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HIV functional

Frank Palella, Xiuhong Li, Samir K Gupta, Michelle M Estrella, John P Phair, Joseph B Margolick, Roger Detels, Lawrence Kingsley, Lisa P Jacobson
BACKGROUND: Factors affecting kidney function and proteinuria among HIV+ and HIV- persons need better characterization. METHODS: We evaluated estimated glomerular filtration rate (eGFR, mL/min per 1.73 m) changes, proteinuria prevalence (a urine protein-to-creatinine ratio [UPCr] of ≥0.2 at two consecutive visits) and associated factors among HIV+ and HIV- men. RESULTS: There were 917 HIV+ men receiving HAART, 159 HIV+ men not receiving HAART, and 1305 HIV- men seen from 10/2003 to 9/2014...
March 20, 2018: AIDS
Li Xu, Jia Liu, Qilong Zhang, Min Li, Jingchi Liao, Weifeng Kuang, Cansheng Zhu, Huan Yi, Fuhua Peng
Objectives Amphotericin B plus flucytosine is the most widely used induction therapy regimen for non-HIV-infected and non-transplant patients; however, the therapeutic outcomes are unsatisfactory, especially when two antifungal drugs are at sub-therapeutic doses. Methods In this study of induction therapy, all non-HIV-infected, non-transplant patients with a first episode of cryptococcal meningitis were divided into two groups. In group I, the patients received amphotericin B plus 5-flucytosine. In group II, in addition to amphotericin B and 5-flucytosine, the patients also received fluconazole...
March 21, 2018: Neurological Research
David Harrich, Hongping Jin
The HIV-1 tat gene encodes a small 86-104 amino acid protein depending on the HIV-1 strain. Tat is essential for HIV-1 replication through interactions with numerous cellular transcription factors. The interaction between Tat and P-TEFb, which is a cellular protein complex composed of cyclin T1 and CDK9, delivers P-TEFb to the newly transcribed viral mRNAs where phosphorylation of RNA polymerase II by CDK9 leads to highly efficient mRNA transcription. It has long been recognized that Tat is a potential anti-HIV-1 target and possibly a viral Achilles' heel...
March 20, 2018: Biochemical Journal
Jiehua Zhou, Daniel Lazar, Haitang Li, Xin Xia, Sangeetha Satheesan, Paige Charlins, Denis O'Mealy, Ramesh Akkina, Sheena Saayman, Marc S Weinberg, John J Rossi, Kevin V Morris
Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy. Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR)...
2018: Theranostics
Nicolas Noël, Béatrice Jacquelin, Nicolas Huot, Cécile Goujard, Olivier Lambotte, Michaela Müller-Trutwin
Human immunodeficiency virus (HIV) induces a persistent and incurable infection. However, the combined antiretroviral treatment (cART) has markedly changed the evolution of the infection and transformed a deadly disease into a manageable chronic infection. Withdrawal of cART generally leads though to resumption of the viral replication. The eradication of the virus from its cellular and anatomical reservoirs remains a goal-to-achieve for a cure. In this context, developing novel therapies contributing to this aim are an important field of research...
March 9, 2018: Cytokine & Growth Factor Reviews
Seong-Hyun Park, Kyung-Lee Yu, Yu-Mi Jung, Seong-Deok Lee, Ji Chang You
Transcription termination factor-1 (TTF-I) is an RNA polymerase 1-mediated transcription terminator and consisting of a C-terminal DNA-binding domain, central domain, and N-terminal regulatory domain. This protein binds to a so-called 'Sal box' composed of an 11-base pair motif. The interaction of TTF-I with the 'Sal box' is important for many cellular events, including efficient termination of RNA polymerase-1 activity involved in pre-rRNA synthesis and formation of a chromatin loop. To further understand the role of TTF-I in human immunodeficiency virus (HIV)-I virus production, we generated various TTF-I mutant forms...
March 20, 2018: BMB Reports
Jacob D Estes, Roger LeGrand, Constantinos Petrovas
Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens...
