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HIV Integration

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https://www.readbyqxmd.com/read/29356365/risk-network-approaches-to-locating-undiagnosed-hiv-cases-in-odessa-ukraine
#1
Pavlo Smyrnov, Leslie D Williams, Ania Korobchuk, Yana Sazonova, Georgios K Nikolopoulos, Britt Skaathun, Ethan Morgan, John Schneider, Tetyana I Vasylyeva, Samuel R Friedman
INTRODUCTION: Providing HIV healthcare and Treatment as Prevention both depend on diagnosing HIV cases, preferably soon after initial infection. We hypothesized that tracing risk networks recruits higher proportions of undiagnosed positives than outreach-based testing or respondent-driven sampling (RDS) in Odessa, Ukraine. METHODS: The Transmission Reduction Intervention Project (TRIP) used risk network tracing to recruit sexual and injection networks of recently-infected and longer-term infected (LTs) seeds (2013 to 2016)...
January 2018: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29355231/pre-exposure-prophylaxis-for-hiv-negative-persons-with-partners-living-with-hiv-uptake-use-and-effectiveness-in-an-open-label-demonstration-project-in-east-africa
#2
Renee Heffron, Kenneth Ngure, Josephine Odoyo, Nulu Bulya, Edna Tindimwebwa, Ting Hong, Lara Kidoguchi, Deborah Donnell, Nelly R Mugo, Elizabeth A Bukusi, Elly Katabira, Stephen Asiimwe, Jennifer Morton, Susan Morrison, Harald Haugen, Andrew Mujugira, Jessica E Haberer, Norma C Ware, Monique A Wyatt, Mark A Marzinke, Lisa M Frenkel, Connie Celum, Jared M Baeten
Introduction: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods: We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa...
November 6, 2017: Gates Open Res
https://www.readbyqxmd.com/read/29346759/nf-%C3%AE%C2%BAb-chromatin-interactions-drive-diverse-phenotypes-by-modulating-transcriptional-noise
#3
Victor C Wong, Victor L Bass, M Elise Bullock, Arvind K Chavali, Robin E C Lee, Walther Mothes, Suzanne Gaudet, Kathryn Miller-Jensen
Noisy gene expression generates diverse phenotypes, but little is known about mechanisms that modulate noise. Combining experiments and modeling, we studied how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the transcription factor nuclear factor κB (NF-κB) and how the HIV genomic integration site modulates noise to generate divergent (low-versus-high) phenotypes of viral activation. We show that TNF-induced transcriptional noise varies more than mean transcript number and that amplification of this noise explains low-versus-high viral activation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346184/synergistic-impact-of-training-followed-by-on-site-support-on-hiv-clinical-practice-a-mixed-design-study-in-uganda-with-pre-post-and-cluster-randomized-trial-components
#4
Sarah Burnett, Norbert Mubiru, Peace Imani, Martin K Mbonye, Leigh Fisher, Robert Colebunders, Yukari C Manabe, Marcia R Weaver
BACKGROUND: Task-shifting can expand antiretroviral therapy access, but little is known about effective approaches to improve clinical practice among mid-level practitioners' (MLP) such as clinical officers, nurses, and midwives. The Integrated Infectious Diseases Capacity-Building Evaluation compared training alone to training combined with on-site support (OSS). METHODS: Two MLP each from 36 health facilities attended the five-week Integrated Management of Infectious Disease training...
January 16, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#5
Shuang Liang, Punsisi Ratnayake, Craig Keinath, Lihui Jia, Robert Wolfe, Ahinsa Ranaweera, David P Weliky
Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29344726/the-safety-and-efficacy-of-elbasvir-and-grazoprevir-in-participants-with-hepatitis-c-virus-genotype-1b-infection
#6
Stefan Zeuzem, Lawrence Serfaty, John Vierling, Wendy Cheng, Jacob George, Jan Sperl, Simone Strasser, Hiromitsu Kumada, Peggy Hwang, Michael Robertson, Janice Wahl, Eliav Barr, Rohit Talwani, Heather Platt
BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks. METHODS: This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks...
