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Hiv and low level viremia

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https://www.readbyqxmd.com/read/30311877/genetic-diversity-in-the-env-v1-v2-region-of-proviral-quasispecies-from-long-term-controller-mhc-typed-cynomolgus-macaques-infected-with-shivsf162p4cy
#1
Alessia Capone, Alessandra Lo Presti, Leonardo Sernicola, Stefania Farcomeni, Flavia Ferrantelli, Maria T Maggiorella, Edward T Mee, Nicola J Rose, Eleonora Cella, Massimo Ciccozzi, Barbara Ensoli, Alessandra Borsetti
Intra-host evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) has been shown by viral RNA analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. However, little is known about the variability of proviral DNA and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (MHC) genotypes, in controllers. Here, we analysed the proviral DNA quasispecies of the env V1-V2 region, in PBMCs and in anatomical compartments of 13 long-term controller monkeys after 3...
October 12, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/30240941/measurement-of-plasma-hiv-1-rna-below-the-limit-of-quantification-20-copies-ml-of-commercial-assays-with-the-integrase-hiv-rna-single-copy-assay
#2
N Margot, D Koontz, S McCallister, J W Mellors, C Callebaut
BACKGROUND: Plasma HIV-1 RNA (viral load, VL) is measured routinely in HIV-infected persons with FDA-approved commercially available assays such as the Cobas-TaqMan HIV-1 Assay v2.0. This assay provides quantification of viremia ≥20 copies/mL. More sensitive methods, able to quantify low-level persistent viremia below the detection limit of commercially available assays, are needed to assess the impact of current HIV cure strategies on viremia. OBJECTIVES: The novel integrase HIV-1 RNA single-copy assay (iSCA) was evaluated for measurement of low-level persistent viremia in clinical trial samples (n = 151) from subjects participating in Gilead HIV clinical research...
September 10, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/30134290/hiv-second-line-failure-and-drug-resistance-at-high-and-low-level-viremia-in-western-kenya
#3
Rami Kantor, Allison Delong, Leeann Schreier, Marissa Reitsma, Emanuel Kemboi, Millicent Orido, Salome Obonge, Robert Boinett, Mary Rono, Wilfred Emonyi, Katie Brooks, Mia Coetzer, Nathan Buziba, Joseph Hogan, Lameck Diero
OBJECTIVE: Characterize failure and resistance above and below guidelines-recommended 1,000 copies/mL virologic threshold, upon 2-line failure. DESIGN: Cross-sectional study. METHODS: Kenyan adults on lopinavir/ritonavir-based 2-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/clinical characteristics and CD4/viral load (VL) were obtained. Participants with detectable VL had a second visit and pol genotyping was attempted in both visits...
August 20, 2018: AIDS
https://www.readbyqxmd.com/read/29925666/marginal-effects-of-systemic-ccr5-blockade-with-maraviroc-on-oral-simian-immunodeficiency-virus-transmission-to-infant-macaques
#4
Egidio Brocca-Cofano, Cuiling Xu, Katherine S Wetzel, Mackenzie L Cottrell, Benjamin B Policicchio, Kevin D Raehtz, Dongzhu Ma, Tammy Dunsmore, George S Haret-Richter, Karam Musaitif, Brandon F Keele, Angela D Kashuba, Ronald G Collman, Ivona Pandrea, Cristian Apetrei
Current approaches do not eliminate all human immunodeficiency virus type 1 (HIV-1) maternal-to-infant transmissions (MTIT); new prevention paradigms might help avert new infections. We administered maraviroc (MVC) to rhesus macaques (RMs) to block CCR5-mediated entry, followed by repeated oral exposure of a CCR5-dependent clone of simian immunodeficiency virus (SIV) mac251 (SIVmac766). MVC significantly blocked the CCR5 coreceptor in peripheral blood mononuclear cells and tissue cells. All control animals and 60% of MVC-treated infant RMs became infected by the 6th challenge, with no significant difference between the number of exposures ( P = 0...
