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Antiviral Therapy

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https://www.readbyqxmd.com/read/28206979/effect-of-gender-and-age-on-the-relative-bioavailability-of-doravirine-results-of-a-phase-i-trial-in-healthy-subjects
#1
Martin O Behm, Ka L Yee, Li Fan, Paul Fackler
BACKGROUND: Doravirine is a potent, once-daily, non-nucleoside reverse transcriptase inhibitor with a distinct resistance profile in Phase 3 development for the treatment of HIV-1. As doravirine may be administered to women and the elderly, we investigated the impact of gender and age in doravirine pharmacokinetics. METHODS: In this Phase 1, open-label, single-period, parallel-group investigation, doravirine 100 mg was administered to 36 healthy subjects in 3 groups: elderly men (n=12, 65-80 years), elderly women (n=12, 65-80 years), and young women (n=12, 18-50 years)...
February 16, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28205506/prospective-surveillance-of-antiviral-resistance-in-hospitalized-infants-less-than-12-months-of-age-with-a-h3n2-influenza-infection-and-treated-with-oseltamivir
#2
Barbara Rath, Xi Chen, Vera Spies, Susann Muehlhans, Patrick Obermeier, Franziska Tief, Lea Seeber, Katharina Karsch, Jeanette Milde, Heino Skopnik, Brunhilde Schweiger, Susanne C Duwe
BACKGROUND: Infants exhibit elevated influenza virus loads and prolonged viral shedding, which may increase the risk for resistance development, especially in cases of suboptimal exposure to antiviral therapy. METHODS: We performed a prospective surveillance of hospitalized infants undergoing oseltamivir therapy during the 2008-2009 and 2011-2012 influenza seasons at two paediatric hospitals in Germany. A total of 37 infants less than one year of age with laboratory confirmed influenza A(H3N2) infection received oseltamivir as per physician's order for 5 days (2008-2009 season: 2mg/kg BID; 2011-2012 season: 2...
February 16, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28198351/therapeutic-drug-monitoring-guided-raltegravir-dosing-for-prevention-of-vertical-transmission-in-a-premature-neonate-born-to-a-woman-living-with-perinatally-acquired-hiv
#3
Denise Kreutzwiser, Nancy Sheehan, Natalie Dayneka, Benoît Lemire, Alison Wong, Lindy Samson, Jason Brophy
We report a case of therapeutic drug monitoring guided raltegravir use for the prevention of vertical HIV transmission in a premature neonate born to a woman living with perinatally acquired HIV and documented resistance to multiple HIV drugs. Maternal viral load was above 1,000 copies/mL at delivery. This case demonstrates delayed raltegravir elimination in a neonate born at 33 weeks gestational age and a need for less frequent raltegravir dosing than is used in older infants and children.
February 15, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28198350/cerebrospinal-fluid-viral-load-and-neopterin-in-hiv-positive-patients-with-undetectable-viraemia
#4
Ilaria Motta, Tiziano Allice, Alessandra Romito, Micol Ferrara, Sara Ecclesia, Daniele Imperiale, Valeria Ghisetti, Giovanni Di Perri, Stefano Bonora, Andrea Calcagno
BACKGROUND: Cerebrospinal fluid (CSF) HIV RNA is commonly used as a marker of compartmental antiviral activity in HIV-positive patients. Undetectable CSF HIV RNA levels have been associated with low CSF neopterin levels and better neurocognitive performances. Aim of this study was to analyse the prevalence and predictors of non-detectable CSF HIV RNA using a commercial assay. METHODS: In adult HIV-positive HAART-treated patients with confirmed plasma HIV RNA <50 copies/mL, CSF HIV RNA (with Roche Amplicor Assay) and neopterin were measured...
February 15, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28198349/impact-of-itpa-gene-polymorphisms-on-the-risk-of-ribavirin-induced-haemolytic-anaemia-using-interferon-free-antivirals-for-chronic-hepatitis-c
#5
Isabella Esposito, Laura Benítez-Gutiérrez, Ana Treviño, Ana Arias, Maria Jesus Citores, Silvia Requena, Vicente Soriano, Valentín Cuervas-Mons, Carmen de Mendoza
BACKGROUND: Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with hemolytic anemia in chronic hepatitis C patients treated with peginterferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce. METHODS: Median hemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic...
February 15, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28195560/impact-of-tenofovir-dose-adjustment-on-both-estimated-glomerular-filtration-rate-and-tenofovir-trough-concentration
#6
Sylvie Bregigeon, Caroline Solas, Olivia Faucher, Véronique Obry-Roguet, Catherine Tamalet, Isabelle Poizot-Martin
BACKGROUND: Tenofovir disoproxil fumarate (TDF)-based regimen is a treatment option for HIV-infected patients. TDF dose adjustment is recommended in patients with impaired renal function. We assessed the impact of TDF dose adjustment on renal function and tenofovir trough concentration. METHODS: Fourteen HIV patients for whom TDF dose was adjusted (1 tablet/48h) because of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m(2), and/or due to a tenofovir trough concentration > 90 ng/mL between 2006 and 2013 were selected...
February 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28195559/selection-of-multi-drug-resistant-influenza-a-and-b-viruses-under-zanamivir-pressure-and-their-replication-fitness-in-ferrets
#7
Ding Yuan Oh, Jacqueline Panozzo, Sophie Vitesnik, Rubaiyea Farrukee, David Piedrafita, Jennifer Mosse, Aeron C Hurt
BACKGROUND: Intravenous zanamivir has been used to treat patients with severe influenza. Because the majority of cases (including immunocompromised patients) require the drug for an extended period of treatment, there is a higher risk that the virus will develop resistance. Therefore, knowing the possible amino acid substitutions that may arise in recently circulating influenza strains under prolonged zanamivir exposure and their impact on antiviral susceptibility is important. METHODS: Influenza A(H1N1)pdm09, A(H3N2) and B virus were serially passaged under increasing zanamivir pressure in vitro...