2018: Frontiers in Immunology
S E M van Opstal, J S van der Zwan, M N Wagener, S K Been, H S Miedema, P D D M Roelofs, E C M van Gorp
Late diagnosis of HIV remains a major challenge in the HIV epidemic. In Europe, about 50% of all people living with HIV are diagnosed late after infection has occurred. Insight into the reasons for late diagnoses is necessary to increase the number of early diagnoses and optimize treatment options. This qualitative study explored the experiences of 34 late-presenters through in-depth semi-structured interviews. A variety of reasons for late diagnoses emerged from our data and led to a division into four groups, characterized by two dimensions...
March 17, 2018: AIDS and Behavior
Beatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu
In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin...
March 14, 2018: Virology
Kelei Li, Zhe Cong, Zhuoying Peng, Ting Chen, Jing Xue, Qiang Wei
CD45 has been reported to regulate the HIV-1 gp120-induced apoptosis of Jurkat cells. Here, we demonstrate that the extracellular domain of CD45 plays an important role in this function. We observed that CD45RO-transfected cells, but not cells transfected with other CD45 isoforms, underwent significant apoptosis induced by gp120. However, a CD45RA-transfected cell line treated with an O-glycan inhibitor was able to undergo apoptosis. The role of the extracellular domain of CD45 was further confirmed using CD45 isoformtransfected cell lines by analyzing the phosphorylation of Lck, which is a direct substrate of CD45 tyrosine phosphatase, and by using an Lck inhibitor...
December 20, 2017: Biological Chemistry
Wannee Kantakamalakul, Suwalee Jangkhum, Silawun Ampol, Porurtai Burupharat, Rutt Chuachoowong, Ruengpung Sutthent, Kovit Pattanapanyasat
BACKGOUND: Intravenous drug users (IVDUs) are among the high-risk groups who are most vulnerable to HIV infection. Several illicit drugs alter host immune function with increased incidence of infections including that of HIV. Many studies of the immune response of NK cells in HIV-1 seronegative IVDUs and HIV-1 seropositive IVDUs have been published from the Western countries and yet no data is available from Thailand. OBJECTIVE: To determine natural killer cell cytotoxicity and lymphocyte subsets in Thai HIV-1 infected intravenous drug users...
March 12, 2018: Asian Pacific Journal of Allergy and Immunology
Annesa Flentje, Kord Kober, Adam Carrico, Torsten B Neilands, Elena Flowers, Nicholas Heck, Bradley Aouizerat
Sexual minority (i.e., non-heterosexual) individuals experience poorer mental and physical health, accounted for in part by the additional burden of sexual minority stress occurring from being situated in a culture favoring heteronormativity. Informed by previous research, the purpose of this study was to identify the relationship between sexual minority stress and leukocyte gene expression related to inflammation, cancer, immune function, and cardiovascular function. Sexual minority men living with HIV who were on anti-retroviral medication, had viral load <200 copies/mL, and had biologically confirmed, recent methamphetamine use completed minority stress measures and submitted blood samples for RNA sequencing on leukocytes...
March 13, 2018: Brain, Behavior, and Immunity
Cliff C Kerr, Salvador Dura-Bernal, Tomasz G Smolinski, George L Chadderdon, David P Wilson
When standard optimization methods fail to find a satisfactory solution for a parameter fitting problem, a tempting recourse is to adjust parameters manually. While tedious, this approach can be surprisingly powerful in terms of achieving optimal or near-optimal solutions. This paper outlines an optimization algorithm, Adaptive Stochastic Descent (ASD), that has been designed to replicate the essential aspects of manual parameter fitting in an automated way. Specifically, ASD uses simple principles to form probabilistic assumptions about (a) which parameters have the greatest effect on the objective function, and (b) optimal step sizes for each parameter...
2018: PloS One
Maartje Dijkstra, Rik H W Van Lunsen, Katherine W Kooij, Udi Davidovich, Rosan A Van Zoest, Ferdinand W M N Wit, Maria Prins, Peter Reiss, Maarten F Schim Van Der Loeff
INTRODUCTION: HIV-1-infected men who have sex with men (MSM) more often experience sexual dysfunctions than the general population. We assessed associations between HIV-1 status and decreased sexual functioning among MSM. METHODS: We used cross-sectional data from 399 HIV-1-infected MSM mostly on combination antiretroviral therapy (cART) and 366 HIV-1-uninfected MSM aged ≥45 years participating in the AGEhIV Cohort Study. The study questionnaire included questions on erectile function, sexual satisfaction, and sexual desire...