September 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29788421/predicting-viral-failure-in-human-immunodeficiency-virus-perinatally-infected-youth-with-persistent-low-level-viremia-on-highly-active-antiretroviral-therapy
#5
Ruth Pereira, David A Ludwig, Sunil Mathew, Claudia Flores, Sady Dominguez, Ivan Gonzalez, Delia Rivera-Hernandez, Gwendolyn B Scott, Charles D Mitchell
Background: Less than optimal adherence with antiretroviral therapy occurs commonly among human immunodeficiency virus HIV)-infected youth. In this study, our object was to identify patterns in the prefailure measurement of viral load (VL) that can reliably predict virological failure (VF) in HIV perinatally infected youth on highly active antiretroviral therapy (HAART). Methods: We conducted a retrospective chart review of HIV-infected youth with low-level viremia (LLV), defined as an HIV VL between the lower limits of detection (20-75 copies/mL) and 1000 copies/mL...
May 19, 2018: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/29760177/epigenetic-promoter-dna-methylation-of-mir-124-promotes-hiv-1-tat-mediated-microglial-activation-via-mecp2-stat3-axis
#6
Palsamy Periyasamy, Annadurai Thangaraj, Ming-Lei Guo, Guoku Hu, Shannon Callen, Shilpa Buch
The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B, which were also accompanied by increased global DNA methylation...
June 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29725333/follicular-dendritic-cells-of-lymph-nodes-as-human-immunodeficiency-virus-simian-immunodeficiency-virus-reservoirs-and-insights-on-cervical-lymph-node
#7
REVIEW
Rajnish S Dave, Pooja Jain, Siddappa N Byrareddy
A hallmark feature of follicular dendritic cells (FDCs) within the lymph nodes (LNs) is their ability to retain antigens and virions for a prolonged duration. FDCs in the cervical lymph nodes (CLNs) are particularly relevant in elucidating human immunodeficiency virus (HIV)-1 infection within the cerebrospinal fluid (CSF) draining LNs of the central nervous system. The FDC viral reservoir in both peripheral LN and CLN, like the other HIV reservoirs, contribute to both low-level viremia and viral resurgence upon cessation or failure of combined antiretroviral therapy (cART)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29683841/monotypic-low-level-hiv-viremias-during-antiretroviral-therapy-are-associated-with-disproportionate-production-of-x4-virions-and-systemic-immune-activation
#8
Marta E Bull, Caroline Mitchell, Jaime Soria, Sheila Styrchak, Corey Williams-Wietzikoski, Jillian Legard, Jennifer McKernan-Mullin, Kelli Kraft, Frankline Onchiri, Joshua Stern, Sarah Holte, Kevin J Ryan, Edward P Acosta, Alberto La Rosa, Robert W Coombs, Eduardo Ticona, Lisa M Frenkel
OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30-1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expanded cells. METHODS: Prospective cohort study of HIV-infected ART-naive Peruvians enrolled prior to ART and followed for 2 years. Plasma HIV RNA and peripheral blood mononuclear cell (PBMC) HIV DNA concentrations were quantified pre-ART from individuals whose plasma HIV RNA was ART-suppressed...
July 17, 2018: AIDS
https://www.readbyqxmd.com/read/29628513/hot-news-impact-of-low-level-viremia-on-treatment-outcomes-during-art-is-it-time-to-revise-the-definition-of-virological-failure
#9
Eva Poveda, Manuel Crespo
The level of HIV-RNA in plasma (HIV viral load) is the main marker used to monitor the virological response to antiretroviral therapy (ART) in HIV-infected patients. The threshold used to define virological suppression has historically been dictated by the limits of detection of the commercial assays used to quantify the plasma viral load. Thus, as more sensitive assays have proliferated and become more widely available, the definition has shifted from < 400 cop/mL with the first generation assays, to < 50 cop/mL, to < 20 cop/mL currently...
January 2018: AIDS Reviews
https://www.readbyqxmd.com/read/29543636/low-level-viremia-is-associated-with-clinical-progression-in-hiv-infected-patients-receiving-antiretroviral-treatment
#10
Enrique Bernal, Jose M Gómez, Inma Jarrín, Alfredo Cano, Angeles Muñoz, Antonia Alcaraz, Arkaitz Imaz, Jose A Iribarren, María Rivero, Piedad Arazo, Félix Gutiérrez
BACKGROUND: The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART). METHODS: We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter...
