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Low level viremia

Alessandra Bandera, Elisa Colella, Giuliano Rizzardini, Andrea Gori, Mario Clerici
Antiretroviral treatment of HIV infection reduces, but does not eliminate, viral replication and down modulates immune activation. The persistence of low level HIV replication in the host, nevertheless, drives a smouldering degree of immune activation that is observed throughout the natural history of disease and is the main driving force sustaining morbidity and mortality. Areas covered: Early start of antiretroviral therapy (ART) and intensive management of behavioural risk factors are possible but, at best, marginally successful ways to manage immune activation...
October 20, 2016: Expert Review of Anti-infective Therapy
Amedeo F Capetti, Gaetana Sterrantino, Maria Vittoria Cossu, GianCarlo Orofino, Giorgio Barbarini, Giuseppe V De Socio, Simona Di Giambenedetto, Antonio Di Biagio, Benedetto M Celesia, Barbara Argenteri, Giuliano Rizzardini
INTRODUCTION: Little information is available on the efficacy and safety of the dual combination of ripivirine plus dolutegravir. This work aims at beginning to fill this gap. METHODS: All HIV-1 infected subjects treated with ripivirine plus dolutegravir between October 2014 and September 2015 in eight Italian centres were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48. RESULTS: One hundred and thirty-two subjects were followed for a median of 24 months, mean 33 months...
2016: PloS One
M L Mzingwane, C T Tiemessen, K L Richter, S H Mayaphi, G Hunt, S M Bowyer
BACKGROUND: Although the use of highly active antiretroviral therapy in HIV positive individuals has proved to be effective in suppressing the virus to below detection limits of commonly used assays, virological failure associated with drug resistance is still a major challenge in some settings. The prevalence and effect of pre-treatment resistance associated variants on virological outcomes may also be underestimated because of reliance on conventional population sequencing data which excludes minority species...
October 12, 2016: Virology Journal
Maximilian Muenchhoff, Emily Adland, Owen Karimanzira, Carol Crowther, Matthew Pace, Anna Csala, Ellen Leitman, Angeline Moonsamy, Callum McGregor, Jacob Hurst, Andreas Groll, Masahiko Mori, Smruti Sinmyee, Christina Thobakgale, Gareth Tudor-Williams, Andrew J Prendergast, Henrik Kloverpris, Julia Roider, Alasdair Leslie, Delane Shingadia, Thea Brits, Samantha Daniels, John Frater, Christian B Willberg, Bruce D Walker, Thumbi Ndung'u, Pieter Jooste, Penny L Moore, Lynn Morris, Philip Goulder
Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml)...
September 28, 2016: Science Translational Medicine
Monika Simmons, Robert Putnak, Peifang Sun, Timothy Burgess, Wayne A Marasco
Passive immunization with anti-dengue virus (DENV) immune serum globulin (ISG) or monoclonal antibodies (Mabs) may serve to supplement or replace vaccination for short-term dengue immune prophylaxis. In the present study, we sought to establish proof-of-concept by evaluating several DENV-neutralizing antibodies for their ability to protect rhesus macaques against viremia following live virus challenge, including human anti-dengue ISG, and a human Mab (Mab11/wt) and its genetically engineered variant (Mab11/mutFc) that is unable to bind to cells with Fc gamma receptors (FcγR) and potentiate antibody-dependent enhancement (ADE)...
September 19, 2016: American Journal of Tropical Medicine and Hygiene
Laura Mazzuti, Maria Antonietta Lozzi, Elisabetta Riva, Paola Maida, Francesca Falasca, Guido Antonelli, Ombretta Turriziani
We assess the concordance between low level HCV values obtained using the VERSANT HCV RNA 1.0 Assay (kPCR) and COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test v2.0. The correlation between the values obtained by the two RT-PCR assays for samples with quantifiable HCV RNA levels revealed that viral load measured by kPCR significantly correlated with that of the CAP/CTM (R=0.644, P<0.0001). The results show a good concordance (n=126/144, 87%); discordant results were mainly observed in the assessment of values below the lower limit of detection of the assays...
September 2016: New Microbiologica
A Gonzalez-Serna, L C Swenson, B Watson, W Zhang, A Nohpal, K Auyeung, J S Montaner, P R Harrigan
Suboptimal untimed plasma drug levels (UDL) have been associated with lower rates of virologic suppression and the emergence of drug resistance. Our aim was to evaluate whether UDL among patients with low-level viremia (LLV) while receiving highly active antiretroviral therapy (HAART) can predict subsequent virologic failure (plasma viral load ≥1000 copies/mL) and emergence of resistance. The first documented LLV episode of 328 consenting patients was analysed in terms of drug levels, viral load and resistance, which were monitored while patients were on a consistent HAART regimen...
