficiency virus type 1 (HIV-1) from a deadly pathogen into a manageable chronic infection. ART is a lifelong therapy which is both expensive and toxic, and HIV can become resistant to it. An alternative to lifelong ART

  15. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.

    Directory of Open Access Journals (Sweden)

    Ussama M Abdel-Motal

    Full Text Available Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS.This study tested the hypothesis that adeno-associated virus (AAV-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc, or "minibody" was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1(bal in an organotypic human vaginal epithelial cell (VEC model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP.This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.

  16. RNA-interference-based gene therapy approaches to HIV type-1 treatment: tackling the hurdles from bench to bedside

    NARCIS (Netherlands)

    Von Eije, Karin J.; Berkhout, Ben

    2009-01-01

    RNA interference (RNAi) is a cellular mechanism that can be induced by small interfering RNAs (siRNAs) to mediate sequence-specific gene silencing by cleavage of the targeted messenger RNA. RNAi can be used as an antiviral approach to silence HIV type-1 (HIV-1) through stable expression of

  17. Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1

    Directory of Open Access Journals (Sweden)

    Emma Chan

    2014-01-01

    Full Text Available Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy strategies. Such approaches could form an important alternative to current anti-HIV-1 drug regimens, especially if combined with strategies to eradicate HIV reservoirs. Autologous CD4+ T cells or their haematopoietic stem cell precursors engineered to express TRIMCyp restriction factors, and provided in a single therapeutic intervention could then be used to restore functional immunity with a pool of cells protected against HIV. We consider the challenges ahead and consider how early clinical phase testing may best be achieved.

  18. The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment.

    Directory of Open Access Journals (Sweden)

    Benjamin B Gelman

    Full Text Available The National NeuroAIDS Tissue Consortium (NNTC performed a brain gene expression array to elucidate pathophysiologies of Human Immunodeficiency Virus type 1 (HIV-1-associated neurocognitive disorders.Twenty-four human subjects in four groups were examined A Uninfected controls; B HIV-1 infected subjects with no substantial neurocognitive impairment (NCI; C Infected with substantial NCI without HIV encephalitis (HIVE; D Infected with substantial NCI and HIVE. RNA from neocortex, white matter, and neostriatum was processed with the Affymetrix® array platform.With HIVE the HIV-1 RNA load in brain tissue was three log(10 units higher than other groups and over 1,900 gene probes were regulated. Interferon response genes (IFRGs, antigen presentation, complement components and CD163 antigen were strongly upregulated. In frontal neocortex downregulated neuronal pathways strongly dominated in HIVE, including GABA receptors, glutamate signaling, synaptic potentiation, axon guidance, clathrin-mediated endocytosis and 14-3-3 protein. Expression was completely different in neuropsychologically impaired subjects without HIVE. They had low brain HIV-1 loads, weak brain immune responses, lacked neuronally expressed changes in neocortex and exhibited upregulation of endothelial cell type transcripts. HIV-1-infected subjects with normal neuropsychological test results had upregulation of neuronal transcripts involved in synaptic transmission of neostriatal circuits.Two patterns of brain gene expression suggest that more than one pathophysiological process occurs in HIV-1-associated neurocognitive impairment. Expression in HIVE suggests that lowering brain HIV-1 replication might improve NCI, whereas NCI without HIVE may not respond in kind; array results suggest that modulation of transvascular signaling is a potentially promising approach. Striking brain regional differences highlighted the likely importance of circuit level disturbances in HIV/AIDS. In

  19. Meeting

    Indian Academy of Sciences (India)

    The Business Meeting of Fellows was held in the Space Applications Centre Auditorium late in the evening on 8 November. There were brief talks by P K Kaw on .... specifically the "Antarctic Ozone. Hole" are well-known. Another recent development relates to the Greenhouse Effect and the Global Warming phenomenon.

  20. Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

    Science.gov (United States)

    Aviran, Sharon; Shah, Priya S.; Schaffer, David V.; Arkin, Adam P.

    2010-01-01

    Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents. PMID:20711350

  1. Computational models of HIV-1 resistance to gene therapy elucidate therapy design principles.

    Directory of Open Access Journals (Sweden)

    Sharon Aviran

    2010-08-01

    Full Text Available Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents.

  2. Immunogenic profiling in mice of a HIV/AIDS vaccine candidate (MVA-B expressing four HIV-1 antigens and potentiation by specific gene deletions.

    Directory of Open Access Journals (Sweden)

    Juan García-Arriaza

    Full Text Available BACKGROUND: The immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B, that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs with immunoregulatory function. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R, known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1beta, respectively (referred as MVA-B DeltaA41L/DeltaB16R. A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+ and CD8(+ T cells, with the CD8(+ T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+ and CD8(+ T-cell immune responses. HIV-1-specific CD4(+ T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+ T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN-specific CD8(+ T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env. CONCLUSIONS/SIGNIFICANCE: These findings revealed that MVA-B and MVA-B DeltaA41L/DeltaB16R

  3. HIV

    African Journals Online (AJOL)

    Introduction. The·human immunodeficiency virus (HIV) can be transmiHed from one person to onother through the use of non-sterile nee- dles, syringes, and other skin-piercing and invasive instruments. Proper .sterilization of all such instruments is therefore important to prevent its transmission. HIV is very sensitive to ...

  4. hiv

    African Journals Online (AJOL)

    2016-03-31

    Mar 31, 2016 ... Indexed By: African Journal Online (AJOL); Texila American University; Genamics; Scholarsteer; EIJASR; CAS-American Chemical. Society; and IRMS Informatics India (J-Gate). ABSTRACT. This study evaluated the effect of HIV infection on CD4 T-lymphocyte depletion in people living with HIV/AIDS.

  5. Locating the Places People Meet New Sexual Partners in a Southern US City to Inform HIV/STI Prevention and Testing Efforts

    Science.gov (United States)

    Khan, Maria R.; Tisdale, Caroline; Norcott, Kathy; Duncan, Jesse; Kaplan, Andrew M.; Weir, Sharon S.

    2012-01-01

    Places where people meet new sex partners can be venues for the delivery of individual and environmental interventions that aim to reduce transmission of HIV and other sexually transmitted infections (STI). Using the Priorities for Local AIDS Control Efforts (PLACE) methodology we identified and characterized venues where people in a southeastern US city with high prevalence of both HIV and STI go to meet new sexual partners. A total of 123 community informants identified 143 public, private and commercial venues where people meet sex partners. Condoms were available at 14% of the venues, although 48% of venue representatives expressed a willingness to host HIV prevention efforts. Interviews with 373 people (229 men, 144 women) socializing at a random sample of 54 venues found high rates of HIV risk behaviors including concurrent sexual partnerships, transactional sex and illicit substance abuse. Risk behaviors were more common among those at certain venue types including those that may be overlooked by public health outreach efforts. The systematic methodology used was successful in locating venues where risky encounters are established and reveal opportunities for targeted HIV prevention and testing programs as well as research. PMID:20614175

  6. Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells.

    Science.gov (United States)

    Mitsuyasu, Ronald T; Merigan, Thomas C; Carr, Andrew; Zack, Jerome A; Winters, Mark A; Workman, Cassy; Bloch, Mark; Lalezari, Jacob; Becker, Stephen; Thornton, Lorna; Akil, Bisher; Khanlou, Homayoon; Finlayson, Robert; McFarlane, Robert; Smith, Don E; Garsia, Roger; Ma, David; Law, Matthew; Murray, John M; von Kalle, Christof; Ely, Julie A; Patino, Sharon M; Knop, Alison E; Wong, Philip; Todd, Alison V; Haughton, Margaret; Fuery, Caroline; Macpherson, Janet L; Symonds, Geoff P; Evans, Louise A; Pond, Susan M; Cooper, David A

    2009-03-01

    Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.

  7. 75 FR 33307 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2010-06-11

    ... public through a conference call phone number. DATES: The meeting will be on June 29, 2010 from 4 p.m. to... conference call phone number provided above. There will be a limited amount of open lines for the public... the meeting. Members of the public who participate using the conference call phone number will be able...

  8. 77 FR 6122 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2012-02-07

    ... Manager, Presidential Advisory Council on HIV/AIDS, Department of Health and Human Services, 200... more than 25 members. Council members are selected from prominent community leaders with particular..., marketing or business, as well as other national leaders held in high esteem from other sectors of society...

  9. 77 FR 25482 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2012-04-30

    ... INFORMATION CONTACT: Mr. Melvin Joppy, Committee Manager, Presidential Advisory Council on HIV/AIDS... members are selected from prominent community leaders with particular expertise in, or knowledge of... well as other national leaders held in high esteem from other sectors of society. Council members are...

  10. 75 FR 57024 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2010-09-17

    .... FOR FURTHER INFORMATION, CONTACT: Mr. Melvin Joppy, Committee Manager, Presidential Advisory Council... community leaders with particular expertise in, or knowledge of, matters concerning HIV and AIDS, public health, global health, philanthropy, marketing or business, as well as other national leaders held in...

  11. In vitro screening of traditional medicines for anti-HIV activity: memorandum from a WHO meeting.

    Science.gov (United States)

    1989-01-01

    Many plant products are being used by patients with acquired immunodeficiency syndrome (AIDS) in some countries without any scientific proof that they possess anti-HIV (human immunodeficiency virus) activity. Traditional healers are now offering their remedies for scientific evaluation, and a few studies provide information on the inhibitory activity against HIV of plants such as Viola yedoensis, Arctium lappa, Epimedium grandiflorum, Glycyrrhiza uralensis and Castanospermum australe. Natural products can be selected for biological screening based on ethnomedical use, random collection or a chemotaxonomic approach (i.e., screening of species of the same botanical family for similar compounds), but the follow-up and selection of plants based on literature leads would seem to be the most cost-effective way of identifying plants with anti-HIV activity. No single in vitro screening methodology for anti-HIV activity is ideal and confirmatory assays in multiple systems are needed to examine completely the potential use of a compound. To promote further research in traditional medicine and AIDS, appropriate institutions will be identified where the different activities for the scientific evaluation of plants and their extracts for possible treatment of AIDS can be carried out. PMID:2633879

  12. Dihydropteroate synthase (DHPS) gene mutation study in HIV-Infected Indian patients with Pneumocystis jirovecii pneumonia.

    Science.gov (United States)

    Tyagi, Anuj Kumar; Mirdha, Bijay Ranjan; Luthra, Kalpana; Guleria, Randeep; Mohan, Anant; Singh, Urvashi Balbir; Samantaray, Jyotish Chandra; Dar, Lalit; Iyer, Venkateswaran K; Chaudhry, Rama

    2010-11-24

    Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations' (55th and 57th codon) association with prior sulfa prophylaxis failure has been reported from both developed and developing countries. We conducted a prospective study to determine the prevalence of P. jirovecii DHPS mutations from 2006 to 2009 on P. jirovecii isolates obtained from HIV-infected patients with a clinical diagnosis of Pneumocystis carinii pneumonia (PCP) admitted to our tertiary care reference health center in New Delhi, India. Detection of P. jirovecii cysts was performed by direct fluorescent antibody (DFA) staining and by Grocott's-Gomori methenamine silver staining (GMS). DNA detection was performed by polymerase chain reaction (PCR) using primers for the major surface glycoprotein (MSG) gene. P. jirovecii DHPS gene was amplified by nested PCR protocol and sequenced for detecting mutations at the 55th and 57th codons. Out of 147 HIV-positive patients with suspected Pneumocystis pneumonia (PCP), 16 (10.8%) PCP positive cases were detected. Of 16 cases, nine (56.2%) were positive by DFA staining, four (25%) were positive by Grocott's-Gomori methenamine silver staining, and all 16 were positive by MSG PCR. DHPS mutations at the 55th and 57th codons were observed in 6.2% of HIV patients studied, which was relatively low compared to reports from developed nations.   Prevalence of Pneumocystis jirovecii DHPS mutations associated with cotrimoxazole treatment failure may be low in the Indian subpopulation of HIV-positive patients and warrants larger studies to elucidate the true picture of Pneumocystis jirovecii sulfa drug resistance in India.

  13. BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region.

    Directory of Open Access Journals (Sweden)

    Atila Iamarino

    Full Text Available Although some studies have shown diversity in HIV integrase (IN genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naïve patients from the São Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes, 17 of subtype F (8 of which were found in recombinant genomes, 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2 that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naïve and 45% of the drug-treated patients had at least 1 raltegravir (RAL or elvitegravir (EVG resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population.

  14. Oxidative stress induced by HIV-1 reverse transcriptase modulates the enzyme's performance in gene immunization.

    Science.gov (United States)

    Isaguliants, Maria; Smirnova, Olga; Ivanov, Alexander V; Kilpelainen, Athina; Kuzmenko, Yulia; Petkov, Stefan; Latanova, Anastasia; Krotova, Olga; Engström, Gunnel; Karpov, Vadim; Kochetkov, Sergey; Wahren, Britta; Starodubova, Elizaveta

    2013-10-01

    HIV-1 infection induces chronic oxidative stress. The resultant neurotoxicity has been associated with Tat protein. Here, we for the first time describe the induction of oxidative stress by another HIV-1 protein, reverse transcriptase (RT). Expression of HIV-1 RT in human embryonic kidney cells generated potent production of the reactive oxygen species (ROS), detected by the fluorescence-based probes. Quantitative RT-PCR demonstrated that expression of RT in HEK293 cells induced a 10- to 15-fold increased transcription of the phase II detoxifying enzymes human quinone oxidoreductase (Nqo1) and heme oxygenase 1 (HO-1), indicating the induction of oxidative stress response. The capacity to induce oxidative stress and stress response appeared to be an intrinsic property of a vast variety of RTs: enzymatically active and inactivated, bearing mutations of drug resistance, following different routes of processing and presentation, expressed from viral or synthetic expression-optimized genes. The total ROS production induced by RT genes of the viral origin was found to be lower than that induced by the synthetic/expression-optimized or chimeric RT genes. However, the viral RT genes induced higher levels of ROS production and higher levels of HO-1 mRNA than the synthetic genes per unit of protein in the expressing cell. The capacity of RT genes to induce the oxidative stress and stress response was then correlated with their immunogenic performance. For this, RT genes were administered into BALB/c mice by intradermal injections followed by electroporation. Splenocytes of immunized mice were stimulated with the RT-derived and control antigens and antigen-specific proliferation was assessed by IFN-γ/IL-2 Fluorospot. RT variants generating high total ROS levels induced significantly stronger IFN-γ responses than the variants inducing lower total ROS, while high levels of ROS normalized per unit of protein in expressing cell were associated with a weak IFN-γ response. Poor

  15. Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect

    DEFF Research Database (Denmark)

    Lund, O; Lund, O S; Gram, G

    1997-01-01

    This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells...... will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction cells that is initially...... transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests...

  16. Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection

    NARCIS (Netherlands)

    van Manen, Daniëlle; Kootstra, Neeltje A.; Boeser-Nunnink, Brigitte; Handulle, Muna Am; Vanʼt Wout, Angélique B.; Schuitemaker, Hanneke

    2009-01-01

    Background: Recently, a genome-wide association analysis revealed single-nucleotide polymorphisms (SNPs) in the gene regions of HLA-C and HCP5 to be associated with viral load at set point and SNPs in the RNF39/ZNRD1 gene region to be associated with HIV-1 disease course. Methods: We Studied whether

  17. High Rates of Anal High-Grade Squamous Intraepithelial Lesions in HIV-Infected Women Who Do Not Meet Screening Guidelines.

    Science.gov (United States)

    Gaisa, Michael; Ita-Nagy, Fanny; Sigel, Keith; Arens, Yotam; Hennessy, Mary Ann; Rodriguez-Caprio, Gabriela; Mullen, Michael; Aberg, Judith A; Cespedes, Michelle

    2017-02-01

    Human immunodeficiency virus (HIV)-infected women have a higher burden of anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) compared with HIV-uninfected women. Guidelines for AC screening in this population are heterogeneous. Here we report outcomes and risk factors for anal HSIL following implementation of universal AC screening offered to all HIV-infected women. Data from women who underwent AC screening with anal cytology from April 2009 to July 2014 were analyzed. Routine clinical data included anal and cervical cytology, demographic/behavioral data, and high-resolution anoscopy (HRA) results. We evaluated the association of cytology with HRA results, and predictors of HSIL pathology, and compared rates of HSIL pathology among women meeting screening guidelines to those who did not. Seven hundred forty-five HIV-infected women were screened with anal cytology. Thirty-nine percent had abnormal anal cytology on initial screen and 15% on secondary screen; 208 women underwent HRA following abnormal anal cytology. HSIL was found in 26% and 18% of anal biopsies following initial and secondary screening, respectively. One woman had AC. Cigarette smoking more than doubled HSIL risk. Among women who underwent AC screening despite not meeting existing guideline criteria, 21% and 10%, respectively, were found to have HSIL on biopsy. Neither meeting criteria for screening nor history of receptive anal sex was significantly associated with HSIL. Anal HSIL is common in HIV-infected women. Substantial numbers of HSIL would have been missed by strictly adhering to existing AC screening guidelines. These results support routine screening of all HIV-infected women regardless of human papillomavirus history or sexual practices. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. Lack of association between intact/deletion polymorphisms of the APOBEC3B gene and HIV-1 risk.

    Directory of Open Access Journals (Sweden)

    Mayumi Imahashi

    Full Text Available The human APOBEC3 family of proteins potently restricts HIV-1 replication APOBEC3B, one of the family genes, is frequently deleted in human populations. Two previous studies reached inconsistent conclusions regarding the effects of APOBEC3B loss on HIV-1 acquisition and pathogenesis. Therefore, it was necessary to verify the effects of APOBEC3B on HIV-1 infection in vivo.Intact (I and deletion (D polymorphisms of APOBEC3B were analyzed using PCR. The syphilis, HBV and HCV infection rates, as well as CD4(+ T cell counts and viral loads were compared among three APOBEC3B genotype groups (I/I, D/I, and D/D. HIV-1 replication kinetics was assayed in vitro using primary cells derived from PBMCs.A total of 248 HIV-1-infected Japanese men who have sex with men (MSM patients and 207 uninfected Japanese MSM were enrolled in this study. The genotype analysis revealed no significant differences between the APOBEC3B genotype ratios of the infected and the uninfected cohorts (p = 0.66. In addition, HIV-1 disease progression parameters were not associated with the APOBEC3B genotype. Furthermore, the PBMCs from D/D and I/I subjects exhibited comparable HIV-1 susceptibility.Our analysis of a population-based matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a negligible role in eliminating HIV-1 in vivo.

  19. European AIDS Clinical Society Standard of Care meeting on HIV and related coinfections: The Rome Statements

    NARCIS (Netherlands)

    Mussini, C.; Antinori, A.; Bhagani, S.; Branco, T.; Brostrom, M.; Dedes, N.; Bereczky, T.; Girardi, E.; Gökengin, D.; Horban, A.; Lacombe, K.; Lundgren, J. D.; Mendao, L.; Mocroft, A.; Oprea, C.; Porter, K.; Podlekareva, D.; Battegay, M.; d'Arminio Monforte, A.; Mulcahy, Fiona; Geretti, Anna Maria; Clumeck, Nathan; Reiss, Peter; Arribas, Jose; Gatell, Jose; Katlama, Christine; Pozniak, Anton; Rockstroh, Jürgen; Youle, Mike; Friis-Møller, Nina; Rusconi, Stefano; Behrens, Georg; de Wit, Stéphane; Furrer, Hansjakob; Wensing, Annemarie; John Gill, M.; Letendre, Scott

    2016-01-01

    The objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future. Data-driven presentations were given on specific topics followed by interactive panel

  20. European AIDS Clinical Society Standard of Care meeting on HIV and related coinfections : The Rome Statements

    NARCIS (Netherlands)

    Mussini, C.; Antinori, A.; Bhagani, S.; Branco, T.; Brostrom, M.; Dedes, N.; Bereczky, T.; Girardi, E.; Gökengin, D.; Horban, A.; Lacombe, K.; Lundgren, J. D.; Mendao, L.; Mocroft, A.; Oprea, C.; Porter, K.; Podlekareva, D.; Battegay, M.; d'Arminio Monforte, A.; Mulcahy, Fiona; Geretti, Anna Maria; Clumeck, Nathan; Reiss, Peter; Arribas, Jose; Gatell, Jose; Katlama, Christine; Pozniak, Anton; Rockstroh, Jürgen; Youle, Mike; Friis-Møller, Nina; Rusconi, Stefano; Behrens, Georg; De Wit, Stéphane; Furrer, Hansjakob; Wensing, Annemarie|info:eu-repo/dai/nl/30817724X; John Gill, M.; Letendre, Scott

    2016-01-01

    Objectives: The objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future. Methods: Data-driven presentations were given on specific topics followed

  1. 76 FR 68462 - Meeting of the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2011-11-04

    ... to the public through a conference call phone number. DATES: The meeting will be on November 22, 2011... be open to the public through a conference call phone number provided above. There will be a limited.... Members of the public who participate using the conference call phone number will be able to listen to the...

  2. RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women’s Interagency HIV Study (WIHS)

    Science.gov (United States)

    Shendre, Aditi; Irvin, Marguerite R; Aouizerat, Bradley E; Wiener, Howard W; Vazquez, Ana I; Anastos, Kathryn; Lazar, Jason; Liu, Chenglong; Karim, Roksana; Limdi, Nita A; Cohen, Mardge H; Golub, Elizabeth T.; Zhi, Degui; Kaplan, Robert C; Shrestha, Sadeep

    2014-01-01

    Background Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women’s Interagency HIV Study (WIHS). Methods CCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel’s method and haplotype association analyses were conducted among the three races separately. Results SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41× 10−5), rs11856930 among Whites (p=5.62× 10−4), and rs2572204 among Blacks (p=2.45× 10−3). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics. Discussion Consistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function. PMID:24561552

  3. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression

    Science.gov (United States)

    Chavali, Arvind K.; Wong, Victor C.; Miller-Jensen, Kathryn

    2015-12-01

    Latent human immunodeficiency virus (HIV) infections occur when the virus occupies a transcriptionally silent but reversible state, presenting a major obstacle to cure. There is experimental evidence that random fluctuations in gene expression, when coupled to the strong positive feedback encoded by the HIV genetic circuit, act as a ‘molecular switch’ controlling cell fate, i.e., viral replication versus latency. Here, we implemented a stochastic computational modeling approach to explore how different promoter activation mechanisms in the presence of positive feedback would affect noise-driven activation from latency. We modeled the HIV promoter as existing in one, two, or three states that are representative of increasingly complex mechanisms of promoter repression underlying latency. We demonstrate that two-state and three-state models are associated with greater variability in noisy activation behaviors, and we find that Fano factor (defined as variance over mean) proves to be a useful noise metric to compare variability across model structures and parameter values. Finally, we show how three-state promoter models can be used to qualitatively describe complex reactivation phenotypes in response to therapeutic perturbations that we observe experimentally. Ultimately, our analysis suggests that multi-state models more accurately reflect observed heterogeneous reactivation and may be better suited to evaluate how noise affects viral clearance.

  4. Carbosilane dendrimers as gene delivery agents for the treatment of HIV infection.

    Science.gov (United States)

    Perisé-Barrios, Ana Judith; Jiménez, José Luis; Domínguez-Soto, Angeles; de la Mata, F Javier; Corbí, Angel L; Gomez, Rafael; Muñoz-Fernandez, María Ángeles

    2014-06-28

    Despite the use of siRNA in the downregulation of HIV-1 replication which has been reported, CD4 T lymphocytes are difficult to transfect with non-viral vectors. We determined whether second generation carbosilane dendrimers (2G-NN16 and 2G-03NN24) may be efficient transfectants in CD4 T lymphocytes. Dendrimers were also tested on macrophages to determine whether they can modify macrophage phenotype and induce an inflammatory response. The nanoconjugate formed by 2G-03NN24/siRNA-Nef presents the highest inhibition of HIV-1 replication. Dendrimers presented safety properties because they did not induce proliferation on CD4 T lymphocytes and decrease the release of TNFα and IL-12p40 by macrophages. Both dendrimers also decrease the phagocytosis activity. Additionally, 2G-03NN24 dendrimer decreases the CCL2 and CCR2 expression in macrophages. Carbosilane dendrimers 2G-NN16 and 2G-03NN24 can be used as efficient non-viral vectors for gene therapy applications, mainly in the treatment of HIV infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Polymorphisms in the interleukin-7 receptor α gene and mortality in untreated HIV-infected individuals

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Thørner, Lise W.; Erikstrup, Christian

    2013-01-01

    OBJECTIVES:: Recently, polymorphisms in the gene encoding the Interleukin-7 receptor α (IL7RA) have been shown to influence the CD4 cell count in HIV-infected individuals. The objective of this study was to examine the impact of 10 single nucleotide polymorphisms (SNPs) in or in close proximity...... to the IL7RA on mortality among 152 untreated HIV-infected in a Zimbabwean cohort. METHODS:: Patients were followed prospectively, median time of follow-up 3.9 year. SNPs were genotyped using competitive allele-specific PCR. Cox regression was used for survival analyses. RESULTS:: We found an increased...... mortality among carriers of the IL7RA, rs6897932, T-allele (hazard ratio (HR): 2.56 (95% CI 1.22-5.35), P = 0.013). This association remained significant after adjusting for age, sex, baseline HIV-RNA and baseline CD4 cell count (HR = 2.36 (95% CI 1.06-2.58), P = 0.036). CONCLUSION:: The results suggest...

  6. HIV reverse transcriptase gene mutations in anti-retroviral treatment naïve rural people living with HIV/AIDS

    Directory of Open Access Journals (Sweden)

    K Mohanakrishnan

    2015-01-01

    Full Text Available This study is designed to find out the mutational variations of reverse transcriptase (RT gene of HIV, after the traditional drug usage among anti-retroviral therapy naïve rural people living with HIV/AIDS. HIV Reactive patients, who were exposed for indigenous medicines such as Siddha, Ayurveda etc., for a minimum period of 6 months were taken for this study. Among 40 patients, two samples (5.55% demonstrated high-level mutational resistance variations for nucleoside RT inhibitor (NRTI and non-NRTI. The predominant polymorphisms detected were K122E (91.7%, V60I (91.7%, V35T (89%, Q207E (89%, D177E (89%, T200A (86.1%, S48T (83.33%, K173A (80.6%.

  7. Development of dengue virus replicons expressing HIV-1 gp120 and other heterologous genes: a potential future tool for dual vaccination against dengue virus and HIV

    Directory of Open Access Journals (Sweden)

    Dayton Andrew I

    2001-11-01

    Full Text Available Abstract Background Toward the goals of providing an additional vector to add to the armamentarium available to HIV vaccinologists and of creating a bivalent vaccine effective against dengue virus and HIV, we have attempted to create vectors which express dengue virus non-structural proteins and HIV immunogens. Previously we reported the successful construction of dengue virus replicons which lack structural genes necessary for virion release and spreading infection in culture but which can replicate intracellularly and abundantly produce dengue non-structural proteins. Here we attempted to express heterologous genetic material from these replicons. Results We cloned into a Δpre-M/E dengue virus replicon genes for either green fluorescent protein (GFP, HIV gp160 or HIV gp120 and tested the ability of these constructs to express dengue virus proteins as well as the heterologous proteins in tissue culture after transfection of replicon RNA. Conclusions Heterologous proteins were readily expressed from these constructs. GFP and gp120 demonstrated minimal or no toxicity. Gp160 expressing replicons were found to express proteins abundantly at 36 hours post transfection, but after 50 hrs of transfection, few replicon positive cells could be found despite the presence of cellular debris positive for replicon proteins. This suggested that gp160 expressed from dengue virus replicons is considerably more toxic than either GFP or gp120. The successful expression of heterologous proteins, including HIV gp120 for long periods in culture suggests this vector system may be useful as a vaccine vector, given appropriate delivery methods.

  8. Development of a Tailored HIV Prevention Intervention for Single Young Men Who Have Sex With Men Who Meet Partners Online: Protocol for the myDEx Project.

    Science.gov (United States)

    Bauermeister, Jose Arturo; Tingler, Ryan C; Demers, Michele; Harper, Gary W

    2017-07-19

    New cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM), aged 18 to 24, underscore the importance of developmentally-informed HIV programs for YMSM. We developed an online intervention focused on risk reduction strategies across different sexual partner types. Intervention activities focus on assisting YMSM reflect on their partner-seeking behaviors, develop sexual decision-making rules to reduce their HIV risks, and consider the adoption of HIV prevention behaviors. This pilot, randomized controlled trial (RCT) aims to examine the feasibility, acceptability, and preliminary efficacy of a tailored, Web-based HIV prevention intervention for single YMSM. We designed a prospective RCT of online-recruited cis-gender men (N=180) who reported recent unprotected anal intercourse, self-report as HIV negative or are unaware of their HIV status, and meet sexual partners through online dating apps. Individuals in the control arm receive an attention-control condition that includes HIV/sexually transmitted infection (STI) information currently available on sex education websites. Individuals in the intervention arm receive a 6-session Web-based program tailored on their demographic information, partner-seeking behaviors and relationship desires, and prior sexual attitudes and behaviors. This tailored content will match HIV prevention messages and safer sex skills with YMSM's outcome expectancies when meeting new partners and thereby help them consider how to integrate safer sex practices into different partner types. Study assessments are taken at baseline, 30-, 60-, and 90-day follow-ups. Intervention acceptability and preliminary efficacy will be explored in sexual risk behaviors and HIV/STI testing. The RCT launched in November 2016 and is ongoing. To date, 180 eligible individuals have been enrolled, consented, and randomized. Of the 120 individuals in the intervention arm, 51.7% (62/120) identify as non-Hispanic white and half of the

  9. Gene-Gene and Gene-Environment Interactions in HIV-Associated Nephropathy: a Focus on the MYH9 Nephropathy Susceptibility Gene

    OpenAIRE

    Núñez, Marina; Saran, Anita M.; Freedman, Barry I.

    2010-01-01

    Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in African Americans. The HIV-1 virus infects podocytes, cells integral to formation of the glomerular filtration barrier, often leading to focal segmental glomerulosclerosis. HIVAN is typically a complication of late-stage HIV infection, associated with low CD4 cell counts and elevated serum HIV RNA levels. Highly active antiretroviral therapy (HAART) is partially protective and has alte...

  10. Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND.

    Directory of Open Access Journals (Sweden)

    Venkata Subba Rao Atluri

    Full Text Available HIV-associated neurocognitive disorders (HAND is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B, which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT(2 Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (≥3 fold down-regulated and 5 genes were significantly (≥3 fold up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1 was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of

  11. The HIV epidemic in the Caribbean: meeting the challenges of achieving universal access to prevention, treatment and care.

    Science.gov (United States)

    Figueroa, J P

    2008-06-01

    The HIV prevalence in the Caribbean is estimated at 1.0% (0.9% - 2%) with 230,000 persons living with HIV/AIDS. HIV rates vary among countries with the Bahamas, Guyana, Haiti and Trinidad and Tobago having HIV rates of 2% or above while Cuba's rate is less than 0.2%. However throughout the Caribbean, HIV rates are significantly higher among those groups most at risk such as commercial sex workers, men who have sex with men and crack/cocaine users. The Caribbean Community (CARICOM) Heads of Governments declared AIDS to be a regional priority in 2001. The Pan Caribbean AIDS Partnership (PANCAP) was formed to lead the regional response to the HIV epidemic. National HIV Programmes have made definite progress in providing ARV treatment to persons with HIV/AIDS and reducing death rates due to AIDS, decreasing HIV mother-to-child transmission and providing a range ofHIVprevention programmes. However HIV stigma remains strong in the Caribbean and sexual and cultural practices put many youth, women and men at risk of HIV The Caribbean has set itself the goal of achieving universal access to HIV prevention, treatment and care. Several challenges need to be addressed. These include reducing HIV stigma, strengthening national responses, scaling-up better quality prevention programmes with greater involvement of vulnerable populations, more supportive HIV policies and wider access to ARV treatment with better adherence. In addition, there needs to be improved coordination among PANCAP partners at the regional level and within countries.

  12. Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect

    DEFF Research Database (Denmark)

    Lund, O; Lund, O S; Gram, G

    1997-01-01

    transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests...

  13. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell

    Science.gov (United States)

    Boullé, Mikaël; Müller, Thorsten G.; Dähling, Sabrina; Jackson, Laurelle; Mahamed, Deeqa; Oom, Lance; Lustig, Gila

    2016-01-01

    Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses. PMID:27812216

  14. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

    Science.gov (United States)

    Boullé, Mikaël; Müller, Thorsten G; Dähling, Sabrina; Ganga, Yashica; Jackson, Laurelle; Mahamed, Deeqa; Oom, Lance; Lustig, Gila; Neher, Richard A; Sigal, Alex

    2016-11-01

    Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

  15. HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence.

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    Wang, Yuge; Kapoor, Pratibha; Parks, Robert; Silva-Sanchez, Aaron; Alam, S Munir; Verkoczy, Laurent; Liao, Hua-Xin; Zhuang, Yingxin; Burrows, Peter; Levinson, Michael; Elgavish, Ada; Cui, Xiangqin; Haynes, Barton F; Schroeder, Harry

    2016-02-01

    Complementarity Determining Region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen-binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection. A preference for use of RF1 promotes the incorporation of tyrosine into CDR-H3 while suppressing the inclusion of hydrophobic or charged amino acids. To test the hypothesis that these evolutionary constraints on DH sequence influence epitope recognition, we used mice with a single DH that has been altered to preferentially use RF2 or inverted RF1. B cells in these mice produce a CDR-H3 repertoire that is enriched for valine or arginine in place of tyrosine. We serially immunized this panel of mice with gp140 from HIV-1 JR-FL isolate and then used enzyme-linked immunosorbent assay (ELISA) or peptide microarray to assess antibody binding to key or overlapping HIV-1 envelope epitopes. By ELISA, serum reactivity to key epitopes varied by DH sequence. By microarray, sera with Ig CDR-H3s enriched for arginine bound to linear peptides with a greater range of hydrophobicity but had a lower intensity of binding than sera containing Ig CDR-H3s enriched for tyrosine or valine. We conclude that patterns of epitope recognition and binding can be heavily influenced by DH germ line sequence. This may help explain why antibodies in HIV-infected patients must undergo extensive somatic mutation in order to bind to specific viral epitopes and achieve neutralization.

  16. Polymorphisms of HIV RT gene among the ART naïve native drug exposed rural PLHA

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    K Mohana Krishnan

    2012-01-01

    Full Text Available Background: The number of people living with human immunodeficiency virus (HIV is increasing day by day in India. The disease has now spread from urban areas to rural areas. The proof reading of the reverse transcriptase enzyme is poor, which may lead to genetic diversity within the HIV strains, which in turn leads to problems like failure or resistance in antiretroviral treatment. This study is designed to find out the polymorphisms of the reverse transcriptase gene of HIV, after the native drug pressure among antiretroviral therapy (ART naïve rural people living with HIV/AIDS (RPLHA. Materials and Methods : A total of 207 HIV-Reactive patients were allowed to take native drugs from the local area and were advised to attend the center for HIV after six months for a follow-up. At the time of the follow-up visit, a second blood sample was taken from 20 reactive native-drug exposed ART-naïve patients. The plasma was separated and transported at 20°C to the YRG Care Center for genotyping. Results: Among the 20 HIV-reactive samples processed for gene sequencing analysis to detect the genotypic variations, only one sample (5% showed high-level mutational resistance variations and the predominant polymorphisms detected were V35T (100%, K122E (94.44%, and V60I (88.88%. Conclusions: The presence of drug-resistance mutations, although minimal, was important, as the drug-resistant strains could spread among the RPLHA and to their sexual partners. There was a definite need to generate a drug resistance database and the polymorphic pattern of Indian strains concern to the future clinical management of the disease, and a vaccine design to contain the disease.

  17. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.

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    Zabrina L Brumme

    2007-07-01

    Full Text Available Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT, Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+ T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other

  18. Emergence of drug resistance-associated mutations in HIV-1 subtype C protease gene in north India.

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    Azam, Mohd; Malik, Abida; Rizvi, Meher; Singh, Supriya; Gupta, Poonam; Rai, Arvind

    2013-12-01

    A major cause of anti-retroviral therapy (ART) failure is the drug resistance-associated mutations in polymerase gene of HIV-1. Paucity of data regarding potential drug resistance to protease inhibitors (PIs) prompted us to carry out this study. Drug resistance (DR) genotyping of the entire protease gene was performed in 104 HIV-1 ART-naive and first-line ART-experienced patients. The DR pattern was analyzed using the Stanford HIV-DR database, International AIDS Society-USA mutation list and REGA algorithm version 8.0. Subtyping was done using Mega 4 and REGA HIV-1 subtyping tool-v2.01. Majority of our sequences 98 (96%) were subtype C and remaining four (3.92%) were subtype A1. In three (2.9%) DE patients, major DR-associated mutation at D30 N and M46I positions were detected. Approximately 70% polymorphisms as minor mutations were observed in protease gene, of which 14 distinct amino acids changes were linked to partial DR such as G16E, K20R, M36I, D60E, I62V, L63P, I64M, H69K, T74A/S, V77I, V82I, I85V, L89M, and I93L. The two major and several minor mutations detected in this study confer low/intermediate levels of resistance to most PIs independently or together. Our results conclude that resistance testing in HIV-1-infected patients should be performed before the initiation of PI therapy for better therapeutic outcome in this region. This information not only will shed light on the extent of current DR in HIV strains but also will aid in patient treatment and drug designing.

  19. In Vivo Safety and Persistence of Endoribonuclease Gene-Transduced CD4+ T Cells in Cynomolgus Macaques for HIV-1 Gene Therapy Model

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    Chono, Hideto; Saito, Naoki; Tsuda, Hiroshi; Shibata, Hiroaki; Ageyama, Naohide; Terao, Keiji; Yasutomi, Yasuhiro; Mineno, Junichi; Kato, Ikunoshin

    2011-01-01

    Background MazF is an endoribonuclease encoded by Escherichia coli that specifically cleaves the ACA sequence of mRNA. In our previous report, conditional expression of MazF in the HIV-1 LTR rendered CD4+ T lymphocytes resistant to HIV-1 replication. In this study, we examined the in vivo safety and persistence of MazF-transduced cynomolgus macaque CD4+ T cells infused into autologous monkeys. Methodology/Principal Findings The in vivo persistence of the gene-modified CD4+ T cells in the peripheral blood was monitored for more than half a year using quantitative real-time PCR and flow cytometry, followed by experimental autopsy in order to examine the safety and distribution pattern of the infused cells in several organs. Although the levels of the MazF-transduced CD4+ T cells gradually decreased in the peripheral blood, they were clearly detected throughout the experimental period. Moreover, the infused cells were detected in the distal lymphoid tissues, such as several lymph nodes and the spleen. Histopathological analyses of tissues revealed that there were no lesions related to the infused gene modified cells. Antibodies against MazF were not detected. These data suggest the safety and the low immunogenicity of MazF-transduced CD4+ T cells. Finally, gene modified cells harvested from the monkey more than half a year post-infusion suppressed the replication of SHIV 89.6P. Conclusions/Significance The long-term persistence, safety and continuous HIV replication resistance of the mazF gene-modified CD4+ T cells in the non-human primate model suggests that autologous transplantation of mazF gene-modified cells is an attractive strategy for HIV gene therapy. PMID:21858176

  20. Serodiagnostic profiles of HIV and HIV pathogenesis in vivo

    NARCIS (Netherlands)

    Goudsmit, J.; Lange, J. M.; Smit, L.; Bakker, M.; Klaver, B.; Danner, S. A.; Coutinho, R. A.

    1988-01-01

    Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies, formation of antigen/antibody complexes and clearance of such complexes. Transient HIV antigenemia appearing generally 6-8 weeks prior to HIV antibody (HIV-Ab) seroconversion and lasting 3-4 months

  1. Abnormalities in alternative splicing of angiogenesis-related genes and their role in HIV-related cancers

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    Mthembu NN

    2017-03-01

    Full Text Available Nonkululeko N Mthembu,1 Zukile Mbita,2 Rodney Hull,1 Zodwa Dlamini1 1Research, Innovation and Engagements, Mangosuthu University of Technology, Durban, 2Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Sovenga, South Africa Abstract: Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer. This aberrant splicing leads to abnormal production of protein and is caused by mutations in cis-acting elements or trans-acting factors in angiogenesis-related genes. Restoring the normal regulation of alternative splicing of angiogenic genes would alter the expression of protein isoforms and may confer normal cell physiology in patients with these cancers. This review highlights the abnormalities in alternative splicing of angiogenesis-related genes and their implication in HIV/AIDS-related cancers. This allows us to gain an insight into the pathogenesis of HIV/AIDS-related cancer and in turn elucidate the therapeutic potential of alternatively spliced genes in HIV/AIDS-related malignancies. Keywords: vascular endothelial growth factor, oncogenic viruses, hypoxia induced factor 1, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, therapies targeting alternative splicing

  2. A Naturally Occurring rev1-vpu Fusion Gene Does Not Confer a Fitness Advantage to HIV-1.

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    Simon M Langer

    Full Text Available Pandemic strains of HIV-1 (group M encode a total of nine structural (gag, pol, env, regulatory (rev, tat and accessory (vif, vpr, vpu, nef genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1 and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown.Examining infectious molecular clones (IMCs of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells. Due to the splicing pattern of viral mRNA, however, these same IMCs also express a regular Vpu protein, which is produced at much higher levels. To investigate the function of the fusion gene, we characterized isogenic IMC pairs differing only in their ability to express a Rev1-Vpu protein. Analysis in transfected HEK293T and infected CD4+ T cells showed that all of these viruses were equally active in known Vpu functions, such as down-modulation of CD4 or counteraction of tetherin. Furthermore, the polymorphism did not affect Vpu-mediated inhibition of NF-кB activation or Rev-dependent nuclear export of incompletely spliced viral mRNAs. There was also no evidence for enhanced replication of Rev1-Vpu expressing viruses in primary PBMCs or ex vivo infected human lymphoid tissues. Finally, the frequency of HIV-1 quasispecies members that encoded a rev1-vpu fusion gene did not change in HIV-1 infected individuals over time.Expression of a rev1-vpu fusion gene does not affect regular Rev and Vpu functions or alter HIV-1 replication in primary target cells. Since there is no evidence for increased replication fitness of rev1-vpu encoding viruses, this polymorphism likely emerged in the context of other mutations within and/or outside the rev1-vpu intergenic region, and may have a neutral phenotype.