July 1, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29514914/reduced-cell-associated-dna-and-improved-viral-control-in-macaques-following-passive-transfer-of-a-single-anti-v2-monoclonal-antibody-and-repeated-shiv-challenges
#11
Ann J Hessell, Mariya B Shapiro, Rebecca Powell, Delphine C Malherbe, Sean P McBurney, Shilpi Pandey, Tracy Cheever, William F Sutton, Christoph Kahl, Byung Park, Susan Zolla-Pazner, Nancy L Haigwood
A high level of V1V2-specific IgG antibodies in vaccinees' sera was the only independent variable that correlated with a reduced risk of HIV acquisition in the RV144 clinical trial. In contrast, IgG avidity, antibody neutralization, and antibody-dependent cellular cytotoxicity each failed as independent correlates of infection. Extended analyses of RV144 samples demonstrated antiviral activity of V1V2-specific vaccine-induced antibodies. V2-specific antibodies have also been associated with protection from SIV, and the V2i-specific subset of human monoclonal antibodies (mAbs), while poor neutralizers, mediate Fc-dependent antiviral functions in vitro The objective of this study was to determine the protective efficacy of a V2i-specific human mAb 830A against mucosal SHIV challenge...
March 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29507105/associations-of-simian-immunodeficiency-virus-siv-specific-follicular-cd8-t-cells-with-other-follicular-t-cells-suggest-complex-contributions-to-siv-viremia-control
#12
Mohammad Arif Rahman, Katherine M McKinnon, Tatiana S Karpova, David A Ball, David J Venzon, Wenjin Fan, Guobin Kang, Qingsheng Li, Marjorie Robert-Guroff
Follicular CD8+ T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29482352/dolutegravir-plus-rilpivirine-as-a-switch-option-in-cart-experienced-patients-96-week-data
#13
Amedeo Ferdinando Capetti, Maria Vittoria Cossu, Gaetana Sterrantino, Giorgio Barbarini, Simona Di Giambenedetto, Giuseppe Vittorio De Socio, GianCarlo Orofino, Antonio Di Biagio, Benedetto M Celesia, Stefano Rusconi, Barbara Argenteri, Giuliano Rizzardini
BACKGROUND: Data from clinical studies confirm the efficacy of switching to dolutegravir (DTG) plus rilpivirine (RPV) in selected patients. OBJECTIVE: The primary objective is to report the 96-week virological suppression in our cohort, assessing the durability of this strategy in complicated situations. The secondary objective is to describe the safety and metabolic profile. METHODS: All patients who had switched to DTG plus RPV between October 1, 2014, and September 30, 2015, were analyzed using a retrospective-prospective design, approved by ethics committees...
August 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29474450/treatment-with-native-heterodimeric-il-15-increases-cytotoxic-lymphocytes-and-reduces-shiv-rna-in-lymph-nodes
#14
Dionysios C Watson, Eirini Moysi, Antonio Valentin, Cristina Bergamaschi, Santhi Devasundaram, Sotirios P Fortis, Jenifer Bear, Elena Chertova, Julian Bess, Ray Sowder, David J Venzon, Claire Deleage, Jacob D Estes, Jeffrey D Lifson, Constantinos Petrovas, Barbara K Felber, George N Pavlakis
B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29467313/reduced-chronic-lymphocyte-activation-following-interferon-alpha-blockade-during-the-acute-phase-of-simian-immunodeficiency-virus-infection-in-rhesus-macaques
#15
Diane Carnathan, Benton Lawson, Joana Yu, Kalpana Patel, James M Billingsley, Gregory K Tharp, Olivia M Delmas, Reem Dawoud, Peter Wilkinson, Charles Nicolette, Mark J Cameron, Rafick-Pierre Sekaly, Steven E Bosinger, Guido Silvestri, Thomas H Vanderford
Pathogenic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection of humans and rhesus macaques (RMs) induces persistently high production of type I interferon (IFN-I), which is thought to contribute to disease progression. To elucidate the specific role of interferon alpha (IFN-α) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.) SIVmac239 infection with a high or a low dose of an antibody (AGS-009) that neutralizes most IFN-α subtypes and were compared with six mock-infused, SIV-infected controls...