August 30, 2016: Clinical Microbiology and Infection
Mariko Sunada, Daisuke Kinoshita, Naoko Furukawa, Minako Kihara, Akira Nishimura, Masako Moriuchi, Hiroyuki Moriuchi
BACKGROUND: Ganciclovir is a therapeutic choice for extremely premature infants with severe postnatal cytomegalovirus disease, but little is known about its optimal dose size and dosing interval for them. CASE PRESENTATION: We treated an extremely premature female infant with postnatal cytomegalovirus infection with intravenous administration of ganciclovir since 49 days of life (postmenstrual age of 31 weeks). After ganciclovir treatment was initiated at a dose of 5 mg/kg every 12 h, cytomegalovirus loads in the peripheral blood were markedly decreased...
August 22, 2016: BMC Pediatrics
Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters
HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry...
August 2016: Medicine (Baltimore)
Chiraz Hamimi, Annie David, Pierre Versmisse, Laurence Weiss, Timothée Bruel, David Zucman, Victor Appay, Arnaud Moris, Marie-Noëlle Ungeheuer, Caroline Lascoux-Combe, Françoise Barré-Sinoussi, Michaela Muller-Trutwin, Faroudy Boufassa, Olivier Lambotte, Gianfranco Pancino, Asier Sáez-Cirión
HIV controllers (HICs), rare HIV-1 infected individuals able to control viral replication without antiretroviral therapy, are characterized by an efficient polyfunctional and cytolytic HIV-specific CD8+ T cell response. The mechanisms underlying the induction and maintenance of such response in many HICs despite controlled viremia are not clear. Dendritic cells play a crucial role in the generation and reactivation of T cell responses but scarce information is available on those cells in HICs. We found that monocyte derived dendritic cells (MDDCs) from HICs are less permissive to HIV-1 infection than cells from healthy donors...
2016: PloS One
Gamze Isitman, Irene Lisovsky, Alexandra Tremblay-McLean, Colin Kovacs, Marianne Harris, Jean-Pierre Routy, Julie Bruneau, Mark A Wainberg, Cécile Tremblay, Nicole F Bernard
Carriage of alleles encoding certain inhibitory natural killer (NK) cell receptor/HLA ligand KIR3DL1/HLA-B combinations is associated with protection from HIV infection and slow time to AIDS, implicating NK cells in HIV control. NK cells also mediate antibody-dependent cellular cytotoxicity (ADCC). ADCC has been identified as a correlate of protection in secondary analyses of the modestly protective RV144 Thai HIV vaccine trial. In ADCC, HIV envelope (Env)-specific antibodies (Abs) bridge HIV-infected or gp120-coated target cells and NK cells expressing CD16 receptors for Ab Fc domains...
October 2016: AIDS Research and Human Retroviruses
Leo Swadling, John Halliday, Christabel Kelly, Anthony Brown, Stefania Capone, M Azim Ansari, David Bonsall, Rachel Richardson, Felicity Hartnell, Jane Collier, Virginia Ammendola, Mariarosaria Del Sorbo, Annette Von Delft, Cinzia Traboni, Adrian V S Hill, Stefano Colloca, Alfredo Nicosia, Riccardo Cortese, Paul Klenerman, Antonella Folgori, Eleanor Barnes
An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen...
August 2, 2016: Vaccines
Mauro Zaccarelli, Maria Mercedes Santoro, Daniele Armenia, Vanni Borghi, William Gennari, Caterina Gori, Federica Forbici, Ada Bertoli, Lavinia Fabeni, Alberto Giannetti, Stefania Cicalini, Rita Bellagamba, Massimo Andreoni, Claudio Maria Mastroianni, Cristina Mussini, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Andrea Antinori
BACKGROUND: Beyond the detection of resistant HIV strains found in plasma samples, archival HIV-DNA in peripheral blood mononuclear cells (PBMCs) might represent a reservoir of additional resistance. OBJECTIVE: To characterize the HIV-1 resistance in PBMCs from patients with suppressed or low-level viremia (50-1000 copies/mL) and evaluate its added value compared to the resistance detected in previous plasma genotypic resistance tests (GRTs). STUDY DESIGN: HIV-1 infected patients selected for treatment change despite low/undetectable viremia were tested...