  3. A Naturally Occurring rev1-vpu Fusion Gene Does Not Confer a Fitness Advantage to HIV-1.

    Science.gov (United States)

    Langer, Simon M; Hopfensperger, Kristina; Iyer, Shilpa S; Kreider, Edward F; Learn, Gerald H; Lee, Lan-Hui; Hahn, Beatrice H; Sauter, Daniel

    2015-01-01

    Pandemic strains of HIV-1 (group M) encode a total of nine structural (gag, pol, env), regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1) and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown. Examining infectious molecular clones (IMCs) of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells. Due to the splicing pattern of viral mRNA, however, these same IMCs also express a regular Vpu protein, which is produced at much higher levels. To investigate the function of the fusion gene, we characterized isogenic IMC pairs differing only in their ability to express a Rev1-Vpu protein. Analysis in transfected HEK293T and infected CD4+ T cells showed that all of these viruses were equally active in known Vpu functions, such as down-modulation of CD4 or counteraction of tetherin. Furthermore, the polymorphism did not affect Vpu-mediated inhibition of NF-кB activation or Rev-dependent nuclear export of incompletely spliced viral mRNAs. There was also no evidence for enhanced replication of Rev1-Vpu expressing viruses in primary PBMCs or ex vivo infected human lymphoid tissues. Finally, the frequency of HIV-1 quasispecies members that encoded a rev1-vpu fusion gene did not change in HIV-1 infected individuals over time. Expression of a rev1-vpu fusion gene does not affect regular Rev and Vpu functions or alter HIV-1 replication in primary target cells. Since there is no evidence for increased replication fitness of rev1-vpu encoding viruses, this polymorphism likely emerged in the context of other mutations within and/or outside the rev1-vpu intergenic region, and may have a neutral phenotype.

  4. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.

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    Alejandra Borjabad

    2011-09-01

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing

  5. Stable gene transfer of CCR5 and CXCR4 siRNAs by sleeping beauty transposon system to confer HIV-1 resistance

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    Akkina Ramesh

    2008-07-01

    Full Text Available Abstract Background Thus far gene therapy strategies for HIV/AIDS have used either conventional retroviral vectors or lentiviral vectors for gene transfer. Although highly efficient, their use poses a certain degree of risk in terms of viral mediated oncogenesis. Sleeping Beauty (SB transposon system offers a non-viral method of gene transfer to avoid this possible risk. With respect to conferring HIV resistance, stable knock down of HIV-1 coreceptors CCR5 and CXCR4 by the use of lentiviral vector delivered siRNAs has proved to be a promising strategy to protect cells from HIV-1 infection. In the current studies our aim is to evaluate the utility of SB system for stable gene transfer of CCR5 and CXCR4 siRNA genes to derive HIV resistant cells as a first step towards using this system for gene therapy. Results Two well characterized siRNAs against the HIV-1 coreceptors CCR5 and CXCR4 were chosen based on their previous efficacy for the SB transposon gene delivery. The siRNA transgenes were incorporated individually into a modified SB transfer plasmid containing a FACS sortable red fluorescence protein (RFP reporter and a drug selectable neomycin resistance gene. Gene transfer was achieved by co-delivery with a construct expressing a hyperactive transposase (HSB5 into the GHOST-R3/X4/R5 cell line, which expresses the major HIV receptor CD4 and and the co-receptors CCR5 and CXCR4. SB constructs expressing CCR5 or CXCR4 siRNAs were also transfected into MAGI-CCR5 or MAGI-CXCR4 cell lines, respectively. Near complete downregulation of CCR5 and CXCR4 surface expression was observed in transfected cells. During viral challenge with X4-tropic (NL4.3 or R5-tropic (BaL HIV-1 strains, the respective transposed cells showed marked viral resistance. Conclusion SB transposon system can be used to deliver siRNA genes for stable gene transfer. The siRNA genes against HIV-1 coreceptors CCR5 and CXCR4 are able to downregulate the respective cell surface proteins

  6. Genetic and functional analysis of a set of HIV-1 envelope genes obtained from biological clones with varying syncytium-inducing capacities.

    NARCIS (Netherlands)

    A.C. Andeweg (Arno); M. Groenink (Maarten); P. Leeflang; R.E.Y. de Goede; A.D.M.E. Osterhaus (Albert); M. Tersmette; M.L. Bosch (Marnix)

    1992-01-01

    textabstractTo study HIV-1 envelope-mediated syncytium formation we have amplified, cloned, expressed, and sequenced individual envelope genes from a set of eight biological HIV-1 clones. These clones were obtained from two patients and display either a syncytium-inducing (SI) or

  7. A candidate HIV/AIDS vaccine (MVA-B lacking vaccinia virus gene C6L enhances memory HIV-1-specific T-cell responses.

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    Juan García-Arriaza

    Full Text Available The vaccinia virus (VACV C6 protein has sequence similarities with the poxvirus family Pox_A46, involved in regulation of host immune responses, but its role is unknown. Here, we have characterized the C6 protein and its effects in virus replication, innate immune sensing and immunogenicity in vivo. C6 is a 18.2 kDa protein, which is expressed early during virus infection and localizes to the cytoplasm of infected cells. Deletion of the C6L gene from the poxvirus vector MVA-B expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (MVA-B ΔC6L had no effect on virus growth kinetics; therefore C6 protein is not essential for virus replication. The innate immune signals elicited by MVA-B ΔC6L in human macrophages and monocyte-derived dendritic cells (moDCs are characterized by the up-regulation of the expression of IFN-β and IFN-α/β-inducible genes. In a DNA prime/MVA boost immunization protocol in mice, flow cytometry analysis revealed that MVA-B ΔC6L enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4+ and CD8+ T-cell memory immune responses, with most of the HIV-1 responses mediated by the CD8+ T-cell compartment with an effector phenotype. Significantly, while MVA-B induced preferentially Env- and Gag-specific CD8+ T-cell responses, MVA-B ΔC6L induced more Gag-Pol-Nef-specific CD8+ T-cell responses. Furthermore, MVA-B ΔC6L enhanced the levels of antibodies against Env in comparison with MVA-B. These findings revealed that C6 can be considered as an immunomodulator and that deleting C6L gene in MVA-B confers an immunological benefit by enhancing IFN-β-dependent responses and increasing the magnitude and quality of the T-cell memory immune responses to HIV-1 antigens. Our observations are relevant for the improvement of MVA vectors as HIV-1 vaccines.

  8. Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state.

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    Elijah M Songok

    Full Text Available To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN from a commercial sex worker cohort in Nairobi and compared their profiles to HIV-1 negative controls. Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA. Output data was analysed through ArrayAssist software (Agilent, San Jose CA. More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR <0.05. Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished HESNs from controls. Pathway analysis through the KEGG signaling database revealed a majority of the impacted pathways (13 of 15, 87% had genes that were significantly down regulated. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, phosphatidyl inositol, natural killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up regulated. We infer that the hallmark of HIV-1 resistance is down regulation of genes in key signaling pathways that HIV-1 depends on for infection.

  9. Frequency and molecular epidemiology of Panton-Valentine leukocidin gene in Staphylococcus aureus colonising HIV-infected patients.

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    Mohd-Zain, Z; Mohd-Nawi, S F A; Adnan, A; Kumar, S

    2017-08-01

    HIV-infected patients pose a high risk of contracting skin and soft tissue infections caused by Staphylococcus aureus. Those who are colonized with methicillin-resistant S. aureus (MRSA) that carry Panton-Valentine leukocidin (PVL) are predisposed to severe infections that could lead to necrotic skin infections. However the association of S. aureus specifically methicillin sensitive S. aureus carrying PVL gene in HIV patients has not been widely reported. Here, we study the prevalence and the molecular epidemiology of PVL-producing S. aureus in HIV-infected patients. Swabs from four body sites of 129 HIV-infected patients were cultured for S. aureus and identified by standard microbiological procedures. The isolates were subjected to antimicrobial susceptibility testing by disk diffusion against penicillin, erythromycin, clindamycin, and cotrimoxazole. PCR was used to detect the PVL gene and genetic relationship between the isolates was determined by using pulse field gel electrophoresis. A total of 51 isolates of S. aureus were obtained from 40 (31%) of the patients. The majority (43.1%) of the isolates were obtained from the anterior nares. Thirteen (25.5%) of all the isolates were resistant to more than one category of antibiotics, with one isolate identified as MRSA. Thirty-eight (74.5%) isolates (including the MRSA isolate) carried PVL gene where the majority (44.7%) of these isolates were from the anterior nares. A dendogram revealed that the isolates were genetically diverse with 37 distinct pulsotypes clustered in 11 groups. S. aureus obtained from multiple sites of the HIV patients were genetically diverse without any clonality observed.

  10. Amplification of the Gp41 gene for detection of mutations conferring resistance to HIV-1 fusion inhibitors on genotypic assay

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    Tanumihardja, J.; Bela, B.

    2017-08-01

    Fusion inhibitors have potential for future use in HIV control programs in Indonesia, so the capacity to test resistance to such drugs needs to be developed. Resistance-detection with a genotypic assay began with amplification of the target gene, gp41. Based on the sequence of the two most common HIV subtypes in Indonesia, AE and B, a primer pair was designed. Plasma samples containing both subtypes were extracted to obtain HIV RNA. Using PCR, the primer pair was used to produce the amplification product, the identity of which was checked based on length under electrophoresis. Eleven plasma samples were included in this study. One-step PCR using the primer pair was able to amplify gp41 from 54.5% of the samples, and an unspecific amplification product was seen in 1.1% of the samples. Amplification failed in 36.4% of the samples, which may be due to an inappropriate primer sequence. It was also found that the optimal annealing temperature for producing the single expected band was 57.2 °C. With one-step PCR, the designed primer pair amplified the HIV-1 gp41 gene from subtypes AE and B. However, further research should be done to determine the conditions that will increase the sensitivity and specificity of the amplification process.

  11. Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-infected brain: novel analysis of retrospective cases.

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    Erick T Tatro

    2010-04-01

    Full Text Available HIV infection disturbs the central nervous system (CNS through inflammation and glial activation. Evidence suggests roles for microRNA (miRNA in host defense and neuronal homeostasis, though little is known about miRNAs' role in HIV CNS infection. MiRNAs are non-coding RNAs that regulate gene translation through post-transcriptional mechanisms. Messenger-RNA profiling alone is insufficient to elucidate the dynamic dance of molecular expression of the genome. We sought to clarify RNA alterations in the frontal cortex (FC of HIV-infected individuals and those concurrently infected and diagnosed with major depressive disorder (MDD. This report is the first published study of large-scale miRNA profiling from human HIV-infected FC. The goals of this study were to: 1. Identify changes in miRNA expression that occurred in the frontal cortex (FC of HIV individuals, 2. Determine whether miRNA expression profiles of the FC could differentiate HIV from HIV/MDD, and 3. Adapt a method to meaningfully integrate gene expression data and miRNA expression data in clinical samples. We isolated RNA from the FC (n = 3 of three separate groups (uninfected controls, HIV, and HIV/MDD and then pooled the RNA within each group for use in large-scale miRNA profiling. RNA from HIV and HIV/MDD patients (n = 4 per group were also used for non-pooled mRNA analysis on Affymetrix U133 Plus 2.0 arrays. We then utilized a method for integrating the two datasets in a Target Bias Analysis. We found miRNAs of three types: A Those with many dysregulated mRNA targets of less stringent statistical significance, B Fewer dysregulated target-genes of highly stringent statistical significance, and C unclear bias. In HIV/MDD, more miRNAs were downregulated than in HIV alone. Specific miRNA families at targeted chromosomal loci were dysregulated. The dysregulated miRNAs clustered on Chromosomes 14, 17, 19, and X. A small subset of dysregulated genes had many 3' untranslated region (3'UTR

  12. Dihydropteroate synthase gene mutation rates in Pneumocystis jirovecii strains obtained from Iranian HIV-positive and non-HIV-positive patients.

    Science.gov (United States)

    Sheikholeslami, Maryam-Fatemeh; Sadraei, Javid; Farnia, Parisa; Forozandeh Moghadam, Mehdi; Emadikochak, Hamid

    2015-05-01

    The dihydropteroate sulfate (DHPS) gene is associated with resistance to sulfa/sulfone drugs in Pneumocystis jirovecii. We investigated the DHPS mutation rate in three groups of Iranian HIV-positive and HIV-negative patients by polymerase chain reaction-restricted fragment length polymorphism analysis. Furthermore, an association between P. jirovecii DHPS mutations and strain typing was investigated based on direct sequencing of internal transcribed spacer region 1 (ITS1) and ITS2. The overall P. jirovecii DHPS mutation rate was (5/34; 14.7%), the lowest rate identified was in HIV-positive patients (1/16; 6.25%) and the highest rate was in malignancies patients (3/11; 27.3%). A moderate rate of mutation was detected in chronic obstructive pulmonary disease (COPD) patients (1/7; 14.3%). Most of the isolates were wild type (29/34; 85.3%). Double mutations in DHPS were detected in patients with malignancies, whereas single mutations at codons 55 and 57 were identified in the HIV-positive and COPD patients, respectively. In this study, two new and rare haplotypes were identified with DHPS mutations. Additionally, a positive relationship between P. jirovecii strain genotypes and DHPS mutations was identified. In contrast, no DHPS mutations were detected in the predominant (Eg) haplotype. This should be regarded as a warning of an increasing incidence of drug-resistant P. jirovecii strains. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients.

    Science.gov (United States)

    Macpherson, Janet L; Boyd, Maureen P; Arndt, Allison J; Todd, Alison V; Fanning, Gregory C; Ely, Julie A; Elliott, Fiona; Knop, Alison; Raponi, Mitch; Murray, John; Gerlach, Wayne; Sun, Lun-Quan; Penny, Ronald; Symonds, Geoff P; Carr, Andrew; Cooper, David A

    2005-05-01

    An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2. Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors. After enrichment for CD4+ T-lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme-containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV-1-positive twin recipient. Marking was assessed over an initial 24-week period and in total over an approximate 4-year period. The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2- and LNL6-gene-containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T-lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat. The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection. Copyright (c) 2005 John Wiley & Sons, Ltd.

  14. Burden of diseases in poor resource countries: meeting the challenges of combating HIV/AIDS, tuberculosis and malaria.

    Science.gov (United States)

    Mhalu, F S

    2005-09-01

    Poverty, ill health and ignorance are closely interlinked and each is a determinant of the other. HIV/AIDS, malaria and tuberculosis are by far the commonest causes of ill-health and death in the poorest countries of the world which happen to be in the tropics and temperate countries in Africa, Asia and South America. Morbidity and mortality from these three diseases have a major socio-economic impact on individuals, communities and nations, due to the vicious cycle of poverty, ill health and ignorance. In Tanzania morbidity due to HIV/AIDS, tuberculosis and malaria leads to irrecoverable losses in productivity, inadequately trained workforce due to absence from training by the sick, heavy health care budgets to treat these otherwise preventable diseases, less competitive economy, higher labour force turnovers and unstable national budgets. If not controlled continuing rise in incidence of HIV/AIDS, malaria and TB may threaten the survival of small enterprises and ability to attract foreign investments leading to a rise in unemployment. Thus, investments in the improvement of health including HIV/AIDS, malaria and TB if done well will bring substantial benefits for the national economy including an increase in productivity. In this paper a review of the impact of HIV/AIDS, TB and malaria in Tanzania is done with an attempt to propose how research can contribute to improved efforts towards more effective prevention and control efforts. The need for multidisplinary research efforts in addressing the three disease conditions is proposed.

  15. Development of hematopoietic stem cell based gene therapy for HIV-1 infection: considerations for proof of concept studies and translation to standard medical practice.

    Science.gov (United States)

    DiGiusto, David L; Stan, Rodica; Krishnan, Amrita; Li, Haitang; Rossi, John J; Zaia, John A

    2013-11-22

    Over the past 15 years we have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC). We propose that the expression of selected RNA-based HIV-1 inhibitors in the CD4+ cells derived from GM-HSPC will protect them from HIV-1 infection and results in a sufficient immune repertoire to control HIV-1 viremia resulting in a functional cure for HIV-1/AIDS. Additionally, it is possible that the subset of protected T cells will also be able to facilitate the immune-based elimination of latently infected cells if they can be activated to express viral antigens. Thus, a single dose of disease resistant GM-HSPC could provide an effective treatment for HIV-1+ patients who require (or desire) an alternative to lifelong antiretroviral chemotherapy. We describe herein the results from several pilot clinical studies in HIV-1 patients and our strategies to develop second generation vectors and clinical strategies for HIV-1+ patients with malignancy who require ablative chemotherapy as part of treatment and others without malignancy. The important issues related to stem cell source, patient selection, conditioning regimen and post-infusion correlative studies become increasingly complex and are discussed herein.

  16. Potential mechanisms for cell-based gene therapy to treat HIV/AIDS

    NARCIS (Netherlands)

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-01-01

    An estimated 35 million people are infected with HIV worldwide. Anti-retroviral therapy (ART) has reduced the morbidity and mortality of HIV-infected patients but efficacy requires strict adherence and the treatment is not curative. Most importantly, the emergence of drug-resistant virus strains and

  17. CCL3L gene copy number and survival in an HIV-1 infected Zimbabwean population

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Thørner, Lise Wegner; Zinyama, Rutendo

    2012-01-01

    The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility and progre...

  18. HIV-1 infection in macrophages and genes involved throughout: Big eaters versus small invaders

    NARCIS (Netherlands)

    Cobos Jiménez, V.

    2014-01-01

    In this thesis we have studied the infectious process of HIV-1 in differently polarized macrophages. The purpose of this research was to identify cellular factors that are involved in HIV-1 infection of macrophages, how these factors affect viral replication and whether their function or expression

  19. Derivation of normal macrophages from human embryonic stem (hES cells for applications in HIV gene therapy

    Directory of Open Access Journals (Sweden)

    Kaufman Dan S

    2006-04-01

    Full Text Available Abstract Background Many novel studies and therapies are possible with the use of human embryonic stem cells (hES cells and their differentiated cell progeny. The hES cell derived CD34 hematopoietic stem cells can be potentially used for many gene therapy applications. Here we evaluated the capacity of hES cell derived CD34 cells to give rise to normal macrophages as a first step towards using these cells in viral infection studies and in developing novel stem cell based gene therapy strategies for AIDS. Results Undifferentiated normal and lentiviral vector transduced hES cells were cultured on S17 mouse bone marrow stromal cell layers to derive CD34 hematopoietic progenitor cells. The differentiated CD34 cells isolated from cystic bodies were further cultured in cytokine media to derive macrophages. Phenotypic and functional analyses were carried out to compare these with that of fetal liver CD34 cell derived macrophages. As assessed by FACS analysis, the hES-CD34 cell derived macrophages displayed characteristic cell surface markers CD14, CD4, CCR5, CXCR4, and HLA-DR suggesting a normal phenotype. Tests evaluating phagocytosis, upregulation of the costimulatory molecule B7.1, and cytokine secretion in response to LPS stimulation showed that these macrophages are also functionally normal. When infected with HIV-1, the differentiated macrophages supported productive viral infection. Lentiviral vector transduced hES cells expressing the transgene GFP were evaluated similarly like above. The transgenic hES cells also gave rise to macrophages with normal phenotypic and functional characteristics indicating no vector mediated adverse effects during differentiation. Conclusion Phenotypically normal and functionally competent macrophages could be derived from hES-CD34 cells. Since these cells are susceptible to HIV-1 infection, they provide a uniform source of macrophages for viral infection studies. Based on these results, it is also now feasible to

  20. Gene expression profiles and protein–protein interaction network analysis in AIDS patients with HIV-associated encephalitis and dementia

    Directory of Open Access Journals (Sweden)

    Shityakov S

    2015-11-01

    Full Text Available Sergey Shityakov,1 Thomas Dandekar,2 Carola Förster1 1Department of Anesthesia and Critical Care, 2Department of Bioinformatics, University of Würzburg, Würzburg, Germany Abstract: Central nervous system dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus type 1 (HIV-1 infection and acquired immunodeficiency virus syndrome (AIDS. Patients with AIDS are usually affected by HIV-associated encephalitis (HIVE with viral replication limited to cells of monocyte origin. To examine the molecular mechanisms underlying HIVE-induced dementia, the GSE4755 Affymetrix data were obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs between the samples from AIDS patients with and without apparent features of HIVE-induced dementia were identified. In addition, protein–protein interaction networks were constructed by mapping DEGs into protein–protein interaction data to identify the pathways that these DEGs are involved in. The results revealed that the expression of 1,528 DEGs is mainly involved in the immune response, regulation of cell proliferation, cellular response to inflammation, signal transduction, and viral replication cycle. Heat-shock protein alpha, class A member 1 (HSP90AA1, and fibronectin 1 were detected as hub nodes with degree values >130. In conclusion, the results indicate that HSP90A and fibronectin 1 play important roles in HIVE pathogenesis.Keywords: microarray, human immunodeficiency virus, differentially expressed genes, protein–protein interaction network, gene ontology, encephalitis, dementia

  1. Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals

    DEFF Research Database (Denmark)

    Eugen-Olsen, J; Iversen, Anton; Garred, P

    1997-01-01

    Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course...

  2. "Gay Boy Talk" Meets "Girl Talk": HIV Risk Assessment Assumptions in Young Gay Men's Sexual Health Communication with Best Friends

    Science.gov (United States)

    Mutchler, Matt G.; McDavitt, Bryce

    2011-01-01

    Young adults, particularly young gay men (YGM), are vulnerable to human immunodeficiency virus (HIV). Yet, little is known about how YGM discuss sexual health issues with their friends ("gay boy talk"). We conducted semi-structured interviews with YGM and their best friends (11 YGM/YGM dyads and 13 YGM/heterosexual female dyads). In this paper, we…

  3. Retroviral and Lentiviral Safety Analysis of Gene-Modified T Cell Products and Infused HIV and Oncology Patients.

    Science.gov (United States)

    Marcucci, Katherine T; Jadlowsky, Julie K; Hwang, Wei-Ting; Suhoski-Davis, Megan; Gonzalez, Vanessa E; Kulikovskaya, Irina; Gupta, Minnal; Lacey, Simon F; Plesa, Gabriela; Chew, Anne; Melenhorst, J Joseph; Levine, Bruce L; June, Carl H

    2018-01-03

    Replication-competent retrovirus/lentivirus (RCR/L) and insertional oncogenesis are potential safety risks with integrating viruses in gene-modified cell therapies. As such, the Food and Drug Administration guidances outline RCR/L-monitoring methods throughout the entire gene therapy treatment cycle. We present data for 17 vector lots, 375 manufactured T cell products, and 308 patients post-infusion across both HIV and oncology indications, showing no evidence of RCR/L. Given our data, a Poisson probability model estimates that a single patient, or a group of patients, would need to be followed for at least 52.8 years to observe one positive RCR/L event, highlighting the unlikelihood of RCR/L development. Additionally, we estimate the median time for lentivirus-modified T cell products to fall below the 1% vector sequence threshold in peripheral or whole blood that would trigger vector integration site analysis. These estimated times are 1.4 months in hematologic malignancies, 0.66 month in solid tumors, and 0.92 month in HIV. Based on these considerable safety data in HIV and oncology and recent Biologics License Applications filed for lentiviral-modified T cell products for hematologic malignancies, this may be an opportune time to re-evaluate the current guidelines for T cell gene therapy product testing and long-term patient monitoring. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  4. Optimizing Tuberculosis Diagnosis in HIV-Infected Inpatients Meeting the Criteria of Seriously Ill in the WHO Algorithm.

    Science.gov (United States)

    Griesel, Rulan; Stewart, Annemie; van der Plas, Helen; Sikhondze, Welile; Rangaka, Molebogeng X; Nicol, Mark P; Kengne, Andre P; Mendelson, Marc; Maartens, Gary

    2017-11-06

    The WHO algorithm for the diagnosis of tuberculosis in seriously ill HIV-infected patients lacks a firm evidence base. We aimed to develop a clinical prediction rule for the diagnosis of tuberculosis and to determine the diagnostic utility of the Xpert MTB/RIF assay in seriously ill HIV-infected patients. We conducted a prospective study among HIV-infected inpatients with any cough duration and WHO-defined danger signs. Culture-positive tuberculosis from any site was the reference standard. A priori selected variables were assessed for univariate associations with tuberculosis. The most predictive variables were assessed in a multivariate logistic regression model and used to establish a clinical prediction rule for diagnosing tuberculosis. We enrolled 484 participants: median age 36 years, 65·5% female, median CD4 count 89 cells/µL, and 35·3% on antiretroviral therapy. Tuberculosis was diagnosed in 52·7% of participants. The c-statistic of our clinical prediction rule (variables: cough ≥14 days, unable to walk unaided, temperature >39 oC, chest radiograph assessment, haemoglobin, and white cell count) was 0·811 (95%CI 0·802, 0·819). The classic tuberculosis symptoms (fever, night sweats, weight loss) added no discriminatory value in diagnosing tuberculosis. Xpert MTB/RIF assay sensitivity was 86·3% and specificity was 96·1%. Our clinical prediction rule had good diagnostic utility for tuberculosis among seriously ill HIV-infected inpatients. Xpert MTB/RIF assay, incorporated into the updated 2016 WHO algorithm, had high sensitivity and specificity in this population. Our findings could facilitate improved diagnosis of tuberculosis among seriously ill HIV-infected inpatients in resource-constrained settings.

  5. Influence of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Interleukin 10 Genes on the Risk of Liver Cirrhosis in HIV-HCV Coinfected Patients.

    Directory of Open Access Journals (Sweden)

    Sara Corchado

    Full Text Available Analysis of the contribution of genetic (single nucleotide polymorphisms (SNP at position -238 and -308 of the tumor necrosis factor alpha (TNF-α and -592 of the interleukin-10 (IL-10 promotor genes and of classical factors (age, alcohol, immunodepression, antirretroviral therapy on the risk of liver cirrhosis in human immunodeficiency (HIV-hepatitis C (HCV virus coinfected patients.Ninety one HIV-HCV coinfected patients (50 of them with chronic hepatitis and 41 with liver cirrhosis and 55 healthy controls were studied. Demographic, risk factors for the HIV-HCV infection, HIV-related (CD4+ T cell count, antiretroviral therapy, HIV viral load and HCV-related (serum ALT concentration, HCV viral load, HCV genotype characteristics and polymorphisms at position -238 and -308 of the tumor necrosis factor alfa (TNF- α and -592 of the interleukin-10 (IL-10 promotor genes were studied.Evolution time of the infection was 21 years in both patients' groups (chronic hepatitis and liver cirrhosis. The group of patients with liver cirrhosis shows a lower CD4+ T cell count at the inclusion in the study (but not at diagnosis of HIV infection, a higher percentage of individuals with previous alcohol abuse, and a higher proportion of patients with the genotype GG at position -238 of the TNF-α promotor gene; polymorphism at -592 of the IL-10 promotor gene approaches to statistical significance. Serum concentrations of profibrogenic transforming growth factor beta1 were significantly higher in healthy controls with genotype GG at -238 TNF-α promotor gene. The linear regression analysis demonstrates that the genotype GG at -238 TNF-α promotor gene was the independent factor associated to liver cirrhosis.It is stressed the importance of immunogenetic factors (TNF-α polymorphism at -238 position, above other factors previously accepted (age, gender, alcohol, immunodepression, on the evolution to liver cirrhosis among HIV-infected patients with established chronic

  6. Does antiretroviral treatment change HIV-1 codon usage patterns in its genes: a preliminary bioinformatics study.

    Science.gov (United States)

    Palanisamy, Navaneethan; Osman, Nathan; Ohnona, Frédéric; Xu, Hong-Tao; Brenner, Bluma; Mesplède, Thibault; Wainberg, Mark A

    2017-01-07

    Codon usage bias has been described for various organisms and is thought to contribute to the regulation of numerous biological processes including viral infections. HIV-1 codon usage has been previously shown to be different from that of other viruses and man. It is evident that the antiretroviral drugs used to restrict HIV-1 replication also select for resistance variants. We wanted to test whether codon frequencies in HIV-1 sequences from treatment-experienced patients differ from those of treatment-naive individuals due to drug pressure affecting codon usage bias. We developed a JavaScript to determine the codon frequencies of aligned nucleotide sequences. Irrespective of subtypes, using HIV-1 pol sequences from 532 treatment-naive and 52 treatment-experienced individuals, we found that pol sequences from treatment-experienced patients had significantly increased AGA (arginine; p = 0.0002***) and GGU (glycine; p = 0.0001***), and decreased AGG (arginine; p = 0.0001***) codon frequencies. The same pattern was not observed when subtypes B and C sequences were analyzed separately. Additionally, irrespective of subtypes, using HIV-1 gag sequences from 524 treatment-naive and 54 treatment-experienced individuals, gag sequences from treatment-experienced patients had significantly increased CUA (leucine; p HIV-1 genome, we show that antiretroviral therapy changed certain HIV-1 codon frequencies in a subtype specific way.

  7. Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

    Directory of Open Access Journals (Sweden)

    Dobson Wendy

    2011-06-01

    Full Text Available Abstract Background RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK family of SR protein kinases on HIV-1 expression and RNA processing was examined. Results Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication. Conclusions Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

  8. 2004 Environmental Mutagen Society Annual Meeting - Genes, Mutations and Disease: The Environmental Connection

    Energy Technology Data Exchange (ETDEWEB)

    Samson, Leona D.

    2004-08-23

    The Meeting consisted of 9 Symposia, 4 Keynote Lectures, 3 Platform Sessions and 4 Poster Sessions. In addition there were Breakfast Meetings for Special Interest Groups designed to inform attendees about the latest advances in environmental mutagenesis research. Several of the topics to be covered at this broad meeting will be of interest to the Department of Energy, Office of Science. The relevance of this meeting to the DOE derives from the fact that low dose radiation may represent one of the most significant sources of human mutations that are attributable to the environment. The EMS membership, and those who attended the EMS Annual Meeting were interested in both chemical and radiation induced biological effects, such as cell death, mutation, teratogenesis, carcinogenesis and aging. These topics thate were presented at the 2004 EMS Annual meeting that were of clear interest to DOE include: human variation in cancer susceptibility, unusual mechanisms of mutation, germ and stem cell mutagenesis, recombination and the maintenance of genomic stability, multiple roles for DNA mismatch repair, DNA helicases, mutation, cancer and aging, Genome-wide transcriptional responses to environmental change, Telomeres and genomic stability: when ends don?t meet, systems biology approach to cell phenotypic decision processes, and the surprising biology of short RNAs. Poster and platform sessions addressed topics related to environmental mutagen exposure, DNA repair, mechanisms of mutagenesis, epidemiology, genomic and proteomics and bioinformatics. These sessions were designed to give student, postdocs and more junior scientists a chance to present their work.

  9. Exon level transcriptomic profiling of HIV-1-infected CD4(+ T cells reveals virus-induced genes and host environment favorable for viral replication.

    Directory of Open Access Journals (Sweden)

    Michaël Imbeault

    Full Text Available HIV-1 is extremely specialized since, even amongst CD4(+ T lymphocytes (its major natural reservoir in peripheral blood, the virus productively infects only a small proportion of cells under an activated state. As the percentage of HIV-1-infected cells is very low, most studies have so far failed to capture the precise transcriptomic profile at the whole-genome scale of cells highly susceptible to virus infection. Using Affymetrix Exon array technology and a reporter virus allowing the magnetic isolation of HIV-1-infected cells, we describe the host cell factors most favorable for virus establishment and replication along with an overview of virus-induced changes in host gene expression occurring exclusively in target cells productively infected with HIV-1. We also establish that within a population of activated CD4(+ T cells, HIV-1 has no detectable effect on the transcriptome of uninfected bystander cells at early time points following infection. The data gathered in this study provides unique insights into the biology of HIV-1-infected CD4(+ T cells and identifies genes thought to play a determinant role in the interplay between the virus and its host. Furthermore, it provides the first catalogue of alternative splicing events found in primary human CD4(+ T cells productively infected with HIV-1.

  10. A novel cell-based high-throughput screen for inhibitors of HIV-1 gene expression and budding identifies the cardiac glycosides.

    Science.gov (United States)

    Laird, Gregory M; Eisele, Evelyn E; Rabi, S Alireza; Nikolaeva, Daria; Siliciano, Robert F

    2014-04-01

    Highly active antiretroviral therapy (HAART) is the mainstay of treatment for HIV-1 infection. While current HAART regimens have been extremely effective, issues of associated toxicity, cost and resistance remain and there is a need for novel antiretroviral compounds to complement the existing therapy. We sought to develop a novel high-throughput method for identifying compounds that block later steps in the life cycle not targeted by current therapy. We designed a high-throughput screen to identify inhibitors of post-integration steps in the HIV-1 life cycle. The screening method was applied to a library of compounds that included numerous FDA-approved small molecules. Among the small molecules that inhibited late stages in HIV-1 replication were members of the cardiac glycoside family. We demonstrate that cardiac glycosides potently inhibit HIV-1 gene expression, thereby reducing the production of infectious HIV-1. We demonstrate that this inhibition is dependent upon the human Na(+)/K(+)-ATPase, but independent of cardiac glycoside-induced increases in intracellular Ca(2+). We have validated a novel high-throughput screen to identify small molecule inhibitors of HIV-1 gene expression, virion assembly and budding. Using this screen, we have demonstrated that a number of FDA-approved compounds developed for other purposes potently inhibit HIV-1 replication, including the cardiac glycosides. Our work indicates that the entire cardiac glycoside family of drugs shows potential for antiretroviral drug development.

  11. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

    Directory of Open Access Journals (Sweden)

    Joan Joseph

    2010-01-01

    Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

  12. Development of a prototype continuity of care record with context-specific links to meet the information needs of case managers for persons living with HIV.

    Science.gov (United States)

    Schnall, Rebecca; Cimino, James J; Bakken, Suzanne

    2012-08-01

    (1) To develop a prototype Continuity of Care Record (CCR) with context-specific links to electronic HIV information resources; and (2) to assess case managers' perceptions regarding the usability of the prototype. We integrated context-specific links to HIV case management information resources into a prototype CCR using the Infobutton Manager and Librarian Infobutton Tailoring Environment (LITE). Case managers (N=9) completed a think-aloud protocol and the Computer System Usability Questionnaire (CSUQ) to evaluate the usability of the prototype. Verbalizations from the think-aloud protocol were summarized using thematic analysis. CSUQ data were analyzed with descriptive statistics. Although participants expressed positive comments regarding the usability of the prototype, the think-aloud protocol also identified the need for improvement in resource labels and for additional resources. On a scale ranging from 1 (strongly agree) to 7 (strongly disagree), the average CSUQ overall satisfaction was 2.25 indicating that users (n=9) were generally satisfied with the system. Mean CSUQ factor scores were: System Usefulness (M=2.13), Information Quality (M=2.46), and Interface Quality (M=2.26). Our novel application of the Infobutton Manager and LITE in the context of case management for persons living with HIV in community-based settings resulted in a prototype CCR with infobuttons that met the majority of case managers' information needs and received relatively positive usability ratings. Findings from this study inform future integration of context-specific links into CCRs and electronic health records and support their use for meeting end-users information needs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Inequalities and Duality in Gene Coexpression Networks of HIV-1 Infection Revealed by the Combination of the Double-Connectivity Approach and the Gini's Method

    Directory of Open Access Journals (Sweden)

    Chuang Ma

    2011-01-01

    Full Text Available The symbiosis (Sym and pathogenesis (Pat is a duality problem of microbial infection, including HIV/AIDS. Statistical analysis of inequalities and duality in gene coexpression networks (GCNs of HIV-1 infection may gain novel insights into AIDS. In this study, we focused on analysis of GCNs of uninfected subjects and HIV-1-infected patients at three different stages of viral infection based on data deposited in the GEO database of NCBI. The inequalities and duality in these GCNs were analyzed by the combination of the double-connectivity (DC approach and the Gini's method. DC analysis reveals that there are significant differences between positive and negative connectivity in HIV-1 stage-specific GCNs. The inequality measures of negative connectivity and edge weight are changed more significantly than those of positive connectivity and edge weight in GCNs from the HIV-1 uninfected to the AIDS stages. With the permutation test method, we identified a set of genes with significant changes in the inequality and duality measure of edge weight. Functional analysis shows that these genes are highly enriched for the immune system, which plays an essential role in the Sym-Pat duality (SPD of microbial infections. Understanding of the SPD problems of HIV-1 infection may provide novel intervention strategies for AIDS.

  14. Meeting the challenges of North-South collaboration: the case of HIV prevention for rural youth, Edo State, Nigeria.

    Science.gov (United States)

    Onokerhoraye, Andrew G; Maticka-Tyndale, Eleanor

    2012-06-01

    Despite the significant contributions of the various North-South research partnerships during the past five decades to enhancing research capacity in the South, they have faced a number of challenges associated with the various partnerships. There have been limited attempts to critically examine the successes and challenges associated with these partnerships. Based on the experiences of implementing the 'HIV Prevention for Rural Youth' programme by a Canadian-Nigerian partnership during a four year period, this paper outlines the successes achieved and the challenges faced. The paper reviews the context of contemporary North-South research collaboration which provided the framework for the implementation of the HIV Prevention for Rural Youth. It then examines the benefits which the implementation of the programme have stimulated as well as the various challenges which confronted the partnership and how they were handled. The implications of the project's implementation experiences for future North-South collaborative research programmes are highlighted.

  15. HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG-seronegative individuals block HIV-1 epithelial transcytosis and neutralize CD4(+) cell infection: an IgA gene and functional analysis.

    Science.gov (United States)

    Tudor, D; Derrien, M; Diomede, L; Drillet, A-S; Houimel, M; Moog, C; Reynes, J-M; Lopalco, L; Bomsel, M

    2009-09-01

    AIDS is mainly a sexually transmitted disease, and accordingly, mucosal tissues are the primary sites of natural human immunodeficiency virus type-1 (HIV-1) transmission. Mucosal immunoglobulin A (IgA) antibody specific for HIV-1 envelope gp41 subunit is one correlate of protection in individuals who are highly sexually exposed to HIV-1 but remain persistently IgG seronegative (HEPS). Understanding these peculiar IgAs at the gene and functional level is possible only with monoclonal IgAs. We have constructed a mucosal Fab IgA library from HEPS and have characterized a series of HIV-1 IgAs specific for gp41 that, in vitro, are transcytosis-blocking and infection-neutralizing. Characterization of their IgA genes shows that Fab specific for the gp41 membrane-proximal region harbors a long heavy-chain CDR3 loop (CDRH3) similar to the two broadly neutralizing IgG monoclonal antibodies, 2F5 and 4E10. Furthermore, the selected Fab IgA shows extensive somatic mutations that cluster in the CDR regions, indicating that affinity maturation due to an antigen-driven process had occurred in HEPS individuals, presumably upon multiple exposures to HIV. This analysis of HEPS monoclonal IgA gives a unique opportunity to correlate an antibody function (resistance to a pathogen in vivo) with an antibody gene. Such neutralizing monoclonal IgAs could be used in microbicide formulation.

  16. 78 FR 44133 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-07-23

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee... on guidance documents issued from the Office of Cellular, Tissue and Gene Therapies, Center for...

  17. 77 FR 63840 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-17

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee..., Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and..., Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, and the...

  18. 76 FR 22405 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-04-21

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee... gene therapy products for the treatment of retinal disorders. Topics to be considered include the...

  19. 75 FR 66381 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-28

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee... Lentiviral Vector Based Gene Therapy Products. FDA intends to make background material available to the...

  20. 75 FR 65640 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-26

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and... Tumor Vaccines and Biotechnology Branch, Office of Cellular, Tissue and Gene Therapies, Center for...

  1. 76 FR 81513 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-12-28

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue, and Gene Therapies Advisory Committee..., Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and... Gene Therapies, Center for Biologics Evaluation and Research, FDA. FDA intends to make background...

  2. Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency

    Directory of Open Access Journals (Sweden)

    Gumez Audrey

    2005-11-01

    Full Text Available Abstract Background The persistence of latent HIV-1 reservoirs is the principal barrier preventing the eradication of HIV-1 infection in patients by current antiretroviral therapy. It is thus crucial to understand the molecular mechanisms involved in the establishment, maintenance and reactivation of HIV-1 latency. Since chromatin remodeling has been implicated in the transcriptional reactivation of the HIV-1 promoter, we assessed the role of the histone deacetylase inhibitor sodium butyrate (NaB on two HIV-1 latently infected cell lines (U1 and ACH-2 gene expression. Results Analysis of microarrays data led us to select two candidate genes: NCoA3 (Nuclear Receptor Coactivator 3, a nuclear receptor coactivator and IRF8 (Interferon Regulatory Factor 8, an interferon regulatory factor. NCoA3 gene expression is upregulated following NaB treatment of latently infected cells whereas IRF8 gene expression is strongly downregulated in the promonocytic cell line following NaB treatment. Their differential expressions were confirmed at the transcriptional and translational levels. Moreover, NCoA3 gene expression was also upregulated after treatment of U1 and ACH-2 cells with phorbol myristyl acetate (PMA but not trichostatin A (TSA and after treatment with NaB of two others HIV-1 latently infected cell lines (OM10.1 and J1.1. IRF8 gene is only expressed in U1 cells and was also downregulated after treatment with PMA or TSA. Functional analyses confirmed that NCoA3 synergizes with Tat to enhance HIV-1 promoter transcription and that IRF8 represses the IRF1-mediated activation through the HIV-1 promoter Interferon-stimulated response element (ISRE. Conclusion These results led us to postulate that NCoA3 could be involved in the transcriptional reactivation of the HIV-1 promoter from latency and that IRF8 may contribute to the maintenance of the latent state in the promonocytic cell line. Implication of these factors in the maintenance or reactivation of the

  3. Evaluation of Touchdown Nested PCR to Circumvent Spurious Priming and Increase Specificity during HIV and GBV-C Gene Amplification

    Directory of Open Access Journals (Sweden)

    SH Falahi

    2010-01-01

    Full Text Available Introduction & Objective: Primer-Template hybridization temperature is one of the important parameters in Nested PCR optimization. Unlike instant temperature for sequence amplification in routine PCR process, Touchdown PCR is a modified form of standard PCR that employs a range of annealing temperature. This study intended to develop a Touchdown Nested PCR in order to circumvent spurious priming and enhancing specify during gene amplification. Materials & Methods: This is an experimental study conducted at Tarbiat Modarres University of Tehran during 2008-2009. Study samples were collected from Digestive Diseases Research Centre- at Shari'ati Hospital and HIV research center – Imam Khomeini Hospital. After extracting the nucleic acid, primer designing for HIV and GBV-C and c-DNA synthesis Nested PCR was performed on negative and positive samples using standard and touchdown protocols. Results: The intended band was observed in all positive samples. No band was observed in any human and viral negative control samples. After electrophoresis of PCR products, non specific band were seen in HIV and GBV-C samples during standard PCR. Using the touchdown protocol, undesirable bands were omitted or significantly decreased. Conclusion: In the present study, despite the formation of uncalled bands in standard reaction using the touchdown method led to omission of non-specific bands without any significant effect on the final products. As for its simplicity, cost and time saving, it seems that using this method is a rational and economical way for fast optimization of PCR reactions.