January 17, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29343582/hiv-replication-and-latency-in-a-humanized-nsg-mouse-model-during-suppressive-oral-combinational-art
#7
Sangeetha Satheesan, Haitang Li, John C Burnett, Mayumi Takahashi, Shasha Li, Shiny Xiaqin Wu, Timothy W Synold, John J Rossi, Jiehua Zhou
Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, they cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343578/a-new-quinoline-brd4-inhibitor-targets-a-distinct-latent-hiv-1-reservoir-for-re-activation-from-other-shock-drugs
#8
Erik Abner, Mateusz Stoszko, Lei Zeng, Heng-Chang Chen, Andrea Izquierdo-Bouldstridge, Tsuyoshi Konuma, Eduard Zorita, Elisa Fanunza, Qiang Zhang, Tokameh Mahmoudi, Ming-Ming Zhou, Guillaume J Filion, Albert Jordan
Upon HIV-1 infection, a reservoir of latently infected resting T cells prevents the eradication of the virus from patients. To achieve complete depletion, the existing virus-suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. We previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol) that is able to reactivate viral transcription in several models of HIV latency including J-Lat cells through an unknown mechanism. MMQO potentiates the activity of known latency-reversing agents (LRAs) or 'shock' drugs such as PKC agonists or HDAC inhibitors...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29338752/structural-alteration-of-dna-induced-by-viral-protein-r-of-hiv-1-triggers-the-dna-damage-response
#9
Kenta Iijima, Junya Kobayashi, Yukihito Ishizaka
BACKGROUND: Viral protein R (Vpr) is an accessory protein of HIV-1, which is potentially involved in the infection of macrophages and the induction of the ataxia-telangiectasia and Rad3-related protein (ATR)-mediated DNA damage response (DDR). It was recently proposed that the SLX4 complex of structure-specific endonuclease is involved in Vpr-induced DDR, which implies that aberrant DNA structures are responsible for this phenomenon. However, the mechanism by which Vpr alters the DNA structures remains unclear...
January 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29338328/avoidance-meaning-and-grief-psychosocial-factors-influencing-engagement-in-hiv-care
#10
Georgia J Michlig, Ryan P Westergaard, Yukyan Lam, Azal Ahmadi, Gregory D Kirk, Andrew Genz, Jeanne Keruly, Heidi Hutton, Pamela J Surkan
Although the introduction of antiretroviral therapy has rendered HIV a chronic illness, inconsistent engagement in HIV care by key populations limits its public health impact. Poor engagement in care is especially prevalent among vulnerable populations with mental health and substance use disorders. Beyond structural and health system considerations, psychosocial factors may present challenges to sustained engagement. We conducted a qualitative study using in-depth interviews with 31 primarily African American, urban-based individuals, many with past or current drug use and mental disorders, living with HIV...
January 17, 2018: AIDS Care
https://www.readbyqxmd.com/read/29335920/clergy-s-beliefs-about-mental-illness-and-their-perception-of-its-treatability-experience-from-a-church-based-prevention-of-mother-to-child-hiv-transmission-pmtct-trial-in-nigeria
#11
Theddeus Iheanacho, Elina Stefanovics, Echezona E Ezeanolue
Clergy participating in the Healthy Beginning Initiative (N = 45), a program utilizing church workers to integrate packages of care into church activities, completed a 43-item self-administered questionnaire assessing their attitudes and beliefs about mental disorders and perception of their treatability. A majority believed that drug/alcohol use, stress and genetic inheritance could cause mental illness and that society needed to adopt more tolerant attitude toward people with mental disorders. Clergy with contact with people with mental disorders were more likely to perceive depression as treatable...
