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https://www.readbyqxmd.com/read/29683434/tandem-bispecific-broadly-neutralizing-antibody-a-novel-approach-to-hiv-1-treatment
#1
Guido Ferrari
The last decade has led to a significant advance in our knowledge of HIV-1 latency and immunity. However, we are still not close to finding a cure for HIV-1. Although combination antiretroviral therapy (cART) has led to increased survival, almost close to that of the general population, it is still not curative. In the current issue of the JCI, Wu et al. studied the prophylactic and therapeutic potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb), BiIA-SG. This bnAb's breadth and potency were highly effective in protection and treatment settings, as measured by complete viremia control following direct infusion, as well as elimination of infected cells and delay in viral rebound when delivered with a recombinant vector...
April 23, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29682308/highlights-from-the-8-th-international-workshop-on-hiv-persistence-during-therapy-12-15-december-2017-miami-fl-usa
#2
EDITORIAL
Christina K Psomas, Alain Lafeuillade, David Margolis, Karl Salzwedel, Mario Stevenson, Nicolas Chomont, Guido Poli, Jean-Pierre Routy
Over 4 days, more than 500 scientists involved in HIV persistence research shared their new unpublished data and designed future perspectives towards ART-free HIV remission. This 8th International Workshop on HIV Persistence followed the format of past conferences but further focused on encouraging participation of young investigators, especially through submission of oral and poster presentations. The topic of the workshop was HIV persistence. Consequently, issues of HIV reservoirs and HIV cure were also addressed...
April 1, 2018: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29682302/impact-of-an-educational-video-as-a-consent-tool-on-knowledge-about-cure-research-among-patients-and-caregivers-at-hiv-clinics-in-south-africa
#3
EDITORIAL
Melany Hendricks, Gonasagrie Nair, Ciara Staunton, Michael Pather, Nigel Garrett, Dianno Baadjies, Martin Kidd, Keymanthri Moodley
Background: Despite increasing access to antiretroviral therapy in low- and middle-income countries, only 54% of eligible individuals were receiving treatment in Africa by 2015. Recent developments in HIV cure research have been encouraging. However, the complex science and procedures of cure research render the informed consent process challenging. Objective: This study evaluates the impact of a video tool on educating participants about HIV cure. Methods: A questionnaire assessing the content of the video was administered to adults recruited from two clinics in South Africa...
April 1, 2018: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29682301/ethical-challenges-in-developing-an-educational-video-to-empower-potential-participants-during-consent-processes-in-hiv-cure-research-in-south-africa
#4
EDITORIAL
Ciara Staunton, Malcolm de Roubaix, Dianno Baatjies, Gill Black, Melany Hendricks, Theresa Rossouw, Keymanthri Moodley
Obtaining consent for HIV research is complex, particularly in low- and middle-income countries. Low levels of education, complexity of science and research processes, confusion about basic elements of research, and socio-economic conditions that make access to medical care difficult have collectively led to concerns about the adequacy of the consent process. Given the exponential growth of HIV prevention and treatment research in South Africa, HIV researchers are increasingly facing challenges obtaining authentic informed consent from potential participants...
April 1, 2018: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29672640/differential-impact-of-transplantation-on-peripheral-and-tissue-associated-viral-reservoirs-implications-for-hiv-gene-therapy
#5
Christopher W Peterson, Jianbin Wang, Claire Deleage, Sowmya Reddy, Jasbir Kaur, Patricia Polacino, Andreas Reik, Meei-Li Huang, Keith R Jerome, Shiu-Lok Hu, Michael C Holmes, Jacob D Estes, Hans-Peter Kiem
Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29670623/human-immune-system-mice-for-the-study-of-human-immunodeficiency-virus-type-1-infection-of-the-central-nervous-system
#6
REVIEW
Teresa H Evering, Moriya Tsuji
Immunodeficient mice transplanted with human cell populations or tissues, also known as human immune system (HIS) mice, have emerged as an important and versatile tool for the in vivo study of human immunodeficiency virus-type 1 (HIV-1) pathogenesis, treatment, and persistence in various biological compartments. Recent work in HIS mice has demonstrated their ability to recapitulate critical aspects of human immune responses to HIV-1 infection, and such studies have informed our knowledge of HIV-1 persistence and latency in the context of combination antiretroviral therapy...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669853/cd32-is-expressed-on-cells-with-transcriptionally-active-hiv-but-does-not-enrich-for-hiv-dna-in-resting-t-cells
#7
Mohamed Abdel-Mohsen, Leticia Kuri-Cervantes, Judith Grau-Exposito, Adam M Spivak, Racheal A Nell, Costin Tomescu, Surya Kumari Vadrevu, Leila B Giron, Carla Serra-Peinado, Meritxell Genescà, Josep Castellví, Guoxin Wu, Perla M Del Rio Estrada, Mauricio González-Navarro, Kenneth Lynn, Colin T King, Sai Vemula, Kara Cox, Yanmin Wan, Qingsheng Li, Karam Mounzer, Jay Kostman, Ian Frank, Mirko Paiardini, Daria Hazuda, Gustavo Reyes-Terán, Douglas Richman, Bonnie Howell, Pablo Tebas, Javier Martinez-Picado, Vicente Planelles, Maria J Buzon, Michael R Betts, Luis J Montaner
The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH 2 phenotype as defined by CXCR3, CCR4, and CCR6...