  4. The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

    Directory of Open Access Journals (Sweden)

    Burger Marieta

    2011-02-01

    Full Text Available Abstract Background One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1 and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1, an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.

  5. Interferon lambda 4 (IFNL4 gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

    Directory of Open Access Journals (Sweden)

    Camila Fernanda da Silveira Alves

    Full Text Available Abstract Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1 are co-infected with hepatitis C virus (HCV. Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815, which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%. IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002. The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001. The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

  6. Different Expression of Interferon-Stimulated Genes in Response to HIV-1 Infection in Dendritic Cells Based on Their Maturation State.

    Science.gov (United States)

    Calonge, Esther; Bermejo, Mercedes; Diez-Fuertes, Francisco; Mangeot, Isabelle; González, Nuria; Coiras, Mayte; Jiménez Tormo, Laura; García-Perez, Javier; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Alcamí, José

    2017-04-15

    Dendritic cells (DCs) are professional antigen-presenting cells whose functions are dependent on their degree of differentiation. In their immature state, DCs capture pathogens and migrate to the lymph nodes. During this process, DCs become resident mature cells specialized in antigen presentation. DCs are characterized by a highly limiting environment for human immunodeficiency virus type 1 (HIV-1) replication due to the expression of restriction factors such as SAMHD1 and APOBEC3G. However, uninfected DCs capture and transfer viral particles to CD4 lymphocytes through a trans -enhancement mechanism in which chemokines are involved. We analyzed changes in gene expression with whole-genome microarrays when immature DCs (IDCs) or mature DCs (MDCs) were productively infected using Vpx-loaded HIV-1 particles. Whereas productive HIV infection of IDCs induced expression of interferon-stimulated genes (ISGs), such induction was not produced in MDCs, in which a sharp decrease in ISG- and CXCR3-binding chemokines was observed, lessening trans -infection of CD4 lymphocytes. Similar patterns of gene expression were found when DCs were infected with HIV-2 that naturally expresses Vpx. Differences were also observed under conditions of restrictive HIV-1 infection, in the absence of Vpx. ISG expression was not modified in IDCs, whereas an increase of ISG- and CXCR3-binding chemokines was observed in MDCs. Overall these results suggest that sensing and restriction of HIV-1 infection are different in IDCs and MDCs. We propose that restrictive infection results in increased virulence through different mechanisms. In IDCs avoidance of sensing and induction of ISGs, whereas in MDCs increased production of CXCR3-binding chemokines, would result in lymphocyte attraction and enhanced infection at the immune synapse. IMPORTANCE In this work we describe for the first time the activation of a different genetic program during HIV-1 infection depending on the state of maturation of DCs

  7. DRD2 and DRD4 genes related to cognitive deficits in HIV-infected adults who abuse alcohol.

    Science.gov (United States)

    Villalba, Karina; Devieux, Jessy G; Rosenberg, Rhonda; Cadet, Jean Lud

    2015-08-27

    HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. The causes of neurocognitive impairment are still unclear. However, several factors have been suggested including the role of genetics. There is evidence suggesting that neurocognitive impairment is heritable and individual differences in cognition are strongly driven by genetic variations. The contribution of genetic variants affecting the metabolism and activity of dopamine may influence these individual differences. The present study explored the relationship between two candidate genes (DRD4 and DRD2) and neurocognitive performance in HIV-infected adults. A total of 267 HIV-infected adults were genotyped for polymorphisms, DRD4 48 bp-variable number tandem repeat (VNTR), DRD2 rs6277 and ANKK1 rs1800497. The Short Category (SCT), Color Trail (CTT) and Rey-Osterrieth Complex Figure Tests (ROCT) were used to measure executive function and memory. Results showed significant associations with the SNP rs6277 and impaired executive function (odds ratio = 3.3, 95% CI 1.2-2.6; p = 0.004) and cognitive flexibility (odds ratio = 1.6, 95% CI 2.0-5.7; p = 0.001). The results were further stratified by race and sex and significant results were seen in males (odds ratio = 3.5, 95% CI 1.5-5.5; p = 0.008) and in African Americans (odds ratio = 3.1, 95% CI 2.3-3.5; p = 0.01). Also, DRD4 VNTR 7-allele was significantly associated with executive dysfunction. The study shows that genetically determined differences in the SNP rs6277 DRD2 gene and DRD4 48 bp VNTR may be risk factors for deficits in executive function and cognitive flexibility.

  8. Immunogenicity and virulence of attenuated vaccinia virus Tian Tan encoding HIV-1 muti-epitope genes, p24 and cholera toxin B subunit in mice.

    Science.gov (United States)

    Du, Shouwen; Wang, Yuhang; Liu, Cunxia; Wang, Maopeng; Zhu, Yilong; Tan, Peng; Ren, Dayong; Li, Xiao; Tian, Mingyao; Yin, Ronglan; Li, Chang; Jin, Ningyi

    2015-07-01

    No effective prophylactic or therapeutic vaccine against HIV-1 in humans is currently available. This study analyzes the immunogenicity and safety of a recombinant attenuated vaccinia virus. A chimeric gene of HIV-1 multi-epitope genes containing CpG ODN and cholera toxin B subunit (CTB) was inserted into Chinese vaccinia virus Tian Tan strain (VTT) mutant strain. The recombinant virus rddVTT(-CCMp24) was assessed for immunogenicity and safety in mice. Results showed that the protein CCMp24 was expressed stably in BHK-21 infected with rddVTT(-CCMp24). And the recombinant virus induced the production of HIV-1 p24 specific immunoglobulin G (IgG), IL-2 and IL-4. The recombinant vaccine induced γ-interferon secretion against HIV peptides, and elicited a certain levels of immunological memory. Results indicated that the recombinant virus had certain immunogenicity to HIV-1. Additionally, the virulence of the recombinant virus was been attenuated in vivo of mice compared with wild type VTT (wtVTT), and the introduction of CTB and HIV Mp24 did not alter the infectivity and virulence of defective vaccinia virus. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application.

    Science.gov (United States)

    Alapati, Deepthi; Morrisey, Edward E

    2017-03-01

    Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations. Recent reports have provided proof of concept by using CRISPR/Cas9 to successfully repair or inactivate mutations in animal models of monogenic human diseases. Potential pulmonary applications of CRISPR/Cas9 gene editing include gene correction of monogenic diseases in pre- or postnatal lungs and ex vivo gene editing of patient-specific airway stem cells followed by autologous cell transplant. Strategies to enhance gene-editing efficiency and eliminate off-target effects by targeting pulmonary stem/progenitor cells and the assessment of short-term and long-term effects of gene editing are important considerations as the field advances. If methods continue to advance rapidly, CRISPR/Cas9-mediated gene editing may provide a novel opportunity to correct monogenic diseases of the respiratory system.

  10. 77 FR 73472 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and...

  11. 76 FR 64951 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-10-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee...

  12. 76 FR 49774 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-08-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee...

  13. A quantitative comparison of anti-HIV gene therapy delivered to hematopoietic stem cells versus CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Borislav Savkovic

    2014-06-01

    Full Text Available Gene therapy represents an alternative and promising anti-HIV modality to highly active antiretroviral therapy. It involves the introduction of a protective gene into a cell, thereby conferring protection against HIV. While clinical trials to date have delivered gene therapy to CD4+T cells or to CD34+ hematopoietic stem cells (HSC, the relative benefits of each of these two cellular targets have not been conclusively determined. In the present analysis, we investigated the relative merits of delivering a dual construct (CCR5 entry inhibitor + C46 fusion inhibitor to either CD4+T cells or to CD34+ HSC. Using mathematical modelling, we determined the impact of each scenario in terms of total CD4+T cell counts over a 10 year period, and also in terms of inhibition of CCR5 and CXCR4 tropic virus. Our modelling determined that therapy delivery to CD34+ HSC generally resulted in better outcomes than delivery to CD4+T cells. An early one-off therapy delivery to CD34+ HSC, assuming that 20% of CD34+ HSC in the bone marrow were gene-modified (G+, resulted in total CD4+T cell counts ≥ 180 cells/ µL in peripheral blood after 10 years. If the uninfected G+ CD4+T cells (in addition to exhibiting lower likelihood of becoming productively infected also exhibited reduced levels of bystander apoptosis (92.5% reduction over non gene-modified (G- CD4+T cells, then total CD4+T cell counts of ≥ 350 cells/ µL were observed after 10 years, even if initially only 10% of CD34+ HSC in the bone marrow received the protective gene. Taken together our results indicate that: 1. therapy delivery to CD34+ HSC will result in better outcomes than delivery to CD4+T cells, and 2. a greater impact of gene therapy will be observed if G+ CD4+T cells exhibit reduced levels of bystander apoptosis over G- CD4+T cells.

  14. Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR RNA.

    Directory of Open Access Journals (Sweden)

    Matthew S Lalonde

    2011-05-01

    Full Text Available The RNA response element TAR plays a critical role in HIV replication by providing a binding site for the recruitment of the viral transactivator protein Tat. Using a structure-guided approach, we have developed a series of conformationally-constrained cyclic peptides that act as structural mimics of the Tat RNA binding region and block Tat-TAR interactions at nanomolar concentrations in vitro. Here we show that these compounds block Tat-dependent transcription in cell-free systems and in cell-based reporter assays. The compounds are also cell permeable, have low toxicity, and inhibit replication of diverse HIV-1 strains, including both CXCR4-tropic and CCR5-tropic primary HIV-1 isolates of the divergent subtypes A, B, C, D and CRF01_AE. In human peripheral blood mononuclear cells, the cyclic peptidomimetic L50 exhibited an IC(50 ∼250 nM. Surprisingly, inhibition of LTR-driven HIV-1 transcription could not account for the full antiviral activity. Timed drug-addition experiments revealed that L-50 has a bi-phasic inhibition curve with the first phase occurring after HIV-1 entry into the host cell and during the initiation of HIV-1 reverse transcription. The second phase coincides with inhibition of HIV-1 transcription. Reconstituted reverse transcription assays confirm that HIV-1 (- strand strong stop DNA synthesis is blocked by L50-TAR RNA interactions in-vitro. These findings are consistent with genetic evidence that TAR plays critical roles both during reverse transcription and during HIV gene expression. Our results suggest that antiviral drugs targeting TAR RNA might be highly effective due to a dual inhibitory mechanism.

  15. HIV exposed seronegative (HESN compared to HIV infected individuals have higher frequencies of telomeric Killer Immunoglobulin-like Receptor (KIR B motifs; Contribution of KIR B motif encoded genes to NK cell responsiveness.

    Directory of Open Access Journals (Sweden)

    Elise Jackson

    Full Text Available Previously, we showed that Killer Immunoglobulin-like Receptor (KIR3DS1 homozygotes (hmz are more frequent in HIV exposed seronegative (HESN than in recently HIV infected (HIV+ individuals. KIR3DS1 encodes an activating Natural Killer (NK cell receptor (NKR. The link between KIR genotype and HIV outcomes likely arises from the function that NK cells acquire through expression of particular NKRs. An initial screen of 97 HESN and 123 HIV+ subjects for the frequency of KIR region gene carriage observed between-group differences for several telomeric KIR region loci. In a larger set of up to 106 HESN and 439 HIV+ individuals, more HESN than HIV+ subjects were KIR3DS1 homozygotes, lacked a full length KIR2DS4 gene and carried the telomeric group B KIR haplotype motif, TB01. TB01 is characterized by the presence of KIR3DS1, KIR2DL5A, KIR2DS3/5 and KIR2DS1, in linkage disequilibrium with each other. We assessed which of the TB01 encoded KIR gene products contributed to NK cell responsiveness by stimulating NK cells from 8 HIV seronegative KIR3DS1 and TB01 motif homozygotes with 721.221 HLA null cells and evaluating the frequency of KIR3DS1+/-KIR2DL5+/-, KIR3DS1+/-KIR2DS1+/-, KIR3DS1+/-KIR2DS5+/- NK cells secreting IFN-γ and/or expressing CD107a. A higher frequency of NK cells expressing, versus not, KIR3DS1 responded to 721.221 stimulation. KIR2DL5A+, KIR2DS1+ and KIR2DS5+ NK cells did not contribute to 721.221 responses or modulate those by KIR3DS1+ NK cells. Thus, of the TB01 KIR gene products, only KIR3DS1 conferred responsiveness to HLA-null stimulation, demonstrating its ligation can activate ex vivo NK cells.

  16. Gene Therapy Strategies to Block HIV-1 Replication by RNA Interference

    NARCIS (Netherlands)

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-01-01

    The cellular mechanism of RNA interference (RNAi) plays an antiviral role in many organisms and can be used for the development of therapeutic strategies against viral pathogens. Persistent infections like the one caused by the human immunodeficiency virus type 1 (HIV-1) likely require a durable

  17. Inhibition of HIV-1 Integrase gene expression by 10-23 DNAzyme

    Indian Academy of Sciences (India)

    2012-06-25

    Jun 25, 2012 ... infection of the incoming HIV-1 virus (Zhang et al. 1999). A single ... considerably more stable for exogenous delivery in biolog- ..... pIN-EGFP resulted in the expression of IN-GFP fusion protein as analysed by fluorescence microscopy. As a control, expression of GFP from plasmid pEGFPN3 was verified in.

  18. Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner.

    Directory of Open Access Journals (Sweden)

    Vaibhav B Shah

    Full Text Available HIV-1 replication is dependent on binding of the viral capsid to the host protein cyclophilin A (CypA. Interference with cyclophilin A binding, either by mutations in the HIV-1 capsid protein (CA or by the drug cyclosporine A (CsA, inhibits HIV-1 replication in cell culture. Resistance to CsA is conferred by A92E or G94D substitutions in CA. The mutant viruses are also dependent on CsA for their replication. Interestingly, infection of some cell lines by these mutants is enhanced by CsA, while infection of others is not affected by the drug. The cells are thus termed nonpermissive and permissive, respectively, for infection by CsA-dependent mutants. The mechanistic basis for the cell type dependence is not well understood, but has been hypothesized to result from a dominant-acting host factor that blocks HIV-1 infection by a mechanism that requires CypA binding to the viral capsid. In an effort to identify a CypA-dependent host restriction factor, we adopted a strategy involving comparative gene expression analysis in three permissive and three non-permissive cell types. We ranked the genes based on their relative overexpression in non-permissive cell types compared to the permissive cell types. Based on specific selection criteria, 26 candidate genes were selected and targeted using siRNA in nonpermissive (HeLa cells. Depletion of none of the selected candidate genes led to the reversal of CsA-dependent phenotype of the A92E mutant. Our data suggest that none of the 26 genes tested is responsible for the dependence of the A92E mutant on CsA. Our study provides gene expression data that may be useful for future efforts to identify the putative CypA-dependent HIV-1 restriction factor and in studies of other cell-specific phenotypes.

  19. HIV and HCV Co-Culture Promotes Profibrogenic Gene Expression through an Epimorphin-Mediated ERK Signaling Pathway in Hepatic Stellate Cells.

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    Lei Shi

    Full Text Available Accelerated fibrosis in patients co-infected with hepatitis C virus (HCV and human immunodeficiency virus (HIV has been a major cause of mortality in the highly active anti-retroviral therapy (HAART era. However, the role of co-infection in accelerating the progression of liver fibrosis, particularly with regard to the effects of co-infection on hepatic stellate cells (HSCs, remains unclear. We hypothesized that HIV and HCV induce liver fibrosis synergistically by altering the regulation of epimorphin production, and thereby indirectly alter HSC function. Here, we examined the effects of epimorphin on HSC proliferation and invasion, and the changes in fibrogenesis-related gene activity in HSCs (LX2 in the presence of inactivated CXCR4-tropic HIV and HCV (JFH1. The combination of HIV and HCV significantly increased epimorphin expression, which increased the proliferation and invasion capabilities of HSCs. Epimorphin also induced the expression of profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP1 in an extracellular signal-regulated kinase (ERK-dependent manner. These data indicated that the effects of HIV/HCV co-infection on hepatic fibrosis might be mediated in part by EPM. Strategies to limit the expression of EPM might represent a novel therapeutic approach to prevent the progression of hepatic fibrosis during HIV/HCV co-infection.

  20. Analysis of HIV-1 protease gene reveals frequent multiple infections followed by recombination among drug treated individuals living in Sao Paulo and Santos, Brazil.

    Directory of Open Access Journals (Sweden)

    Edsel Renata De Morais Nunes

    Full Text Available The present study investigated the prevalence of HIV-1 multiple infections in a population composed by 47 patients under HAART failure and enrolled at the National DST/AIDS, Program, Ministry of Health, Brazil.Detection of multiple infections was done using a previously published RFLP assay for the HIV-1 protease gene, which is able of distinguishing between infections caused by a single or multiple HIV-1 subtypes. Samples with multiple infections were cloned, and sequence data submitted to phylogenetic analysis. We were able to identify 17 HIV-1 multiple infections out of 47 samples. Multiple infections were mostly composed by a mixture of recombinant viruses (94%, with only one case in which protease gene pure subtypes B and F were recovered. This is the first study that reports the prevalence of multiple infections and intersubtype recombinants in a population undergoing HAART in Brazil. Based on the data there was a steep increase of multiple infections after the introduction of the combined antiretroviral therapy in Brazil. Cases of multiple infections may be associated with HIV-1 genetic diversity through recombination allowing for the generation of viruses showing a combination of resistance mutations.

  1. Expression of Werner and Bloom syndrome genes is differentially regulated by in vitro HIV-1 infection of peripheral blood mononuclear cells.

    Science.gov (United States)

    Bordi, L; Amendola, A; Ciccosanti, F; Abbate, I; Camilloni, G; Capobianchi, M R

    2004-11-01

    In HIV infection, continuous immune activation leads to accelerated ageing of the adaptive immune system, similar to that observed in elderly people. We investigated the expression of WRN and BLM (genes involved in disorders characterized by premature ageing, genomic instability and cancer predisposition) in peripheral blood mononuclear cells (PBMC) activated in vitro with phytohaemagglutinin (PHA) and infected with different HIV-1 strains. The steady state levels of mRNA were analysed by reverse transcription-polymerase chain reaction (RT-PCR), and protein expression was assayed using immunocytochemistry and Western blot techniques. In uninfected PBMC, PHA stimulation induced an increase in BLM mRNA and protein expression, while WRN expression remained virtually unchanged. When PBMC were infected in vitro with a lymphotropic HIV-1 strain, the level of BLM mRNA showed a peak at 24 h of infection, followed by a decline to uninfected culture levels. A similar result failed to be seen using an R5-tropic HIV-1 strain. In accordance with mRNA expression, in HIV-infected cultures PBMC were stained more frequently and more intensely by a BLM-specific antibody as compared to uninfected cultures, staining peaking at 24. Conversely, WRN expression was not modulated by HIV-1. The proportion of cells showing BLM up-regulation, established by immunocytochemical staining, was much greater than the proportion of productively infected PBMC, as established by proviral DNA measurement. This result indicates that BLM up-regulation is probably a result of an indirect bystander cell effect. Activation of the BLM gene in infected PBMC suggests that premature ageing could be a further immunopathogenetic mechanism involved in HIV-induced immunodeficiency, and points to a possible new candidate target for innovative therapeutic intervention.

  2. Polymorphisms in the IFNγ, IL-10, and TGFβ Genes May Be Associated with HIV-1 Infection

    Directory of Open Access Journals (Sweden)

    Felipe Bonfim Freitas

    2015-01-01

    Full Text Available Objective. This study investigated possible associations between the TNFα-308G/A, IFN+874A/T, IL-6-174C/G, IL-10-1082A/G, and TGFβ-509C/T polymorphisms with HIV-1 infection, in addition to correlation of the polymorphisms with clinical markers of AIDS progression, such as levels of CD4+/CD8+ T lymphocytes and plasma viral load. Methods. A total of 216 individuals who were infected with HIV-1 and on antiretroviral therapy (ART and 294 individuals from the uninfected control group were analyzed. Results. All individuals evaluated were negative for total anti-HBc, anti-HCV, anti-T. pallidum, and anti-HTLV-1/2. The polymorphisms were identified by PCR-RFLP. Individuals presenting the IFN+874A allele as well as the AA genotype were more frequent in the HIV-1 infected group compared to the control group (P<0.05, in addition to having lower levels of CD4+ T lymphocytes. The CD8+ T lymphocytes count was significantly lower in individuals with the IL-10-1082 GG genotype. The TGFβ-509TT genotype was associated with higher plasma viral load. Conclusions. The results suggest that the presence of the IFN+874A allele confers susceptibility to HIV-1 infection and a decrease in the number of CD4+ T lymphocytes. In addition, the genotype associated with high serum levels of TGFβ may be associated with an increase in plasma viral load.

  3. Engineering and Validation of a Vector for Concomitant Expression of Rare Transfer RNA (tRNA and HIV-1 nef Genes in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Siti Aisyah Mualif

    Full Text Available Relative ease in handling and manipulation of Escherichia coli strains make them primary candidate to express proteins heterologously. Overexpression of heterologous genes that contain codons infrequently used by E. coli is related with difficulties such as mRNA instability, early termination of transcription and/or translation, deletions and/or misincorporation, and cell growth inhibition. These codon bias -associated problems are addressed by co-expressing ColE1-compatible, rare tRNA expressing helper plasmids. However, this approach has inadequacies, which we have addressed by engineering an expression vector that concomitantly expresses the heterologous protein of interest, and rare tRNA genes in E. coli. The expression vector contains three (argU, ileY, leuW rare tRNA genes and a useful multiple cloning site for easy in-frame cloning. To maintain the overall size of the parental plasmid vector, the rare tRNA genes replaced the non-essential DNA segments in the vector. The cloned gene is expressed under the control of T7 promoter and resulting recombinant protein has a C-terminal 6His tag for IMAC-mediated purification. We have evaluated the usefulness of this expression vector by expressing three HIV-1 genes namely HIV-1 p27 (nef, HIV-1 p24 (ca, and HIV-1 vif in NiCo21(DE3 E.coli and demonstrated the advantages of using expression vector that concomitantly expresses rare tRNA and heterologous genes.

  4. Claudin-1 gene variants and susceptibility to hepatitis C infection in HIV-1 infected intravenous drug users (an ANRS case-control study).

    Science.gov (United States)

    Ghosn, Jade; Fouquet, Baptiste; Quertainmont, Yann; Salmon, Dominique; Sahali, Sabrinel; Rioux, Christophe; Duvivier, Claudine; Mole, Martine; Delfraissy, Jean-François; Misrahi, Micheline

    2015-04-01

    Hepatitis C virus (HCV) seroprevalence is highly diverse among human immunodeficiency virus-1 (HIV-1) infected patients, ranging between 10% of HIV-1 infected homo-bisexuel men, to >92% in patients infected with HIV-1 who acquired HIV-1 through intravenous drug use. Thus, being HCV-free while having acquired HIV-1 via intravenous drug use is a rare situation. Claudin-1 is a protein involved in intracellular tight-junctions and has been identified as a major cellular co-receptor for HCV infection. Our objective was to determine whether Claudin-1 gene (CLDN1) mutations might be involved in natural resistance to HCV infection. We conducted a case-control study. All recruited patients acquired HIV-1 infection via intravenous drug use route before 1995. The case study patients remained free from HCV infection (negative anti-HCV antibodies and HCV-RNA). The control study patients was co-infected with HCV (positive anti-HCV antibodies). Direct genomic sequencing of the CLDN1 gene coding region and adjacent intron/exons junctions was performed from peripheral blood mononuclear cells. A total of 138 Caucasian patients were enrolled. Twenty-two patients (cases) were free from HCV infection and 116 (controls) were co-infected with HCV. We found single nucleotide polymorphisms (SNPs) described previously with no significant differences in allele frequencies between cases and controls. In conclusion, despite being a major cellular co-receptor for HCV entry in vitro, we did not identify any specific substitution in CLDN1 gene coding region in our study patients highly exposed but resistant to HCV infection in vivo. Other cellular co-factors involved in HCV infection should be investigated in this highly-exposed intravenous drug users patients. © 2015 Wiley Periodicals, Inc.

  5. GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.

    Science.gov (United States)

    Kulkarni, Smita; Jadhav, Sushama; Khopkar, Priyanka; Sane, Suvarna; Londhe, Rajkumar; Chimanpure, Vaishali; Dhilpe, Veronica; Ghate, Manisha; Yelagate, Rajendra; Panchal, Narayan; Rahane, Girish; Kadam, Dilip; Gaikwad, Nitin; Rewari, Bharat; Gangakhedkar, Raman

    2017-07-21

    Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p HIV-1 Quant assay compared well with Abbott HIV-1 m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

  6. Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Olga Krotova

    Full Text Available Our objective is to create gene immunogens targeted against drug-resistant HIV-1, focusing on HIV-1 enzymes as critical components in viral replication and drug resistance. Consensus-based gene vaccines are specifically fit for variable pathogens such as HIV-1 and have many advantages over viral genes and their expression-optimized variants. With this in mind, we designed the consensus integrase (IN of the HIV-1 clade A strain predominant in the territory of the former Soviet Union and its inactivated derivative with and without mutations conferring resistance to elvitegravir. Humanized IN gene was synthesized; and inactivated derivatives (with 64D in the active site mutated to V with and without elvitegravir-resistance mutations were generated by site-mutagenesis. Activity tests of IN variants expressed in E coli showed the consensus IN to be active, while both D64V-variants were devoid of specific activities. IN genes cloned in the DNA-immunization vector pVax1 (pVaxIN plasmids were highly expressed in human and murine cell lines (>0.7 ng/cell. Injection of BALB/c mice with pVaxIN plasmids followed by electroporation generated potent IFN-γ and IL-2 responses registered in PBMC by day 15 and in splenocytes by day 23 after immunization. Multiparametric FACS demonstrated that CD8+ and CD4+ T cells of gene-immunized mice stimulated with IN-derived peptides secreted IFN-γ, IL-2, and TNF-α. The multi-cytokine responses of CD8+ and CD4+ T-cells correlated with the loss of in vivo activity of the luciferase reporter gene co-delivered with pVaxIN plasmids. This indicated the capacity of IN-specific CD4+ and CD8+ T-cells to clear IN/reporter co-expressing cells from the injection sites. Thus, the synthetic HIV-1 clade A integrase genes acted as potent immunogens generating polyfunctional Th1-type CD4+ and CD8+ T cells. Generation of such response is highly desirable for an effective HIV-1 vaccine as it offers a possibility to attack virus

  7. Transient gene expression optimization and expression vector comparison to improve HIV-1 VLP production in HEK293 cell lines.

    Science.gov (United States)

    Fuenmayor, Javier; Cervera, Laura; Gutiérrez-Granados, Sonia; Gòdia, Francesc

    2017-11-04

    Transient gene expression (TGE) has been used at small and medium scale for the production of biologicals in sufficient quantities to perform pre-clinical and characterization studies. Polyethyleneimine (PEI)-mediated transfection offers a low toxicity and non-expensive method for cell transfection. DNA and PEI concentration for transient gene expression has been extensively optimized in order to increase product titers. However, the possibility to extrapolate the optimal concentrations found for a specific bioprocess when expression vectors or cell lines need to be changed has not been investigated.In this work, the combination of three different HEK293 cell lines with three different vectors was studied for the production of HIV-1 virus-like particles (VLPs). The concentration of DNA and PEI was optimized for the nine combinations. The obtained results were very similar in all cases (DNA = 2.34 ± 0.18 μg/mL and PEI = 5.81 ± 0.18 μg/mL), revealing that transfection efficiency is not dependent on the cell line or vector type, but on DNA and PEI quantities. Furthermore, two of the cell lines tested stably expressed a protein able to recognize specific origins of replication: HEK293T/SV40 and HEK293E/oriP. Origins of replication were included in the vector sequences in order to test their capacity to increase production titers. HEK293T/SV40 resulted in a decrease of cell density and productivity of 2.3-fold compared to a control plasmid. On the other hand, HEK293E/OriP platform enabled a threefold improvement in HIV-1 VLP production keeping the same cell densities and viabilities compared to a control plasmid.

  8. Virulence meets metabolism: Cra and KdpE gene regulation in enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Njoroge, Jacqueline W; Nguyen, Y; Curtis, Meredith M; Moreira, Cristiano G; Sperandio, Vanessa

    2012-10-16

    Gastrointestinal (GI) bacteria sense diverse environmental signals as cues for differential gene regulation and niche adaptation. Pathogens such as enterohemorrhagic Escherichia coli (EHEC), which causes bloody diarrhea, use these signals for the temporal and energy-efficient regulation of their virulence factors. One of the main virulence strategies employed by EHEC is the formation of attaching and effacing (AE) lesions on enterocytes. Most of the genes necessary for the formation of these lesions are grouped within a pathogenicity island, the locus of enterocyte effacement (LEE), whose expression requires the LEE-encoded regulator Ler. Here we show that growth of EHEC in glycolytic environments inhibits the expression of ler and consequently all other LEE genes. Conversely, growth within a gluconeogenic environment activates expression of these genes. This sugar-dependent regulation is achieved through two transcription factors: KdpE and Cra. Both Cra and KdpE directly bind to the ler promoter, and Cra's affinity to this promoter is catabolite dependent. Moreover, we show that the Cra and KdpE proteins interact in vitro and that KdpE's ability to bind DNA is enhanced by the presence of Cra. Cra is important for AE lesion formation, and KdpE contributes to this Cra-dependent regulation. The deletion of cra and kdpE resulted in the ablation of AE lesions. One of the many challenges that bacteria face within the GI tract is to successfully compete for carbon sources. Linking carbon metabolism to the precise coordination of virulence expression is a key step in the adaptation of pathogens to the GI environment. IMPORTANCE An appropriate and prompt response to environmental cues is crucial for bacterial survival. Cra and KdpE are two proteins found in both nonpathogenic and pathogenic bacteria that regulate genes in response to differences in metabolite concentration. In this work, we show that, in the deadly pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7

  9. Where genes meet environment-integrating the role of gut luminal contents, immunity and pancreas in type 1 diabetes.

    Science.gov (United States)

    Scott, Fraser W; Pound, Lynley D; Patrick, Christopher; Eberhard, Chandra E; Crookshank, Jennifer A

    2017-01-01

    The rise in new cases of type 1 diabetes (T1D) in genetically susceptible individuals over the past half century has been attributed to numerous environmental "triggers" or promoters such as enteroviruses, diet, and most recently, gut bacteria. No single cause has been identified in humans, likely because there are several pathways by which one can develop T1D. There is renewed attention to the role of the gut and its immune system in T1D pathogenesis based largely on recent animal studies demonstrating that altering the gut microbiota affects diabetes incidence. Although T1D patients display dysbiosis in the gut microbiome, it is unclear whether this is cause or effect. The heart of this question involves several moving parts including numerous risk genes, diet, viruses, gut microbiota, timing, and loss of immune tolerance to β-cells. Most clinical trials have addressed only one aspect of this puzzle using some form of immune suppression, without much success. The key location where our genes meet and deal with the environment is the gastrointestinal tract. The influence of all of its major contents, including microbes, diet, and immune system, must be understood as part of the integrative biology of T1D before we can develop durable means of preventing, treating, or curing this disease. In the present review, we expand our previous gut-centric model based on recent developments in the field. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Toward a Durable Anti-HIV Gene Therapy Based on RNA Interference

    NARCIS (Netherlands)

    Berkhout, Ben

    2009-01-01

    Basic research in the field of molecular biology led to the discovery of the mechanism of RNA interference (RNAi) in Caenorhabditis elegans in 1998. RNAi is now widely appreciated as an important gene control mechanism in mammals, and several RNAi-based gene-silencing applications have already been

  11. Use of T7 gene 6 exonuclease and phosphorothioated primers for the manipulation of HIV-1 infectious clones.

    Science.gov (United States)

    da Costa, L J; Tanuri, A

    1998-05-01

    A method is described for the efficient substitution, deletion or insertion of any desired DNA sequence into any viral infectious clones without the limitation of naturally occurring restriction sites. The technique employs the polymerase chain reaction combined with the resistance of 2'-deoxynucleotides 5'-O-(1-thiotriphosphate) dNTPs [S] bonds (phosphorothiate bonds) to the 5'-3' double strand specific T7 gene 6 exonuclease (T7 Exo) digestion. Primers used to amplify the DNA target regions being manipulated present three phosphorothioate bonds from the fifteenth base at the 5' end. The enzyme activity was shown to be completely inhibited by the presence of more than one phosphorothioate residue at the 5' end of the DNA molecules. When the amplification products are submitted to the exonuclease digestion the hydrolytic T7 Exo activity generates a short single strand DNA tail which contains the nucleotide integrity of the 3' strand. Since the ends of two independently amplified products overlap they can regenerate a stable recombinant structure when further combined in the same reaction tube in the presence of T4 DNA ligase. This new method can be used for manipulating an HIV-1 full-length clone belonging to subtype D replacing the env (gp120) gene for an F subtype sequence.

  12. Genetic variability of the VP1 gene of BK and JC polyomaviruses in HIV-infected patients

    Directory of Open Access Journals (Sweden)

    Karalić Danijela

    2015-01-01

    Full Text Available Human polyomaviruses, BK virus (BKV and JC virus (JCV, are world widely distributed in human population. After primary infection, BKV and JCV establish latency in kidneys and upper part of urinary tract. In seropositive healthy individuals asymptomatic reactivation of both viruses occurs in in 0.5-20%. On the other hand, reactivation of these viruses in imunosuppressed patients, primarily in patients with T cell immunodeficiency, can lead to development of polyomavirus-associated diseases. Some of these diseases such as progressive multifocal leukoencephalopathy (PML, polyomavirus-induced nephropathy (PVN, hemorrhagic cystitis (HC are life-threatening diseases with high mortality and morbidity rate. However, they do not affect all immunosuppressed patients, suggesting that other factors, such as genetic variability of BKV and JCV, can contribute to their occurrence. Immunosuppression leads to increased levels of replication of both viruses. Increased levels of replication are associated with higher incidence of mutations in the VP1 gene. Mutations, especially those located in outer loops, may lead to changed tropism and generation of more aggressive variants of BKV and JCV. This review is focused on clinical significance of BK and JC virus infection in immunosuppressed patients, especially in HIV-infected, and sequence changes in the VP1 gene that can contribute to selection of more virulent variants of BKV and JCV via adaptive evolution.

  13. The use of mobile phone apps by Australian gay and bisexual men to meet sex partners: an analysis of sex-seeking repertoires and risks for HIV and STIs using behavioural surveillance data.

    Science.gov (United States)

    Hull, Peter; Mao, Limin; Prestage, Garrett; Zablotska, Iryna; de Wit, John; Holt, Martin

    2016-04-19

    Mobile phone apps are now the most popular method that Australian gay men use to find sex partners. Partner-seeking mobile phone apps use location functions to identify like-minded men and display their proximity. This study examines whether meeting partners via mobile apps is associated with a greater risk of HIV and sexually transmitted infections (STIs) than with other ways of meeting partners. Data were analysed from the Gay Community Periodic Surveys, community-based, cross-sectional surveys conducted in Australian state capital cities between 2010 and 2014. χ(2) tests and multinomial logistic regression were used to analyse differences in risk profiles of men who used different methods to meet partners. Data were analysed from 36 428 men who participated in the Gay Community Periodic Surveys between 2010 and 2014. In 2014, 4116 men reported meeting sex partners with the use of mobile apps, increasing from 23.9% in 2011 to 42.5% in 2014. Men who used a combination of online and offline methods reported a greater number of sex partners and were more likely to report a recent STI than men who used online methods only or offline methods only. There has been a steep increase in the use of mobile phone apps by gay men in Australia to meet male partners. However, men who use a combination of mobile phone apps, internet websites and offline places to meet partners appear to be at increased risk of STIs or HIV compared with men who use a narrower range of online and offline methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Conservation of functional domains and limited heterogeneity of HIV-1 reverse transcriptase gene following vertical transmission

    Directory of Open Access Journals (Sweden)

    Ahmad Nafees

    2005-05-01

    Full Text Available Abstract Background The reverse transcriptase (RT enzyme of human immunodeficiency virus type 1 (HIV-1 plays a crucial role in the life cycle of the virus by converting the single stranded RNA genome into double stranded DNA that integrates into the host chromosome. In addition, RT is also responsible for the generation of mutations throughout the viral genome, including in its own sequences and is thus responsible for the generation of quasi-species in HIV-1-infected individuals. We therefore characterized the molecular properties of RT, including the conservation of functional motifs, degree of genetic diversity, and evolutionary dynamics from five mother-infant pairs following vertical transmission. Results The RT open reading frame was maintained with a frequency of 87.2% in five mother-infant pairs' sequences following vertical transmission. There was a low degree of viral heterogeneity and estimates of genetic diversity in mother-infant pairs' sequences. Both mothers and infants RT sequences were under positive selection pressure, as determined by the ratios of non-synonymous to synonymous substitutions. Phylogenetic analysis of 132 mother-infant RT sequences revealed distinct clusters for each mother-infant pair, suggesting that the epidemiologically linked mother-infant pairs were evolutionarily closer to each other as compared with epidemiologically unlinked mother-infant pairs. The functional domains of RT which are responsible for reverse transcription, DNA polymerization and RNase H activity were mostly conserved in the RT sequences analyzed in this study. Specifically, the active sites and domains required for primer binding, template binding, primer and template positioning and nucleotide recruitment were conserved in all mother-infant pairs' sequences. Conclusion The maintenance of an intact RT open reading frame, conservation of functional domains for RT activity, preservation of several amino acid motifs in epidemiologically

  15. The Budapest Meeting 2005. Intensified networking on ethics of science : The case of reproductive cloning, germline gene therapy and human dignity

    NARCIS (Netherlands)

    van Steendam, Guido; Dinnyes, Andras; Mallet, Jacques; Roosendaal, Hans E.

    2006-01-01

    This paper reports on the meeting of the Sounding Board of the EU Reprogenetics Project that was held in Budapest, Hungary, 6–9 November 2005. The Reprogenetics Project runs from 2004 until 2007 and has a brief to study the ethical aspects of human reproductive cloning and germline gene therapy.

  16. Potent cross-reactive immune response against the wild-type and drug-resistant forms of HIV reverse transcriptase after the chimeric gene immunization.

    Science.gov (United States)

    Starodubova, Elizaveta; Boberg, Andreas; Ivanov, Alexander; Latyshev, Oleg; Petrakova, Natalia; Kuzmenko, Yulia; Litvina, Marina; Chernousov, Alexander; Kochetkov, Sergey; Karpov, Vadim; Wahren, Britta; Isaguliants, Maria G

    2010-02-23

    HIV reverse transcriptase (RT) can be considered as a target and an instrument of immunotherapy aimed at limiting the emergence and spread of drug-resistant HIV. The chimeric genes coding for the wild-type and multi-drug-resistant RT (RT1.14) fused to lysosome-associated membrane protein 1 (LAMP-1) were injected intramuscularly into BALB/c mice. The immune response was assessed by ELISpot, cytokine ELISA intracellular IFN-gamma staining, and antibody ELISA. The genes for RT- and RT1.14-LAMP fusions (RT-LAMP and RT1.14-LAMP) were immunogenic generating a mixed Th1/Th2-profile of immune response, while the wild-type RT gene induced only weak immune response. Specific secretion of Th1-cytokines increased with increasing level of RT modification: RTgene fusions generated a cross-reactive T-cell response against epitopes harboring drug-resistance mutations and their wild-type variants. Gene immunization induced specific IgG (10(3)), and transient serum IgA (10(2)). Low immunogenicity of the parental RT may be explained by tolerance to the enzyme that is a common endogenous retroviral antigen. Potent immune recognition of RT after immunization with chimeric RT genes indicates that this tolerance could be overcome. Immunization with mutant HIV genes may represent an immunotherapeutical supplement to antiretroviral treatment preventing the emergence of drug resistance. Copyright 2009 Elsevier Ltd. All rights reserved.

  17. Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin.

    Science.gov (United States)

    Petersen, Tess; Lee, Yu-Jin; Osinusi, Anu; Amorosa, Valerianna K; Wang, Crystal; Kang, Minhee; Matining, Roy; Zhang, Xiao; Dou, Diana; Umbleja, Triin; Kottilil, Shyam; Peters, Marion G

    2016-07-01

    A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500 mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ.