March 15, 2018: AIDS
Siti Azdiah Abdul Aziz, Megan Mcstea, Nor Syuhada Ahmad Bashah, Meng Li Chong, Sasheela Ponnampalavanar, Sharifah Faridah Syed Omar, Helmi Sulaiman, Iskandar Azwa, Maw Pin Tan, Adeeba Kamarulzaman, Reena Rajasuriar, Shahrul Bahyah Kamaruzzaman
OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes. DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging. METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls...
March 15, 2018: AIDS
Laura Tarancon-Diez, Rebeca S De Pablo-Bernal, José Luis Jiménez, Ana I Álvarez-Ríos, Miguel Genebat, Isaac Rosado-Sánchez, María-Ángeles Muñoz-Fernández, Ezequiel Ruiz-Mateos, Manuel Leal
OBJECTIVE: Cardiovascular diseases (CVDs) are one of the main causes of morbimortality in HIV-infected patients on suppressive antiretroviral therapy. The objective of this work was to evaluate the role of single nucleotide polymorphisms (SNPs) in lipopolysaccharide (LPS) Toll-like receptor 4 (TLR4) and CVDs occurrence in HIV-infected patients. Additionally, the functional consequences of carrying these SNPs were analyzed. METHODS: The association of TLR4 SNPs, Asp299Gly/Thr399Ile with CVDs occurrence was analyzed using multivariate logistic regression models...
March 15, 2018: AIDS
Alison G Abraham, Long Zhang, Keri Calkins, Adrienne Tin, Andrew Hoofnagle, Frank J Palella, Michelle M Estrella, Lisa P Jacobson, Mallory D Witt, Lawrence A Kingsley, Todd T Brown
OBJECTIVE: Despite effective antiretroviral therapy (HAART) and durable viral suppression, many HIV-infected individuals still do not achieve CD4+ cell count (CD4) normalization. Vitamin D has immunoregulatory functions, including inducing the development of T cells, and higher levels may improve CD4 rebound. DESIGN: Longitudinal study of men from the Multicenter AIDS Cohort Study who virally suppressed following HAART initiation and had pre- and post-HAART 25[OH]D and 1,25[OH]2D measurements and repeated measures of CD4...
March 15, 2018: AIDS
Thomas Joshua Pasvol, Caroline Foster, Sarah Fidler
PURPOSE OF REVIEW: Successful roll-out of paediatric antiretroviral therapy (ART) has led to a significant increase in survival of adolescents and young people growing up with HIV. Those on suppressive ART since childhood represent a unique group particularly well positioned to interrupt ART and achieve post-treatment control (PTC), or HIV remission. This maybe a consequence of early and sustained treatment since infancy, the small size of the HIV reservoir, the presence of a functioning thymus and a more 'flexible' immune system better able to respond to novel immune therapeutic interventions when compared with adults who acquired HIV at a time of immunological maturity and thymic involution...
March 14, 2018: Current Opinion in HIV and AIDS
Rose Nabatanzi, Stephen Cose, Moses Joloba, Sarah Rowland Jones, Damalie Nakanjako
HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery...
March 15, 2018: AIDS Research and Therapy
Ornella Sortino, Elizabeth Richards, Joana Dias, Edwin Leeansyah, Johan K Sandberg, Irini Sereti
: Chronic HIV-1 infection is associated with lower frequencies and functional impairment of mucosa-associated invariant T (MAIT) cells. We evaluated IL-7 treatment to restore MAIT cells in peripheral blood of chronically HIV-1-infected individuals on antiretroviral therapy. IL-7 led to increased relative and absolute levels of MAIT cells, and this expansion occurred primarily in the CD8 subset. These results suggest that IL-7 may represent a therapeutic intervention for the restoration of MAIT cells in chronic HIV-1 infection...
March 27, 2018: AIDS
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