April 18, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29666702/an-evaluation-of-treatment-outcomes-in-a-cohort-of-clients-on-the-dots-strategy-2012-2016
#8
Ato Kwamena Tetteh, Edward Agyarko, Joseph Otchere, Langbong Bimi, Irene Ayi
We present, for the first time, an evaluation of treatment outcomes in a cohort at a TB referral centre in the Central Region of Ghana. Of the 213 clients placed on DOTS, 59.2% (126/213) were sputum smear-positive. An overall cure rate of 90.2% (51.6% cured + 37.6% completed) and a death rate of 8.5% (18/213) were estimated. Of the number of clients who died, 5.7% (12/213) were males ( χ 2 = 2.891, p = 0.699; LR = 3.004, p = 0.699). Deaths were only recorded among clients who were > 19 years old ( χ 2 = 40...
2018: Tuberculosis Research and Treatment
https://www.readbyqxmd.com/read/29664020/accumulation-of-follicular-cd8-t-cells-in-pathogenic-siv-infection
#9
Sara Ferrando-Martinez, Eirini Moysi, Amarendra Pegu, Sarah Andrews, Krystelle Nganou Makamdop, David Ambrozak, Adrian B McDermott, David Palesch, Mirko Paiardini, George N Pavlakis, Jason M Brenchley, Daniel Douek, John R Mascola, Constantinos Petrovas, Richard A Koup
LN follicles constitute major reservoir sites for HIV/SIV persistence. Cure strategies could benefit from the characterization of CD8+ T cells able to access and eliminate HIV-infected cells from these areas. In this study, we provide a comprehensive analysis of the phenotype, frequency, localization, and functionality of follicular CD8+ T cells (fCD8+) in SIV-infected nonhuman primates. Although disorganization of follicles was a major factor, significant accumulation of fCD8+ cells during chronic SIV infection was also observed in intact follicles, but only in pathogenic SIV infection...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29651411/-leishmania-antigenuria-to-predict-initial-treatment-failure-and-relapse-in-visceral-leishmaniasis-hiv-coinfected-patients-an-exploratory-study-nested-within-a-clinical-trial-in-ethiopia
#10
Johan van Griensven, Bewketu Mengesha, Tigist Mekonnen, Helina Fikre, Yegnasew Takele, Emebet Adem, Rezika Mohammed, Koert Ritmeijer, Florian Vogt, Wim Adriaensen, Ermias Diro
Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods: Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+)...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29649077/circulating-cxcr5-expressing-cd8-t-cells-are-major-producers-of-il-21-and-associate-with-limited-hiv-replication
#11
Federico Perdomo-Celis, Natalia A Taborda, Maria T Rugeles
BACKGROUND: Despite advances made with the highly active anti-retroviral therapy (HAART) in the control of the human immunodeficiency virus 1 (HIV) infection, a cure has not been achieved due to the persistence of viral reservoirs. The major HIV reservoirs remain in the lymphoid follicles due to, among other factors, the partial absence of CD8T-cells in these structures. Recently, lymphoid follicle-confined and circulating CD8T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms which could help to control HIV replication...
April 10, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29643243/inefficient-hiv-1-trans-infection-of-cd4-t-cells-by-macrophages-from-hiv-1-nonprogressors-is-associated-with-altered-membrane-cholesterol-and-dc-sign
#12
Diana C DeLucia, Charles R Rinaldo, Giovanna Rappocciolo
Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4+ T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643011/the-effect-of-antiretroviral-intensification-with-dolutegravir-on-residual-virus-replication-in-hiv-infected-individuals-a-randomised-placebo-controlled-double-blind-trial
#13
Thomas A Rasmussen, James H McMahon, J Judy Chang, Jennifer Audsley, Ajantha Rhodes, Surekha Tennakoon, Ashanti Dantanarayana, Tim Spelman, Tina Schmidt, Stephen J Kent, Vincent Morcilla, Sarah Palmer, Julian H Elliott, Sharon R Lewin
BACKGROUND: Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment. METHODS: In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia...