  18. Coexistencia de variantes HIV-1 com insercao dipeptidica no gene da transcriptase reversa

    Directory of Open Access Journals (Sweden)

    Aline Aki Tanikawa

    2013-08-01

    Full Text Available O objetivo desta comunicação foi descrever a detecção de coexistência de variantes HIV-1 com inserções de dois aminoácidos entre os códons 69 e 70 da transcriptase reversa. Tais variantes foram isoladas de paciente do sexo masculino, 16 anos de idade, em tratamento no interior do estado de São Paulo. Após confirmação de falha terapêutica, foi realizado teste de resistência a antirretrovirais, a partir do qual foram detectadas duas variantes contendo inserções dos aminoácidos Ser-Gly/Ser-Ala no códon 69 da transcriptase reversa, além da mutação T69S. Tais inserções possuem baixa prevalência, não foram relatadas em caráter de coexistência no Brasil e estão relacionadas com a resistência a múltiplas drogas, tornando o achado relevante do ponto de vista epidemiológico.

  19. Down modulation of HIV-1 gene expression using a procaryotic RNA-binding protein

    NARCIS (Netherlands)

    Berkhout, B.; Jeang, K. T.

    1990-01-01

    The coat protein of the single stranded RNA bacteriophages acts as a translational repressor by binding with high affinity to a target RNA that encompasses the ribosomal binding site of the replicase gene. We have expressed this procaryotic RNA-binding protein in mammalian cells. Using the coat

  20. The Budapest Meeting 2005 intensified networking on ethics of science: the case of reproductive cloning, germline gene therapy and human dignity.

    Science.gov (United States)

    Van Steendam, Guido; Dinnyés, András; Mallet, Jacques; Meloni, Rolando; Casabona, Carlos Romeo; González, Jorge Guerra; Kure, Josef; Szathmáry, Eörs; Vorstenbosch, Jan; Molnár, Péter; Edbrooke, David; Sándor, Judit; Oberfrank, Ferenc; Cole-Turner, Ron; Hargittai, István; Littig, Beate; Ladikas, Miltos; Mordini, Emilio; Roosendaal, Hans E; Salvi, Maurizio; Gulyás, Balázs; Malpede, Diana

    2006-10-01

    This paper reports on the meeting of the Sounding Board of the EU Reprogenetics Project that was held in Budapest, Hungary, 6-9 November 2005. The Reprogenetics Project runs from 2004 until 2007 and has a brief to study the ethical aspects of human reproductive cloning and germline gene therapy. Discussions during The Budapest Meeting are reported in depth in this paper as well as the initiatives to involve the participating groups and others in ongoing collaborations with the goal of forming an integrated network of European resources in the fields of ethics of science.

  1. Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.

    Science.gov (United States)

    Abdel-Motal, U M; Harbison, C; Han, T; Pudney, J; Anderson, D J; Zhu, Q; Westmoreland, S; Marasco, W A

    2014-09-01

    Topical microbicides are a leading strategy for prevention of HIV mucosal infection to women; however, numerous pharmacokinetic limitations associated with coitally related dosing strategy have contributed to their limited success. Here we test the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 minibody gene to the lower genital tract of female rhesus macaques (Rh) can provide prolonged expression of b12 minibodies in the cervical-vaginal secretions. Gene transfer studies demonstrated that, of various green fluorescent protein (GFP)-expressing AAV serotypes, AAV-6 most efficiently transduced freshly immortalized and primary genital epithelial cells (PGECs) of female Rh in vitro. In addition, AAV-6-b12 minibody transduction of Rh PGECs led to inhibition of SHIV162p4 transmigration and virus infectivity in vitro. AAV-6-GFP could also successfully transduce vaginal epithelial cells of Rh when applied intravaginally, including p63+ epithelial stem cells. Moreover, intravaginal application of AAV-6-b12 to female Rh resulted in prolonged minibody detection in their vaginal secretions throughout the 79-day study period. These data provide proof of principle that AAV-6-mediated delivery of anti-HIV broadly neutralizing antibody (BnAb) genes to the lower genital tract of female Rh results in persistent minibody detection for several months. This strategy offers promise that an anti-HIV-1 genetic microbicide strategy may be possible in which topical application of AAV vector, with periodic reapplication as needed, may provide sustained local BnAb expression and protection.

  2. A cost-effective melting temperature assay for the detection of single-nucleotide polymorphism in the MBL2 gene of HIV-1-infected children

    Directory of Open Access Journals (Sweden)

    Arraes L.C.

    2006-01-01

    Full Text Available We report a fast (less than 3 h and cost-effective melting temperature assay method for the detection of single-nucleotide polymorphisms in the MBL2 gene. The protocol, which is based on the Corbett Rotor Gene real time PCR platform and SYBR Green I chemistry, yielded, in the cohorts studied, sensitive (100% and specific (100% PCR amplification without the use of costly fluorophore-labeled probes or post-PCR manipulation. At the end of the PCR, the dissociation protocol included a slow heating from 60º to 95ºC in 0.2ºC steps, with an 8-s interval between steps. Melting curve profiles were obtained using the dissociation software of the Rotor Gene-3000 apparatus. Samples were analyzed in duplicate and in different PCR runs to test the reproducibility of this technique. No supplementary data handling is required to determine the MBL2 genotype. MBL2 genotyping performed on a cohort of 164 HIV-1-positive Brazilian children and 150 healthy controls, matched for age and sex and ethnic origin, yielded reproducible results confirmed by direct sequencing of the amplicon performed in blind. The three MBL2 variants (Arg52Cys, Gly54Asp, Gly57Glu were grouped together and called allele 0, while the combination of three wild-type alleles was called allele A. The frequency of the A/A homozygotes was significantly higher among healthy controls (0.68 than in HIV-infected children (0.55; P = 0.0234 and the frequency of MBL2 0/0 homozygotes was higher among HIV-1-infected children than healthy controls (P = 0.0296. The 0 allele was significantly more frequent among the 164 HIV-1-infected children (0.29 than among the 150 healthy controls (0.18; P = 0.0032. Our data confirm the association between the presence of the mutated MBL2 allele (allele 0 and HIV-1 infection in perinatally exposed children. Our results are in agreement with the literature data which indicate that the presence of the allele 0 confers a relative risk of 1.37 for HIV-1 infection through

  3. The impact of HIV-1 genetic diversity on the efficacy of a combinatorial RNAi-based gene therapy

    NARCIS (Netherlands)

    Herrera-Carrillo, E.; Berkhout, B.

    2015-01-01

    A hurdle for human immunodeficiency virus (HIV-1) therapy is the genomic diversity of circulating viruses and the possibility that drug-resistant virus variants are selected. Although RNA interference (RNAi) is a powerful tool to stably inhibit HIV-1 replication by the expression of antiviral short

  4. 75 FR 5091 - Office of the Director, National Institutes of Health; Notice of Meeting

    Science.gov (United States)

    2010-02-01

    ... HIV-infected individuals; and premature aging in HIV-infected individuals. An update also will be provided on the OARAC Working Groups for HIV Treatment and Prevention Guidelines. Place: National... theme of the meeting will be ``HIV/AIDS and Aging.'' The meeting will address issues related to...

  5. 75 FR 60132 - Office of the Director, National Institutes of Health; Notice of Meeting

    Science.gov (United States)

    2010-09-29

    ... the meeting will be ``HIV/AIDS and Adolescents.'' The meeting will focus on research to address: The epidemiology of HIV infection among adolescents; HIV prevention, treatment and care for adolescents; biological... youth in AIDS clinical research. An update also will be provided on the OARAC Working Groups for HIV...

  6. Creating Genetic Resistance to HIV

    Science.gov (United States)

    Burnett, John C.; Zaia, John A.; Rossi, John J.

    2012-01-01

    HIV/AIDS remains a chronic and incurable disease, in spite of the notable successes of highly active antiretroviral therapy. Gene therapy offers the prospect of creating genetic resistance to HIV that supplants the need for antiviral drugs. In sight of this goal, a variety of anti-HIV genes have reached clinical testing, including gene-editing enzymes, protein-based inhibitors, and RNA-based therapeutics. Combinations of therapeutic genes against viral and host targets are designed to improve the overall antiviral potency and reduce the likelihood of viral resistance. In cell-based therapies, therapeutic genes are expressed in gene modified T lymphocytes or in hematopoietic stem cells that generate an HIV-resistant immune system. Such strategies must promote the selective proliferation of the transplanted cells and the prolonged expression of therapeutic genes. This review focuses on the current advances and limitations in genetic therapies against HIV, including the status of several recent and ongoing clinical studies. PMID:22985479

  7. HIV Transmission

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... on HIV Syndicated Content Website Feedback HIV/AIDS HIV Transmission Language: English (US) Español (Spanish) Recommend on ...

  8. The role genes encoding of killer cell immunoglobulin-like receptors (KIRs) and their ligands in susceptibility to and progression of HIV infection.

    Science.gov (United States)

    Błachowicz, Olga; Zwolińska, Katarzyna

    2016-12-31

    NK cells are a part of the innate antiviral response. Their activity is regulated by signals from the surface receptors. Some of them, known as killer cell immunoglobulin-like receptors (KIRs), determine the quality and intensity of the immunological response, together with their ligands (HLA class I). KIR genes are very polymorphic, and this is reflected in the NK activity modulation. The stimulation of NK cells, especially in the early stages of the infection, can reduce the transmission of HIV or slow down the progression of infection. The varied KIR/HLA repertoire is a limiting factor for the risk of HIV infection and disease progression. Such diversity enables optimal regulation of NK cells and maintenance of the balance between activation to eliminate infected cells and inhibition. The control of NK cell activity via KIR3DL1/3DS1 and HLA-Bw4 (especially Bw4-80I) seems to be very important in the HIV context. With a few exceptions, it leads to a reduction of susceptibility to HIV infection and better viremia control, and slows down depletion of CD4+ T cells. Incompatibility of sexual partners for KIRs and HLA may oblige NK cells from the exposed partner to reject incoming cells from the HIV-positive partner. The presence of the inhibitory KIR, in the absence of its ligand, results in a lower threshold of NK cell activation, which reduces the chance of infection. The presence of an inhibitory receptor with a low affinity to the ligand (KIR2DL3+HLA-C1) is associated with lower susceptibility, and the effective NK cell inhibition (KIR2DL2+HLA-C1) results in increased susceptibility to HIV infection. The advantage of activating KIRs, especially in the presence of their ligands, is associated with higher cytolytic abilities, and thus reduced risk of HIV infection. If the virus is not eliminated in an early stage of infection, massive activation of NK is unfavorable due to the excessive stimulation of the immune system.

  9. Inhibition of HIV-1 gene expression by Sam68ΔC: multiple targets but a common mechanism?

    Directory of Open Access Journals (Sweden)

    Cochrane Alan

    2009-03-01

    Full Text Available Abstract Two recent publications have explored the mechanisms by which a mutant of the host protein Sam68 blocks HIV-1 structural protein synthesis and expands its activity to encompass Nef. Although the two studies propose different mechanisms for the responses observed, it is possible that a common activity is responsible. Understanding how this Sam68 mutant discriminates among the multiple viral mRNAs promises to reveal unique properties of HIV-1 RNA metabolism.

  10. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.

    Science.gov (United States)

    Samson, M; Libert, F; Doranz, B J; Rucker, J; Liesnard, C; Farber, C M; Saragosti, S; Lapoumeroulie, C; Cognaux, J; Forceille, C; Muyldermans, G; Verhofstede, C; Burtonboy, G; Georges, M; Imai, T; Rana, S; Yi, Y; Smyth, R J; Collman, R G; Doms, R W; Vassart, G; Parmentier, M

    1996-08-22

    HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 (ref.1) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains, and the orphan receptor LESTR (also called fusin) allows infection by strains adapted for growth in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele of CCR-5 is present at a high frequency in caucasian populations (allele frequency, 0.092), but is absent in black populations from Western and Central Africa and Japanese populations. A 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains. In a cohort of HIV-1 infected caucasian subjects, no individual homozygous for the mutation was found, and the frequency of heterozygotes was 35% lower than in the general population. White blood cells from an individual homozygous for the null allele were found to be highly resistant to infection by M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for primary HIV-1 strains. The lower frequency of heterozygotes in seropositive patients may indicate partial resistance.

  11. HIV-Associated Tuberculosis

    Directory of Open Access Journals (Sweden)

    Kogieleum Naidoo

    2011-01-01

    Full Text Available The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6.

  12. The AP-1 binding sites located in the pol gene intragenic regulatory region of HIV-1 are important for viral replication.

    Directory of Open Access Journals (Sweden)

    Laurence Colin

    Full Text Available Our laboratory has previously identified an important intragenic region in the human immunodeficiency virus type 1 (HIV-1 genome, whose complete functional unit is composed of the 5103 fragment, the DNaseI-hypersensitive site HS7 and the 5105 fragment. These fragments (5103 and 5105 both exhibit a phorbol 12-myristate 13-acetate (PMA-inducible enhancer activity on the herpes simplex virus thymidine kinase promoter. Here, we characterized the three previously identified AP-1 binding sites of fragment 5103 by showing the PMA-inducible in vitro binding and in vivo recruitment of c-Fos, JunB and JunD to this fragment located at the end of the pol gene. Functional analyses demonstrated that the intragenic AP-1 binding sites are fully responsible for the PMA-dependent enhancer activity of fragment 5103. Moreover, infection of T-lymphoid Jurkat and promonocytic U937 cells with wild-type and mutant viruses demonstrated that mutations of the intragenic AP-1 sites individually or in combination altered HIV-1 replication. Importantly, mutations of the three intragenic AP-1 sites led to a decreased in vivo recruitment of RNA polymerase II to the viral promoter, strongly supporting that the deleterious effect of these mutations on viral replication occurs, at least partly, at the transcriptional level. Single-round infections of monocyte-derived macrophages confirmed the importance of intragenic AP-1 sites for HIV-1 infectivity.

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: HIV/AIDS and Drug Abuse: Intertwined ... Press Office Meetings & Events Media Guide Get this Publication Español View Webisodes View Videos "After the Party" " ...

  14. HIV-1 receptor binding site-directed antibodies using a VH1-2 gene segment orthologue are activated by Env trimer immunization.

    Directory of Open Access Journals (Sweden)

    Marjon Navis

    2014-08-01

    Full Text Available Broadly neutralizing antibodies (bNAbs isolated from chronically HIV-1 infected individuals reveal important information regarding how antibodies target conserved determinants of the envelope glycoprotein (Env spike such as the primary receptor CD4 binding site (CD4bs. Many CD4bs-directed bNAbs use the same heavy (H chain variable (V gene segment, VH1-2*02, suggesting that activation of B cells expressing this allele is linked to the generation of this type of Ab. Here, we identify the rhesus macaque VH1.23 gene segment to be the closest macaque orthologue to the human VH1-2 gene segment, with 92% homology to VH1-2*02. Of the three amino acids in the VH1-2*02 gene segment that define a motif for VRC01-like antibodies (W50, N58, flanking the HCDR2 region, and R71, the two identified macaque VH1.23 alleles described here encode two. We demonstrate that immunization with soluble Env trimers induced CD4bs-specific VH1.23-using Abs with restricted neutralization breadth. Through alanine scanning and structural studies of one such monoclonal Ab (MAb, GE356, we demonstrate that all three HCDRs are involved in neutralization. This contrasts to the highly potent CD4bs-directed VRC01 class of bNAb, which bind Env predominantly through the HCDR2. Also unlike VRC01, GE356 was minimally modified by somatic hypermutation, its light (L chain CDRs were of average lengths and it displayed a binding footprint proximal to the trimer axis. These results illustrate that the Env trimer immunogen used here activates B cells encoding a VH1-2 gene segment orthologue, but that the resulting Abs interact distinctly differently with the HIV-1 Env spike compared to VRC01.

  15. Association Between the Interleukin-10-1082G/A, -592C/A, -819C/T Gene Polymorphism and HIV-1 Susceptibility: A Meta-Analysis.

    Science.gov (United States)

    Jiang, Caixiao; Liu, Shujun; Liu, Shuxia; Li, Zhanzhan; Chen, Peng; Chen, Lizhang

    2017-01-01

    The Interleukin-10 (IL-10) gene polymorphism influences the pathogenesis and evolution of HIV-1 disease. Many studies in this regard have evaluated the association between this polymorphism and HIV-1 susceptibility, yet, the exact relationship between them remains ambiguous and contradictory. A systematic literature search was conducted and the found case-control studies assessing the association between IL-10-1082G/A, -592C/A, -819C/T gene polymorphism and HIV-1 susceptibility were analyzed. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated by a fixed effect model. In general, no significant relationship was found between IL-10-1082G/A gene polymorphism and susceptibility to HIV-1 infection (A vs. G genotype model: OR = 0.97, 95% CI = 0.81-1.23, p = .775; GG vs. AA+AG model: OR = 0.98, 95% CI = 0.76-1.27, p = .867; GG+AG vs. AA model: OR = 0.97, 95% CI = 0.70-1.35, p = .852; GG vs. AA model: OR = 0.88, 95% CI = 0.67-1.15, p = .348; AG vs. AA model: OR = 0.96, 95% CI = 0.67-1.37, p = .811; GG+AA vs. AG model: OR = 1.03, 95% CI = 0.74-1.43, p = .886). IL-10-529C/A gene polymorphism might lead to a decreased risk of HIV-1 infection (A vs. G genotype model: OR = 0.88, 95% CI = 0.73-1.06, p = .166; GG vs. AA+AG model: OR = 0.94, 95% CI = 0.80-1.11, p = .447; GG+AG vs. AA model: OR = 0.75, 95% CI = 0.61-0.92, p = .005; GG vs. AA model: OR = 0.73, 95% CI = 0.57-0.93, p = .012; AG vs. AA model: OR = 0.74, 95% CI = 0.60-0.92, p = .0.007; GG+AA vs. AG model: OR = 1.11, 95% CI = 0.72-1.71, p = .641). IL-10-819C/T gene polymorphism might lead to an increased risk of HIV-1 infection (A vs. G genotype model: OR = 1.25, 95% CI = 1.04-1.50, p = .019; GG vs. AA+AG model: OR = 1.29, 95% CI = 0.81-2.01, p = .278; GG+AG vs. AA model: OR = 1.42, 95% CI = 1.05-1.93, p = .023; GG vs

  16. A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo.

    Science.gov (United States)

    Wang, Wei; Yao, Nan; Ju, Bin; Dong, Zhihui; Cong, Zhe; Jiang, Hong; Qin, Chuan; Wei, Qiang

    2014-06-01

    Human immunodeficiency virus (HIV)-1 subtype CRF01_AE is one of the major HIV-1 subtypes that dominate the global epidemic. However, its drug resistance, associated mutations, and viral fitness have not been systemically studied, because available chimeric simian-HIVs (SHIVs) usually express the HIV-1 reverse transcriptase (rt) gene of subtype B HIV-1, which is different from subtype CRF01_AE HIV-1. In this study, a recombinant plasmid, pRT-SHIV/AE, was constructed to generate a chimeric RT-SHIV/AE by replacing the rt gene of simian immunodeficiency virus (SIVmac239) with the counterpart of Chinese HIV-1 subtype CRF01_AE. The infectivity, replication capacity, co-receptor tropism, drug sensitivity, and genetic stability of RT-SHIV/AE were characterized. The new chimeric RT-SHIV/AE effectively infected and replicated in human T cell line and rhesus peripheral blood mononuclear cells (rhPBMC). The rt gene of RT-SHIV/AE lacked the common mutation (T215I) associated with drug resistance. RT-SHIV-AE retained infectivity and immunogenicity, similar to that of its counterpart RT-SHIV/TC virus following intravenous inoculation in Chinese rhesus macaque. RT-SHIV-AE was more sensitive to nucleoside reverse transcriptase inhibitors (NRTIs) than the RT-SHIV/TC. RT-SHIV/AE was genetically stable in Chinese rhesus macaque. The new chimeric RT-SHIV/AE may be a valuable tool for evaluating the efficacy of the rt-based antiviral drugs against the subtype CRF01_AE HIV-1. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  17. A workshop report on HIV mHealth synergy and strategy meeting to review emerging evidence-based mHealth interventions and develop a framework for scale-up of these interventions.

    Science.gov (United States)

    Karanja, Sarah; Mbuagbaw, Lawrence; Ritvo, Paul; Law, Judith; Kyobutungi, Catherine; Reid, Graham; Ram, Ravi; Estambale, Benson; Lester, Richard

    2011-01-01

    mHealth is a term used to refer to mobile technologies such as personal digital assistants and mobile phones for healthcare. mHealth initiatives to support care and treatment of patients are emerging globally and this workshop brought together researchers, policy makers, information, communication and technology programmers, academics and civil society representatives for one and a half days synergy meeting in Kenya to review regional evidence based mHealth research for HIV care and treatment, review mHealth technologies for adherence and retention interventions in anti-retroviral therapy (ART) programs and develop a framework for scale up of evidence based mHealth interventions. The workshop was held in May 2011 in Nairobi, Kenya and was funded by the Canadian Global Health Research Initiatives (GHRI) and the US Centre for Disease Control and Prevention (CDC). At the end of the workshop participants came up with a framework to guide mHealth initiatives in the region and a plan to work together in scaling up evidence based mHealth interventions. The participants acknowledged the importance of the meeting in setting the pace for strengthening and coordinating mHealth initiatives and unanimously agreed to hold a follow up meeting after three months.

  18. Effect of CYP2B6 Gene Polymorphisms on Efavirenz Plasma Concentrations in Chinese Patients with HIV Infection.

    Science.gov (United States)

    Meng, Xianmin; Yin, Kang; Wang, Jiangrong; Dong, Ping; Liu, Li; Shen, Yinzhong; Shen, Li; Ma, Qing; Lu, Hongzhou; Cai, Weimin

    2015-01-01

    The main aim of this study was to investigate the effect of CYP2B6 gene polymorphisms on efavirenz (EFV) plasma concentrations in Han Chinese patients with human immunodeficiency virus (HIV) infection. In total, 322 patients were recruited for study. EFV plasma concentrations at steady-state were determined using high-performance liquid chromatography. Genotyping for seven single nucleotide polymorphisms (SNPs), including 171+967C>A, 171+3212C>T, 171+4335T>C, 516G>T, 785A>G, 1295-913G>A, and *1355A>G of CYP2B6, was performed using ligase detection reaction (LDR). SPSS 18.0 and Haploview 4.2 were applied for statistical analyses. The average EFV concentration of patients was 2.35±2.09 μg/mL. Overall, 22% patients displayed EFV concentrations out of the therapeutic range of 1-4 μg/mL (13.1% 4 μg/mL). We observed significant association of 171+967C>A, 171+4335T>C, 516G>T, 785A>G and *1355A>G with high plasma EFV levels (pEFV concentrations > 4 μg/mL were 56.7%, 56.7% and 60%, respectively. We observed strong linkage disequilibrium for 171+967C>A, 171+4335T>C, 516G>T and 785A>G, resulting in five haplotypes. The frequencies of the five haplotypes (high to low) were as follows: CCTG (0.328), ACTG (0.280), ACCT (0.189), ATTG (0.186) and ACCG (0.017). The frequency of CCTG (0.524) in patients with EFV plasma concentrations EFV concentrations > 4 μg/mL, relative to other patient groups. Average EFV concentrations of patients carrying ACTG (1.78 μg/mL), ACCT (7.50 μg/mL), and ATTG (1.92 μg/mL) haplotypes were markedly higher than those of patients carrying the CCTG haplotype. The predictive accuracy of ACCT for EFV > 4 μg/mL was 81%. Chinese patients administered standard doses of EFV require therapeutic drug monitoring or personalized medication management. Based on the current findings, we propose that 171+4335T>C, 516G>T, 785A>G and haplotype ACCT may be effectively used as genomic markers for EFV, which should aid in improving the efficacy of EFV

  19. Differential expression of Werner and Bloom syndrome genes in the peripheral blood of HIV-1 infected patients.

    Science.gov (United States)

    Bordi, Licia; Gioia, Cristiana; Lalle, Eleonora; Piselli, Pierluca; Poccia, Fabrizio; Capobianchi, Maria R; Amendola, Alessandra

    2007-02-01

    Human immunodeficiency virus (HIV)-induced immunodeficiency and immune-system aging share some analogies. Since Werner (WRN) and Bloom (BLM) helicases are crucial in cell repair and aging, their peripheral blood mononuclear cells (PBMC) mRNA levels were compared in HIV-1 infected patients and in normal donors. The mean levels of WRN mRNA were 3.7-fold higher in PBMCs from HIV-1 infected individuals in comparison to healthy donors, whereas BLM mRNA mean levels were slightly higher, although not significantly. WRN increase was positively correlated to CD4 and CD8 T-cell numbers, and also the percentage of naive T lymphocytes, and was observed also in T-cell subsets. Interestingly, a general trend toward increased WRN mRNA levels in individuals with lower viral load was observed, without association with patient age, time of seroconversion, and on/off antiretroviral therapy regimen. On the whole, this study shows that WRN and BLM are differentially modulated in HIV infection, as WRN--but not BLM--is significantly increased, suggesting that mechanisms different from defect or loss of helicase function, observed in WRN and BLM syndromes, may be at the basis of T-cell aging in HIV infection.

  20. High-level HIV-1 Nef transient expression in Nicotiana benthamiana using the P19 gene silencing suppressor protein of Artichoke Mottled Crinckle Virus

    Directory of Open Access Journals (Sweden)

    Bianco Linda

    2009-11-01

    Full Text Available Abstract Background In recent years, different HIV antigens have been successfully expressed in plants by either stable transformation or transient expression systems. Among HIV proteins, Nef is considered a promising target for the formulation of a multi-component vaccine due to its implication in the first steps of viral infection. Attempts to express Nef as a single protein product (not fused to a stabilizing protein in transgenic plants resulted in disappointingly low yields (about 0.5% of total soluble protein. In this work we describe a transient expression system based on co-agroinfiltration of plant virus gene silencing suppressor proteins in Nicotiana benthamiana, followed by a two-step affinity purification protocol of plant-derived Nef. Results The effect of three gene silencing viral suppressor proteins (P25 of Potato Virus X, P19 of either Artichoke Mottled Crinckle virus and Tomato Bushy Stunt virus on Nef transient expression yield was evaluated. The P19 protein of Artichoke Mottled Crinckle virus (AMCV-P19 gave the highest expression yield in vacuum co-agroinfiltration experiments reaching 1.3% of total soluble protein, a level almost three times higher than that previously reported in stable transgenic plants. The high yield observed in the co-agroinfiltrated plants was correlated to a remarkable decrease of Nef-specific small interfering RNAs (siRNAs indicating an effective modulation of RNA silencing mechanisms by AMCV-P19. Interestingly, we also showed that expression levels in top leaves of vacuum co-agroinfiltrated plants were noticeably reduced compared to bottom leaves. Moreover, purification of Nef from agroinfiltrated tissue was achieved by a two-step immobilized metal ion affinity chromatography protocol with yields of 250 ng/g of fresh tissue. Conclusion We demonstrated that expression level of HIV-1 Nef in plant can be improved using a transient expression system enhanced by the AMCV-P19 gene silencing suppressor

  1. High-level HIV-1 Nef transient expression in Nicotiana benthamiana using the P19 gene silencing suppressor protein of Artichoke Mottled Crinckle Virus.

    Science.gov (United States)

    Lombardi, Raffaele; Circelli, Patrizia; Villani, Maria Elena; Buriani, Giampaolo; Nardi, Luca; Coppola, Valentina; Bianco, Linda; Benvenuto, Eugenio; Donini, Marcello; Marusic, Carla

    2009-11-20

    In recent years, different HIV antigens have been successfully expressed in plants by either stable transformation or transient expression systems. Among HIV proteins, Nef is considered a promising target for the formulation of a multi-component vaccine due to its implication in the first steps of viral infection. Attempts to express Nef as a single protein product (not fused to a stabilizing protein) in transgenic plants resulted in disappointingly low yields (about 0.5% of total soluble protein). In this work we describe a transient expression system based on co-agroinfiltration of plant virus gene silencing suppressor proteins in Nicotiana benthamiana, followed by a two-step affinity purification protocol of plant-derived Nef. The effect of three gene silencing viral suppressor proteins (P25 of Potato Virus X, P19 of either Artichoke Mottled Crinckle virus and Tomato Bushy Stunt virus) on Nef transient expression yield was evaluated. The P19 protein of Artichoke Mottled Crinckle virus (AMCV-P19) gave the highest expression yield in vacuum co-agroinfiltration experiments reaching 1.3% of total soluble protein, a level almost three times higher than that previously reported in stable transgenic plants. The high yield observed in the co-agroinfiltrated plants was correlated to a remarkable decrease of Nef-specific small interfering RNAs (siRNAs) indicating an effective modulation of RNA silencing mechanisms by AMCV-P19. Interestingly, we also showed that expression levels in top leaves of vacuum co-agroinfiltrated plants were noticeably reduced compared to bottom leaves. Moreover, purification of Nef from agroinfiltrated tissue was achieved by a two-step immobilized metal ion affinity chromatography protocol with yields of 250 ng/g of fresh tissue. We demonstrated that expression level of HIV-1 Nef in plant can be improved using a transient expression system enhanced by the AMCV-P19 gene silencing suppressor protein. Moreover, plant-derived Nef was purified, with

  2. The Changes of Positive Selection Within env Gene of HIV-1 B', CRF07_BC and CRF08_BC from China Over Time.

    Science.gov (United States)

    Li, Tingting; Sun, Binlian; Jiang, Yanyan; Zeng, Haiyan; Li, Yanpeng; Wang, Yan; Yang, Rongge

    2017-01-01

    It is not clear about the possible evolutionary changes of the three predominant strains of HIV-1 in China over the course of the epidemic. Envelope (env) gene of HIV-1 is a good target for this evolutionary pressure for its enriched epitopes. We collected 159 full or part of env sequences sampled between 1997 and 2010 from database of China, we calculated the genetic distance, detected the positively selected sites by PAML suite and then compared the number using Fisher's exact test between the early period 1997 to 2003 and the late period 2004 to 2010. We found that the diversity of env genes had increased significantly and the positively selected sites were significantly becoming more over time. V2, V4, and C3 regions had suffered an increase positive selection pressure, while V1, V3, V5 and other conserved regions were relatively stable. Several sites were widely selected and compactly located in C3 and V4, five sites were consecutive in V4.There were two common positively selected sites in all groups: 413T in gp120 and 619L in gp41. The common positively selected sites identified in our study implied that they are important in viral survival and adaptation. Based on the role of V3 region in coreceptor determination and disease progression, our results suggested that the virulence of HIV-1 in China might be stable in the short time span. Given the overall increased tendency of positively selection sites in env, we might predict a less virulent state in the long run. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

    Directory of Open Access Journals (Sweden)

    Francesc Vidal

    Full Text Available This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients.The study groups were made of 99 patients (efficacy pharmacogenetic substudy and of 114 patients (safety pharmacogenetic substudy. Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively. Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses.As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons. Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004. In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01. With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04. Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively, neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively. In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01 and thrombocytopenia (OR

  4. Where Public Health Meets Human Rights: Integrating Human Rights into the Validation of the Elimination of Mother-to-Child Transmission of HIV and Syphilis.

    Science.gov (United States)

    Kismödi, Eszter; Kiragu, Karusa; Sawicki, Olga; Smith, Sally; Brion, Sophie; Sharma, Aditi; Mworeko, Lilian; Iovita, Alexandrina

    2017-12-01

    In 2014, the World Health Organization (WHO) initiated a process for validation of the elimination of mother-to-child transmission (EMTCT) of HIV and syphilis by countries. For the first time in such a process for the validation of disease elimination, WHO introduced norms and approaches that are grounded in human rights, gender equality, and community engagement. This human rights-based validation process can serve as a key opportunity to enhance accountability for human rights protection by evaluating EMTCT programs against human rights norms and standards, including in relation to gender equality and by ensuring the provision of discrimination-free quality services. The rights-based validation process also involves the assessment of participation of affected communities in EMTCT program development, implementation, and monitoring and evaluation. It brings awareness to the types of human rights abuses and inequalities faced by women living with, at risk of, or affected by HIV and syphilis, and commits governments to eliminate those barriers. This process demonstrates the importance and feasibility of integrating human rights, gender, and community into key public health interventions in a manner that improves health outcomes, legitimizes the participation of affected communities, and advances the human rights of women living with HIV.

  5. Evolution of the HIV-1 Envelope Glycoprotein Genes and Neutralizing Antibody Response in an Individual with Broadly Cross Neutralizing Antibodies

    Science.gov (United States)

    2010-08-31

    1994, 140: 1 05-130. 51. Pantaleo G, Graziosi C, Demarest JF, Butini L, Montroni M, Fox CH, Orenstein JM, Kotler DP, Fauci AS: HIV infection is...Pizzo PA, Schnittman SM, Kotler DP, Fauci AS: Lymphoid organs function as major reservoirs for human immunodeficiency virus. Proc Natl Acad Sci US

  6. A combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape

    NARCIS (Netherlands)

    Lebbink, Robert Jan; de Jong, Dorien C M; Wolters, Femke; Kruse, Elisabeth M; van Ham, Petra M; Wiertz, Emmanuel J H J; Nijhuis, Monique

    2017-01-01

    HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle

  7. Post-transcriptional m6A editing of HIV-1 mRNAs enhances viral gene expression

    Science.gov (United States)

    Kennedy, Edward M.; Bogerd, Hal P.; Kornepati, Anand V. R.; Kang, Dong; Ghoshal, Delta; Marshall, Joy B.; Poling, Brigid C.; Tsai, Kevin; Gokhale, Nandan S.; Horner, Stacy M.; Cullen, Bryan R.

    2016-01-01

    Summary Covalent addition of a methyl group to the adenosine N6 (m6A) is an evolutionarily conserved and common RNA modification that is thought to modulate several aspects of RNA metabolism. While the presence of multiple m6A editing sites on diverse viral RNAs was reported starting almost 40 years ago, how m6A editing affects virus replication has remained unclear. Here, we used photo-crosslinking-assisted m6A sequencing techniques to precisely map several m6A editing sites on the HIV-1 genome and report that they cluster in the HIV-1 3’ untranslated region (3'UTR). Viral 3'UTR m6A sites or analogous cellular m6A sites strongly enhanced mRNA expression in cis by recruiting the cellular YTHDF m6A “reader” proteins. Reducing YTHDF expression inhibited, while YTHDF overexpression enhanced, HIV-1 protein and RNA expression, and virus replication in CD4+ T cells. These data identify m6A editing, and the resultant recruitment of YTHDF proteins, as major positive regulators of HIV-1 mRNA expression. PMID:27117054

  8. RT-PCR analysis of Candida albicans ALS gene expression in a hyposalivatory rat model of oral candidiasis and in HIV-positive human patients.

    Science.gov (United States)

    Green, Clayton B; Marretta, Sandra Manfra; Cheng, Georgina; Faddoul, Fady F; Ehrhart, E J; Hoyer, Lois L

    2006-03-01

    ALS gene expression was studied in the hyposalivatory rat model of oral candidiasis and in clinical specimens collected from HIV-positive patients to assess similarities in expression patterns between the model system and clinical isolates. Two Candida albicans strains, SC5314 and OY-2-76, were used in the rat model system and infection progressed for 3 or 5 days. The strains produced similar oral lesions at 3 days. At 5 days, strain OY-2-76 produced more superficial lesions containing relatively more yeast forms compared to invasive hyphal forms observed for strain SC5314. For all infections, the most severe lesions were observed on the tongue and gingiva overlying the mandible. ALS transcripts were easier to detect by RT-PCR later in infection and under other conditions where more fungal cells were present. Expression of ALS1, ALS2, ALS3 and ALS4 was observed in rats infected for 3 days with ALS5 and ALS9 transcripts detected after 5 days of infection. Expression of ALS6 was observed in a single specimen from a 5-day infection while ALS7 transcript was never found. Expression of all ALS genes was observed in oral clinical material collected from HIV-positive patients although ALS6 and ALS7 transcripts required an extra PCR amplification step to be detected. Overall, the patterns of ALS gene expression were similar between the rat model and human clinical specimens, suggesting that the model would be useful for studying the phenotype of al delta/al delta mutant strains.

  9. HIV Prevention

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Collapse All Is abstinence the only 100% effective HIV prevention option? Yes. Abstinence means not having oral, ...

  10. HIV Testing

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... All Collapse All Should I get tested for HIV? CDC recommends that everyone between the ages of ...

  11. Long-term vector integration site analysis following retroviral mediated gene transfer to hematopoietic stem cells for the treatment of HIV infection.

    Directory of Open Access Journals (Sweden)

    Jun Hayakawa

    Full Text Available We previously reported the efficacy of nonmyeloablative allogeneic transplantation in 2 HIV positive recipients, one of whom received retrovirus transduced hematopoietic stem cells to confer resistance to HIV. Here we report an assessment of retroviral integration sites (RISs recovered out to 3 years post-transplantation. We identified 213 unique RISs from the patient's peripheral blood samples by linear amplification-mediated PCR (LAM-PCR. While vector integration patterns were similar to that previously reported, only 3.76% of RISs were common among early (up to 3 months and late samples (beyond 1 year. Additionally, common integration sites were enriched among late samples (14.9% vs. 36.8%, respectively. Three RISs were found near or within known oncogenes, but 2 were limited to early timepoints. Interestingly, an integration site near the MDS1 gene was detected in long-term follow-up samples; however, the overall contribution of MDS1 integrated clone remained stably low during follow-up.

  12. Effects of PPARγ and RBP4 gene variants on metabolic syndrome in HIV-infected patients with anti-retroviral therapy.

    Directory of Open Access Journals (Sweden)

    Yuan-Pin Hung

    Full Text Available BACKGROUND: PPARγ and RBP4 are known to regulate lipid and glucose metabolism and insulin resistance. The influences of PPARγ (C1431T and Pro12Ala and RBP4 (-803GA polymorphisms on metabolic syndrome in HIV-infected patients receiving anti-retroviral therapy were examined in this study. MATERIALS AND METHODS: A cross-sectional study of HIV-1 infected adults with antiretroviral therapy for more than one year in the National Cheng Kung University Hospital was conducted. The gene polymorphisms were determined by quantitative PCR. RESULTS: Ninety-one patients were included in the study. Eighty-two (90.1% patients were males with a mean age of 44.4 years. For the C1431T polymorphism in PPARγ, while patients with the T allele (48.4% had trends toward lower rate of hypertriglyceridemia, the borderline significance together with insignificant power did not support the protective effect of the T allele against development of hypertriglyceridemia. For the Pro12Ala polymorphism in PPARγ, although patients with the Pro/Ala genotype (8.8% had a higher level of serum LDL (138.0 vs. 111.5 mg/dl, P = 0.04 and trends toward higher rates of hypercholesterolemia and serum LDL>110 mg/dl, these variables were found to be independent of the Pro/Ala genotype in the multivariate analysis. For the -803GA polymorphism in RBP4, patients with the A allele (23.1% more often had insulin resistance (HOMA>3.8; 33.3 vs. 8.7%, P = 0.01 and more often received anti-hypoglycemic drugs (14.3 vs. 1.4%, P = 0.04. The detrimental effect of the A allele in RBP4 -803GA polymorphism on development of insulin resistance was supported by the multivariate analysis adjusting for covariates. CONCLUSION: The impacts of PPARγ C1431T and Pro12Ala polymorphisms on metabolism in HIV-infected patients are not significant. RBP4 -803GA polymorphism has increased risk of insulin resistance in HIV-infected patients with anti-retroviral therapy.

  13. Human anti-V3 HIV-1 monoclonal antibodies encoded by the VH5-51/VL lambda genes define a conserved antigenic structure.

    Science.gov (United States)

    Gorny, Miroslaw K; Sampson, Jared; Li, Huiguang; Jiang, Xunqing; Totrov, Maxim; Wang, Xiao-Hong; Williams, Constance; O'Neal, Timothy; Volsky, Barbara; Li, Liuzhe; Cardozo, Timothy; Nyambi, Phillipe; Zolla-Pazner, Susan; Kong, Xiang-Peng

    2011-01-01

    Preferential usage of immunoglobulin (Ig) genes that encode antibodies (Abs) against various pathogens is rarely observed and the nature of their dominance is unclear in the context of stochastic recombination of Ig genes. The hypothesis that restricted usage of Ig genes predetermines the antibody specificity was tested in this study of 18 human anti-V3 monoclonal Abs (mAbs) generated from unrelated individuals infected with various subtypes of HIV-1, all of which preferentially used pairing of the VH5-51 and VL lambda genes. Crystallographic analysis of five VH5-51/VL lambda-encoded Fabs complexed with various V3 peptides revealed a common three dimensional (3D) shape of the antigen-binding sites primarily determined by the four complementarity determining regions (CDR) for the heavy (H) and light (L) chains: specifically, the H1, H2, L1 and L2 domains. The CDR H3 domain did not contribute to the shape of the binding pocket, as it had different lengths, sequences and conformations for each mAb. The same shape of the binding site was further confirmed by the identical backbone conformation exhibited by V3 peptides in complex with Fabs which fully adapted to the binding pocket and the same key contact residues, mainly germline-encoded in the heavy and light chains of five Fabs. Finally, the VH5-51 anti-V3 mAbs recognized an epitope with an identical 3D structure which is mimicked by a single mimotope recognized by the majority of VH5-51-derived mAbs but not by other V3 mAbs. These data suggest that the identification of preferentially used Ig genes by neutralizing mAbs may define conserved epitopes in the diverse virus envelopes. This will be useful information for designing vaccine immunogen inducing cross-neutralizing Abs.

  14. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections.

    Science.gov (United States)

    Suligoi, Barbara; Regine, Vincenza; Raimondo, Mariangela; Rodella, Anna; Terlenghi, Luigina; Caruso, Arnaldo; Bagnarelli, Patrizia; Capobianchi, Maria Rosaria; Zanchetta, Nadia; Ghisetti, Valeria; Galli, Claudio

    2017-10-26

    Detecting recent HIV infections is important to evaluate incidence and monitor epidemic trends. We aimed to evaluate the diagnostic performance and accuracy of the avidity index (AI) for discriminating for recent HIV infections. We collected serum samples from HIV-1 positive individuals: A) with known date of infection (midpoint in time between last HIV-negative and first HIV-positive test); B) infected for >1 year. Samples were divided into two aliquots: one diluted with phosphate buffered saline (PBS) and the other with 1 M guanidine. Both aliquots were assayed by the Architect HIV Ag/Ab Combo 4th generation assay (Abbott). We compared AI found in recent (RI=HIV subtype had no impact on AI misclassifications. All individuals in group A reached the AI threshold of 0.80 within 24 months after seroconversion. The AI is an accurate serological marker for discriminating recent from established HIV infections and meets WHO requirements for HIV incidence assays.