May 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29465595/discordant-csf-plasma-hiv-1-rna-in-individuals-on-virologically-suppressive-antiretroviral-therapy-in-western-india
#16
Ameet N Dravid, Kartik Natrajan, Milind M Kulkarni, Chinmay K Saraf, Uma S Mahajan, Sachin D Kore, Niranjan M Rathod, Umakant S Mahajan, Rustom S Wadia
Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) <1000 copies/mL (virologically suppressed) were included. Among these, individuals presenting with neurologic symptoms during follow-up were assessed for CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29433430/sesotho-trial-switch-either-near-suppression-or-thousand-switch-to-second-line-versus-who-guided-standard-of-care-for-unsuppressed-patients-on-first-line-art-with-viremia-below-1000-copies-ml-protocol-of-a-multicenter-parallel-group-open-label-randomized-clinical
#17
RANDOMIZED CONTROLLED TRIAL
Alain Amstutz, Bienvenu Lengo Nsakala, Fiona Vanobberghen, Josephine Muhairwe, Tracy Renée Glass, Beatrice Achieng, Mamorena Sepeka, Katleho Tlali, Lebohang Sao, Kyaw Thin, Thomas Klimkait, Manuel Battegay, Niklaus Daniel Labhardt
BACKGROUND: The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence...
February 12, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29425228/kshv-oral-shedding-and-plasma-viremia-result-in-significant-changes-in-the-extracellular-tumorigenic-mirna-expression-profile-in-individuals-infected-with-the-malaria-parasite
#18
Minako Ikoma, Soren Gantt, Corey Casper, Yuko Ogata, Qing Zhang, Ryan Basom, Michael R Dyen, Timothy M Rose, Serge Barcy
Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). Both KSHV and HIV infections are endemic in Uganda, where KS is among the most common cancers in HIV-infected individuals. Recent studies examined the use of small RNAs as biomarkers of disease, including microRNAs (miRNAs), with viral and tumor-derived miRNAs being detected in exosomes from individuals with KSHV-associated malignancies. In the current study, the host and viral extracellular mature miRNA expression profiles were analyzed in blood of KS-negative individuals in Uganda, comparing those with or without KSHV detectable from the oropharynx...
2018: PloS One
https://www.readbyqxmd.com/read/29424783/repeat-testing-of-low-level-hiv-1-rna-assay-performance-and-implementation-in-clinical-trials
#19
Kirsten White, Will Garner, Lilian Wei, Joseph J Eron, Lijie Zhong, Michael D Miller, Hal Martin, Andrew Plummer, Cecilia Tran-Muchowski, Kim Lindstrom, James Porter, David Piontkowsky, Angela Light, Heinz Reiske, Erin Quirk
OBJECTIVE: Assess the performance of HIV-1 RNA repeat testing of stored samples in cases of low-level viremia during clinical trials. DESIGN: Prospective and retrospective analysis of randomized clinical trial samples and reference standards. METHODS: To evaluate assay variability of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, v2.0, three separate sources of samples were utilized: the World Health Organization (WHO) HIV reference standard (assayed using 50 independent measurements at six viral loads <200 copies/ml), retrospective analysis of four to six aliquots of plasma samples from four clinical trial participants, and prospective repeat testing of 120 samples from participants in randomized trials with low-level viremia...
May 15, 2018: AIDS
https://www.readbyqxmd.com/read/29417417/arterial-inflammation-in-young-patients-with-human-immunodeficiency-virus-infection-a-cross-sectional-study-using-f-18-fdg-pet-ct
#20
Ismaheel O Lawal, Alfred O Ankrah, Gbenga O Popoola, Thabo Lengana, Mike M Sathekge
BACKGROUND: HIV infection is associated with the risk of development of atherosclerosis at a younger age. We compared arterial inflammation in HIV-infected and HIV-uninfected patients with otherwise low-risk factors for cardiovascular disease (CVD) using FDG PET/CT. METHODS: 242 patients aged 18-40 years with low-risk factors for CVD consisting of 121 HIV-infected patients and 121 HIV-uninfected age- and gender-matched controls were studied, mean age = 34.95 ± 5...
February 7, 2018: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
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