April 6, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29623213/a-case-of-oropharyngeal-ureaplasma-urealyticum-infection-in-a-human-immunodeficiency-virus-positive-bisexual-male-co-infected-with-human-papilloma-virus-and-treponema-pallidum
#14
Nazneen Arif Suri, Sujeesh Sebastian, Deepika Yadav, Neena Khanna, Benu Dhawan
Introduction: Management strategies for sexually transmitted infections (STIs) in their extragenital forms address Neisseria gonorrhoeae and Chlamydia trachomatis alone; whereas increased rates of isolation of other STI agents have been reported from various parts of the world. Their extragenital presence as a reservoir of infection emphasizes the need to screen and treat them at these sites. Case presentation: A 35-year-old human immunodeficiency virus 1 infected bisexual male presented with urethral discharge and multiple ano-genital warts...
March 2018: JMM Case Reports
https://www.readbyqxmd.com/read/29620933/dynamics-of-lymphocyte-reconstitution-following-hematopoietic-transplantation-during-chronic-lcmv-infection
#15
Mitra Bhattacharyya, Pablo Penaloza-MacMaster
Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of cured a HIV infection involved the use of this clinical procedure, highlighting the potential use of this therapy for curing many chronic diseases. However, little is known about how chronic viral infection influences lymphocyte reconstitution after bone marrow transplantation. To address this, we infected mice with chronic lymphocytic choriomeningitis virus (LCMV), and performed bone marrow transplantation to assess lymphocyte reconstitution...
March 18, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29616024/simian-immunodeficiency-virus-siv-specific-chimeric-antigen-receptor-t-cells-engineered-to-target-b-cell-follicles-and-suppress-siv-replication
#16
Kumudhini Preethi Haran, Agnes Hajduczki, Mary S Pampusch, Gwantwa Mwakalundwa, Diego A Vargas-Inchaustegui, Eva G Rakasz, Elizabeth Connick, Edward A Berger, Pamela J Skinner
There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh) located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV)-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh) cells using antiviral chimeric antigen receptor (CAR) T cells co-expressing the follicular homing chemokine receptor CXCR5...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29611626/quinoxaline-and-quinoxaline-1-4-di-n-oxides-an-emerging-class-of-antimycobacterials
#17
REVIEW
Rangappa S Keri, Sudam S Pandule, Srinivasa Budagumpi, Bhari M Nagaraja
Tuberculosis (TB) is a highly dreaded, infectious, chronic, airborne disease affecting more than two million people all around the world, with more than eight million cases every calendar year. TB is the second leading infectious cause of death after HIV/AIDS. Over the past few decades, numerous efforts have been undertaken to develop new anti-TB agents. The current frontline therapy for TB consists of administering three or more different drugs (usually isoniazid, rifampin, pyrazinamide, and ethambutol) over an extended period of time...
April 3, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29609878/a-new-class-of-antiretroviral-enabling-innate-immunity-by-protecting-apobec3-from-hiv-vif-dependent-degradation
#18
REVIEW
Ryan P Bennett, Jason D Salter, Harold C Smith
The infectivity of HIV depends on overcoming APOBEC3 (A3) innate immunity, predominantly through the expression of the viral protein Vif, which induces A3 degradation in the proteasome. Disruption of the functional interactions of Vif enables A3 mutagenesis of the HIV genome during viral replication, which can result in a broadly neutralizing antiviral effect. Vif function requires self-association along with interactions with A3 proteins, protein chaperones, and factors of the ubiquitination machinery and these are described here as a potential platform for novel antiviral drug discovery...
March 30, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29596334/tackling-hiv-persistence-pharmacological-versus-crispr-based-shock-strategies
#19
REVIEW
Gilles Darcis, Atze T Das, Ben Berkhout
Jan Svoboda studied aspects of viral latency, in particular with respect to disease induction by avian RNA tumor viruses, which were later renamed as part of the extended retrovirus family. The course of retroviral pathogenesis is intrinsically linked to their unique property of integrating the DNA copy of the retroviral genome into that of the host cell, thus forming the provirus. Retroviral latency has recently become of major clinical interest to allow a better understanding of why we can effectively block the human immunodeficiency virus type 1 (HIV-1) in infected individuals with antiviral drugs, yet never reach a cure...
March 29, 2018: Viruses
https://www.readbyqxmd.com/read/29596108/hepatocellular-carcinoma-after-sustained-virological-response-with-interferon-free-regimens-in-hiv-hcv-coinfected-patients
#20
Nicolás Merchante, Francisco Rodríguez-Arrondo, Boris Revollo, Esperanza Merino, Sofía Ibarra, María J Galindo, Marta Montero, Miguel García-Deltoro, Antonio Rivero-Juárez, Francisco Téllez, Marcial Delgado-Fernández, María J Ríos-Villegas, María A García, Francisco J Vera-Méndez, Guillermo Ojeda-Burgos, Miguel A López-Ruz, Luis Metola, Mohamed Omar, María Remedios Alemán-Valls, Koldo Aguirrebengoa, Joseba Portu, Miguel Raffo, Juan Macías, Juan A Pineda
OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/HCV-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy...
March 28, 2018: AIDS
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