  15. Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel.

    Science.gov (United States)

    Banin, Eyal; Bandah-Rozenfeld, Dikla; Obolensky, Alexey; Cideciyan, Artur V; Aleman, Tomas S; Marks-Ohana, Devora; Sela, Malka; Boye, Sanford; Sumaroka, Alexander; Roman, Alejandro J; Schwartz, Sharon B; Hauswirth, William W; Jacobson, Samuel G; Hemo, Itzhak; Sharon, Dror

    2010-12-01

    The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A > T; IVS2-2A > T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families. A total of 33 patients (four now deceased) had the severe childhood blindness known as Leber congenital amaurosis (LCA), making it the most common cause of retinal degeneration in this population. Haplotype analysis in seven of the patients revealed a shared homozygous region, indicating a population-specific founder mutation. The age of the RPE65 founder mutation was estimated to have emerged 100-230 (mean, 153) generations ago, suggesting it originated before the establishment of the Jewish community in North Africa. Individuals with this RPE65 mutation were characterized with retinal studies to determine if they were candidates for gene replacement, the recent and only therapy to date for this otherwise incurable blindness. The step from molecular anthropological studies to application of genetic medicine was then taken, and a representative of this patient subgroup was treated with subretinal rAAV2-RPE65 gene therapy. An increase in vision was present in the treated area as early as 15 days after the intervention. This process of genetically analyzing affected isolated populations as a screen for gene-based therapy suggests a new paradigm for disease diagnosis and treatment.

  16. A macaque model of HIV-1 infection

    OpenAIRE

    Hatziioannou, Theodora; Ambrose, Zandrea; Chung, Nancy P. Y.; Piatak, Michael; Yuan, Fang; Trubey, Charles M.; Coalter, Vicky; Kiser, Rebecca; Schneider, Doug; Smedley, Jeremy; Pung, Rhonda; Gathuka, Mercy; Estes, Jacob D.; Veazey, Ronald S.; KewalRamani, Vineet N.

    2009-01-01

    The lack of a primate model that utilizes HIV-1 as the challenge virus is an impediment to AIDS research; existing models generally employ simian viruses that are divergent from HIV-1, reducing their usefulness in preclinical investigations. Based on an understanding of species-specific variation in primate TRIM5 and APOBEC3 antiretroviral genes, we constructed simian-tropic (st)HIV-1 strains that differ from HIV-1 only in the vif gene. We demonstrate that such minimally modified stHIV-1 stra...

  17. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

    DEFF Research Database (Denmark)

    Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm

    2016-01-01

    AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed...... to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL

  18. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load.

    Science.gov (United States)

    Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm; Larsen, Margit Hørup; Kronborg, Gitte; Pedersen, Court; Larsen, Carsten Schade; Pedersen, Gitte; Gerstoft, Jan; Obel, Niels; Ullum, Henrik

    2016-07-01

    Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VLC), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects. The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART. The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The diagnostic performance of a single GeneXpert MTB/RIF assay in an intensified tuberculosis case finding survey among HIV-infected prisoners in Malaysia.

    Directory of Open Access Journals (Sweden)

    Haider Abdulrazzaq Abed Al-Darraji

    Full Text Available Delays in tuberculosis (TB diagnosis, particularly in prisons, is associated with detrimental outcomes. The new GeneXpert MTB/RIF assay (Xpert offers accurate and rapid diagnosis of active TB, but its performance in improving case detection in high-transmission congregate settings has yet to be evaluated. We assessed the diagnostic accuracy of a single Xpert assay in an intensified case finding survey among HIV-infected prisoners in Malaysia.HIV-infected prisoners at a single site provided two early-morning sputum specimens to be examined using fluorescence smear microscopy, BACTEC MGIT 960 liquid culture and a single Xpert. The sensitivity, specificity, negative and positive predictive values of Xpert were calculated relative to gold-standard results using MGIT 960 liquid culture. Relevant clinical and demographic data were used to examine correlates of active TB disease.The majority of enrolled subjects with complete data (N=125 were men (90.4%, age <40 years (61.6% and had injected drugs (75.2%. Median CD4 lymphocyte count was 337 cells/µL (IQR 149-492; only 19 (15.2% were receiving antiretroviral therapy. Of 15 culture-positive TB cases, single Xpert assay accurately detected only eight previously undiagnosed TB cases, resulting in a sensitivity, specificity, positive predictive value and negative predictive value of 53.3% (95% CI 30.12-75.2%, 100% (95% CI 96.6-100%, 100% (95% CI 67.56-100% and 94.0% (95% CI 88.2-97.1%, respectively. Only 1 of 15 (6.7% active TB cases was smear-positive. The prevalence (12% of undiagnosed active pulmonary TB (15 of 125 prisoners was high and associated with longer duration of drug use (AOR 1.14, 95% CI 1.03-1.26, for each year of drug use.Single Xpert assay improved TB case detection and outperformed AFB smear microscopy, but yielded low screening sensitivity. Further examination of the impact of HIV infection on the diagnostic performance of the new assay alongside other screening methods in correctional

  20. Pathogenesis of HIV and its implications for serodiagnosis and monitoring of antiviral therapy

    NARCIS (Netherlands)

    Goudsmit, J.; Lange, J. M.; Krone, W. J.; Teunissen, M. B.; Epstein, L. G.; Danner, S. A.; van den Berg, H.; Breederveld, C.; Smit, L.; Bakker, M.

    1987-01-01

    Human immunodeficiency virus (HIV) is lymphotropic and neurotropic. In vivo clinical and immunological abnormalities develop in a large proportion of long-term HIV antibody seropositive persons. Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies,

  1. HIV Life Cycle

    Science.gov (United States)

    ... healthier lives. ART also reduces the risk of HIV transmission (the spread of HIV to others). HIV attacks and destroys ... lives. HIV medicines also reduce the risk of HIV transmission (the spread of HIV to others). What are the seven ...

  2. Women and HIV

    Science.gov (United States)

    ... Consumer Information by Audience For Women Women and HIV: Get the Facts on HIV Testing, Prevention, and Treatment Share Tweet Linkedin Pin ... How can you lower your chance of HIV? HIV Quick Facts What is HIV? HIV is the ...

  3. Treatment for HIV

    Science.gov (United States)

    ... and Public Home » Treatment » Treatment Decisions and HIV HIV/AIDS Menu Menu HIV/AIDS HIV/AIDS Home ... here Enter ZIP code here Treatment Decisions and HIV for Veterans and the Public Treatment for HIV: ...

  4. The high stability of the triple helices formed between short purine oligonucleotides and SIV/HIV-2 vpx genes is determined by the targeted DNA structure.

    Science.gov (United States)

    Svinarchuk, F; Monnot, M; Merle, A; Malvy, C; Fermandjian, S

    1995-10-11

    In our previous works we have shown that the oligonucleotides 5'-GGGGAGGGGGAGG-3' and 5'-GGAGGGGGAGGGG-3' give very stable and specific triplexes with their target double stranded DNAs [Svinarchuk, F., Bertrand, J.-R. and Malvy, C. (1994) Nucleic Acids Res., 22, 3742-3747; Svinarchuk, F., Paoletti, J. and Malvy, C. (1995) J. Biol. Chem., 270, 14 068-14,071]. The target for the invariable part of these oligonucleotides, 5'-GGAGGGGGAGG-3', is found in a highly conserved 20 bp long purine/pyrimidine tract of the vpx gene of the SIV and HIV-2 viruses and could be a target for oligonucleotide directed antivirus therapy. Here were report on the ability of four purine oligonucleotides with different lengths (11-, 14-, 17- and 20-mer) to form triplexes with the purine/pyrimidine stretch of the vpx gene. Triplex formation was tested by joint dimethyl sulfate (DMS) footprint, gel-retardation assay, circular dichroism (CD) and UV-melting studies. Dimethyl sulfate footprint studies revealed the antiparallel orientation of the third strand to the purine strand of the Watson-Crick duplex. However, the protection of the guanines at the ends of the target sequence decreased as the length of the third strand oligonucleotide increased. Melting temperature studies provided profiles with only one transition for all of the triplexes. The melting temperatures of the triplexes were found to be the same as for the targeted duplex in the case of the 11- and 14-mer third strands while for the 17- and 20-mer third strands the melting temperature of the triplexes were correspondingly 4 and 8 degrees C higher than for the duplex. Heating and cooling melting curves were reversible for all of the tested triplexes except one with the 20-mer third strand oligonucleotide. Circular dichroism spectra showed the ability of the target DNA to adopt an A-like DNA conformation. Upon triplex formation the A-DNA form becomes even more pronounced. This effect depends on the length of the third strand

  5. More epigenetic hits than meets the eye: microRNAs and genes associated with the tumorigenesis of retinoblastoma

    Directory of Open Access Journals (Sweden)

    Adriana H.O. Reis

    2012-12-01

    Full Text Available Retinoblastoma (RB, a childhood neoplasia of the retinoblasts, can occur unilaterally or bilaterally, with one or multiple foci per eye. RB is associated with somatic loss-of-function of both alleles of the tumor suppressor gene RB1. Hereditary forms emerge due to germline loss-of-function mutations in RB1 alleles. RB has long been the prototypic ‘‘model’’ cancer ever since Knudson’s ‘‘two-hit’’ hypothesis. However, a simple two-hit model for RB is challenged by an increasing number of studies documenting additional hits that contribute to RB development. Here we review the genetics and epigenetics of RB with a focus on the role of small noncoding RNAs (microRNAs and on novel findings indicating the relevance of DNA methylation in the development and prognosis of this neoplasia. Studies point to an elaborated landscape of genetic and epigenetic complexity, in which a number of events and pahtways play crucial roles in the origin and prognosis of RB. These include roles for microRNAs, inprinted loci, and parent-of-origin contributions to RB1 regulation and RB progression. This complexity is also manifested in the structure of the RB1 locus itself: it includes numerous repetitive DNA segments and retrotransposon insertion elements, some of which are actively transcribed from the RB1 locus. Altogether, we conclude that RB1 loss of function represents the tip of an iceberg of events that determine RB development, progression, severity, and disease risk. Comprehensive assessment of personalized RB risk will require genetic and epigenetic evaluations beyond RB1 protein coding sequences.

  6. Dendrimers as Potential Therapeutic Tools in HIV Inhibition

    Directory of Open Access Journals (Sweden)

    Xiangbo Li

    2013-07-01

    Full Text Available The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection.

  7. The cell biology of HIV-1 and other retroviruses

    Directory of Open Access Journals (Sweden)

    Mouland Andrew J

    2006-11-01

    Full Text Available Abstract In recognition of the growing influence of cell biology in retrovirus research, we recently organized a Summer conference sponsored by the American Society for Cell Biology (ASCB on the Cell Biology of HIV-1 and other Retroviruses (July 20–23, 2006, Emory University, Atlanta, Georgia. The meeting brought together a number of leading investigators interested in the interplay between cell biology and retrovirology with an emphasis on presentation of new and unpublished data. The conference was arranged from early to late events in the virus replication cycle, with sessions on viral fusion, entry, and transmission; post-entry restrictions to retroviral infection; nuclear import and integration; gene expression/regulation of retroviral Gag and genomic RNA; and assembly/release. In this review, we will attempt to touch briefly on some of the highlights of the conference, and will emphasize themes and trends that emerged at the meeting. Meeting report The conference began with a keynote address from W. Sundquist on the biochemistry of HIV-1 budding. This presentation will be described in the section on Assembly and Release of Retroviruses.

  8. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  9. Stem cell-based therapies for HIV/AIDS.

    Science.gov (United States)

    Pernet, Olivier; Yadav, Swati Seth; An, Dong Sung

    2016-08-01

    One of the current focuses in HIV/AIDS research is to develop a novel therapeutic strategy that can provide a life-long remission of HIV/AIDS without daily drug treatment and, ultimately, a cure for HIV/AIDS. Hematopoietic stem cell-based anti-HIV gene therapy aims to reconstitute the patient immune system by transplantation of genetically engineered hematopoietic stem cells with anti-HIV genes. Hematopoietic stem cells can self-renew, proliferate and differentiate into mature immune cells. In theory, anti-HIV gene-modified hematopoietic stem cells can continuously provide HIV-resistant immune cells throughout the life of a patient. Therefore, hematopoietic stem cell-based anti-HIV gene therapy has a great potential to provide a life-long remission of HIV/AIDS by a single treatment. Here, we provide a comprehensive review of the recent progress of developing anti-HIV genes, genetic modification of hematopoietic stem progenitor cells, engraftment and reconstitution of anti-HIV gene-modified immune cells, HIV inhibition in in vitro and in vivo animal models, and in human clinical trials. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.

    Directory of Open Access Journals (Sweden)

    Irina A Zalenskaya

    Full Text Available Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. Therefore, it is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides using a microarray gene expression profiling strategy.To this end, we compared transcriptomes of human vaginal cells (Vk2/E6E7 treated with well-characterized pro-inflammatory (PIC and non-inflammatory (NIC compounds. PICs included compounds with different mechanisms of action. Gene expression was analyzed using Affymetrix U133 Plus 2 arrays. Data processing was performed using GeneSpring 11.5 (Agilent Technologies, Santa Clara, CA.Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by PICs compared to NICs, thus distinguishing between these two groups. Functional analysis mapped 14 of these genes to immune and inflammatory responses. This was confirmed by the fact that PICs induced NFkB pathway activation in Vk2 cells. By testing microbicide candidates previously characterized in clinical trials we demonstrated that the selected PIC-associated genes properly identified compounds with mucosa-altering effects. The discriminatory power of these genes was further demonstrated after culturing vaginal cells with vaginal bacteria. Prevotella bivia, prevalent bacteria in the disturbed microbiota of bacterial vaginosis, induced strong upregulation of seven selected PIC-associated genes, while a commensal Lactobacillus gasseri associated to vaginal health did not cause any changes.In vitro evaluation of the immunoinflammatory potential of microbicides using the PIC-associated genes defined in this study could help in the initial screening of candidates prior

  11. Engineering HIV-Resistant, Anti-HIV Chimeric Antigen Receptor T Cells.

    Science.gov (United States)

    Hale, Malika; Mesojednik, Taylor; Romano Ibarra, Guillermo S; Sahni, Jaya; Bernard, Alison; Sommer, Karen; Scharenberg, Andrew M; Rawlings, David J; Wagner, Thor A

    2017-03-01

    The treatment or cure of HIV infection by cell and gene therapy has been a goal for decades. Recent advances in both gene editing and chimeric antigen receptor (CAR) technology have created new therapeutic possibilities for a variety of diseases. Broadly neutralizing monoclonal antibodies (bNAbs) with specificity for the HIV envelope glycoprotein provide a promising means of targeting HIV-infected cells. Here we show that primary human T cells engineered to express anti-HIV CARs based on bNAbs (HIVCAR) show specific activation and killing of HIV-infected versus uninfected cells in the absence of HIV replication. We also show that homology-directed recombination of the HIVCAR gene expression cassette into the CCR5 locus enhances suppression of replicating virus compared with HIVCAR expression alone. This work demonstrates that HIV immunotherapy utilizing potent bNAb-based single-chain variable fragments fused to second-generation CAR signaling domains, delivered directly into the CCR5 locus of T cells by homology-directed gene editing, is feasible and effective. This strategy has the potential to target HIV-infected cells in HIV-infected individuals, which might help in the effort to cure HIV. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the News NIDA Notes Podcasts E-Newsletters Public Education Projects Contact the Press Office Meetings & Events Media ... found at USA.gov . Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the News NIDA Notes Podcasts E-Newsletters Public Education Projects Contact the Press Office Meetings & Events Media ... Plan Search Share Print Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Badges Other Resources Strategic Plan Search Share Print Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn ... Service Announcements Other Government Observances for Substance Abuse Education Contact the Press Office Meetings & Events Media Guide ... NIDA Home Site Map Accessibility Privacy FOIA(NIH) Working at ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: Drug Use and Viral Infections : Describes ... Press Office Meetings & Events Media Guide Get this Publication Español View Webisodes View Videos "After the Party" " ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... News NIDA Notes Podcasts E-Newsletters Public Education Projects Contact the Press Office Meetings & Events Media Guide ... Search Share Print Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn the ...

  17. Psychosocial Aspects of HIV and AIDS and the Evaluation of Preventive Strategies: Report on a WHO Meeting (Lisbon, Portugal, May 28-June 1, 1990). WHO Regional Publications, European Series, No. 36.

    Science.gov (United States)

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    The spread of Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) depends very much on the way people behave. Individuals from some groups have been successfully persuaded to modify behaviors that put them at increased risk of HIV infection. The salient questions for future AIDS prevention and control programs are…

  18. Pyrosequencing of the genital microbiotas of HIV-seropositive and -seronegative women reveals Lactobacillus iners as the predominant Lactobacillus Species.

    Science.gov (United States)

    Spear, Gregory T; Gilbert, Douglas; Landay, Alan L; Zariffard, Reza; French, Audrey L; Patel, Pranjal; Gillevet, Patrick M

    2011-01-01

    The species of vaginal lactobacilli in HIV-seropositive and -seronegative women were determined by 16S gene pyrosequencing. Lactobacillus iners sequences were the predominant lactobacillus sequences in 66% of HIV(+) women and 90% of HIV(-) women. This has implications for resistance of HIV(+) and HIV(-) women to genital colonization by pathogenic organisms.

  19. Host genetic factors in susceptibility to HIV-1 infection and ...

    Indian Academy of Sciences (India)

    to influence the rate of AIDS progression in HIV-1 infected individuals. The candidate host genes suspected to influence the rate of progression from HIV to AIDS can be divided into three categories: (i) genes encoding cell-surface receptors or lig- ands for these proteins; (ii) genes within human leukocyte antigens (HLA) that ...

  20. The "STEP-wise" future of adenovirus-based HIV vaccines.

    Science.gov (United States)

    Patterson, L J

    2011-01-01

    The HIV pandemic continues to be a public health crisis with over 30 million people currently living with the disease and, depending on the estimate, another 2 - 2.8 million infected annually. The disappointing results of the first Phase II study of a highly immunogenic adenovirus-vectored vaccine, named the STEP trial, was a wake up call to both the clinical and preclinical HIV vaccine fields. A vaccine designed only to elicit T cells and including a single HIV gene insert, will not be sufficient to reduce transmission or lower viremia in people. Additionally, future use of adenovirus-based vectored vaccines needs to be carefully planned with respect to vector type, gene inserts, route of immunization and risk factors among subject volunteers. The initial observation of a transient, increased risk of infection in Ad5 seropositive, uncircumcised men who have sex with men (MSM) is still unexplained, and may yet be considered simply a random event. The vaccine field has not given up on adenoviruses and there is continued interest in pursuing these highly immunogenic vectors, either in combination approaches with DNA, use of rare serotypes with low seroprevalence, or those derived from simian origin. Finally, evaluation of replicating adenovirus vectors known to be capable of inducing potent cellular, humoral, and mucosal immunity will be vital to meeting our future goal of an effective HIV vaccine.

  1. Mycobacterium tuberculosis modulates the gene interactions to activate the HIV replication and faster disease progression in a co-infected host.

    Science.gov (United States)

    Toor, Jaideep S; Singh, Sukhvinder; Sharma, Aman; Arora, Sunil K

    2014-01-01

    Understanding of the chronic immune activation, breakdown of immune defense and synergistic effect between HIV and Mycobacterium tuberculosis (Mtb) may provide essential information regarding key factors involved in the pathogenesis of HIV disease. In this study, we aimed to highlight a few of the immunological events that may influence and accelerate the progression of HIV disease in the presence of co-infecting Mtb. A cross-sectional study was performed on cohorts, including anti-tubercular therapy (ATT) naïve active pulmonary tuberculosis (PTB) patients, antiretroviral therapy (ART) naïve HIV-1 infected individuals at different stages of disease, ATT and ART naïve HIV-PTB co-infected individuals and healthy controls. A significantly higher T-regulatory cell (Treg) frequency coupled with the high FoxP3 expression in the CD4 T-cells indicated an immunosuppressive environment in the advance stage of HIV-1 infection. This is further substantiated by high HO-1 expression favoring TB co-infection. Functionally, this change in Treg frequency in HIV-1 infected individuals correlated well with suppression of T-cell proliferation. Mtb infection seems to facilitate the expansion of the Treg pool along with increased expression of FoxP3, specifically the variant-1, as evident from the data in HIV-1 co-infected as well as in patients with only PTB. A significantly lower expression of HO-1 in co-infected individuals compared to patients with only HIV-infection having comparable CD4 count correlated well with increased expression of CCR5 and CxCR4 as well as NF-κB and inflammatory cytokines IL-6 and TNF-α, which collectively may contribute to enhanced viral replication and increased cell death, hence faster disease progression in co-infected individuals.

  2. Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients.

    Directory of Open Access Journals (Sweden)

    Pere Domingo

    Full Text Available To assess in a cohort of Caucasian patients exposed to stavudine (d4T the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40∶01 carriage with HIV/Highly active antiretroviral therapy (HAART-associated lipodystrophy syndrome (HALS.Three-hundred and thirty-six patients, 187 with HALS and 149 without HALS, and 72 uninfected subjects were recruited. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Polymorphisms in the thymidylate synthase (TS and methylene-tetrahydrofolate reductase (MTHFR genes were determined by direct sequencing, HLA-B genotyping by PCR-SSOr Luminex Technology, and intracellular levels of stavudine triphosphate (d4T-TP by a LC-MS/MS assay method.HALS was associated with the presence of a low expression TS genotype polymorphism (64.7% vs. 42.9%, OR = 2.43; 95%CI: 1.53-3.88, P<0.0001. MTHFR gene polymorphisms and HLA-B*40∶01 carriage were not associated with HALS or d4T-TP intracellular levels. Low and high expression TS polymorphisms had different d4T-TP intracellular levels (25.60 vs. 13.60 fmol/10(6 cells, P<0.0001. Independent factors associated with HALS were(OR [95%CI]: (a Combined TS and MTHFR genotypes (p = 0.006, reference category (ref.: 'A+A'; OR for 'A+B' vs. ref.: 1.39 [0.69-2.80]; OR for 'B+A' vs. ref.: 2.16 [1.22-3.83]; OR for 'B+B' vs. ref.: 3.13, 95%CI: 1.54-6.35, (b maximum viral load ≥5 log10 (OR: 2.55, 95%CI: 1.56-4.14, P = 0.001, (c use of EFV (1.10 [1.00-1.21], P = 0.008, per year of use.HALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*40∶01 carriage in Caucasian patients with long-term exposure to stavudine.

  3. Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients.

    Science.gov (United States)

    Domingo, Pere; Mateo, Maria Gracia; Pruvost, Alain; Torres, Ferran; Salazar, Juliana; Gutierrez, Maria Del Mar; Domingo, Joan Carles; Fernandez, Irene; Villarroya, Francesc; Vidal, Francesc; Baiget, Montserrat; de la Calle-Martín, Oscar

    2013-01-01

    To assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40∶01 carriage with HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). Three-hundred and thirty-six patients, 187 with HALS and 149 without HALS, and 72 uninfected subjects were recruited. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Polymorphisms in the thymidylate synthase (TS) and methylene-tetrahydrofolate reductase (MTHFR) genes were determined by direct sequencing, HLA-B genotyping by PCR-SSOr Luminex Technology, and intracellular levels of stavudine triphosphate (d4T-TP) by a LC-MS/MS assay method. HALS was associated with the presence of a low expression TS genotype polymorphism (64.7% vs. 42.9%, OR = 2.43; 95%CI: 1.53-3.88, P<0.0001). MTHFR gene polymorphisms and HLA-B*40∶01 carriage were not associated with HALS or d4T-TP intracellular levels. Low and high expression TS polymorphisms had different d4T-TP intracellular levels (25.60 vs. 13.60 fmol/10(6) cells, P<0.0001). Independent factors associated with HALS were(OR [95%CI]: (a) Combined TS and MTHFR genotypes (p = 0.006, reference category (ref.): 'A+A'; OR for 'A+B' vs. ref.: 1.39 [0.69-2.80]; OR for 'B+A' vs. ref.: 2.16 [1.22-3.83]; OR for 'B+B' vs. ref.: 3.13, 95%CI: 1.54-6.35), (b) maximum viral load ≥5 log10 (OR: 2.55, 95%CI: 1.56-4.14, P = 0.001), (c) use of EFV (1.10 [1.00-1.21], P = 0.008, per year of use). HALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*40∶01 carriage in Caucasian patients with long-term exposure to stavudine.

  4. 78 FR 15022 - Office of the Director, National Institutes of Health; Notice of Meeting

    Science.gov (United States)

    2013-03-08

    ... update will be provided on the latest changes made to the Federal HIV treatment and prevention guidelines..., diagnosis, assessment, treatment, and prevention of Neuro-AIDS and HIV-associated neurological disorders... topic of the meeting will be HIV-associated Neurological Manifestations and Disorders. The speakers at...

  5. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  6. Minor Contribution of Chimeric Host-HIV Readthrough Transcripts to the Level of HIV Cell-Associated gag RNA

    NARCIS (Netherlands)

    Pasternak, A.O.; DeMaster, L.K.; Kootstra, N.A.; Reiss, P.; O'Doherty, U.; Berkhout, B.

    2016-01-01

    Cell-associated HIV unspliced RNA is an important marker of the viral reservoir. HIV gag RNA-specific assays are frequently used to monitor reservoir activation. Because HIV preferentially integrates into actively transcribed genes, some of the transcripts detected by these assays may not represent

  7. Exploring Social Networking Technologies as Tools for HIV Prevention for Men Who Have Sex With Men.

    Science.gov (United States)

    Ramallo, Jorge; Kidder, Thomas; Albritton, Tashuna; Blick, Gary; Pachankis, John; Grandelski, Valen; Grandeleski, Valen; Kershaw, Trace

    2015-08-01

    Social networking technologies are influential among men who have sex with men (MSM) and may be an important strategy for HIV prevention. We conducted focus groups with HIV positive and negative participants. Almost all participants used social networking sites to meet new friends and sexual partners. The main obstacle to effective HIV prevention campaigns in social networking platforms was stigmatization based on homosexuality as well as HIV status. Persistent stigma associated with HIV status and disclosure was cited as a top reason for avoiding HIV-related conversations while meeting new partners using social technologies. Further, social networking sites have different social etiquettes and rules that may increase HIV risk by discouraging HIV status disclosure. Overall, successful interventions for MSM using social networking technologies must consider aspects of privacy, stigma, and social norms in order to enact HIV reduction among MSM.

  8. Logic Meeting

    CERN Document Server

    Tugué, Tosiyuki; Slaman, Theodore

    1989-01-01

    These proceedings include the papers presented at the logic meeting held at the Research Institute for Mathematical Sciences, Kyoto University, in the summer of 1987. The meeting mainly covered the current research in various areas of mathematical logic and its applications in Japan. Several lectures were also presented by logicians from other countries, who visited Japan in the summer of 1987.

  9. Stem Cell--Based Therapies for HIV/AIDS

    OpenAIRE

    Pernet, Olivier; Yadav, Swati Seth; An, Dong Sung

    2016-01-01

    One of the current focuses in HIV/AIDS research is to develop a novel therapeutic strategy that can provide a life-long remission of HIV/AIDS without daily drug treatment and ultimately a cure for HIV/AIDS. Hematopoietic stem cell based anti-HIV gene therapy aims to reconstitute patient immune system by transplantation of genetically engineered hematopoietic stem cells with anti-HIV genes. Hematopoietic stem cells can self renew, proliferate and differentiate into mature immune cells. In theo...

  10. Short communication: SDF1-3'A gene mutation is correlated with increased susceptibility to HIV type 1 infection by sexual transmission in Han Chinese.

    Science.gov (United States)

    Wang, Yueyun; Wang, Xiaohui; Peng, Ji; Chen, Lin; Cheng, Jinquan; Nie, Shaofa; Feng, Tiejian; Zhao, Guanglu; Zhao, Jin; Shi, Xiangdong

    2008-11-01

    Limited information is available on host genetic polymorphisms that confer resistance to HIV-1 infection in Han Chinese who persistently remain seronegative (HEPS) despite high exposure to HIV-1 through unprotected sexual activity with known HIV-1-seropositive spouses or long-term sexual partners. The aim of this study was to investigate the correlation of CCR5-Delta32, CCR2b-64I, and SDF1-3'A polymorphisms with susceptibility to HIV-1 infection through sexual transmission in Han Chinese. A cross-sectional study was used to analyze the differences in allelic frequencies of CCR5-Delta32, CCR2b-64I, and SDF1-3'A among HEPS, healthy HIV-unexposed individuals, and HIV-1-seropositive individuals. Restriction fragment length polymorphism (RFLP) analysis was used for genotype determination. The CCR5-Delta32 mutation was not detected in the three groups (n = 260). The allelic frequencies of CCR2b-64I were 21.57%, 21.63%, and 22.12% in the three groups, respectively. There was no significant difference among the three groups in CCR2b-64I distribution. The allelic frequencies of SDF1-3'A were 20.19%, 28.37%, and 29.33% in the three groups, respectively. There was a significant difference in the allelic distribution of SDF1-3'A between HEPS and healthy HIV-unexposed individuals (p = 0.023), as well as between HEPS and HIV-1-seropositive individuals (p = 0.049). Statistical analysis showed that the allelic distributions on CCR2b-64I and SDF1-3'A were in equilibrium according to the Hardy-Weinberg equation. The mutant genotypes of CCR5-Delta32 and CCR2b-64I were not correlated with HIV-1 infection through sexual transmission in Han Chinese. SDF1- 3'A was associated with a high risk of HIV-1 infection through sexual transmission in Han Chinese.

  11. Envisioning Women-Centered HIV Care: Perspectives from Women Living with HIV in Canada.

    Science.gov (United States)

    O'Brien, Nadia; Greene, Saara; Carter, Allison; Lewis, Johanna; Nicholson, Valerie; Kwaramba, Gladys; Ménard, Brigitte; Kaufman, Elaina; Ennabil, Nourane; Andersson, Neil; Loutfy, Mona; de Pokomandy, Alexandra; Kaida, Angela

    Women comprise nearly one-quarter of people living with human immunodeficiency virus (HIV) in Canada. Compared with men, women living with HIV experience inequities in HIV care and health outcomes, prompting a need for gendered and tailored approaches to HIV care. Peer and academic researchers from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study conducted focus groups to understand women's experience of seeking care, with the purpose of identifying key characteristics that define a women-centered approach to HIV care. Eleven focus groups were conducted with 77 women living with HIV across Quebec, Ontario, and British Columbia, Canada. Women envisioned three central characteristics of women-centered HIV care, including i) coordinated and integrated services that address both HIV and women's health care priorities, and protect against exclusion from care due to HIV-related stigma, ii) care that recognizes and responds to structural barriers that limit women's access to care, such as violence, poverty, motherhood, HIV-related stigma, and challenges to safe disclosure, and iii) care that fosters peer support and peer leadership in its design and delivery to honor the diversity of women's experiences, overcome women's isolation, and prioritize women's ownership over the decisions that affect their lives. Despite advances in HIV treatment and care, the current care landscape is inadequate to meet women's comprehensive care needs. A women-centered approach to HIV care, as envisioned by women living with HIV, is central to guiding policy and practice to improve care and outcomes for women living with HIV in Canada. Copyright © 2017 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  12. An In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression.

    Directory of Open Access Journals (Sweden)

    Gilles Darcis

    2015-07-01

    Full Text Available The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET bromodomain inhibitors (BETi are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC agonists (prostratin, bryostatin-1 and ingenol-B, which are known to activate NF-κB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151. Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latency-reversing agents (LRAs and that their combinations led to synergistic activation of HIV-1 expression at the viral mRNA and protein levels. Mechanistically, combined treatments led to higher activations of P-TEFb and NF-κB than the corresponding individual drug treatments. Importantly, we observed in ex vivo cultures of CD8+-depleted PBMCs from 35 cART-treated HIV-1+ aviremic patients that the percentage of reactivated cultures following combinatory bryostatin-1+JQ1 treatment was identical to the percentage observed with anti-CD3+anti-CD28 antibodies positive control stimulation. Remarkably, in ex vivo cultures of resting CD4+ T cells isolated from 15 HIV-1+ cART-treated aviremic patients, the combinations bryostatin-1+JQ1 and ingenol-B+JQ1 released infectious viruses to levels similar to that obtained with the positive control stimulation. The potent effects of these two combination treatments were already detected 24 hours post-stimulation. These results constitute the first demonstration of LRA

  13. Deletion of the vaccinia virus gene A46R, encoding for an inhibitor of TLR signalling, is an effective approach to enhance the immunogenicity in mice of the HIV/AIDS vaccine candidate NYVAC-C.

    Directory of Open Access Journals (Sweden)

    Beatriz Perdiguero

    Full Text Available Viruses have developed strategies to counteract signalling through Toll-like receptors (TLRs that are involved in the detection of viruses and induction of proinflammatory cytokines and IFNs. Vaccinia virus (VACV encodes A46 protein which disrupts TLR signalling by interfering with TLR: adaptor interactions. Since the innate immune response to viruses is critical to induce protective immunity, we studied whether deletion of A46R gene in a NYVAC vector expressing HIV-1 Env, Gag, Pol and Nef antigens (NYVAC-C improves immune responses against HIV-1 antigens. This question was examined in human macrophages and in mice infected with a single A46R deletion mutant of the vaccine candidate NYVAC-C (NYVAC-C-ΔA46R. The viral gene A46R is not required for virus replication in primary chicken embryo fibroblast (CEF cells and its deletion in NYVAC-C markedly increases TNF, IL-6 and IL-8 secretion by human macrophages. Analysis of the immune responses elicited in BALB/c mice after DNA prime/NYVAC boost immunization shows that deletion of A46R improves the magnitude of the HIV-1-specific CD4 and CD8 T cell immune responses during adaptive and memory phases, maintains the functional profile observed with the parental NYVAC-C and enhances anti-gp120 humoral response during the memory phase. These findings establish the immunological role of VACV A46R on innate immune responses of macrophages in vitro and antigen-specific T and B cell immune responses in vivo and suggest that deletion of viral inhibitors of TLR signalling is a useful approach for the improvement of poxvirus-based vaccine candidates.

  14. Public meetings

    CERN Multimedia

    Staff Association

    2017-01-01

    Do you have questions about the elections to the Staff Council, 2017 MERIT exercise, EVE and School, LD to IC exercise, CHIS, the Pension Fund… Come get informed and ask your questions at our public meetings. These public meetings are also an opportunity to get the more information on current issues. Benefit from this occasion to get the latest news and to discuss with the representatives of the statutory body that is the Staff Association!

  15. Low Prevalence of Pneumocystis pneumonia (PCP) but High Prevalence of Pneumocystis dihydropteroate synthase (dhps) Gene Mutations in HIV-Infected Persons in Uganda

    Science.gov (United States)

    Taylor, Steve M.; Meshnick, Steven R.; Worodria, William; Andama, Alfred; Cattamanchi, Adithya; Davis, J. Lucian; Yoo, Samuel D.; Byanyima, Patrick; Kaswabuli, Sylvia; Goodman, Carol D.; Huang, Laurence

    2012-01-01

    Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in patients infected with HIV, but its burden is incompletely characterized in those areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care hospital in Uganda and of putative P. jirovecii drug resistance by mutations in fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129 consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr). PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP-positive patients. In these 5 fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation. No non-synonymous dhfr mutations were detected. PCP is an important cause of pneumonia in patients newly-diagnosed with HIV in Uganda, is associated with high mortality, and putative molecular evidence of drug resistance is prevalent. Given the reliability of field diagnosis in our cohort, future studies in sub-Saharan Africa can investigate the clinical impact of these genotypes. PMID:23166805

  16. Phenotype and envelope gene diversity of nef-deleted HIV-1 isolated from long-term survivors infected from a single source

    Directory of Open Access Journals (Sweden)

    Sullivan John S

    2007-07-01

    Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with attenuated, nef-deleted variants of human immunodeficiency virus type 1 (HIV-1 acquired from a single source. Long-term prospective studies have demonstrated that the SBBC now comprises slow progressors (SP as well as long-term nonprogressors (LTNP. Convergent evolution of nef sequences in SBBC SP and LTNP indicates the in vivo pathogenicity of HIV-1 in SBBC members is dictated by factors other than nef. To better understand mechanisms underlying the pathogenicity of nef-deleted HIV-1, we examined the phenotype and env sequence diversity of sequentially isolated viruses (n = 2 from 3 SBBC members. Results The viruses characterized here were isolated from two SP spanning a three or six year period during progressive HIV-1 infection (subjects D36 and C98, respectively and from a LTNP spanning a two year period during asymptomatic, nonprogressive infection (subject C18. Both isolates from D36 were R5X4 phenotype and, compared to control HIV-1 strains, replicated to low levels in peripheral blood mononuclear cells (PBMC. In contrast, both isolates from C98 and C18 were CCR5-restricted. Both viruses isolated from C98 replicated to barely detectable levels in PBMC, whereas both viruses isolated from C18 replicated to low levels, similar to those isolated from D36. Analysis of env by V1V2 and V3 heteroduplex tracking assay, V1V2 length polymorphisms, sequencing and phylogenetic analysis showed distinct intra- and inter-patient env evolution. Conclusion Independent evolution of env despite convergent evolution of nef may contribute to the in vivo pathogenicity of nef-deleted HIV-1 in SBBC members, which may not necessarily be associated with changes in replication capacity or viral coreceptor specificity.

  17. Get Tested for HIV

    Science.gov (United States)

    ... The Basics: What Is HIV? What is HIV? HIV stands for human immunodeficiency virus. This is the virus that causes AIDS. There is no cure yet for HIV/AIDS, but there are treatments that can help ...

  18. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... that may be present in rare strains of HIV. The test may not detect a drug-resistant strain of ... Less Common Questions Related Content On This Site Tests: HIV Viral Load ; CD4 Count ; HIV Antibody and HIV ...

  19. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV ... antiretroviral drugs. With genotypic resistance testing, the genetic code of the HIV a person has been infected ...

  20. HIV Medication Adherence

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Medication Adherence Last Reviewed: January 17, 2018 Key ...

  1. HIV and Immunizations

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV and Immunizations Last Reviewed: February 6, 2018 Key ...

  2. HIV/AIDS

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most ...

  3. HIV and AIDS

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español HIV and AIDS KidsHealth / For Kids / HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

  4. HIV and Rheumatic Disease

    Science.gov (United States)

    ... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  5. HIV Treatment: The Basics

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Treatment: The Basics Last Reviewed: January 18, 2018 ...

  6. HIV and Pregnancy

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG HIV and Pregnancy Home For Patients Search FAQs HIV ... HIV and Pregnancy FAQ113, July 2017 PDF Format HIV and Pregnancy Pregnancy What is human immunodeficiency virus ( ...

  7. HIV/AIDS Coinfection

    Science.gov (United States)

    ... Delta Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Disease Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  8. [HIV lipodystrophy].

    Science.gov (United States)

    Snopková, S; Matýsková, M; Povolná, K; Polák, P; Husa, P

    2010-12-01

    Combined antiretroviral therapy results in extraordinary decrease of morbidity and mortality of HIV-infected patients and in an essential change of the HIV/AIDS disease prognosis. However, long-term intake of antiretroviral medicaments is related to occurrence of metabolic and morphological abnormalities, of which some have been combined into a new syndrome--the so called HIV lipodystrophy. The HIV lipodystrophy syndrome covers metabolic and morphological changes. Metabolic changes include dyslipidaemia with hypercholesterolaemia and/or hypertriglyceridaemia, insulin resistance with hyperinsulinaemia and hyperlaktataemia. Morphological changes have the nature of lipoatrophia (loss of subcutaneous fat--on the cheeks, on extremities, on buttocks and marked prominence of surface veins) or lipohypertrophia (growth of fat tissue--on the chest, in the dorsocervical area, lipomatosis of visceral tissues and organs, fat accumulation in the abdominal area). Several HIV lipodystrophy features are very similar to the metabolic syndrome of the general population. That is why this new syndrome represents a prospective risk of premature atherosclerosis and increase of the cardiovascular risk in young HIV positive individuals. The article mentions major presented studies dealing with the relation of antiretroviral treatment and the cardiovascular risk. The conclusions of the studies are not unequivocal--this is, among others, given by the reason that their length is short from the viewpoint of atherogenesis. The major risk of subclinical atherosclerosis acceleration seems to be related to the deep immunodeficiency and low number of CD4+ lymphocytes and florid, uncontrolled HIV infection with a high number of HIV-1 RNA copies actually circulating in the plasma. The question, whether metabolic and morphological changes related to HIV and cART carry a similar atherogenic potential as in the general population, remains open for future.

  9. CCR5Δ32 mutation and HIV infection: basis for curative HIV therapy.

    Science.gov (United States)

    Allers, Kristina; Schneider, Thomas

    2015-10-01

    The C-C chemokine receptor 5 (CCR5) is expressed on potential human immunodeficiency virus (HIV) target cells and serves as the predominant co-receptor for viral entry during initial transmission and through the early stages of infection. A homozygous Δ32 mutation in the CCR5 gene prevents CCR5 cell surface expression and thus confers resistance to infection with CCR5-tropic HIV strains. Transplantation of hematopoietic stem cells from a CCR5Δ32/Δ32 donor was previously successful in eliminating HIV from the recipient's immune system, suggesting that targeted CCR5 disruption can lead to an HIV cure. Therefore, intense work is currently being carried out on CCR5 gene-editing tools to develop curative HIV therapy. Here, we review the natural function of CCR5, the progress made on CCR5 gene editing to date and discuss the current limitations. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. HIV prevalence, sociodemographic characteristics, and sexual behaviors among transwomen in Mexico City.