September 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Q J Sheng, Y Ding, B J Li, H Bai, C Zhang, C Han, Y X Fan, Y W Li, X G Dou
OBJECTIVE: To observe the success rate of telbivudine (LdT) for the prevention of perinatal transmission of hepatitis B virus (HBV) and the incidence of alanine aminotransferase (ALT) elevation during LdT treatment and after LdT withdrawal in HBV-infected pregnant woman with high viremia in immune-tolerant phase and receiving LdT treatment at the end of pregnancy, and to evaluate the efficacy of LdT in the prevention of perinatal transmission and the safety for pregnant women. METHODS: Pregnant women infected with HBV in immune-tolerant phase who had normal ALT levels (≤40 U/L) and high viremia (HBV DNA ≥6 log10 IU/ml) with positive HBeAg were enrolled as subjects...
April 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Sally A Baylis, Victor M Corman, Edgar Ong, Jeffrey M Linnen, C Micha Nübling, Johannes Blümel
BACKGROUND: It is now recognized that blood donors may be silently infected with hepatitis E virus (HEV) and that plasma pools used in the manufacture of plasma-derived medicinal products may also contain detectable virus RNA. The occurrence of HEV-infected blood and plasma donors can vary considerably depending on local epidemiology. STUDY DESIGN AND METHODS: Manufacturing plasma pools from North America, Europe, the Middle East, and Asia were examined for the presence of HEV using transcription-mediated amplification of HEV RNA; confirmatory testing was performed using real-time reverse transcription polymerase chain reaction and sequencing...
October 2016: Transfusion
Guannan Geng, Bingfeng Liu, Cancan Chen, Kang Wu, Jun Liu, Yijun Zhang, Ting Pan, Jun Li, Yue Yin, Junsong Zhang, Feng Huang, Fei Yu, Jingliang Chen, Xiancai Ma, Jie Zhou, Ersheng Kuang, Chao Liu, Weiping Cai, Hui Zhang
Although combined antiretroviral therapy (cART) successfully decreases plasma viremia to undetectable levels, the complete eradication of human immunodeficiency virus type 1 (HIV-1) remains impractical because of the existence of a viral reservoir, mainly in resting memory CD4(+) T cells. Various cytokines, protein kinase C activators, and histone deacetylase inhibitors (HDACi) have been used as latency-reversing agents (LRAs), but their unacceptable side effects or low efficiencies limit their clinical use...
September 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Joanna M Schaenman, Yael Korin, Tiffany Sidwell, Fadi Kandarian, Nicholas Harre, David Gjertson, Erik L Lum, Uttam Reddy, Edmund Huang, Phuong T Pham, Suphamai Bunnapradist, Gabriel M Danovitch, Jefferey Veale, H Albin Gritsch, Elaine F Reed
BACKGROUND: BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control. METHODS: Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation...
July 7, 2016: Transplantation
Shaomei Zhu, Tingting Li, Bochao Liu, Yuxia Xu, Yachun Sun, Yilin Wang, Yuanzhan Wang, Lifang Shuai, Zixuan Chen, Jean-Pierre Allain, Chengyao Li
UNLABELLED: A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection...
September 15, 2016: Journal of Virology
Areej Alshorman, Chathuri Samarasinghe, Wenlian Lu, Libin Rong
HIV latency remains a major obstacle to viral elimination. The activation rate of latently infected cells may depend on the age of latent infection. In this paper, we develop a model of HIV infection including age-structured latently infected cells. We mathematically analyse the model and use numerical simulations with different activation functions to show that the model can explain the persistence of low-level viremia and the latent reservoir stability in patients on therapy. Sensitivity tests suggest that the model is robust to the changes of most parameters but is sensitive to the relative magnitude of the net generation rate and the long-term activation rate of latently infected cells...
June 24, 2016: Journal of Biological Dynamics
Laura Mazzuti, Maria Antonietta Lozzi, Elisabetta Riva, Paola Maida, Francesca Falasca, Guido Antonelli, Ombretta Turriziani
We assess the concordance between low level HCV values obtained using the VERSANT HCV RNA 1.0 Assay (kPCR) and COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test v2.0. The correlation between the values obtained by the two RT-PCR assays for samples with quantifiable HCV RNA levels revealed that viral load measured by kPCR significantly correlated with that of the CAP/CTM (R=0.644, P <0.0001). The results show a good concordance (n=126/144, 87%); discordant results were mainly observed in the assessment of values below the lower limit of detection of the assays...
June 10, 2016: New Microbiologica
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