January 15, 2018: Journal of Religion and Health
https://www.readbyqxmd.com/read/29335234/a-patient-held-smartcard-with-a-unique-identifier-and-an-mhealth-platform-to-improve-the-availability-of-prenatal-test-results-in-rural-nigeria-demonstration-study
#12
Semiu Olatunde Gbadamosi, Chuka Eze, John Olajide Olawepo, Juliet Iwelunmor, Daniel F Sarpong, Amaka Grace Ogidi, Dina Patel, John Okpanachi Oko, Chima Onoka, Echezona Edozie Ezeanolue
BACKGROUND: Community-based strategies to test for HIV, hepatitis B virus (HBV), and sickle cell disease (SCD) have expanded opportunities to increase the proportion of pregnant women who are aware of their diagnosis. In order to use this information to implement evidence-based interventions, these results have to be available to skilled health providers at the point of delivery. Most electronic health platforms are dependent on the availability of reliable Internet connectivity and, thus, have limited use in many rural and resource-limited settings...
January 15, 2018: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29334885/2016-united-kingdom-national-guideline-on-the-sexual-health-care-of-men-who-have-sex-with-men
#13
Dan Clutterbuck, David Asboe, Tristan Barber, Carol Emerson, Nigel Field, Stuart Gibson, Gwenda Hughes, Rachael Jones, Martin Murchie, Achyuta V Nori, Michael Rayment, Ann Sullivan
This guideline is intended for use in UK Genitourinary medicine clinics and sexual health services but is likely to be of relevance in all sexual health settings, including general practice and Contraception and Sexual Health (CASH) services, where men who have sex with men (MSM) seek sexual health care or where addressing the sexual health needs of MSM may have public health benefits. For the purposes of this document, MSM includes all gay, bisexual and all other males who have sex with other males and both cis and trans men...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29332992/experiment-design-for-early-molecular-events-in-hiv-infection
#14
Aditya Jagarapu, LaMont Cannon, Ryan Zurakowski
The recent introduction of integrase inhibitors to the HIV antiviral repertoire permits us to create in vitro experiments that reliably terminate HIV infection at the point of chromosomal integration. This allows us to isolate the dynamics of a single round of infection, without needing to account for the influence of multiple overlapping rounds of infection. By measuring the various nucleic acid concentrations in a population of infected target cells at multiple time points, we can infer the rates of these molecular events with great accuracy, which allows us to compare the rates between target cells with different functional phenotypes...
May 2017: Proceedings of the ... American Control Conference
https://www.readbyqxmd.com/read/29329553/inhibitors-of-the-integrase-transportin-sr2-interaction-block-hiv-nuclear-import
#15
Jonas Demeulemeester, Jolien Blokken, Stéphanie De Houwer, Lieve Dirix, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Frauke Christ, Zeger Debyser
BACKGROUND: Combination antiretroviral therapy efficiently suppresses HIV replication in infected patients, transforming HIV/AIDS into a chronic disease. Viral resistance does develop however, especially under suboptimal treatment conditions such as poor adherence. As a consequence, continued exploration of novel targets is paramount to identify novel antivirals that do not suffer from cross-resistance with existing drugs. One new promising class of targets are HIV protein-cofactor interactions...
January 12, 2018: Retrovirology
https://www.readbyqxmd.com/read/29329386/the-role-of-service-readiness-and-health-care-facility-factors-in-attrition-from-option-b-in-haiti-a-joint-examination-of-electronic-medical-records-and-service-provision-assessment-survey-data
#16
Lauren Lipira, Christopher Kemp, Jean Wysler Domercant, Jean Guy Honoré, Kesner Francois, Nancy Puttkammer
Background: Option B+ is a strategy wherein pregnant or breastfeeding women with HIV are enrolled in lifelong antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) of HIV. In Haiti, attrition from Option B+ is problematic and variable across health care facilities. This study explores service readiness and other facility factors as predictors of Option B+ attrition in Haiti. Methods: This analysis used longitudinal data from 2012 to 2014 from the iSanté electronic medical record system and cross-sectional data from Haiti's 2013 Service Provision Assessment...