    Science.gov (United States)

    Colchero, M Arantxa; Cortés-Ortiz, María Alejandra; Romero-Martínez, Martín; Vega, Hamid; González, Andrea; Román, Ricardo; Franco-Núñez, Aurora; Bautista-Arredondo, Sergio

    2015-01-01

    To present results from HIV testing, knowledge of HIV status and socioeconomic factors associated with the probability of having a HIV positive result among transwomen (TW) in Mexico. In 2012, we conducted an HIV seroprevalence survey to 585 TW in Mexico City in three strata: gathering places, the Condesa HIV Clinic and in four detention centers. We estimated the prevalence of HIV in each strata and applied a probit model to the overall sample to analyze factors associated with the probability of a HIV positive result. The prevalence of HIV was 19.8% in meeting places; 31.9% in detention centers and 64% among the participants of the clinic. Age, low education and number of sexual partners was positively associated with HIV. Results from the study provide relevant information to design HIV prevention interventions tailored to the needs of the TW population.

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/hiv/pubs/faq/faq1.htm ). ...

  12. [Microbiological diagnosis of HIV infection].

    Science.gov (United States)

    López-Bernaldo de Quirós, Juan Carlos; Delgado, Rafael; García, Federico; Eiros, José M; Ortiz de Lejarazu, Raúl

    2007-12-01

    Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure.

  13. HIV Among Asians

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Asians in the United States Format: Select ...

  14. Living with HIV

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Syndicated Content Website Feedback HIV/AIDS Living With HIV Language: English (US) Español (Spanish) Recommend on Facebook ...

  15. HIV among Transgender People

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Transgender People Format: Select One PDF [227K] ...

  16. Co-detection of Panton-Valentine leukocidin encoding genes and cotrimoxazole resistance in Staphylococcus aureus in Gabon: implications for HIV-patients' care

    NARCIS (Netherlands)

    Kraef, Christian; Alabi, Abraham S.; Peters, Georg; Becker, Karsten; Kremsner, Peter G.; Rossatanga, Elie G.; Mellmann, Alexander; Grobusch, Martin P.; Zanger, Philipp; Schaumburg, Frieder

    2015-01-01

    Patients infected with the human immuno deficiency virus (HIV) are frequently exposed to antimicrobial agents. This might have an impact on the resistance profile, genetic background and virulence factors of colonizing Staphylococcus aureus. Sub-Saharan Africa is considered to be endemic for

  17. Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

    African Journals Online (AJOL)

    Administrator

    African Journal of Biotechnology Vol. 6 (10), pp. 1225-1232, 16 May 2007 ... out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated ... A background in vitro cytogenetic control analysis using HIV-1/SIVcpz GAG, POL and ENV genes was done. Of the 339 enzymes used, 238 ...

  18. low level of transmitted hiv drug resistance at two hiv care centres in ...

    African Journals Online (AJOL)

    David Ofori-Adjei

    2013-06-01

    Jun 1, 2013 ... the protease (PR) and reverse transcriptase (RT) genes amplified and sequenced. The sequences were then analyzed for HIV drug resistance mutations using Stan- ford University HIV Drug Resistance Database. Results: Only two individuals were found with major. HIVDR mutations: one each in the PR ...

  19. Measurements of Immune Responses for Establishing Correlates of Vaccine Protection Against HIV

    OpenAIRE

    Burgers, Wendy A.; Manrique, Amapola; Masopust, David; McKinnon, Lyle R.; Reynolds, Matthew R.; Rolland, Morgane; BLISH, Catherine; Chege, Gerald K.; Curran, Rhonda; Fischer, William; Herrera, Carolina; Sather, D. Noah

    2012-01-01

    Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of pro...

  20. Public meeting

    CERN Multimedia

    HR Department

    2010-01-01

    Dear Colleagues, I am pleased to invite you to a public meeting which will be held on Thursday 11 November 2010 at 2:30 p.m., in the Main Auditorium (welcome coffee from 2 p.m.) In this meeting Sigurd Lettow, Director for Administration and General Infrastructure will present the Management’s proposals towards restoring full funding of the Pension Fund. The meeting will follow discussions which took place with the Staff Association, at the Standing Concertation Committee (CCP) of 1 November 2010 and will be held with the Members States, at the Tripartite Employment Conditions Forum (TREF) of 4 November 2010. You will be able to attend this presentation in the Main Auditorium or via the webcast. The Management will also be available to reply to your questions on this subject. Best regards, Anne-Sylvie Catherin

  1. ACCU Meeting

    CERN Multimedia

    PH Department

    2010-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 9 June 2010 At 9:15 a.m. in room 60-6-002 Chairperson’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Report on services from GS department CERN Global Network An update on Safety at CERN Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairperson in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel (76592) ...

  2. ACCU Meeting

    CERN Multimedia

    PH Department

    2011-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 9 March 2011 At 9:15 a.m. in room 60-6-002   Chairperson's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Report on services from GS department Update on Safety at CERN The new account management system Users’ Office news Any Other Business Agenda for the next meeting   Anyone wishing to raise any points under item 10 is invited to send them to the Chairperson in writing or by e-mail to Michael.Hauschild@cern.ch Michael Hauschild (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel (76592) Belgium ...

  3. ACCU MEETING

    CERN Multimedia

    PH Department

    2010-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 8 September 2010 at 9:15 a.m. in Room 60-6-002 Chairperson’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Report on services from GS Department An update on Safety at CERN The CERN Summer Student program Bringing Library services to users Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Chairperson in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): ...

  4. ACCU Meeting

    CERN Multimedia

    PH Department

    2010-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 8 December 2010 at 9:15 a.m. in room 60-6-002 Chairperson's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Report on services from GS department The CERN Ombuds The new account management system Crèche progress + Restaurants Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Chairperson in writing or by e-mail to Michael.Hauschild@cern.ch   Michael Hauschild (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): ...

  5. Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage

    Directory of Open Access Journals (Sweden)

    Caldwell Maeve

    2005-09-01

    Full Text Available Abstract Background Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly to cells of the central nervous system (CNS. Improvements in the biosafety of viral vectors are paramount as lentiviral vectors move into human clinical trials. This study investigates the packaging relationship between gene transfer (vector and Gag-Pol expression constructs of HIV-1, HIV-2 and SIV. Cross-packaged vectors expressing GFP were assessed for RNA packaging, viral vector titre and their ability to transduce rat primary glial cell cultures and human neural stem cells. Results HIV-1 Gag-Pol demonstrated the ability to cross package both HIV-2 and SIV gene transfer vectors. However both HIV-2 and SIV Gag-Pol showed a reduced ability to package HIV-1 vector RNA with no significant gene transfer to target cells. An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors. Conclusion This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional.

  6. Exhaustive genotyping of the interferon alpha receptor 1 (IFNAR1) gene and association of an IFNAR1 protein variant with AIDS progression or susceptibility to HIV-1 infection in a French AIDS cohort.

    Science.gov (United States)

    Diop, G; Hirtzig, T; Do, H; Coulonges, C; Vasilescu, A; Labib, T; Spadoni, J-L; Therwath, A; Lathrop, M; Matsuda, F; Zagury, J-F

    2006-11-01

    We have undertaken a systematic genomic approach in order to explore the role of the interferon alpha (IFN-alpha) pathway in AIDS disease development. As it is very difficult to genotype the IFN-alpha gene itself since it has many pseudo-genes, we have focused our interest on the genetic polymorphisms of the IFN-alpha receptor 1 (IFNAR1). We genotyped the Genetics of Resistance to Immunodeficiency Virus (GRIV) cohort composed of patients with extreme profiles of progression to AIDS, slow progressors (SP) and rapid progressors (RP), as well as seronegative controls (CTR). We identified 19 single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) greater than 1% among which two were newly characterized by our study. We found putative associations with AIDS disease development for four SNP alleles and for three haplotypes. The most interesting signals were found for two SNPs in linkage disequilibrium, the SNP IFNAR1_18339 corresponding to a Val168Leu mutation in the extracellular domain of the protein and the intronic SNP, IFNAR1_30127. The intronic SNP IFNAR1_30127 yielded a strong signal both when comparing SP with CTR (P=0.002) and RP with CTR (P=0.005) while IFNAR1_18339 yielded a smaller signal because less patients were analyzed; these SNPs could thus be involved in AIDS progression or in susceptibility to human immunodeficiency virus 1 (HIV-1) infection. Interestingly, two independent studies have previously pointed out the SNP IFNAR1_18339 in susceptibility to multiple sclerosis and to malaria. This is the first work investigating the polymorphisms of the IFNAR1 gene in AIDS. Our results which point out a possible role for the IFN-alpha pathway in susceptibility to HIV-1 infection or progression to AIDS need a necessary confirmation by genomic studies in other AIDS cohorts.

  7. Emerging quinolones resistant transfer genes among gram-negative bacteria, isolated from faeces of HIV/AIDS patients attending some Clinics and Hospitals in the City of Benin, Edo State, Nigeria

    Directory of Open Access Journals (Sweden)

    Enabulele IO

    2006-12-01

    Full Text Available A survey of 1431 gram-negative bacilli from June 2001 to September 2005 were obtained from the faeces of 920 HIV/AIDS patients attending some Clinics and Hospitals in Benin City, Nigeria, were screened for quinolones resistance gene. The HIV/AIDS patients CD4 cells range was ≤14/mm3 ≥800/mm3 of blood. Out of the 1431 isolates, 343 (23.9% were resistance to quinolones with a MIC ≥4μg/ml for norfloxacin, ciprofloxacin and pefloxacin while a MIC of ≥32 µg/ml for nalidixic acid. The screened isolates include Pseudomonas aeruginosa 64(18.7%, E coli 92(26.8%, Klebsiella pneumoniae 53(15.4%, Salmonella typhi 39(11.4%, Shigella dysenteriae 36(10.5%, Proteus mirabilis 34(9.9% and Serratia marcescens 25(7.3%. The average resistance of the isolates to the various quinolones ranged from 42.7% to 66.7%. Klebsiella were the most resistant isolates with a mean resistance of 66.7% while Proteus were the less resistant isolates with a mean resistance of 42.7%. Most isolates were resistant to Nalidixic acid followed by norfloxacin while the less resistant were to the pefloxacin. The frequency of qnr genes transfer to EJRifr as recipient ranged from 2 x 10-2 to 6 x 10-6 with an average of 2 plasmids per cell. The molecular weight of the plasmids ranged from <2.9kbp to <5.5 kbp. This indicated that plasmids allowed the movement of genetic materials including qnr resistant genes between bacteria species and genera in Benin City, Nigeria.

  8. Public meetings

    CERN Multimedia

    Staff Association

    2014-01-01

      Public meetings : Come and talk about your future employment conditions !   The Staff Association will come and present the results of our survey on the 2015 five-yearly review. Following the survey, the topics discussed, will be contract policy, recognition of merit (MARS), working time arrangements and family policy. After each meeting and around a cup of coffee or tea you will be able to continue the discussions. Do not hesitate to join us, the five-yearly review, it is with YOU!

  9. STAFF MEETING

    CERN Multimedia

    2004-01-01

    I would like to invite all members of the CERN Personnel to a meeting on Tuesday 13 January 2004 at 4:00 p.m. - Main Auditorium (bldg. 500) to convey my best wishes for the new year and to present a perspective of CERN's future activities. Closed-circuit transmission of the meeting will be available in the Council Chamber and in the AB Auditorium (Meyrin), the AB Auditorium (Prévessin), the IT Auditorium (bldg. 31) and the AT Auditorium (bldg. 30). A simultaneous translation into English will be available in the main Auditorium. Robert AYMAR

  10. STAFF MEETING

    CERN Multimedia

    2003-01-01

    I would like to invite all members of the CERN Personnel to a meeting on Tuesday 13 January 2004 at 4:00 p.m. - Main Auditorium (bldg. 500) to convey my best wishes for the new year and to present a perspective of CERN's future activities. Closed-circuit transmission of the meeting will be available in the Council Chamber and in the AB Auditorium (Meyrin), the AB Auditorium (Prévessin), the IT Auditorium (bldg. 31) and the AT Auditorium (bldg. 30). A simultaneous translation into English will be available in the main Auditorium. Robert AYMAR

  11. STAFF MEETING

    CERN Multimedia

    Robert Aymar

    2005-01-01

    I would like to invite all members of the CERN Personnel to a meeting on Thursday 12 January 2006 at 4:00 p.m. - Main Auditorium (bldg. 500) to convey my best wishes for the new year, to review CERN's activities during 2005 and to present the perspectives for this coming year. Closed-circuit transmission of the meeting will be available in the Council Chamber and in the AB Auditorium (Meyrin), the AB Auditorium (Prévessin), the IT Auditorium (bldg. 31) and the AT Auditorium (bldg. 30). A simultaneous translation into English will be available in the main Auditorium. Best wishes for the festive season Robert AYMAR

  12. Staff meeting

    CERN Multimedia

    2006-01-01

    I would like to invite all members of the CERN Personnel to a meeting on Thursday 18 January 2007 at 3:00 p.m. Main Auditorium (bldg.. 500) to convey my best wishes for the new year, to review CERN's activities during 2006 and to present the perspectives for this special year of the LHC start-up. Closed-circuit transmission of the meeting will be available in the Council Chamber and in the AB Auditorium (Meyrin), the AB Auditorium (Prévessin), the IT Auditorium (bldg.. 31) and the AT Auditorium (bldg.. 30). Simultaneous translation into English will be available in the main Auditorium. Robert AYMAR

  13. Cumulative effects of HIV illness and caring for children orphaned by AIDS on anxiety symptoms among adults caring for children in HIV-endemic South Africa.

    Science.gov (United States)

    Kuo, Caroline; Cluver, Lucie; Casale, Marisa; Lane, Tyler

    2014-06-01

    Adults caring for children in HIV-endemic communities are at risk for poor psychological outcomes. However, we still have a limited understanding of how various HIV impacts--including caregiver's own HIV illness, responsibilities of caring for a child orphaned by AIDS, or both--affect psychological outcomes among caregivers. Furthermore, few studies have explored the relationship between stigma, HIV, and psychological outcomes among caregivers of children in HIV-endemic communities. A cross-sectional survey conducted from 2009 to 2010 assessed anxiety among 2477 caregivers of children in HIV-endemic South Africa. Chi-square tested differences in anxiety among caregivers living with HIV, caregivers of a child orphaned by AIDS, and caregivers affected with both conditions. Multivariate logistic regressions identified whether the relationship between HIV impacts and anxiety remained after controlling for socio-demographic co-factors. Mediation analysis tested the relationship between stigma, HIV, and anxiety. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were two and a half times greater among caregivers living with HIV compared to nonaffected caregivers. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were greatest among caregivers living with HIV and caring for a child orphaned by AIDS. Exposure to AIDS-related stigma partially mediated the relationship between HIV and anxiety. Interventions are needed to address caregiver psychological health, particularly among caregivers affected with both conditions of living with HIV and caring for a child orphaned by AIDS.

  14. Cumulative Effects of HIV Illness and Caring for Children Orphaned by AIDS on Anxiety Symptoms Among Adults Caring for Children in HIV-Endemic South Africa

    Science.gov (United States)

    Cluver, Lucie; Casale, Marisa; Lane, Tyler

    2014-01-01

    Abstract Adults caring for children in HIV-endemic communities are at risk for poor psychological outcomes. However, we still have a limited understanding of how various HIV impacts—including caregiver's own HIV illness, responsibilities of caring for a child orphaned by AIDS, or both—affect psychological outcomes among caregivers. Furthermore, few studies have explored the relationship between stigma, HIV, and psychological outcomes among caregivers of children in HIV-endemic communities. A cross-sectional survey conducted from 2009 to 2010 assessed anxiety among 2477 caregivers of children in HIV-endemic South Africa. Chi-square tested differences in anxiety among caregivers living with HIV, caregivers of a child orphaned by AIDS, and caregivers affected with both conditions. Multivariate logistic regressions identified whether the relationship between HIV impacts and anxiety remained after controlling for socio-demographic co-factors. Mediation analysis tested the relationship between stigma, HIV, and anxiety. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were two and a half times greater among caregivers living with HIV compared to nonaffected caregivers. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were greatest among caregivers living with HIV and caring for a child orphaned by AIDS. Exposure to AIDS-related stigma partially mediated the relationship between HIV and anxiety. Interventions are needed to address caregiver psychological health, particularly among caregivers affected with both conditions of living with HIV and caring for a child orphaned by AIDS. PMID:24901465

  15. Avaliação do polimorfismo no gene da metilenotetrahidrofolato redutase e concentração de folato e vitamina B12 em pacientes portadores do HIV-1 em tratamento com anti-retrovirais Evaluation of the polymorphisms in methylenetetrahydrofolate reductase gene and the levels of folate and B12 in HIV-infected patients under antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Iran Malavazi

    2004-12-01

    Full Text Available Neste trabalho, investigamos concentração da vitamina B12 e folato, considerando-se a influência dos genótipos da metilenotetrahidrofolato redutase, o perfil imunológico e a terapia antiretroviral utilizada na população brasileira portadora do HIV. Um grupo de 86 indivíduos portadores do HIV-1 e 29 doadores de sangue foram recrutados para compor a casuística. Entre os infectados pelo HIV-1, observou-se menor concentração de B12 no grupo com maior número de linfócitos TCD4+. Não encontramos diferença na distribuição genotípica para as mutações MTHFR C677T e A1298C entre infectados e não infectados pelo HIV-1. Indivíduos portadores do HIV, genótipo C677C, apresentaram concentrações menores de B12 em relação ao grupo controle de mesmo genótipo. A terapia antiretroviral não mostrou qualquer influência nos valores de folato e vitamina B12. Estudos adicionais são necessários para reavaliar a prevalência de menores concentrações de B12 e folato e de hiperhomocisteinemia na população portadora do HIV sob a ótica do uso de HAART e da melhoria na sobrevida dos pacientes.In this study we sought to investigate the B12 and folate levels regarding the influence of methylenetetrahydrofolate reductase genotypes, immunological profile and antiretroviral therapy in the Brazilian HIV-infected population. The study group comprised 89 HIV-infected individuals and 29 blood donors. There was a decrease in the B12 levels in the HIV-infected group with higher TCD4+ lymphocyte counts. No differences in the genotype distribution for methylenetetrahydrofolate reductase polymorphisms between the HIV-infected individuals and the controls were found. HIV-infected individuals carrying the C677C genotype presented lower B12 levels (313.91 ± 154.05 than those with the same genotype in the control group (408.27 ± 207.69. Also, the antiretroviral therapy was not a source of variation of the folate and B12 serum levels. Further studies are

  16. HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

    Directory of Open Access Journals (Sweden)

    Xinli Lu

    Full Text Available New human immunodeficiency virus type 1 (HIV-1 diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF01_AE (53.4%, CRF07_BC (23.4%, subtype B (15.9%, and unique recombinant forms URFs (4.9%. Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx, unknown before in Hebei, were first found among men who have sex with men (MSM. All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%, CRF01_AE/B (23.3%, B/C (16.7%, CRF01_AE/C (13.3%, CRF01_AE/B/A2 (3.3% and CRF01_AE/BC/A2 (3.3%, plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

  17. Frequency of human immunodeficiency virus type-2 in hiv infected patients in Maputo City, Mozambique

    Directory of Open Access Journals (Sweden)

    Bhatt Nilesh

    2011-08-01

    Full Text Available Abstract The HIV/AIDS pandemic is primarily caused by HIV-1. Another virus type, HIV-2, is found mainly in West African countries. We hypothesized that population migration and mobility in Africa may have facilitated the introduction and spreading of HIV-2 in Mozambique. The presence of HIV-2 has important implications for diagnosis and choice of treatment of HIV infection. Hence, the aim of this study was to estimate the prevalence of HIV-2 infection and its genotype in Maputo, Mozambique. HIV-infected individuals (N = 1,200 were consecutively enrolled and screened for IgG antibodies against HIV-1 gp41 and HIV-2 gp36 using peptide-based enzyme immunoassays (pepEIA. Specimens showing reactivity on the HIV-2 pepEIA were further tested using the INNO-LIA immunoblot assay and HIV-2 PCR targeting RT and PR genes. Subtype analysis of HIV-2 was based on the protease gene. After screening with HIV-2 pepEIA 1,168 were non-reactive and 32 were reactive to HIV-2 gp36 peptide. Of this total, 30 specimens were simultaneously reactive to gp41 and gp36 pepEIA while two samples reacted solely to gp36 peptide. Only three specimens containing antibodies against gp36 and gp105 on the INNO-LIA immunoblot assay were found to be positive by PCR to HIV-2 subtype A. The proportion of HIV-2 in Maputo City was 0.25% (90%CI 0.01-0.49. The HIV epidemic in Southern Mozambique is driven by HIV-1, with HIV-2 also circulating at a marginal rate. Surveillance program need to improve HIV-2 diagnosis and consider periodical survey aiming to monitor HIV-2 prevalence in the country.

  18. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2002-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 4 December 2002 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Fellows, Associates and Summer Student Programmes Particle Data Book distribution Revoking Computer accounts Equipment insurance on site Reports from ACCU representatives on other committees Users' Office news Any Other Business Dates for meetings in 2003 Agenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch   ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (74837...

  19. Board meetings

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ruxandra Staicu

    Purpose: Board meetings. Date(s):. 2015-11-16 to 2015-11-19. Destination(s):. Ottawa. Airfare: $5,596.11. Other. Transportation: $67.54. Accommodation: $340.45. Meals and. Incidentals: $175.39. Other: $0.00. Total: $6,179.49. Comments: 2015-2016 Travel and Hospitality Expense. Reports for Shainoor Khoja, Governor.

  20. Board meetings

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ruxandra Staicu

    Purpose: Board meetings. Date(s):. 2015-07-13 to 2015-07-14. Destination(s):. Ottawa. Airfare: $5,687.53. Other Transportation: $60.14. Accommodation: $344.56. Meals and. Incidentals: $150.00. Other: Total: $6,242.23. Comments: 2015-2016 Travel and Hospitality Expense. Reports for Shainoor Khoja, Governor.

  1. ACCU MEETING

    CERN Document Server

    Chris Onions (Secretary)

    2000-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 December 2000 At 10 a.m. in the 6th floor Conference Room, Main Building Chairman's remarks Adoption of the agenda News from the CERN Management Minutes of the previous meeting Matters arising Equal Opportunities at CERN The Summer Student programme CERN Programme for Physics High School Teachers Users' Office News Any Other Business Dates for Meetings in 2001 Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets) : Austria G. Neuhofer (74094) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Re...

  2. ACCU MEETING

    CERN Document Server

    2000-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 December 2000 At 10 a.m. in the 6th floor Conference Room, Main Building Chairman's remarks Adoption of the agenda News from the CERN Management Minutes of the previous meeting Matters arising Equal Opportunities at CERN The Summer Student programme CERN Programme for Physics High School Teachers Users' Office News Any Other Business Dates for Meetings in 2001 Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets) :   Austria G. Neuhofer (74094) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958)...

  3. ACCU MEETING

    CERN Multimedia

    Chris Onions (Secretary)

    2001-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 5 December 2001 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 2. Adoption of the agenda 3. Minutes of the previous meeting 4. Matters arising 5. News from the CERN Management 6. Housing 7. Restaurant Surveillance Committee 8. Users' Office news 9. Election of ACCU chairman 10. Any Other Business 11. Dates for meetings in 2002 12. Agenda for the next meetingAnyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland A. Kiiskinen (79387) Fr...

  4. ACCU MEETING

    CERN Document Server

    Chris Onions (Secretary)

    2001-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 5 December 2001 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 2. Adoption of the agenda 3. Minutes of the previous meeting 4. Matters arising 5. News from the CERN Management 6. Housing 7. Restaurant Surveillance Committee 8. Users' Office news 9. Election of ACCU chairman 10. Any Other Business 11. Dates for meetings in 2002 12. Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria  W. Adam  (71661) Belgium  G. Wilquet  (74664) Bulgaria  R. Tzenov  (77958) Czech Republic  P. Závada&am...

  5. ACCU Meeting

    CERN Multimedia

    PH Department

    2011-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 15 June 2011 At 9:15 a.m. in room 60-6-002 Chairperson’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Report on services from GS department Update on Safety at CERN Reports from ACCU representatives on other Committees a. Scientific Information Policy Board (SIPB) b. IT Service Review Meeting (ITSRM) c. GS User Commission Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairperson in writing or by e-mail to Michael.Hauschild@cern.ch Michael Hauschild (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in bra...

  6. Crisis meeting

    CERN Multimedia

    Staff Association

    2014-01-01

      To all CERN staff: your rights are at risk ! We invite you to come to a crisis meeting on Wednesday 2nd April at 10:30 a.m., Auditorium, Main Building, Meyrin site. Your presence is crucial, we are ALL concerned !

  7. Crisis meeting

    CERN Multimedia

    Staff Association

    2015-01-01

    To all CERN staff: your rights are at risk! We invite you to come to a crisis meeting on Thursday 7th May 2015 at 9 a.m., Auditorium, Main Building, Meyrin site. Your presence is crucial, we are ALL concerned!

  8. Novel Approaches to Inhibit HIV Entry

    Directory of Open Access Journals (Sweden)

    Chukwuka A. Didigu

    2012-02-01

    Full Text Available Human Immunodeficiency Virus (HIV entry into target cells is a multi-step process involving binding of the viral glycoprotein, Env, to its receptor CD4 and a coreceptor—either CCR5 or CXCR4. Understanding the means by which HIV enters cells has led to the identification of genetic polymorphisms, such as the 32 base-pair deletion in the ccr5 gene (ccr5∆32 that confers resistance to infection in homozygous individuals, and has also resulted in the development of entry inhibitors—small molecule antagonists that block infection at the entry step. The recent demonstration of long-term control of HIV infection in a leukemic patient following a hematopoietic stem cell transplant using cells from a ccr5∆32 homozygous donor highlights the important role of the HIV entry in maintaining an established infection and has led to a number of attempts to treat HIV infection by genetically modifying the ccr5 gene. In this review, we describe the HIV entry process and provide an overview of the different classes of approved HIV entry inhibitors while highlighting novel genetic strategies aimed at blocking HIV infection at the level of entry.

  9. When genome-based approach meets the ‘old but good’: revealing genes involved in the antibacterial activity of Pseudomonas sp. P482 against soft rot pathogens.

    Directory of Open Access Journals (Sweden)

    Dorota Magdalena Krzyżanowska

    2016-05-01

    Full Text Available Dickeya solani and Pectobacterium carotovorum subsp. brasili¬ense are recently established species of bacterial plant pathogens causing black leg and soft rot of many vegetables and ornamental plants. Pseudomonas sp. strain P482 inhibits the growth of these pathogens, a desired trait considering the limited measures to combat these diseases. In this study, we determined the genetic background of the antibacterial activity of P482, and established the phylogenetic position of this strain.Pseudomonas sp. P482 was classified as Pseudomonas donghuensis. Genome mining revealed that the P482 genome does not contain genes determining the synthesis of known antimicrobials. However, the ClusterFinder algorithm, designed to detect atypical or novel classes of secondary metabolite gene clusters, predicted 18 such clusters in the genome. Screening of a Tn5 mutant library yielded an antimicrobial negative transposon mutant. The transposon insertion was located in a gene encoding an HpcH/HpaI aldolase/citrate lyase family protein. This gene is located in a hypothetical cluster predicted by the ClusterFinder, together with the downstream homologues of four nfs genes, that confer production of a nonfluorescent siderophore by P. donghuensis HYST. Site-directed inactivation of the HpcH/HpaI aldolase gene, the adjacent short chain dehydrogenase gene, as well as a homologue of an essential nfs cluster gene, all abolished the antimicrobial activity of the P482, suggesting their involvement in a common biosynthesis pathway. However, none of the mutants showed a decreased siderophore yield, neither was the antimicrobial activity of the wild type P482 compromised by high iron bioavailability.A genomic region comprising the nfs cluster and three upstream genes is involved in the antibacterial activity of P. donghuensis P482 against D. solani and P. carotovorum subsp. brasiliense. The genes studied are unique to the two known P. donghuensis strains. This study

  10. Cancer Virology and HIV Think Tank | Center for Cancer Research

    Science.gov (United States)

    Cancer Virology and HIV Think Tank Friday, December 15, 2017 9:30 AM - 3:30 PM Abstract submission deadline: November 29, 2017 Porter Neuroscience Center (Building 35A) Room 620/630 Atrium Space Please mark your calendars for the Cancer Virology and HIV Think Tank Meeting on December 15! This is an annual meeting hosted by the CCR Center of Excellence in HIV/AIDS and Cancer Virology that focuses on the exchange of information about the biology of cancer-associated viruses.

  11. Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

    DEFF Research Database (Denmark)

    Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

    2007-01-01

    OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose...... determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free oestradiol and testosterone were decreased...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression...

  12. Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

    DEFF Research Database (Denmark)

    Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

    2007-01-01

    determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free oestradiol and testosterone were decreased......OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression...

  13. Staff meeting

    CERN Multimedia

    2007-01-01

    I would like to invite all members of the CERN Personnel to a meeting on Wednesday 16 January 2008 at 3:00 p.m. Main Auditorium (bldg 500) to convey my best wishes for the new year, to review CERN’s activities during 2007 and to present the perspectives for 2008, the year of the LHC start-up. Closed-circuit transmission of the meeting will be available in the Council Chamber and in the AB Auditorium (Meyrin), the AB Auditorium (Prévessin), the IT Auditorium (Bldg. 31) and the AT Auditorium (Bldg. 30). Simultaneous translation into English will be available in the main Auditorium. Best wishes for the festive season! Robert AYMAR

  14. Public meetings

    CERN Multimedia

    Staff Association

    2012-01-01

    MARS PENSIONS CONTRACT POLICY GENERAL INFORMATION   PUBLIC MEETINGS COME AND BE INFORMED! Public meetings Monday 15 Oct. 2 pm Amphi IT, 31-3-004 Meyrin Wednesday 17 Oct. 10 am Amphi BE, 864-1-D02 Prévessin Thursday 18 Oct. 10 am Salle du Conseil/ Council Chamber 503-1-001 Meyrin Thursday 18 Oct. 2 pm Filtration Plant, 222-R-001(in English) Meyrin   Overview of the topics to be discussed Recognition of Merit – MARS Outcome of last exercise 2007 to 2012 : lessons learned Pension Fund Capital preservation policy : what is it ? Contract policy LC2IC statistics SA proposal General information CVI 2013 Voluntary programmes (PRP, SLS)  

  15. ACCU Meeting

    CERN Document Server

    Chris Onions

    2005-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 7 December 2005 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Closure of computer accounts upon CERN contract expiry Reports from ACCU representatives on other committees Users' Office news Election of ACCU Chair Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets). Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) ...

  16. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 8 September 2004 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management The Visits Service Lifetime of Computer Accounts Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tsenov (79573) Czech Republic P. Závada (75877) Denmark P. Hansen (75941) Finland K. Lassila-Perini (79354) France F. Bauer (...

  17. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 8 September 2004 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management The Visits Service Lifetime of Computer Accounts Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tsenov (79573) Czech Republic P. Závada (75877) Denmark P. Hansen (75941) Finland K. Lassila-Perini (79354) France F. Bauer (7...

  18. ACCU meeting

    CERN Document Server

    PH Department

    2008-01-01

    DRAFT Agenda for the meeting to be heldon Wednesday 5 March 2008 At 9:15 a.m. in room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management An update on Safety at CERN The CERN Ombudsperson proposal Childcare initiative Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) BelgiumnC. Vander Velde (71539) Bulgaria Czech Republic P. Závada (75877) Denm...

  19. ACCU MEETING

    CERN Document Server

    PH Department

    2008-01-01

    DRAFT Agenda for the meeting to be heldon Wednesday 5 March 2008 At 9:15 a.m. in room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management An update on Safety at CERN The CERN Ombudsperson proposal Childcare initiative Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) BelgiumnC. Vander Velde (71539) Bulgaria Czech Republic P. Závada (75877) Denm...

  20. ACCU MEETING

    CERN Multimedia

    Chris Onions (Secretary)

    2001-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 12 September 2001 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda News from the CERN Management Minutes of the previous meeting Matters arising Logistics and Self-service stores EP Space management follow-up How to improve IT User Support? Users' Office News Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail to Roger.Jones@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland A. Kiiskin...

  1. ACCU MEETING

    CERN Multimedia

    Chris Onions (Secretary)

    2001-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 June 2001 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda News from the CERN Management Minutes of the previous meeting Matters arising Logistics and Self-service stores EP Space management follow-up How to improve IT User Support? Users' Office News Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail to Roger.Jones@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland A. Kiis...

  2. ACCU Meeting

    CERN Multimedia

    2003-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 September 2003 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 8. Registration plans for portables 2. Adoption of the agenda 9. Reports from ACCU representatives 3. Minutes of the previous meeting on other committees 4. Matters arising 10. Users' Office news 5. News from the CERN Management 11. Any Other Business 6. The Press Office 12. Agenda for the next meeting 7. Equal Opportunities Commission Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): AustriaW. Adam (71661) Norway H. Helstrup (73601) Belgium G. Wilquet (74664) Poland Z. Hajduk (75917) Bulgari...

  3. ACCU Meeting

    CERN Multimedia

    2003-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 September 2003 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 7. Equal Opportunities Commission 2. Adoption of the agenda 8. Registration plans for portables 3. Minutes of the previous meeting 9. Reports from ACCU representatives on other committees 4. Matters arising 10. Users' Office news 5. News from the CERN Management 11. Any Other Business 6. The Press Office 12. Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Norway H. Helstrup (73601) Belgium G. Wilquet (74664) Poland Z. Hajduk (75917) Bulgar...

  4. ACCU MEETING

    CERN Multimedia

    2003-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 5 March 2003 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 7. Equipment insurance on site 2. Adoption of the agenda,8. ACCU reporting mechanisms in the different countries 3. Minutes of the previous meeting9. Reports from ACCU representatives on other committees 4. Matters arising10. Users' Office news 5. News from the CERN Management11. Any Other Business 6. CHIS news and follow-up of survey12. Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661)NorwayH. Helstrup (73601) Belgium G. Wilquet (74664) Poland Z. Hajduk (7591...

  5. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 9 June 2004 at 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Update on CERN's 50th anniversary celebrations Report from the EPOG (European Particle Physics Outreach Group) Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark P. Hansen (75941...

  6. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2005-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 7 September 2005 At 9:15 a.m. in room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Logistics at CERN Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finland K. Lassila-Perini (79354) France F. Bauer S. Laplace...

  7. ACCU Meeting

    CERN Multimedia

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 March 2004 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 6. The PH Department 2. Adoption of the agenda 7. Reports from ACCU representatives on other committees 3. Minutes of the previous meeting 8. Users' Office news 4. News from the CERN Management 9. Any Other Business 5. Matters arising 10. Agenda for the next meeting Anyone wishing to raise any points under item 9 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Norway H. Helstrup (73601) Belgium G. Wilquet (74664) Poland Z. Hajduk (75917) Bulgaria R. Tsenov (79573) Portugal P. Bordalo (74704) Czech Republic P. Závada ...

  8. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 March 2004 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting News from the CERN Management Matters arising The PH Department Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 9 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark P. Hansen (75941) Finland E. Tuominen (71534) France F. Bauer (71247) L. Serin...

  9. ACCU MEETING

    CERN Multimedia

    2003-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 December 2003 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 8. Report from IT division on Computing matters 2. Adoption of the agenda 9. Young Particle Physicists Association 3. Minutes of the previous meeting 10. Reports from ACCU representatives on other committees 4. Matters arising 11. Users' Office news 5. News from the CERN Management 12. Election of the ACCU Chair 6. Report from the new Director-General 13. Any Other Business 7. CERN's 50th anniversary 14. Agenda for the next meeting Anyone wishing to raise any points under item 13 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (716...

  10. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 9 June 2004 at 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Update on CERN's 50th anniversary celebrations Report from the EPOG (European Particle Physics Outreach Group) Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tsenov (79573) Czech Republic P. Závada (75877) Denmark P. Hansen (75941) Finlan...

  11. ACCU MEETING

    CERN Multimedia

    2003-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 December 2003 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 8. Report from IT division on Computing matters 2. Adoption of the agenda 9. Young Particle Physicists Association 3. Minutes of the previous meeting 10. Reports from ACCU representatives on other committees 4. Matters arising 11. Users' Office news 5. News from the CERN Management 12. Election of the ACCU Chair 6. Report from the new Director-General 13. Any Other Business 7. CERN's 50th anniversary 14. Agenda for the next meeting Anyone wishing to raise any points under item 13 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Ada...

  12. ACCU MEETING

    CERN Multimedia

    2003-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 11 June 2003 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 7. Reports from ACCU representatives 2. Adoption of the agenda on other committees 3. Minutes of the previous meeting 8. Users' Office news 4. Matters arising 9. Any Other Business 5. News from the CERN Management 10. Agenda for the next meeting 6. Property Protection at CERN Anyone wishing to raise any points under item 9 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Norway H. Helstrup (73601) Belgium G. Wilquet (74664) Poland Z. Hajduk (75917) Bulgaria R. Tsenov (74837) Portugal P. Bordalo (74704) Czech Republic ...

  13. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2005-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 8 June 2005 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Logistics at CERN Open Access Publishing Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tsenov (79573) Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finland K. Lassila-Perini ...

  14. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2006-01-01

    DRAFT Agenda of the meeting to be held on Wednesday 8 March 2006 At 9:15 a.m. in Room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Proposal for a centralised access control service Report from PH Space Management Policy Board Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under Item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives on ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) ...

  15. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2005-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 9 March 2005 At 9:15 a.m. in room 160-1-009 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Purchasing procedures at CERN Reports from ACCU representatives on other committees Users' Office news CERN Clubs Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tsenov (79573) Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finland K. Las...

  16. ACCU MEETING

    CERN Multimedia

    2003-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 5 March 2003 At 9:15 a.m. in room 60-6-002 1. Chairman's remarks 7. Equipment insurance on site 2. Adoption of the agenda 8. ACCU reporting mechanisms in the different countries 3. Minutes of the previous meeting 9. Reports from ACCU representatives on other committees 4. Matters arising 10. Users' Office news 5. News from the CERN Management 11. Any Other Business 6. Health Insurance news and follow-up of survey 12. Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Norway H. Helstrup (73601) Belgium G. Wil...

  17. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2006-01-01

    DRAFT Agendafor the meeting to be held on Wednesday 8 March 2006At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Proposal for a centralised access control service Report from PH Space Management Policy Board Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Fin...

  18. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 8 December 2004 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting The effects of the reorganization of CERN's structure, one year on Matters arising News from the CERN Management Computer Security The new CERN Dosimeter Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tsenov (79573) Czech Republic P. Závada (75877) Denmark P. Hansen (7594...

  19. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2004-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 8 December 2004 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting The effects of the reorganization of CERN's structure, one year on Matters arising News from the CERN Management Computer Security The new CERN Dosimeter Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tsenov (79573) Czech Republic P. Závada (75877) Denmark P. Hansen (75941) Finl...

  20. ACCU MEETING

    CERN Multimedia

    PH Department

    2008-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 11 June 2008 At 9:15 a.m. in Room 60-6-002 1.\tChairman’s remarks 2.\tAdoption of the agenda 3.\tMinutes of the previous meeting 4.\tMatters arising 5.\tNews from the CERN Management 6.\tAn update on safety at CERN 7.\tChildcare initiative 8.\tReports from ACCU representatives on other committees 9.\tUsers’ Office news 10.\tAny Other Business 11.\tAgenda for the next meeting Anyone wishing to raise any points under Item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium C. Vander Velde (71539) Bulgaria Czech Republic P. Závada (75...

  1. ACCU MEETING

    CERN Multimedia

    PH Department

    2009-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 9 September 2009 At 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks 2.\tAdoption of the agenda 3.\tMinutes of the previous meeting 4.\tMatters arising 5.\tNews from the CERN Management 6.\tCode of conduct 7.\tEqual Opportunities at CERN 8.\tAn update on safety at CERN 9.\tThe CERN shuttle service 10.\tReports from ACCU representatives on other committees 11.\tUsers’ Office news 12.\tOther business 13.\tAgenda of the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives on ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel (76592) Belgium C. Vander Velde (71539) Bulgaria Czech Re...

  2. ACCU MEETING

    CERN Multimedia

    PH Department

    2008-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 September 2008 At 9:15 a.m. in Room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management An update on Safety at CERN Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 9 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria, W. Adam (71661) Belgium, C. Vander Velde (71539) Bulgaria Czech Republic, P. Závada (75877) Denmark, J.B. Hansen (...

  3. ACCU MEETING

    CERN Multimedia

    PH Department

    2009-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 11 March 2009 At 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks 2.\tAdoption of the agenda 3.\tMinutes of the previous meeting 4.\tMatters arising 5.\tNews from the CERN Management 6.\tThe CERN Press Office 7.\tAn update on Safety at CERN 8.\tThe Burotel project 9.\tReports from ACCU representatives on other committees 10.\tUsers’ Office news 11.\tAny Other Business 12.\tAgenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel () Belgium C. Vander Velde (71539) Bulgaria C...

  4. ACCU Meeting

    CERN Multimedia

    PH Department

    2008-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 11 June 2008 At 9:15 a.m. in room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management An update on Safety at CERN Childcare initiative Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria - W. Adam (71661) Belgium - C. Vander Velde (71539) Bulgaria Czech Republic - P. Závada (75877) Denmark - J.B. Hansen...

  5. ACCU MEETING

    CERN Multimedia

    PH Department

    2009-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 9 September 2009 At 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks 2.\tAdoption of the agenda 3.\tMinutes of the previous meeting 4.\tMatters arising 5.\tNews from the CERN Management 6.\tCode of Conduct 7.\tEqual Opportunities at CERN 8.\tAn update on Safety at CERN 9.\tThe CERN shuttle service 10.\tReports from ACCU representatives on other committees 11.\tUsers’ Office news 12.\tAny Other Business 13.\tAgenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel (76592) Belgium C. Vander Velde (71539) Bulgaria Cze...

  6. ACCU MEETING

    CERN Multimedia

    PH Department

    2009-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 11 March 2009 At 9:15 a.m. in room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management The CERN Press Office An update on Safety at CERN The Burotel project Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel () Belgium C. Vander Velde (71539) Bulgaria Czech Republic P. Závada (75877) Denmark...

  7. ACCU MEETING

    CERN Multimedia

    PH Department

    2009-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 June 2009At 9:15 a.m. in room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management CERN Social Services User services in GS Department An update on Safety at CERN Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to mailto:Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria - G. Walzel (76592) Belgium - C. Vander Velde (71539) Bulgaria Czech Republic - P. Závada (7587...

  8. ACCU MEETING

    CERN Multimedia

    PH Department

    2008-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 3 December 2008 at 9:15 a.m. in Room 60-6-002 1.\tChairman’s remarks 2.\tAdoption of the agenda 3.\tMinutes of the previous meeting 4.\tMatters arising 5.\tNews from the CERN Management 6.\tReport from the new Director-General 7.\tReport on the Fellows and Associates programme 8.\tAn update on Safety at CERN 9.\tReports from ACCU representatives on other committees 10.\tUsers’ Office news 11.\tAny Other Business 12.\tAgenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium C. ...

  9. ACCU MEETING

    CERN Multimedia

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 12 September 2007 at 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks7.\tCar sharing pilot project 2.\tAdoption of the agenda\t8.\tReports from ACCU representatives on other committees 3.\tMinutes of the previous meeting9.\tUsers’ Office newss 4.\tMatters arising10.\tAny Other Business 5.\tNews from the CERN Management11.\tAgenda for the next meeting 6.\tLogistics and transport at CERN Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria\tW. Adam (71661)NorwayG. Løvhøiden (73176)Belgium\tG. Wilquet (74664)PolandM. Witek (78967)...

  10. ACCU MEETING

    CERN Multimedia

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 5 December 2007 at 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks7.\tEmergency Services at CERN 2.\tAdoption of the agenda\t8.\tThe Meyrin Tram project 3.\tMinutes of the previous meeting9.\tReports from ACCU representatives on other committees 4.\tMatters arising10.\tUsers’ Office news 5.\tNews from the CERN Management11.\tElection of ACCU Chair 6. LHC 2008 start-up events 6.\tLogistics and transport at CERN 12.\tAny Other Business 13.\tAgenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Aust...

  11. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2002-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 12 June 2002 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management PIE procedures CERN Cars EP Electronics Advisory Board Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch   ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland E. Tuominen (71534) France F. Bauer (71247) L. Serin (71143) Germany H. Kroha ...

  12. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2002-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 March 2002 At 9:15 a.m. in the Council Chamber Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Follow-up on Space Management Users' Desktop needs PIE procedures Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland E. Tuominen (71534) France F. Bauer L. Serin (712...

  13. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2002-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 12 June 2002 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management PIE procedures CERN Cars EP Electronics Advisory Board Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch   ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland E. Tuominen (71534) France F. Bauer (71247) L. Serin (71143) Germany H. Kroha...

  14. ACCU MEETING

    CERN Multimedia

    Chris Onions / EP Division

    2001-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 June 2001 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda News from the CERN Management Minutes of the previous meeting Matters arising EP Space management Cars Housing EDH from the User's point of view VRVS Users' Office News Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland A. Kiiskinen (79387) France M. Déj...

  15. ACCU MEETING

    CERN Multimedia

    2000-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 13 September 2000 At 10 a.m. in the 6th floor Conference Room, Main Building 1. Chairman's remarks 2. Adoption of the agenda 3. News from the CERN Management 4. Minutes of the previous meeting 5. Matters arising 6. Report from the Scientific Information Policy Board 7. Report from ETT Division: The Press Office 8. Update on Computing Issues 9. Users' Office News 10. Any Other Business 11. Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail to Bryan Pattison (Secretary). ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets) : Austria G. Neuhofer (74094) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Z vada (75...

  16. ACCU MEETING

    CERN Document Server

    Chris Onions

    2001-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 7 March 2001 At 9:15 a.m. in the 6th floor Conference Room, Main Building Chairman's remarks Adoption of the agenda News from the CERN Management Minutes of the previous meeting Matters arising Video-conferencing/recording Fellows programme Operational Circular No. 6 EP Space management Update on Computing Issues Users' Office News Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary)  ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic...

  17. ACCU MEETING

    CERN Multimedia

    Bryan Pattison

    2000-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 13 September 2000 At 10 a.m. in the 6th floor Conference Room, Main Building1. Chairman's remarks2. Adoption of the agenda3. News from the CERN Management4. Minutes of the previous meeting5. Matters arising6. Report from the Scientific Information Policy Board7. Report from ETT Division: The Press Office8. Update on Computing Issues9. Users' Office News10. Any Other Business11. Agenda for the next meetingAnyone wishing to raise any points under item 10 is invited to send them to the Secretary in writing via the CERN Users' Office or by e-mail toBryan Pattison(Secretary).ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets) :Austria G. Neuhofer (74094)Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958)Czech Republic P. Závada (75877)Den...

  18. ACCU MEETING

    CERN Multimedia

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 12 September 2007 at 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks6.\tLogistics and transport at CERN2.\tAdoption of the agenda\t7.\tCar sharing pilot project3.\tMinutes of the previous meeting8.\tReports from ACCU representatives on other committees4.\tMatters arising9.\tUsers’ Office newss5.\tNews from the CERN Management10.\tAny Other Business11.\tAgenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria\tW. Adam (71661)NorwayG. Løvhøiden (73176)Belgium\tG. Wilquet (74664)PolandM. Witek (78967)Bulgaria\tPortugalP...

  19. ACCU MEETING

    CERN Multimedia

    2006-01-01

    DRAFT Agenda of the meeting to be held on Wednesday 6 September 2006 at 9:15 a.m. in Room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Report on Fellows and Associates Programme Overview of safety at CERN Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under Item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finland K....

  20. ACCU MEETING

    CERN Multimedia

    2006-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 September 2006 at 9:15 a.m. in room 60-6-002 1.     Chairman's remarks 2.     Adoption of the agenda 3.     Minutes of the previous meeting 4.     Matters arising 5.     News from the CERN Management 6.     Report on Fellows and Associates programme 7.     Overview of safety at CERN 8.     Reports from ACCU representatives on other committees 9.     Users' Office news 10.  Any Other Business 11.  Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets):Austria W. Adam  (71661) Belgium G. Wilquet (74664) Bulgaria ...

  1. ACCU Meeting

    CERN Multimedia

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 7 March 2007 at 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Car-sharing pilot project Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 9 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finland K. Lassila-Perini (79354) France F. Kunne S. ...

  2. ACCU Meeting

    CERN Multimedia

    2006-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 December 2006 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Safety at CERN Car sharing pilot project CERN Public Web Sites and Intranet Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria   Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finl...

  3. ACCU Meeting

    CERN Multimedia

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 7 March 2007 at 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Car-sharing pilot project Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 9 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finland K. Lassila-Perini (79354) France F. Kunne S. La...

  4. ACCU MEETING

    CERN Multimedia

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 13 June 2007 at 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks 6.\tDosimetry at CERN 2.\tAdoption of the agenda 7.\tStatus of collaborative tools at CERN 3.\tMinutes of the previous meeting 8.\tReports from ACCU representatives on other committees 4.\tMatters arising 9.\tUsers’ Office newss 5.\tNews from the CERN Management 10.\tAny Other Business 11.\tAgenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Norway G. Løvhøiden (73176) Belgium G. Wilquet (74664) Poland M. Witek (78967) Bulgaria Portugal...

  5. ACCU MEETING

    CERN Multimedia

    2006-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 6 December 2006 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Safety at CERN Car sharing pilot project CERN Public Web Sites and Intranet Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria   Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finl...

  6. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 13 June 2007 at 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Dosimetry at CERN Status of collaborative tools at CERN Reports from ACCU representatives on other committees Users' Office newss Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) Denmark J.B. Hansen (75941) Finland K. Lassila-Perini (7935...

  7. ACCU meeting

    CERN Multimedia

    2007-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 5 December 2007 At 9:15 a.m. in room 60-6-002 1.\tChairman’s remarks 2.\tAdoption of the agenda 3.\tMinutes of the previous meeting 4.\tMatters arising 5.\tNews from the CERN Management 6.\tLHC 2008 start-up events 7.\tEmergency Services at CERN 8.\tThe Meyrin Tram project 9.\tReports from ACCU representatives on other committees 10.\tUsers’ Office news 11.\tElection of ACCU Chair 12.\tAny Other Business 13.\tAgenda for the next meeting Anyone wishing to raise any points under item 12 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilq...

  8. ACCU MEETING

    CERN Multimedia

    PH Department

    2011-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 7 September 2011 at 9:15 a.m. in room 60-6-002   Chairperson's remarks Adoption of the agenda      Minutes of the previous meeting Matters arising       News from the CERN Management Report on services from GS department Report on new CHIS rules Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 9 is invited to send them to the Chairperson in writing or by e-mail to Michael.Hauschild@cern.ch Michael Hauschild (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria M. Jeitler (76307) Belgium C. Vander Velde (Chairperson)...

  9. ACCU MEETING

    CERN Multimedia

    Chris Onions

    2002-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 11 September 2002 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Health Insurance Questionnaire Host States Relations Service Update on EP Space management Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria R. Tzenov (77958) Czech Republic P. Závada (75877) Denmark A. Waananen (75941) Finland E. Tuominen (71534) France F. Bauer (71247) L. Serin (...

  10. ACCU Meeting

    CERN Document Server

    Chris Onions

    2006-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 14 June 2006 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Car sharing pilot project The CERN Document Server : the portal to Open Access Videoconferencing and collaborative tools at CERN Reports from ACCU representatives on other committees Users'Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (75877) ...

  11. ACCU Meeting

    CERN Multimedia

    Chris Onions

    2006-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 14 June 2006 At 9:15 a.m. in room 60-6-002 Chairman's remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Car sharing pilot project The CERN Document Server : the portal to Open Access Videoconferencing and collaborative tools at CERN Reports from ACCU representatives on other committees Users' Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium G. Wilquet (74664) Bulgaria Czech Republic P. Závada (7...

  12. ACCU MEETING

    CERN Multimedia

    PH Department

    2010-01-01

    DRAFT Agenda for the meeting to be held on Wednesday 10 March 2010 At 9:15 a.m. in room 60-6-002 Chairperson’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Report on services from GS department An update on Safety at CERN Reports from ACCU representatives on other committees Users’ Office news Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 10 is invited to send them to the Chairman in writing or by e-mail to Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives on ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel (76592) Belgium C. Vander Velde (Chairperson) (71539) Bulgaria Czech Republic S. Nemecek (71144) ...

  13. ACCU Meeting

    CERN Multimedia

    Chris Onions

    DRAFT Agenda for the meeting to be held on Wednesday 9 December 2009 At 9:15 a.m. in Room 60-6-002 Chairman’s remarks Adoption of the agenda Minutes of the previous meeting Matters arising News from the CERN Management Restaurant No. 1 extension An update on Safety at CERN Reports from ACCU representatives on other committees Users’ Office news Election of the ACCU Chair Any Other Business Agenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria G. Walzel (76592) Belgium C. Vander Velde (71539) Bulgaria Czech Republic P. Záv...

  14. Optimal Use of Raltegravir (Isentress® in the Treatment of HIV-Infected Adults – Canadian Consensus Guidelines

    Directory of Open Access Journals (Sweden)

    Anita Rachlis

    2009-01-01

    Full Text Available BACKGROUND AND OBJECTIVES: A meeting of a Canadian group with significant experience and knowledge in HIV management, consisting of five physicians, a pharmacist and an AIDS researcher, was convened. Their goal was to develop guidance for Canadian HIV-treating physicians on the appropriate use of raltegravir (MK-0518, Isentress®, Merck Frosst Canada Inc in HIV-infected adults.

  15. HIV DNA Integration

    Science.gov (United States)

    Craigie, Robert; Bushman, Frederic D.

    2012-01-01

    Retroviruses are distinguished from other viruses by two characteristic steps in the viral replication cycle. The first is reverse transcription, which results in the production of a double-stranded DNA copy of the viral RNA genome, and the second is integration, which results in covalent attachment of the DNA copy to host cell DNA. The initial catalytic steps of the integration reaction are performed by the virus-encoded integrase (IN) protein. The chemistry of the IN-mediated DNA breaking and joining steps is well worked out, and structures of IN-DNA complexes have now clarified how the overall complex assembles. Methods developed during these studies were adapted for identification of IN inhibitors, which received FDA approval for use in patients in 2007. At the chromosomal level, HIV integration is strongly favored in active transcription units, which may promote efficient viral gene expression after integration. HIV IN binds to the cellular factor LEDGF/p75, which promotes efficient infection and tethers IN to favored target sites. The HIV integration machinery must also interact with many additional host factors during infection, including nuclear trafficking and pore proteins during nuclear entry, histones during initial target capture, and DNA repair proteins during completion of the DNA joining steps. Models for some of the molecular mechanisms involved have been proposed, but important details remain to be clarified. PMID:22762018

  16. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  17. Subtype Classification of Iranian HIV-1 Sequences Registered in the HIV Databases, 2006-2013

    Science.gov (United States)

    Baesi, Kazem; Moallemi, Samaneh; Farrokhi, Molood; Alinaghi, Seyed Ahmad Seyed; Truong, Hong–Ha M.

    2014-01-01

    Background The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. Methods All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods. Results A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. Conclusions Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies. PMID:25188443

  18. Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013.

    Directory of Open Access Journals (Sweden)

    Kazem Baesi

    Full Text Available BACKGROUND: The rate of human immunodeficiency virus type 1 (HIV-1 infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. METHODS: All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ and Maximum Parsimony methods. RESULTS: A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. CONCLUSIONS: Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. About HIV/AIDS. ( https://www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 – ... HIV and to help us Send the Message . Get the Facts What are HIV and AIDS? HIV ( ...

  1. Disseminated tuberculosis in an HIV-infected child: rifampicin resistance detected by GeneXpert in a lymph node aspirate but not in cerebrospinal fluid.

    Science.gov (United States)

    Gamell, Anna; Ntamatungiro, Alex John; Battegay, Manuel; Letang, Emilio

    2015-08-03

    A 9-year-old HIV-infected child previously treated with inadequate doses of antitubercular drugs based on weight was admitted 5 months after initial tuberculosis (TB) diagnosis with acute hemiplegia and inguinal lymphadenopathies in a rural hospital in Tanzania. He was diagnosed with TB meningitis and lymphadenitis using Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay. Rifampicin resistance was detected in the lymph node aspirate but not in the cerebrospinal fluid. His TB therapy was optimised based on available medications and antiretroviral treatment was initiated 6 weeks later. Despite these efforts, the clinical evolution was poor and the child died 12 weeks after admission. 2015 BMJ Publishing Group Ltd.

  2. 78 FR 64221 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment; Notice of...

    Science.gov (United States)

    2013-10-28

    ... Hepatitis and STD Prevention and Treatment; Notice of Meeting In accordance with section l0(a)(2) of the... meeting. Name: CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment Dates... related to prevention and control of HIV/AIDS, Viral Hepatitis and other STDs, the support of health care...

  3. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  4. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.

    Science.gov (United States)

    Yoder, Alyson C; Guo, Kejun; Dillon, Stephanie M; Phang, Tzu; Lee, Eric J; Harper, Michael S; Helm, Karen; Kappes, John C; Ochsenbauer, Christina; McCarter, Martin D; Wilson, Cara C; Santiago, Mario L

    2017-02-01

    Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF) HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a molecular blueprint

  5. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria

    Science.gov (United States)

    Dillon, Stephanie M.; Phang, Tzu; Lee, Eric J.; Helm, Karen; Kappes, John C.; McCarter, Martin D.

    2017-01-01

    Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF) HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a molecular blueprint

  6. Public meetings

    CERN Multimedia

    Staff Association

    2014-01-01

      MARS 2015 FIVE YEARLY REVIEW CONTRACT POLICY PENSION FUND GENERAL INFORMATION   COME AND BE INFORMED! PUBLIC MEETINGS Friday 3rd October at 10 am Amphi BE, 864-1-D02 Prévessin Friday 3rd October at 2 pm Salle du Conseil / Council Chamber, 503-1-001 (in English) Meyrin Monday 6th October at 10 am Kjell Johnsen Auditorium, 30-7-018 Meyrin Monday 6th October at 2 pm Salle du Conseil / Council Chamber, 503-1-001 Meyrin  

  7. Staff meeting

    CERN Multimedia

    2007-01-01

    Dear Colleagues, 2007 is a very special year for CERN. I would like to review the status of our activities with you, and I invite you to a presentation on Wednesday 27 June 2007 at 3:00 p.m. Main Auditorium (bldg. 500) Closed-circuit transmission of the meeting will be available in the Council Chamber and in the AB Auditorium (Meyrin), the AB Auditorium (Prévessin), the IT Auditorium (bldg. 31) and the AT Auditorium (bldg. 30). Simultaneous translation into English will be available in the Main Auditorium. Robert AYMAR

  8. HIV-1

    African Journals Online (AJOL)

    the two major issues of stopping the AIDS epidemic and reducing poverty are addressed. Nevertheless ... affected by the same HIV epidemic as the general adult population. The resulting high absentee rates due to .... Streptococcus pneumoniae and non~typhoidal Salmonella. In the case of a Herxheimer-type reaction, ...

  9. HIV-1

    African Journals Online (AJOL)

    Leaders of the world's most powerful countries recently agreed at the G8 Summit (July 22-23, 2000) to ..... way to reduce these early deaths by reducing this toxic reaction.22 Prospective controlled trials in the .... strong leadership, they need to acknowledge the link between tuberculosis and HIV, and they need to show a ...

  10. Panel discussion on vaccine development to meet U.S. and international needs. Strategies for reducing the disincentives to HIV vaccine development: description of a successful public-private sector international collaboration.

    Science.gov (United States)

    Bronnenkant, L

    1994-01-01

    A representative of Finishing Enterprises, the world's largest manufacturer of intrauterine contraceptive devices (IUDs), discusses how to alter the balance of incentives-disincentives to expedite the development of HIV vaccines for international evaluation. Three main disincentives exist for private manufacturers in the United States to develop a new HIV vaccine to be used in developing countries, outside the profitable North American and western European markets: 1) low profit margin because of limited money, time, and resources. Medium and large-sized corporations are more concerned with a high return on their investment owing to stockholder pressure than with the human benefit of that investment. 2) Lengthy regulatory approval process. The current regulatory process in the US is tedious, time-consuming, and costly. 3) Liability risk. The United States is the most litigious society in the world. Suits filed against US corporations involved in drug manufacture incur legal defence costs, which make an already low profit margin HIV vaccine even lower. Finishing Enterprises' IUD program aimed at providing the safest and most effective IUD at an affordable price in a socially responsible way. The Population Council developed the Copper T and retained the patent rights. They and other international health authorities, such as the World Health Organization, conducted or monitored international clinical trials to determine safety and efficacy. Private foundations and public donor agencies funded these activities. When donor agencies committed to volume purchases for their commodity programs, Finishing Enterprises could commit to volume pricing. Whenever high-margin private sector sales occur, Population Council receives a royalty payment. Thus, the disincentives were overcome: 1) Low profit margin was less an issue for a small, private company created specifically to manufacture IUDs and guaranteed volume orders. 2) Lengthy regulatory approval processes were avoided by

  11. Get Tested for HIV

    Science.gov (United States)

    ... AIDS from other websites National Women and Girls HIV/AIDS Awareness Day Blog topics HIV and AIDS Breaking Down ... t Miss a Beat National Women and Girls HIV/AIDS Awareness Day National Women's Health Week Supporting Nursing Moms ...

  12. Asymptomatic HIV infection

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000682.htm Asymptomatic HIV infection To use the sharing features on this page, please enable JavaScript. Asymptomatic HIV infection is a phase of HIV/AIDS during which ...

  13. Generation of an HIV-1-Resistant Immune System with CD34+ Hematopoietic Stem Cells Transduced with a Triple-Combination Anti-HIV Lentiviral Vector

    OpenAIRE

    Walker, Jon E.; Chen, Rachel X.; McGee, Jeannine; Nacey, Catherine; Pollard, Richard B; Abedi, Mehrdad; Bauer, Gerhard; Nolta, Jan A; Anderson, Joseph S.

    2012-01-01

    HIV gene therapy has the potential to offer an alternative to the use of current small-molecule antiretroviral drugs as a treatment strategy for HIV-infected individuals. Therapies designed to administer HIV-resistant stem cells to an infected patient may also provide a functional cure, as observed in a bone marrow transplant performed with hematopoietic stem cells (HSCs) homozygous for the CCR5-Δ32-bp allele. In our current studies, preclinical evaluation of a combination anti-HIV lentiviral...

  14. ACCU MEETING

    CERN Multimedia

    PH Department

    2008-01-01

    DRAFT Agenda for the meetingto be held on Wednesday 3 December 2008 at 9:15 a.m.in Room 60-6-002 1.\tChairman’s remarks 2.\tAdoption of the agenda 3.\tMinutes of the previous meeting 4.\tMatters arising 5.\tNews from the CERN Management 6.\tReport from the new Director-General 7.\tReport on the Fellows and Associates programme 8.\tAn update on Safety at CERN 9.\tReports from ACCU representatives on other committees 10.\tUsers’ Office news 11.\tAny Other Business 12.\tAgenda for the next meeting Anyone wishing to raise any points under item 11 is invited to send them to the Chairman in writing or by e-mail to Christopher.Onions@cern.ch Chris Onions (Secretary) ACCU is the forum for discussion between the CERN Management and the representatives of CERN Users to review the practical means taken by CERN for the work of Users of the Laboratory. The User Representatives to ACCU are (CERN internal telephone numbers in brackets): Austria W. Adam (71661) Belgium C. Va...

  15. Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice.

    Directory of Open Access Journals (Sweden)

    Guangming Li

    2014-07-01

    Full Text Available The role of plasmacytoid dendritic cells (pDC in human immunodeficiency virus type 1 (HIV-1 infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment.

  16. The use of mobile phone apps by Australian gay and bisexual men to meet sex partners : an analysis of sex-seeking repertoires and risks for HIV and STIs using behavioural surveillance data

    NARCIS (Netherlands)

    Hull, Peter; Mao, Limin; Prestage, Garrett; Zablotska, Iryna; de Wit, John; Holt, Martin

    2016-01-01

    BACKGROUND: Mobile phone apps are now the most popular method that Australian gay men use to find sex partners. Partner-seeking mobile phone apps use location functions to identify like-minded men and display their proximity. This study examines whether meeting partners via mobile apps is associated

  17. Making meetings work

    OpenAIRE

    Ochs, M.A.; Van Solingen, R.

    2004-01-01

    Every one of us has spent many hours, days, maybe even years in meetings. We all have experienced good meetings and bad meetings. Do software engineers spend large portions of their time in meetings? What factors make such meetings successful? This article presents the results of an industrial measurement study conducted to determine why some meetings are successful while other are not.

  18. Sero- and Molecular Epidemiology of HIV-1 in Papua Province, Indonesia

    Directory of Open Access Journals (Sweden)

    Muhammad Qushai Yunifiar M

    2017-11-01

    Full Text Available Background: human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS cause serious health problems and affect the Indonesian economy. Papua province has the highest prevalence of HIV infection in the country; however, epidemiological data are limited. Therefore, in order to reveal the current situation of HIV/AIDS in Papua province, sero- and molecular epidemiological studies of HIV were conducted. Methods: serological tests were conducted on 157 healthy individuals from the general population residing in Paniai, Papua. In addition, a molecular epidemiological study was then conducted on HIV type 1 (HIV-1 genes derived from infected individuals. Peripheral blood samples from HIV-1-positive individuals and 15 additionally enrolled, previously confirmed HIV-1-positive individuals were subjected to a genotypic analysis. Results: serological tests revealed that 2 out of 157 (1.27% healthy individuals were HIV-positive. In addition, HIV-1 subtyping revealed that subtype B and CRF01_AE were the major subtype and circulating recombinant form (CRF of HIV-1 prevalent in the region, while subtype A1 and a recombinant form including viral gene fragments of CRF01_AE and subtype B was also detected. In addition, HIV drug resistance-associated major mutations were detected in the reverse transcriptase gene derived from infected individual on antiretroviral therapy. Conclusion: these results provide important information for clearer understanding on the current situation of HIV/AIDS in Papua province in Indonesia.

  19. Meeting report : fungal its workshop (october 2012)

    NARCIS (Netherlands)

    Bates, Scott T; Ahrendt, Steven; Bik, Holly M; Bruns, Thomas D; Caporaso, J Gregory; Cole, James; Dwan, Michael; Fierer, Noah; Gu, Dai; Houston, Shawn; Knight, Rob; Leff, Jon; Lewis, Christopher; Maestre, Juan P; McDonald, Daniel; Nilsson, R Henrik; Porras-Alfaro, Andrea; Robert, Vincent; Schoch, Conrad; Scott, James; Taylor, D Lee; Parfrey, Laura Wegener; Stajich, Jason E

    2013-01-01

    This report summarizes a meeting held in Boulder, CO USA (19-20 October 2012) on fungal community analyses using ultra-high-throughput sequencing of the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA (rRNA) genes. The meeting was organized as a two-day workshop, with the

  20. Meeting Venus

    Science.gov (United States)

    Sterken, Christiaan; Aspaas, Per Pippin

    2013-06-01

    On 2-3 June 2012, the University of Tromsoe hosted a conference about the cultural and scientific history of the transits of Venus. The conference took place in Tromsoe for two very specific reasons. First and foremost, the last transit of Venus of this century lent itself to be observed on the disc of the Midnight Sun in this part of Europe during the night of 5 to 6 June 2012. Second, several Venus transit expeditions in this region were central in the global enterprise of measuring the scale of the solar system in the eighteenth century. The site of the conference was the Nordnorsk Vitensenter (Science Centre of Northern Norway), which is located at the campus of the University of Tromsoe. After the conference, participants were invited to either stay in Tromsoe until the midnight of 5-6 June, or take part in a Venus transit voyage in Finnmark, during which the historical sites Vardoe, Hammerfest, and the North Cape were to be visited. The post-conference program culminated with the participants observing the transit of Venus in or near Tromsoe, Vardoe and even from a plane near Alta. These Proceedings contain a selection of the lectures delivered on 2-3 June 2012, and also a narrative description of the transit viewing from Tromsoe, Vardoe and Alta. The title of the book, Meeting Venus, refers the title of a play by the Hungarian film director, screenwriter and opera director Istvan Szabo (1938-). The autobiographical movie Meeting Venus (1991) directed by him is based on his experience directing Tannhauser at the Paris Opera in 1984. The movie brings the story of an imaginary international opera company that encounters a never ending series of difficulties and pitfalls that symbolise the challenges of any multicultural and international endeavour. As is evident from the many papers presented in this book, Meeting Venus not only contains the epic tales of the transits of the seventeenth, eighteenth and nineteenth centuries, it also covers the conference

  1. Meetings and meeting modeling in smart surroundings

    NARCIS (Netherlands)

    op den Akker, Hendrikus J.A.; Heylen, Dirk K.J.; Nijholt, Antinus; Nishida, T.

    2004-01-01

    In this paper we survey our research on smart meeting rooms and its relevance for augmented reality meeting support and virtual reality generation of meetings in real-time or off-line. Intelligent real-time and off-line generation requires understanding of what is going on during a meeting. The

  2. Meetings and Meeting Modeling in Smart Environments

    NARCIS (Netherlands)

    Nijholt, Antinus; op den Akker, Hendrikus J.A.; Heylen, Dirk K.J.

    In this paper we survey our research on smart meeting rooms and its relevance for augmented reality meeting support and virtual reality generation of meetings in real time or off-line. The research reported here forms part of the European 5th and 6th framework programme projects multi-modal meeting

  3. HIV Transmission Patterns Among The Netherlands, Suriname, and The Netherlands Antilles: A Molecular Epidemiological Study

    NARCIS (Netherlands)

    Kramer, Merlijn A.; Cornelissen, Marion; Paraskevis, Dimitrios; Prins, Maria; Coutinho, Roel A.; van Sighem, Ard I.; Sabajo, Lesley; Duits, Ashley J.; Winkel, Cai N.; Prins, Jan M.; van der Ende, Marchina E.; Kauffmann, Robert H.; Op de Coul, Eline L.

    2011-01-01

    We aimed to study patterns of HIV transmission among Suriname, The Netherlands Antilles, and The Netherlands. Fragments of env, gag, and pol genes of 55 HIV-infected Surinamese, Antillean, and Dutch heterosexuals living in The Netherlands and 72 HIV-infected heterosexuals living in Suriname and the

  4. Clinical Applications of Genome Editing to HIV Cure.

    Science.gov (United States)

    Wang, Cathy X; Cannon, Paula M

    2016-12-01

    Despite significant advances in HIV drug treatment regimens, which grant near-normal life expectancies to infected individuals who have good virological control, HIV infection itself remains incurable. In recent years, novel gene- and cell-based therapies have gained increasing attention due to their potential to provide a functional or even sterilizing cure for HIV infection with a one-shot treatment. A functional cure would keep the infection in check and prevent progression to AIDS, while a sterilizing cure would eradicate all HIV viruses from the patient. Genome editing is the most precise form of gene therapy, able to achieve permanent genetic disruption, modification, or insertion at a predesignated genetic locus. The most well-studied candidate for anti-HIV genome editing is CCR5, an essential coreceptor for the majority of HIV strains, and the lack of which confers HIV resistance in naturally occurring homozygous individuals. Genetic disruption of CCR5 to treat HIV has undergone clinical testing, with seven completed or ongoing trials in T cells and hematopoietic stem and progenitor cells, and has shown promising safety and potential efficacy profiles. Here we summarize clinical findings of CCR5 editing for HIV therapy, as well as other genome editing-based approaches under pre-clinical development. The anticipated development of more sophisticated genome editing technologies should continue to benefit HIV cure efforts.

  5. Public meetings

    CERN Multimedia

    Staff Association

    2013-01-01

    MARS SURVEY 5YR 2015 GENERAL INFORMATION ELECTIONS 2013   COME AND BE INFORMED! Public meetings Tuesday 1st Oct. 10 am Amphi IT, 31-3-004 Meyrin Tuesday 1st Oct. 2 pm Council Chamber, 503-1-001 Meyrin Friday 4 Oct. 10 am Amphi BE, 864-1-D02 Prévessin Monday 7 Oct. 2 pm Council Chamber, 503-1-001 (in English) Meyrin Tuesday 8 Oct. 10 am Amphi Kjell Johnsen, 30-7-018 Meyrin   Overview of the topics to be discussed Recognition of Merit – MARS Outcome of last exercise 2007 to 2013: lessons learned Survey: five-yearly review, give us your opinion General information CVI 2014 Voluntary programmes (PRP, SLS) Elections 2013 Renewal of the Staff Council 2014 - 2015  

  6. 76 FR 65205 - Office of the Director, National Institutes of Health; Notice of Meeting

    Science.gov (United States)

    2011-10-20

    ... and treatment of comorbidities and clinical complications among MSM. An update will be provided on the...: Opportunities and Challenges.'' The meeting will focus on: the evolving HIV/AIDS epidemic in the U.S. and internationally; HIV prevention research in MSM; behavioral research in MSM; engaging MSM in vaccine clinical...

  7. Culture, community networks, and HIV/AIDS outreach opportunities in a south Indian Siddha organization.

    Science.gov (United States)

    Baban, Kaylan; Ikeda, Scott; Pooran, Deeangelee; Hennig, Nils; Indyk, Debbie; Sacks, Henry; Carter, George

    2006-01-01

    Gandeepam is an NGO in rural south India, with an HIV prevalence rate estimated at 2-7 times the national average. Aside from several outreach programs, Gandeepam practices Siddha medicine. Evaluate Gandeepam's strengths and opportunities to promote HIV education. Three weeks of observing clinic practice, meeting patients, and discussing organizational structure. A survey of attitudes toward HIV was completed. Gandeepam reaches a broad cross-section of its community, and effectively disseminates information. No primary HIV prevention efforts were observed. Current strengths include an established network for information dissemination, and a strong community reputation. Tremendous social obstacles for disseminating effective HIV prevention messages remain.

  8. Assessment of HIV-1 entry inhibitors by MLV/HIV-1 pseudotyped vectors

    Directory of Open Access Journals (Sweden)

    Thaler Sonja

    2005-09-01

    Full Text Available Abstract Background Murine leukemia virus (MLV vector particles can be pseudotyped with a truncated variant of the human immunodeficiency virus type 1 (HIV-1 envelope protein (Env and selectively target gene transfer to human cells expressing both CD4 and an appropriate co-receptor. Vector transduction mimics the HIV-1 entry process and is therefore a safe tool to study HIV-1 entry. Results Using FLY cells, which express the MLV gag and pol genes, we generated stable producer cell lines that express the HIV-1 envelope gene and a retroviral vector genome encoding the green fluorescent protein (GFP. The BH10 or 89.6 P HIV-1 Env was expressed from a bicistronic vector which allowed the rapid selection of stable cell lines. A codon-usage-optimized synthetic env gene permitted high, Rev-independent Env expression. Vectors generated by these producer cells displayed different sensitivity to entry inhibitors. Conclusion These data illustrate that MLV/HIV-1 vectors are a valuable screening system for entry inhibitors or neutralizing antisera generated by vaccines.

  9. Pathobiology of HIV in the Human Monocyte-Macrophage

    Science.gov (United States)

    1993-12-03

    transcriptional regulation of HIV as well as characterization of functional genes. The development of antisense constructs within the adenoassociated virus vectors...13 treated (B) and (D) cells (day 5, 50 AdN ceramide) vith HIV positive serum. (A) and (B): U-l. cells, (C) and (D) : O-10.1 cells. Fig. 4

  10. molecular biology approach to the search for novel hiv proteases ...

    African Journals Online (AJOL)

    The application of recombinant DNA and polymerase chain reaction (PCR) techniques to the mapped genes would elaborate their protein products. The vulnerability of the HIV to the protein products could then be developed into potential drugs, which could be tested in the animal models of HIV infection before subjection ...

  11. Comparative transcriptome analysis of PBMC from HIV patients pre- and post-antiretroviral therapy

    DEFF Research Database (Denmark)

    Zhao, Fang-Jie; Ma, Jinmin; Huang, Lihua

    2017-01-01

    . To understand HIV interactions with host immune cells during HAART, the transcriptomes of peripheral blood mononuclear cells (PBMC) from HIV patients and HIV negative volunteers before and two weeks after HAART initiation were analyzed using RNA sequencing (RNA-Seq) technology. Differentially expressed genes......-associated hypertensions, providing new insights into HIV pathology and novel strategies for developing anti-HIV target. More importantly, we demonstrated that comparative transcriptome analysis is a very powerful tool to identify infection related DEGs using a very small number of samples. This approach could be easily...... to HIV infections in the literature, which demonstrates the credibility of the method. The newly identified HIV-related genes (up-regulated: ACSL1, GPR84, GPR97, ADM, LRG1; down-regulated: RASSF1, PATL2) were empirically validated using qRT-PCR. The Gene Set Enrichment Analysis (GSEA) was also used...

  12. In vitro separation and expansion of CD4 lymphocytes from HIV-infected individuals without activation of HIV infection

    DEFF Research Database (Denmark)

    Nielsen, S D; Nielsen, Jens Ole; Hansen, J E

    1997-01-01

    In order to offer a gene therapy-based treatment against AIDS, it is likely to be necessary to harvest and culture CD4 cells from HIV-positive patients without activating the HIV infection. We have used a magnetic cell sorting (MACS) system to enrich CD4 cells. Using positive selection, CD4 cells...

  13. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication.

    Science.gov (United States)

    Di Nunzio, Francesca; Fricke, Thomas; Miccio, Annarita; Valle-Casuso, Jose Carlos; Perez, Patricio; Souque, Philippe; Rizzi, Ermanno; Severgnini, Marco; Mavilio, Fulvio; Charneau, Pierre; Diaz-Griffero, Felipe

    2013-05-25

    The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants for the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Chemokines and chemokine receptors in susceptibility to HIV-1 infection and progression to AIDS.

    Science.gov (United States)

    Chatterjee, Animesh; Rathore, Anurag; Vidyant, Sanjukta; Kakkar, Kavita; Dhole, Tapan N

    2012-01-01

    A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals.

  15. Chemokines and Chemokine Receptors in Susceptibility to HIV-1 Infection and Progression to AIDS

    Directory of Open Access Journals (Sweden)

    Animesh Chatterjee

    2012-01-01

    Full Text Available A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals.

  16. Fruitful meeting

    CERN Multimedia

    Mike Lamont

    2010-01-01

    The annual meeting for the LHC Performance Workshop was held in Chamonix from 25 to 29 January 2010 in the Centre de Congrès Le Majestic. The Workshop focused on how to reach the maximum operating energy.   The LHC Performance Workshop took place between 25 and 29 January 2010 in a rather chilly Chamonix. Following the successful start of beam commissioning last year, there remain a number of important questions about the near future of the machine. Topics discussed included the maximum operational energy that will be possible in 2010 and the steps need to go above the planned 2010 start-up energy of 3.5 TeV. Of particular importance were the required splice and magnet consolidation measures that would be demanded by an increase above this energy.  The energy in the magnets and beams will always represent a considerable threat, and the possible impact of an incident and the potential measures required to speed up a recovery were put on the table. Safety is critical and there were...

  17. Public meeting

    CERN Multimedia

    Staff Association

    2015-01-01

    Last Monday at 9 a.m. the Council Chamber was full, with several people standing, for the public meeting of the Staff Association. Simultaneously, many of our colleagues followed the presentations in the Amphitheatre in Prévessin. We would like to thank all of you for the interest you have shown and for your feedback. In the introduction we explained how the Staff Association represents the staff in its discussions with Management and Member States, and how the staff itself defined, by its participation in the 2013 staff survey, the priority assigned to various points related to the employment conditions. The position of the Staff Association regarding the new contract policy, to be implemented as of 31 March 2015 after approval by Council, was stated. Then, in the framework of the 2015 five-yearly review, the general approach that we would like to see for the new career structure, was explained. Concerning diversity, based on what we know about the situation in other international organiza...

  18. HIV Structural Database

    Science.gov (United States)

    SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

  19. Identification of Host Micro RNAs That Differentiate HIV-1 and HIV-2 Infection Using Genome Expression Profiling Techniques

    Directory of Open Access Journals (Sweden)

    Krishnakumar Devadas

    2016-05-01

    Full Text Available While human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2 share many similar traits, major differences in pathogenesis and clinical outcomes exist between the two viruses. The differential expression of host factors like microRNAs (miRNAs in response to HIV-1 and HIV-2 infections are thought to influence the clinical outcomes presented by the two viruses. MicroRNAs are small non-coding RNA molecules which function in transcriptional and post-transcriptional regulation of gene expression. MiRNAs play a critical role in many key biological processes and could serve as putative biomarker(s for infection. Identification of miRNAs that modulate viral life cycle, disease progression, and cellular responses to infection with HIV-1 and HIV-2 could reveal important insights into viral pathogenesis and provide new tools that could serve as prognostic markers and targets for therapeutic intervention. The aim of this study was to elucidate the differential expression profiles of host miRNAs in cells infected with HIV-1 and HIV-2 in order to identify potential differences in virus-host interactions between HIV-1 and HIV-2. Differential expression of host miRNA expression profiles was analyzed using the miRNA profiling polymerase chain reaction (PCR arrays. Differentially expressed miRNAs were identified and their putative functional targets identified. The results indicate that hsa-miR 541-3p, hsa-miR 518f-3p, and hsa-miR 195-3p were consistently up-regulated only in HIV-1 infected cells. The expression of hsa-miR 1225-5p, hsa-miR 18a* and hsa-miR 335 were down modulated in HIV-1 and HIV-2 infected cells. Putative functional targets of these miRNAs include genes involved in signal transduction, metabolism, development and cell death.

  20. Highlights from the 5th Annual Meeting of the Italian Society of Virology.

    Science.gov (United States)

    Salata, Cristiano; Calistri, Arianna; Palù, Giorgio

    2006-07-01

    The 5th National Congress of the Italian Society of Virology (SIV) was attended by junior- and senior-level virologists to promote interactions and scientific collaborations among the different areas of Virology and allied sciences. The invited and selected lecturers covered the following topics: General Virology and Viral Genetics; Virus-host Interaction and Pathogenesis; Viral Oncogenesis; Viral Immunology and Vaccines; Anti-viral Therapy; Innovative Diagnostics; Viral Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata and Palù, 2004; Salata et al., 2005), a specific topic was thoroughly covered in a roundtable. This year the elected subject was "HIV: determinants of pathogenicity and clinical implications." The final program and the abstract book can be found at the web site http://www.siv-virologia.it. This report summarizes the lessons learned from the plenary lectures and the selected oral presentations of the 2005 meeting. Copyright 2006 Wiley-Liss, Inc.

  1. Social media use and HIV transmission risk behavior among ethnically diverse HIV-positive gay men: results of an online study in three U.S. states.

    Science.gov (United States)

    Hirshfield, Sabina; Grov, Christian; Parsons, Jeffrey T; Anderson, Ian; Chiasson, Mary Ann

    2015-10-01

    Though Black and Hispanic men who have sex with men (MSM) are at an increased risk for HIV, few HIV risk reduction interventions that target HIV-positive MSM, and even fewer that use technology, have been designed to target these groups. Despite similar rates of social media and technology use across racial/ethnic groups, online engagement of minority MSM for HIV prevention efforts is low. Since minority MSM tend to have less representation in online HIV prevention studies, the goals of this online anonymous study of HIV-positive gay-identified men were to test the feasibility of conducting targeted recruitment by race/ethnicity and sexual orientation, to assess technology and social media use, and to assess global HIV transmission risk. In 2011, an anonymous online survey was conducted among 463 members of an HIV-positive personals website. Emails were sent to a subset of HIV-positive male members who self-identified as gay. While 57 % were White, substantial proportions of participants were Black (20 %) or Hispanic (18 %). Median age was 46 (range 18-79). Men who reported using 3 or more websites or apps to meet sex partners were significantly more likely to report anal intercourse (AOR 4.43, p social media use, and sexual risk among a diverse sample of HIV-positive gay men. Efficacy trials of technology-based HIV prevention interventions targeting high-risk minority HIV-positive MSM are warranted.