January 10, 2018: International Health
https://www.readbyqxmd.com/read/29325561/workforce-patterns-in-the-prevention-of-mother-to-child-transmission-of-hiv-in-c%C3%A3-te-d-ivoire-a-qualitative-model
#17
Brianne H Rowan, Julia Robinson, Adam Granato, Claire Konan Bla, Seydou Kouyaté, Guy Vincent Djety, Kouamé Abo, Ahoua Koné, Stephen Gloyd
BACKGROUND: Côte d'Ivoire continues to struggle with one of the highest rates of mother-to-child HIV transmission in West Africa, previously thought to be in part due to suboptimal workforce patterns. This study aimed to understand the process through which workforce patterns impact prevention of mother-to child transmission of HIV (PMTCT) program success, from the perspective of healthcare workers in Côte d'Ivoire. METHODS: A total of 142 semi-structured interviews were conducted with physicians, midwives, nurses, community counselors, social workers, pharmacists, management personnel and health aides from a nationally representative sample of 48 PMTCT sites across Côte d'Ivoire...
January 11, 2018: Human Resources for Health
https://www.readbyqxmd.com/read/29324358/regulatory-cd4-t-cells-inhibit-hiv-1-expression-of-other-cd4-t-cell-subsets-via-interactions-with-cell-surface-regulatory-proteins
#18
Mingce Zhang, Tanya O Robinson, Alexandra Duverger, Olaf Kutsch, Sonya L Heath, Randy Q Cron
During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system. This suppression was mediated in part via multiple inhibitory surface proteins expressed on Tregs...
January 8, 2018: Virology
https://www.readbyqxmd.com/read/29322867/implementing-voluntary-medical-male-circumcision-using-an-innovative-integrated-health-systems-approach-experiences-from-21-districts-in-zimbabwe
#19
Caryl Feldacker, Batsirai Makunike-Chikwinya, Marrianne Holec, Aaron F Bochner, Abby Stepaniak, Robert Nyanga, Sinokuthemba Xaba, Peter H Kilmarx, Amy Herman-Roloff, Taurayi Tafuma, Mufuta Tshimanga, Vuyelwa T Sidile-Chitimbire, Scott Barnhart
BACKGROUND: Despite increased support for voluntary medical male circumcision (VMMC) to reduce HIV incidence, current VMMC progress falls short. Slow progress in VMMC expansion may be partially attributed to emphasis on vertical (stand-alone) over more integrated implementation models that are more responsive to local needs. In 2013, the ZAZIC consortium began implementation of a 5-year, integrated VMMC program jointly with Ministry of Health and Child Care (MoHCC) in Zimbabwe. OBJECTIVE: To explore ZAZIC's approach emphasizing existing healthcare workers and infrastructure, increasing program sustainability and resilience...
2018: Global Health Action
https://www.readbyqxmd.com/read/29321329/a-cyclin-binding-motif-in-human-samhd1-is-required-for-its-hiv-1-restriction-dntpase-activity-tetramer-formation-and-efficient-phosphorylation
#20
Corine St Gelais, Sun Hee Kim, Victoria V Maksimova, Olga Buzovetsky, Kirsten Knecht, Caitlin Shepard, Baek Kim, Yong Xiong, Li Wu
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) regulates intracellular deoxynucleoside triphosphate (dNTP) levels and functions as a retroviral restriction factor through its dNTP triphosphohydrolase (dNTPase) activity. Human SAMHD1 interacts with cell cycle regulatory proteins cyclin A2, cyclin-dependent kinase 1 (CDK1), and CDK2. This interaction mediates phosphorylation of SAMHD1 at threonine 592 (T592), which negatively regulates HIV-1 restriction. We previously reported that the interaction is mediated, at least in part, through a cyclin-binding motif (RXL, aa...
January 10, 2018: Journal of Virology
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