  2. Dermatomyositis and HIV

    Directory of Open Access Journals (Sweden)

    Mamata Chand

    2016-12-01

    Full Text Available HIV has been linked to several autoimmune disorders since its emergence in the 1980s. By affecting different cells and pathways in the immune system, HIV induces the development of certain autoimmune diseases while prohibiting the emergence of others. Dermatomyositis has been rarely described in patients with HIV. We present a case of dermatomyositis in a patient with HIV and explore the pathogenesis of autoimmune disorders in HIV focusing on dermatomyositis.

  3. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    2011-06-09

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses National HIV Testing Day, an annual observance which raises awareness of the importance of knowing one's HIV status and encourages at-risk individuals to get an HIV test.  Created: 6/9/2011 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 6/9/2011.

  4. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    2012-11-26

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.  Created: 11/26/2012 by Division of HIV/AIDS Prevention.   Date Released: 11/26/2012.

  5. Side Effects of HIV Medicines: HIV and Hepatotoxicity

    Science.gov (United States)

    ... Find HIV Treatment Services HIV and Mental Health HIV and Nutrition and Food Safety Print This Fact Sheet Entire Series Related Content AIDSource | HIV Treatment: Side Effects Need Help? Call 1-800- ...

  6. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

    OpenAIRE

    Di Nunzio, Francesca; Fricke, Thomas; Miccio, Annarita; Valle-Casuso, Jose Carlos; Perez, Patricio; Souque, Philippe; Rizzi, Ermanno; Severgnini, Marco; Mavilio, Fulvio; Charneau, Pierre; Diaz-Griffero, Felipe

    2013-01-01

    The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a def...

  7. Molecular analysis of critical sequences within the EBNA-2 type 1 gene from Epstein-Barr virus isolates from patients with infectious mononucleosis, tonsillar hyperplasia, and HIV infection

    NARCIS (Netherlands)

    Al-Homsi, A. S.; Berger, C.; van Baarle, D.; Kersten, M. J.; Klein, M. R.; McQuain, C.; van Oers, R.; Knecht, H.

    1998-01-01

    EBNA-2 is the first protein to be detected after infection of primary B lymphocytes by Epstein-Barr virus (EBV) and plays an essential role as transcriptional activator in EBV-induced lymphocyte transformation. We analysed by PCR and sequencing regions of the EBNA-2 type 1 gene from isolates from 13

  8. Insertion of vaccinia virus C7L host range gene into NYVAC-B genome potentiates immune responses against HIV-1 antigens

    National Research Council Canada - National Science Library

    Nájera, José Luis; Gómez, Carmen Elena; García-Arriaza, Juan; Sorzano, Carlos Oscar; Esteban, Mariano

    2010-01-01

    ... while maintaining an attenuated phenotype in mice. In an effort to improve the immunogenicity of NYVAC, we have developed a novel poxvirus vector by inserting the VACV host-range C7L gene into the genome of NYVAC-B, a recombinant virus that expresses...

  9. HIV Transmission in a State Prison System, 1988–2005

    Science.gov (United States)

    Jafa, Krishna; McElroy, Peter; Fitzpatrick, Lisa; Borkowf, Craig B.; MacGowan, Robin; Margolis, Andrew; Robbins, Ken; Youngpairoj, Ae Saekhou; Stratford, Dale; Greenberg, Alan; Taussig, Jennifer; Shouse, R. Luke; LaMarre, Madeleine; McLellan-Lemal, Eleanor; Heneine, Walid; Sullivan, Patrick S.

    2009-01-01

    Introduction HIV prevalence among state prison inmates in the United States is more than five times higher than among nonincarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. We investigated 88 HIV seroconversions reported from 1988–2005 among male Georgia prison inmates. Methods We analyzed medical and administrative data to describe seroconverters' HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. We sequenced the gag, env, and pol genes of seroconverters' HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. We combined risk, genetic, and administrative data to describe prison HIV transmission networks. Results Forty-one (47%) seroconverters were diagnosed with HIV from July 2003–June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0–0.10) and tattooing (OR = 0.03, 95% CI: prison after their HIV diagnosis than before. Of 67 seroconverters' specimens tested, 33 (49%) fell into one of 10 genetically-related clusters; of these, 25 (76%) reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61%) of 13 antiretroviral-naïve and 21 (40%) of 52 antiretroviral-treated seroconverters were antiretroviral-resistant. Discussion Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates. PMID:19412547

  10. HIV transmission in a state prison system, 1988-2005.

    Directory of Open Access Journals (Sweden)

    Krishna Jafa

    Full Text Available INTRODUCTION: HIV prevalence among state prison inmates in the United States is more than five times higher than among nonincarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. We investigated 88 HIV seroconversions reported from 1988-2005 among male Georgia prison inmates. METHODS: We analyzed medical and administrative data to describe seroconverters' HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. We sequenced the gag, env, and pol genes of seroconverters' HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. We combined risk, genetic, and administrative data to describe prison HIV transmission networks. RESULTS: Forty-one (47% seroconverters were diagnosed with HIV from July 2003-June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0-0.10 and tattooing (OR = 0.03, 95% CI: <0.01-0.20 in prison after their HIV diagnosis than before. Of 67 seroconverters' specimens tested, 33 (49% fell into one of 10 genetically-related clusters; of these, 25 (76% reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61% of 13 antiretroviral-naïve and 21 (40% of 52 antiretroviral-treated seroconverters were antiretroviral-resistant. DISCUSSION: Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates.

  11. HIV transmission in a state prison system, 1988-2005.

    Science.gov (United States)

    Jafa, Krishna; McElroy, Peter; Fitzpatrick, Lisa; Borkowf, Craig B; Macgowan, Robin; Margolis, Andrew; Robbins, Ken; Youngpairoj, Ae Saekhou; Stratford, Dale; Greenberg, Alan; Taussig, Jennifer; Shouse, R Luke; Lamarre, Madeleine; McLellan-Lemal, Eleanor; Heneine, Walid; Sullivan, Patrick S

    2009-01-01

    HIV prevalence among state prison inmates in the United States is more than five times higher than among nonincarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. We investigated 88 HIV seroconversions reported from 1988-2005 among male Georgia prison inmates. We analyzed medical and administrative data to describe seroconverters' HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. We sequenced the gag, env, and pol genes of seroconverters' HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. We combined risk, genetic, and administrative data to describe prison HIV transmission networks. Forty-one (47%) seroconverters were diagnosed with HIV from July 2003-June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0-0.10) and tattooing (OR = 0.03, 95% CI: prison after their HIV diagnosis than before. Of 67 seroconverters' specimens tested, 33 (49%) fell into one of 10 genetically-related clusters; of these, 25 (76%) reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61%) of 13 antiretroviral-naïve and 21 (40%) of 52 antiretroviral-treated seroconverters were antiretroviral-resistant. Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates.

  12. HIV Integration Site Analysis of Cellular Models of HIV Latency with a Probe-Enriched Next-Generation Sequencing Assay.

    Science.gov (United States)

    Sunshine, Sara; Kirchner, Rory; Amr, Sami S; Mansur, Leandra; Shakhbatyan, Rimma; Kim, Michelle; Bosque, Alberto; Siliciano, Robert F; Planelles, Vicente; Hofmann, Oliver; Ho Sui, Shannan; Li, Jonathan Z

    2016-05-01

    Antiretroviral therapy (ART) is successful in the suppression of HIV but cannot target and eradicate the latent proviral reservoir. The location of retroviral integration into the human genome is thought to play a role in the clonal expansion of infected cells and HIV persistence. We developed a high-throughput targeted sequence capture assay that uses a pool of HIV-specific probes to enrich Illumina libraries prior to deep sequencing. Using an expanded clonal population of ACH-2 cells, we demonstrate that this sequence capture assay has an extremely low false-positive rate. This assay assessed four cellular models commonly used to study HIV latency and latency-reversing agents: ACH-2 cells, J-Lat cells, the Bcl-2-transduced primary CD4(+)model, and the cultured TCM(central memory) CD4(+)model. HIV integration site characteristics and genes were compared between these cellular models and to previously reported patient data sets. Across these cellular models, there were significant differences in integration site characteristics, including orientation relative to that of the host gene, the proportion of clonally expanded sites, and the proportion located within genic regions and exons. Despite a greater diversity of minority integration sites than expected in ACH-2 cells, their integration site characteristics consistently differed from those of the other models and from the patient samples. Gene ontology analysis of highly represented genes from the patient samples found little overlap with HIV-containing genes from the cell lines. These findings show that integration site differences exist among the commonly used cellular models of HIV latency and in comparison to integration sites found in patient samples. Despite the success of ART, currently there is no successful therapy to eradicate integrated proviruses. Cellular models of HIV latency are used to test the efficacy of latency-reversing agents, but it is unclear how well these models reflect HIV integration

  13. RNA Interference Therapies for an HIV-1 Functional Cure.

    Science.gov (United States)

    Scarborough, Robert J; Gatignol, Anne

    2017-12-27

    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. Here, we review RNA interference pathways in mammalian cells and the design of therapeutic small RNAs that use these pathways to target pathogenic RNA sequences. Studies that have been performed to identify anti-HIV-1 RNA interference therapeutics are also reviewed and perspectives on their use in combination gene therapy to functionally cure HIV-1 infection are provided.

  14. HIV prevention among transgender women in Latin America: implementation, gaps and challenges

    OpenAIRE

    Alfonso Silva-Santisteban; Shirley Eng; Gabriela de la Iglesia; Carlos Falistocco; Rafael Mazin

    2016-01-01

    Introduction: Transgender women are the population most vulnerable to HIV in Latin America, with prevalence between 18 and 38%. Although the region has improved antiretroviral coverage, there is an urgent need to strengthen HIV prevention for key populations to meet regional targets set by governments. We conducted an assessment on the state of HIV prevention among transgender women in Latin America. Methods: We conducted a desk review of Global AIDS Response Progress Reports, national strate...

  15. CD26/dipeptidyl peptidase IV (CD26/DPPIV is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

    Directory of Open Access Journals (Sweden)

    Meyers Adrienne FA

    2010-11-01

    Full Text Available Abstract Background Design of effective vaccines against the human immunodeficiency virus (HIV-1 continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway. Results A quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV + and 100 HIV negative controls (HIV Neg showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml than the HIV Neg (910 ng/ml and HIV + (870 ng/ml, p Conclusion HIV resistant sex workers have a high expression of CD26/DPPIV in tandem with lowered immune activation markers. This may suggest a novel role for CD26/DPPIV in protection against HIV infection in vivo.

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and the disease it causes (AIDS) are often linked and referred to as "HIV/AIDS." HIV can ... HIV Related? Drug misuse and addiction have been linked with HIV/AIDS since the beginning of the ...

  17. Global HIV/AIDS Epidemic

    Science.gov (United States)

    ... Policy The Global HIV/AIDS Epidemic The Global HIV/AIDS Epidemic Published: Nov 29, 2017 Facebook Twitter ... 2001-FY 2018 Request The Global Response to HIV/AIDS International efforts to combat HIV began in ...

  18. HIV / AIDS: An Unequal Burden

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 ... high-risk category, emphasizes Dr. Cargill. Photo: iStock HIV and Pregnancy Are there ways to help HIV- ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the ...

  20. HIV/AIDS in Women

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV often ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 – ... and to help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human ...

  2. A framework for HIV/AIDS vaccine research in Zimbabwe | Gomo ...

    African Journals Online (AJOL)

    A framework for HIV/AIDS vaccine research in Zimbabwe. ... In recognition of this need, African scientists convened a consultative meeting in Kenya under the auspices of the Joint United Nations Programme on AIDS (UNAIDS) to discuss strategies to accelerate the development of HIV vaccines in Africa. This paper ...

  3. Assessment of laboratory test utilization for HIV/AIDS care in urban ...

    African Journals Online (AJOL)

    tools in HIV care. Laboratory processing failures and turnaround times are unacceptably high for viral load analysis. Alternative strategies need to be considered in order to meet laboratory monitoring needs. Introduction. With increasing access to antiretroviral therapy for HIV- infected individuals in resource-limited settings, ...

  4. In vitro separation and expansion of CD4 lymphocytes from HIV-infected individuals without activation of HIV infection

    DEFF Research Database (Denmark)

    Nielsen, S D; Nielsen, Jens Ole; Hansen, J E

    1997-01-01

    In order to offer a gene therapy-based treatment against AIDS, it is likely to be necessary to harvest and culture CD4 cells from HIV-positive patients without activating the HIV infection. We have used a magnetic cell sorting (MACS) system to enrich CD4 cells. Using positive selection, CD4 cells...... expression and no loss of polyclonality. Only in two of six cultures were we able to detect HIV-antigen production, and using an LTR-PCR and an RT assay, we did not find activation of the HIV infection during the culture period. Thus, the method described separates and expands CD4 cells from HIV......-positive patients without activation of the HIV infection....

  5. Altering cell death pathways as an approach to cure HIV infection.

    Science.gov (United States)

    Badley, A D; Sainski, A; Wightman, F; Lewin, S R

    2013-07-11

    Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-specific immunity, reducing inflammation and activation of latency have all been the subject of recent excellent reviews. We now propose an additional avenue of research towards a cure for HIV: targeting HIV apoptosis regulatory pathways. The central enigma of HIV disease is that HIV infection kills most of the CD4 T cells that it infects, but those cells that are spared subsequently become a latent reservoir for HIV against which current medications are ineffective. We propose that if strategies could be devised which would favor the death of all cells which HIV infects, or if all latently infected cells that release HIV would succumb to viral-induced cytotoxicity, then these approaches combined with effective ART to prevent spreading infection, would together result in a cure for HIV. This premise is supported by observations in other viral systems where the relationship between productive infection, apoptosis resistance, and the development of latency or persistence has been established. Therefore we propose that research focused at understanding the mechanisms by which HIV induces apoptosis of infected cells, and ways that some cells escape the pro-apoptotic effects of productive HIV infection are critical to devising novel and rational approaches to cure HIV infection.

  6. Action without frontiers. SADC meeting.

    Science.gov (United States)

    Klouda, T

    1997-02-01

    The factors which affect AIDS and the transmission of HIV transcend national, racial, cultural, religious, political, and programmatic boundaries. The European Union and the Southern African Development Community (SADC) jointly held a conference in Lilongwe, Malawi, during December 4-6 to bring together senior officials from a wide range of development sectors in the 12 countries of the SADC region to examine the potential for regional, comprehensive action on relevant issues. Conference outcomes will be reviewed and agreed upon at a future regional ministerial meeting. Origins of the conference, innovative aspects of the conference, and regional and sectoral involvement are discussed. Employment, mining, medical drugs, education, and tourism were discussed extensively at the conference as separate sectors.

  7. Silencing of HIV-1 with RNA interference: a multiple shRNA approach

    NARCIS (Netherlands)

    ter Brake, Olivier; Konstantinova, Pavlina; Ceylan, Mustafa; Berkhout, Ben

    2006-01-01

    Double-stranded RNA can induce gene silencing via a process known as RNA interference (RNAi). Previously, we have shown that stable expression of a single shRNA targeting the HIV-1 Nef gene strongly inhibits HIV-1 replication. However, this was not sufficient to maintain inhibition. One of the

  8. HIV multidisciplinary teams work: support services improve access to and retention in HIV primary care.

    Science.gov (United States)

    Sherer, R; Stieglitz, K; Narra, J; Jasek, J; Green, L; Moore, B; Shott, S; Cohen, M

    2002-08-01

    The multidisciplinary team model of HIV care evolved out of necessity due to the diverse characteristics and needs of people living with HIV disease. Though it is now accepted as the international standard of care, it represents a significant departure from methods of care for other infectious diseases, and debate continues regarding the effectiveness of its interventions. The debate has been largely uninformed by data; for example, little is known about the relationship between ancillary support services and primary care outcomes. We hypothesized that support services increase access to and retention in HIV primary care in an inner city public hospital clinic. We conducted a retrospective analysis of clinical data sets on 2,647 patients at the CORE Center, Chicago from 1997-1998 to investigate the relationship between four support services-case management (CM), transportation (TRANS), mental health (MH) and chemical dependency (CD)-and access to and retention in HIV primary care. We found that patients who received each of these services were significantly more likely to receive any care, regular care and had more visits than patients with no service, and retention increased by 15-18%. Female gender, younger age, self-pay status and IDU predicted less regular care. Need for all services was substantial and significantly greater in women. Outcomes improved to the greatest extent among patients who needed and received each service. We conclude that support services significantly increased access to and retention in HIV primary care. Our findings validate the multidisciplinary team model of HIV care, and suggest that health services that are tailored to the express needs of patients lead to better care and improved health outcomes. Further testing of changes in health care delivery to meet the rapidly changing needs of people living with HIV disease and respond to the constantly changing practice of HIV medicine is urgently needed to maintain and extend the advances

  9. HIV Infection and Osteoarticular Tuberculosis: Strange Bedfellows

    Directory of Open Access Journals (Sweden)

    B. Hodkinson

    2016-01-01

    Full Text Available We report the case of a 47-year-old female patient with rheumatoid arthritis and HIV infection presenting with a 3-week history of a painful swollen knee, increased serum inflammatory markers, and a low CD4 lymphocyte count. The diagnosis of TB arthritis was made by synovial fluid culture, GeneXpert/PCR, and confirmed by histopathology of a synovial biopsy. A mini literature review suggests that although HIV infection is associated with extrapulmonary TB, osteoarticular TB is a relatively unusual presentation in an HIV positive patient. The diagnostic utility of the GeneXpert test is explored. We also describe the patient’s good response to an intra-articular corticosteroid injection in combination with standard anti-TB therapy.

  10. FDA-Approved HIV Medicines

    Science.gov (United States)

    ... Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets FDA-Approved HIV Medicines Search Search ... This Fact Sheet Entire Series Related Content AIDSource | Treatment: Medication FDA Approval of ... | HIV/AIDS Medicines Drugs That Fight HIV-1 HIV and ...

  11. Enhancing HIV Treatment Access and Outcomes Amongst HIV Infected Children and Adolescents in Resource Limited Settings.

    Science.gov (United States)

    Goga, Ameena Ebrahim; Singh, Yagespari; Singh, Michelle; Noveve, Nobuntu; Magasana, Vuyolwethu; Ramraj, Trisha; Abdullah, Fareed; Coovadia, Ashraf H; Bhardwaj, Sanjana; Sherman, Gayle G

    2017-01-01

    Introduction Increasing access to HIV-related care and treatment for children aged 0-18 years in resource-limited settings is an urgent global priority. In 2011-2012 the percentage increase in children accessing antiretroviral therapy was approximately half that of adults (11 vs. 21 %). We propose a model for increasing access to, and retention in, paediatric HIV care and treatment in resource-limited settings. Methods Following a rapid appraisal of recent literature seven main challenges in paediatric HIV-related care and treatment were identified: (1) lack of regular, integrated, ongoing HIV-related diagnosis; (2) weak facility-based systems for tracking and retention in care; (3) interrupted availability of dried blood spot cards (expiration/stock outs); (4) poor quality control of rapid HIV testing; (5) supply-related gaps at health facility-laboratory interface; (6) poor uptake of HIV testing, possibly relating to a fatalistic belief about HIV infection; (7) community-associated reasons e.g. non-disclosure and weak systems for social support, resulting in poor retention in care. Results To increase sustained access to paediatric HIV-related care and treatment, regular updating of Policies, review of inter-sectoral Plans (at facility and community levels) and evaluation of Programme implementation and impact (at national, subnational, facility and community levels) are non-negotiable critical elements. Additionally we recommend the intensified implementation of seven main interventions: (1) update or refresher messaging for health care staff and simple messaging for key staff at early childhood development centres and schools; (2) contact tracing, disclosure and retention monitoring; (3) paying particular attention to infant dried blood spot (DBS) stock control; (4) regular quality assurance of rapid HIV testing procedures; (5) workshops/meetings/dialogues between health facilities and laboratories to resolve transport-related gaps and to facilitate return of

  12. False-negative post-18-month confirmatory HIV tests in HIV DNA PCR-positive children: a retrospective analysis.

    Science.gov (United States)

    Garcia-Prats, Anthony J; Draper, Heather R; Sanders, Jill E; Agrawal, Anurag K; Mohapi, Edith Q; Schutze, Gordon E

    2012-09-24

    The WHO guidelines for children less than 18 months old diagnosed with HIV based on presumptive clinical diagnosis or one virologic test recommend confirmatory HIV antibody testing after 18 months of age. This study describes post-18-month HIV test results following this WHO-recommended confirmatory testing strategy. Case series and retrospective review of routine program data. Children enrolled at the Baylor Children's Clinical Center of Excellence, a pediatric and family HIV clinic in Maseru, Lesotho from December 2005 through January 2009 with a positive HIV DNA PCR at less than 18 months of age and HIV rapid test results after 18 months of age were included. Post-18-month confirmatory HIV test results are described. Factors associated with non-positive confirmatory rapid tests were determined using binary logistic regression. Of the 109 children meeting inclusion criteria, 22 (20.2%) had negative and 27 (24.8%) discordant confirmatory rapid tests. Forty-six of these 49 were on antiretroviral therapy (ART). Among these 49, 11 of 24 post-18-month HIV DNA PCRs were negative, whereas nine of 10 post-18-month HIV ELISAs were positive; 29 were definitively and 17 probably HIV-infected, two were uninfected, and one had undetermined status. Only age less than 9 months at ART initiation (odds ratio 4.25, P = 0.002) was associated with non-positive rapid tests. False-negative post-18-month confirmatory rapid tests and HIV DNA PCRs in children on ART are common, associated with early ART initiation, and may lead to inappropriate ART discontinuation and discharge from care of truly HIV-infected children.

  13. HIV-associated neurocognitive disorders

    Directory of Open Access Journals (Sweden)

    Zahir Vally

    2011-12-01

    Full Text Available HIV infection is associated with disturbances in brain function referred to as HIV-associated neurocognitive disorders (HAND. This literature review outlines the recently revised diagnostic criteria for the range of HAND from the earliest to the more advanced stages: (i asymptomatic neurocognitive impairment; (ii mild neurocognitive disorder; and (iii HIV-associated dementia. Relevant literature is also reviewed regarding the differential impact upon component cognitive domains known to be affected in HAND, which in turn should ideally be targeted during clinical and neuropsychological assessments: psychomotor and information processing speed, learning and memory, attention and working memory, speech and language, executive functioning and visuospatial functioning. A discussion outlining the neuropsychological tools used in the diagnostic screening of HAND is also included. The central mechanisms of HAND appear to revolve primarily around psychomotor slowing and cognitive control over mental operations, possibly reflecting the influence of disrupted fronto-striatal circuits on distributed neural networks critical to cognitive functions. The accurate assessment and diagnosis of HAND depends on meeting the need for statistically sound neuropsychological assessment techniques that may be used confidently in assessing South African populations, as well as the development of relevant norms for comparison of test performance data.

  14. 77 FR 58854 - Office of the Director, National Institutes of Health; Notice of Meeting

    Science.gov (United States)

    2012-09-24

    ... meeting will focus on research to address: animal and tissue models to study HIV risk and prevention in.... App.), notice is hereby given of a meeting of the Office of AIDS Research Advisory Council. The...: Office of AIDS Research Advisory Council. Date: November 8, 2012. Time: 8:30 a.m. to 5 p.m. Agenda: The...

  15. iTRAQ based investigation of plasma proteins in HIV infected and HIV/HBV coinfected patients - C9 and KLK are related to HIV/HBV coinfection.

    Science.gov (United States)

    Sun, Tao; Liu, Li; Wu, Ao; Zhang, Yujiao; Jia, Xiaofang; Yin, Lin; Lu, Hongzhou; Zhang, Lijun

    2017-10-01

    Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) share similar routes of transmission, and rapid progression of hepatic and immunodeficiency diseases has been observed in coinfected individuals. Our main objective was to investigate the molecular mechanism of HIV/HBV coinfections. We selected HIV infected and HIV/HBV coinfected patients with and without Highly Active Antiretroviral Therapy (HAART). Low abundance proteins enriched using a multiple affinity removal system (MARS) were labeled with isobaric tags for relative and absolute quantitation (iTRAQ) kits and analyzed using liquid chromatography-mass spectrometry (LC-MS). The differential proteins were analyzed by Gene Ontology (GO) database. A total of 41 differential proteins were found in HIV/HBV coinfected patients as compared to HIV mono-infected patients with or without HAART treatment, including 7 common HBV-regulated proteins. The proteins involved in complement and coagulation pathways were significantly enriched, including plasma kallikrein (KLK) and complement component C9 (C9). C9 and KLK were verified to be down-regulated in HIV/HBV coinfected patients through ELISA analysis. The present iTRAQ based proteomic analyses identified 7 proteins that are related to HIV/HBV coinfection. HBV might influence hepatic and immune functions by deregulating complement and coagulation pathways. C9 and KLK could potentially be used as targets for the treatment of HIV/HBV coinfections. Copyright © 2017. Published by Elsevier Ltd.

  16. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  17. The Oral Bacterial Communities of Children with Well-Controlled HIV Infection and without HIV Infection.

    Directory of Open Access Journals (Sweden)

    Brittany E Goldberg

    Full Text Available The oral microbial community (microbiota plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section of patients undergoing routine dental care. Multiple specimens from different sampling sites in the mouth were collected for each patient. The goal of the study was to observe the potential diversity of the oral microbiota among individual patients, sample locations, HIV status and various dental characteristics. We found that there were significant differences in the microbiome among the enrolled patients, and between sampling locations. The analysis was complicated by uneven enrollment in the patient cohorts, with only five HIV-negative patients enrolled in the study and by the rapid improvement in the health of HIV-infected children between the time the study was conceived and completed. The generally good oral health of the HIV-negative patients limited the number of dental plaque samples that could be collected. We did not identify significant differences between well-controlled HIV-positive patients and HIV-negative controls, suggesting that well-controlled HIV-positive patients essentially harbor similar oral flora compared to patients without HIV. Nor were significant differences in the oral microbiota identified between different teeth or with different dental characteristics. Additional studies are

  18. Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal ...

    African Journals Online (AJOL)

    Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients. M Held, M Laubscher, L Workman, HJ Zar, R Dunn ...

  19. Pyrosequencing of the Genital Microbiotas of HIV-Seropositive and -Seronegative Women Reveals Lactobacillus iners as the Predominant Lactobacillus Species▿

    OpenAIRE

    Spear, Gregory T.; Gilbert, Douglas; Landay, Alan L.; Zariffard, Reza; French, Audrey L.; Patel, Pranjal; Gillevet, Patrick M.

    2010-01-01

    The species of vaginal lactobacilli in HIV-seropositive and -seronegative women were determined by 16S gene pyrosequencing. Lactobacillus iners sequences were the predominant lactobacillus sequences in 66% of HIV+ women and 90% of HIV− women. This has implications for resistance of HIV+ and HIV− women to genital colonization by pathogenic organisms.

  20. Successful Parent Meetings.

    Science.gov (United States)

    Foster, Suzanne M.

    1994-01-01

    Key ingredients to successful parent meetings include planning with parents and including the children; assessing parents' needs and interests; planning the details of the meeting, such as meeting place, transportation, child care arrangements, and refreshments and activities; and planning the key elements of the meeting, such as presentations and…

  1. Seeking information about HIV/AIDS: a qualitative study of health literacy among people living with HIV/AIDS in a low prevalence context.

    Science.gov (United States)

    Zukoski, Ann P; Thorburn, Sheryl; Stroud, Josh

    2011-11-01

    People living with HIV/AIDS in rural and low HIV prevalence areas face a number of challenges including stigma, limited access to specialized medical care, lack of an HIV/AIDS specialist and fear which may interfere with their ability to find and use information to manage their health. With a large number of HIV cases located in non-metropolitan and rural areas in the US, more research is needed to better understand the health seeking behaviors of individuals living in this context. This study examined how 16 individuals living with HIV sought out information to meet their health needs. In qualitative semi-structured interviews, we explored participants' primary sources of information, types of information sought, and barriers to accessing information. The sample was comprised of people living with HIV/AIDS (PLWHA) who resided in a predominantly rural area with low HIV prevalence. The majority of participants relied on a combination of sources including their HIV/AIDS physician, the Internet, a Ryan-White caseworker and a staff member of a community-based support organization to meet their informational needs. Information sought focused primarily on drug regimens, drug side effects, or drug research. Participants shared barriers to accessing information including stigma, fear, concern about disclosure, and feelings of futility and anger. Findings point to a need to expand health literacy research and interventions to address broader social and structural barriers to health improvement for PLWHA, especially among those living in rural and low HIV prevalence areas.

  2. Cytoplasmic HIV-RNA in monocytes determines microglial activation and neuronal cell death in HIV-associated neurodegeneration.

    Science.gov (United States)

    Faissner, Simon; Ambrosius, Björn; Schanzmann, Kirsten; Grewe, Bastian; Potthoff, Anja; Münch, Jan; Sure, Ulrich; Gramberg, Thomas; Wittmann, Sabine; Brockmeyer, Norbert; Uberla, Klaus; Gold, Ralf; Grunwald, Thomas; Chan, Andrew

    2014-11-01

    Despite highly active antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) are still highly prevalent. Direct neurotoxicity of microglia activated by HIV-infected monocytes independent from viral replication may account for this observation. To investigate underlying molecular and viral determinants, human monocytoid cells (U937) transduced with HIV-particles were co-cultured with primary human microglia or astrocytes. Using genetically-engineered HIV-particles key steps of infection were examined. Levels of pro-inflammatory/neurotoxic cytokines were investigated in co-culture supernatants by flow cytometry. Neurotoxicity mediated by the supernatants was analysed using primary cortical rat neurons. To corroborate our findings, cytokine profiles in cerebrospinal fluid (CSF) of neuropsychologically asymptomatic HIV positive (HIV(+)) patients (n=45) were correlated with neurofilament H (NfH) as surrogate of neuronal/axonal degeneration. In contrast to direct exposure of HIV to microglia, only the presence of HIV-transduced monocytoid cells strongly activated human microglia as evidenced by enhanced secretion of CXCL10, CCL5, CCL2, and IL-6 (1.3-7.1-fold; pHIV-transduced monocytoid cells was limited. Using different mutant HIV-particles we show that the presence of cytoplasmic HIV-RNA in monocytoid cells is the viral determinant for this unique microglial activation pattern and subsequent neuronal cell death; reverse transcription and expression of viral genes were not essential. In CSF of presymptomatic HIV(+) patients, CXCL10, CCL5 and IL-6 were correlated with NfH as surrogate marker of neurodegeneration as well as CSF-pleocytosis. In conclusion, cytosolic viral RNA in monocytes is mandatory for subsequent microglial activation and neurotoxicity; activated astrocytes may augment neuroinflammation. In addition, neuroinflammation and neurodegeneration occur even in preclinical HIV(+) patients and are associated with cytokines regulated in vitro. Our

  3. HIV-1, human interaction database: current status and new features.

    Science.gov (United States)

    Ako-Adjei, Danso; Fu, William; Wallin, Craig; Katz, Kenneth S; Song, Guangfeng; Darji, Dakshesh; Brister, J Rodney; Ptak, Roger G; Pruitt, Kim D

    2015-01-01

    The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database', available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions, serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein-human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12,786 protein-protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14,102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set. Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. Transcriptome analysis of monocyte-HIV interactions

    Directory of Open Access Journals (Sweden)

    Tran Huyen

    2010-06-01

    Full Text Available Abstract Background During HIV infection and/or antiretroviral therapy (ART, monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions. Results Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19 for the development of the abacavir hypersensitivity reaction were suggested. Conclusions Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV. Background Both macrophages and T lymphocyte subsets express the CD4 receptor and either the CXCR4 and/or the CCR5 coreceptor which confer susceptibility to infection with the Human Immunodeficiency Virus

  5. The feasibility of incorporating Vpx into lentiviral gene therapy vectors

    Directory of Open Access Journals (Sweden)

    Samantha A McAllery

    2016-01-01

    Full Text Available While current antiretroviral therapy has significantly improved, challenges still remain in life-long targeting of HIV-1 reservoirs. Lentiviral gene therapy has the potential to deliver protective genes into the HIV-1 reservoir. However, inefficient reverse transcription (RT occurs in HIV-1 reservoirs during lentiviral gene delivery. The viral protein Vpx is capable of increasing lentiviral RT by antagonizing the restriction factor SAMHD1. Incorporating Vpx into lentiviral vectors could substantially increase gene delivery into the HIV-1 reservoir. The feasibility of this Vpx approach was tested in resting cell models utilizing macrophages and dendritic cells. Our results showed Vpx exposure led to increased permissiveness of cells over a period that exceeded 2 weeks. Consequently, significant lower potency of HIV-1 antiretrovirals inhibiting RT and integration was observed. When Vpx was incorporated with anti-HIV-1 genes inhibiting either pre-RT or post-RT stages of the viral life-cycle, transduction levels significantly increased. However, a stronger antiviral effect was only observed with constructs that inhibit pre-RT stages of the viral life cycle. In conclusion this study demonstrates a way to overcome the major delivery obstacle of gene delivery into HIV-1 reservoir cell types. Importantly, incorporating Vpx with pre-RT anti-HIV-1 genes, demonstrated the greatest protection against HIV-1 infection.

  6. The Impact of HIV Co-Infection on the Genomic Response to Sepsis

    Science.gov (United States)

    Huson, Michaëla A. M.; Scicluna, Brendon P.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Cremer, Olaf L.; Bonten, Marc J. M.; Schultz, Marcus J.; Franitza, Marek; Toliat, Mohammad R.; Nürnberg, Peter; Grobusch, Martin P.; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID:26871709

  7. The Impact of HIV Co-Infection on the Genomic Response to Sepsis.

    Science.gov (United States)

    Huson, Michaëla A M; Scicluna, Brendon P; van Vught, Lonneke A; Wiewel, Maryse A; Hoogendijk, Arie J; Cremer, Olaf L; Bonten, Marc J M; Schultz, Marcus J; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Grobusch, Martin P; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis.

  8. Mechanisms of HIV persistence in HIV reservoirs.

    Science.gov (United States)

    Mzingwane, Mayibongwe L; Tiemessen, Caroline T

    2017-03-01

    The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half-life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia. Some anatomical reservoirs that may harbor such cells include the brain and the central nervous system, the gastrointestinal tract and the gut-associated lymphoid tissue and other lymphoid organs, and the genital tract. The presence of immune cells and other HIV susceptible cells, occurring in differing compositions in anatomical reservoirs, coupled with variable and poor drug penetration that results in suboptimal drug concentrations in some sites, are all likely factors that fuel the continued low-level replication and persistent viremia during treatment. Latently, HIV-infected CD4+ T cells harboring replication-competent virus, HIV cell-to-cell spread, and HIV-infected T cell homeostatic proliferation due to chronic immune activation represent further drivers of this persistent HIV viremia during highly active antiretroviral therapy. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Transcriptomic assay of CD8+ T cells in treatment-naïve HIV, HCV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Jin Zhao

    Full Text Available BACKGROUND: Co-infection with HIV and HCV is very common. It is estimated that over 5 million people are co-infected with HIV and HCV worldwide. Accumulated evidence shows that each virus alters the course of infection of the other one. CD8+ T cells play a crucial role in the eradication of viruses and infected target cells. To the best of our knowledge, no one has investigated the gene expression profiles in HIV/HCV-co-infected individuals. METHODOLOGY: Genome-wide transcriptomes of CD8+ T cells from HIV/HCV-co-infected or mono-infected treatment-naïve individuals were analyzed by microarray assays. Pairwise comparisons were performed and differentially expressed genes were identified followed by quantitative real-time PCR (qRT-PCR validation. Directed Acyclic Graphs (DAG from Web-based Gene SeT AnaLysis Toolkit (WebGestalt and DAVID bioinformatics resources 6.7 (the Database for Annotation, Visualization, and Integrated Discovery were used to discover the Gene Ontology (GO categories with significantly enriched gene numbers. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG pathways were also obtained by using WebGestalt software. RESULTS AND CONCLUSIONS: A total of 110, 24 and 72 transcript IDs were shown to be differentially expressed (> 2-fold and p<0.05 in comparisons between HCV- and HIV-mono-infected groups, HIV/HCV-co-infected and HIV-mono-infected groups, and HIV/HCV-co-infected and HCV-mono-infected groups, respectively. In qRT-PCR assay, most of the genes showed similar expressing profiles with the observation in microarray assays. Further analysis revealed that genes involved in cell proliferation, differentiation, transcriptional regulation and cytokine responses were significantly altered. These data offer new insights into HIV/HCV co-infections, and may help to identify new markers for the management and treatment of HIV/HCV co-infections.

  10. Targeting TRIM5α in HIV Cure Strategies for the CRISPR-Cas9 Era

    Directory of Open Access Journals (Sweden)

    Daryl Anne Victoria Weatherley

    2017-11-01

    Full Text Available In the past decade, studies of innate immune activity against HIV-1 and other retroviruses have revealed a powerful array of host factors that can attack the virus at various stages of its life cycle in human and primate cells, raising the prospect that these antiviral factors could be manipulated in immunotherapeutic strategies for HIV infection. This has not proved straightforward: while HIV accessory genes encode proteins that subvert or destroy many of these restriction factors, others, such as human TRIM5α show limited potency against HIV-1. However, HIV-1 is much more susceptible to simian versions of TRIM5α: could this information be translated into the development of an effective gene therapy for HIV infection? Reigniting research into the restriction factor TRIM5α in the era of superior gene editing technology such as CRISPR-Cas9 presents an exciting opportunity to revisit this prospect.

  11. HIV: Treatment and Comorbidity

    NARCIS (Netherlands)

    C. Rokx (Casper)

    2016-01-01

    markdownabstractClinicians worldwide strive to improve HIV care for their patients. Antiretroviral therapy prevents HIV related mortality and is lifelong. A clinical evaluation of these treatment strategies is necessary to identify strategies that may jeopardize treatment effectiveness and patient

  12. HIV and Hepatitis B

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Hepatitis B Last Reviewed: July 24, 2017 ...

  13. HIV and Tuberculosis (TB)

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Tuberculosis (TB) Last Reviewed: July 26, 2017 ...

  14. HIV/AIDS Basics

    Science.gov (United States)

    ... Partner Spotlight Awareness Days Get Tested Find an HIV testing site near you. Enter ZIP code or ... AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets ...

  15. Travelers' Health: HIV Infection

    Science.gov (United States)

    ... Share Compartir Chapter 3 - Histoplasmosis Chapter 3 - Influenza HIV Infection Philip J. Peters, John T. Brooks INFECTIOUS AGENT ... skin (see Chapter 8, Health Care Workers ). EPIDEMIOLOGY HIV infection occurs worldwide. As of the end of 2014, ...

  16. HIV Resistance Testing

    Science.gov (United States)

    ... 2016 Select a Language: Fact Sheet 126 HIV Resistance Testing WHAT IS RESISTANCE? HOW DOES RESISTANCE DEVELOP? ... one or more ARVs. This is called transmitted resistance. The more that HIV multiplies, the more mutations ...

  17. Mouth Problems and HIV

    Science.gov (United States)

    ... AIDS > Mouth Problems and HIV Mouth Problems and HIV Main Content This information is for people who ... fever blisters. Sometimes Yes Prescription pill can reduce healing time and frequency of outbreaks. Click to enlarge ...

  18. Value for Money in Donor HIV Funding.

    Science.gov (United States)

    Linnemayr, Sebastian; Ryan, Gery W; Liu, Jenny; Palar, Kartika

    2012-01-01

    Countries with the highest burden of human immunodeficiency virus (HIV) disease are heavily reliant on donor funding from such sources as the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria for their HIV programs. In recent years, commitments from these organizations have flattened while demand for HIV/AIDS care continues to rise. To meet the continued need for more HIV services in developing countries, existing resources need to be better leveraged, i.e., to provide improved value for the money. This article examines options for improving value for money in HIV funding by using a case study that focuses on the two largest funders, PEPFAR and the Global Fund, with funding for antiretroviral therapy (ART) as its leading example. The authors' assessment of available input and output data suggests that current spending allocations across direct and indirect services are not based on increasing value for money. The authors recommend that expenditure data for PEPFAR be made available to the public in a transparent fashion on an annual basis in a usable format and that the Global Fund make its data accessible for each program funded. They find that program output indicators to track indirect services are incomplete and need to be further developed. The trade-off between providing current services and providing future ones needs to be stated clearly, and funding decisions made accordingly. Finally, given projections that funding for HIV will likely not increase, particularly for low-income countries facing the highest HIV burden, an explicit emphasis on improving value for money by finding ways to better leverage existing monies is imperative.

  19. Curr Opin HIV AIDS

    OpenAIRE

    Zewdie, D.; Cahn, P.; McClure, C; Bataringaya, J.

    2008-01-01

    PURPOSE OF REVIEW: There is growing recognition that greater investment in research is needed to expand our knowledge and understanding of how to scale up HIV programmes effectively and equitably in the context of weak health systems. Current debates acknowledge that there remains a gap in evidence on how HIV resources can best be managed to contribute to building health system capacity; how to integrate HIV interventions into primary healthcare systems; and how HIV scale-up is affecting othe...

  20. HIV protease inhibitor resistance

    NARCIS (Netherlands)

    Wensing, Annemarie M.J.; Fun, Axel; Nijhuis, Monique

    2017-01-01

    HIV protease is pivotal in the viral replication cycle and directs the formation of mature infectious virus particles. The development of highly specific HIV protease inhibitors (PIs), based on thorough understanding of the structure of HIV protease and its substrate, serves as a prime example of