February 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28195558/elevated-pre-treatment-il-18-level-is-associated-with-hbeag-seroconversion-in-hiv-hbv-coinfection
#8
Yijia Li, Jing Xie, Huanling Wang, Yang Han, Nidan Wang, Chloe L Thio, Taisheng Li
BACKGROUND: In hepatitis B virus (HBV) infected patients, hepatitis B e antigen (HBeAg) seroconversion is associated with better outcomes. Interleukin-18 (IL-18) controls hepatitis B replication in a mouse model. However, its role in treatment response in HIV/HBV co-infected patients is unknown. METHODS: We enrolled 35 treatment-naïve, HBeAg positive, HIV/HBV co-infected patients. HBV DNA, HIV RNA, CD4 cell count, HBV surface antigen (HBsAg) quantification (qHBsAg), HBeAg quantification (qHBeAg) and IL-18 levels were measured prior to, at 24 and 48 weeks of HBV-active combination antiretroviral therapy (cART)...
February 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28165327/itpase-activity-modulates-the-severity-of-anaemia-in-hcv-related-cirrhosis-treated-with-ribavirin-containing-interferon-free-regimens
#9
Nicola Coppola, Stefania De Pascalis, Vincenzo Messina, Giovanni Di Caprio, Salvatore Martini, Giorgio de Stefano, Mario Starace, Gianfranca Stornaiuolo, Maria Stanzione, Tiziana Ascione, Carmine Minichini, Vincenzo Sangiovanni, Rosa Zampino, Federica Calò, Luca Rinaldi, Marcello Persico, Alessandro Federico, Antonio Riccardo Buonomo, Guglielmo Borgia, Giovanni Battista Gaeta, Pietro Filippini, Ivan Gentile
BACKGROUND: To investigate the association between inosine triphosphatase (ITPase) activity and the degree of anemia occurring during directly acting antiviral (DAA)/ribavirin (RBV)-based therapy in patients with cirrhosis. METHODS: In a multicenter, prospective study 227 patients with HCV-related cirrhosis treated with DAA and RBV were enrolled. All patients were screened for the rs1127354 and rs7270101 ITPA single nucleotide polymorphisms using direct sequencing...
February 6, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28121292/ranpirnase-eradicates-human-papillomavirus-in-cultured-cells-and-heals-anogenital-warts-in-a-phase-i-study
#10
Luis Squiquera, Debra J Taxman, Sarah A Brendle, Roberto Torres, Jamie Sulley, Thomas Hodge, Neil Christensen, David Sidransky
BACKGROUND: Human papillomaviruses (HPV), the causative agent of anogenital warts, are the most prevalent sexually transmitted infectious agents, and wart treatment poses a persistent challenge. We assessed the safety and efficacy of treating HPV with ranpirnase, an endoribonuclease from the Northern Leopard frog that has been used extensively in Phase III oncology trials. METHODS: As initial verification of ranpirnase antiviral activity, we assessed its ability to eliminate papillomaviruses in cultured cells...
January 25, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28106531/preclinical-characterization-of-the-novel-hcv-ns3-protease-inhibitor-gs-9256
#11
Huiling Yang, Chris Yang, Yujin Wang, Gerry Rhodes, Margaret Robinson, Guofeng Cheng, Xiaoping Qi, Hongmei Mo, Yang Tian, Rowchanak Pakdaman, X Christopher Sheng, Choung U Kim, William E Delaney
BACKGROUND: GS-9256 is an inhibitor of hepatitis C virus (HCV) NS3 protease with a macrocyclic structure and novel phosphinic acid pharmacophore. METHODS: Key preclinical properties of GS-9256 including in vitro antiviral activity, cross-resistance, and pharmacokinetic properties were investigated in non-human species. RESULTS: In genotype (GT) 1b Huh-luc cells with a replicon encoding luciferase, GS-9256 had a mean EC50 value of 20.0 nM, with minimal cytotoxicity...
January 20, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28091393/viral-blips-were-infrequent-in-treatment-naive-adults-treated-with-rilpivirine-emtricitabine-tenofovir-df-or-efavirenz-emtricitabine-tenofovir-df-through-96-weeks
#12
Danielle P Porter, Rima Kulkarni, Will Garner, Michael D Miller, Kirsten L White
BACKGROUND: The clinical impact of transient episodes of HIV viremia (viral blips) on virologic failure and resistance development is not fully understood. Here we investigated the blip frequency and virologic outcomes of HIV-1-infected subjects experiencing viral blips among treatment-naïve subjects initiating therapy on rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF through 96 weeks of treatment. METHODS: Subjects treated with at least one dose of study drug and with at least one post-baseline HIV-1 RNA value were included in this analysis...
January 16, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28091392/the-impact-of-viral-load-and-time-to-onset-of-cytomegalovirus-replication-on-long-term-graft-survival-after-kidney-transplantation
#13
Tomas Reischig, Martin Kacer, Petra Hruba, Pavel Jindra, Ondrej Hes, Daniel Lysak, Mirko Bouda, Ondrej Viklicky
BACKGROUND: Asymptomatic cytomegalovirus (CMV) infection is associated with graft dysfunction and failure. However, no study assessed CMV viral load in terms of the risk for graft failure. METHODS: In prospective cohort of kidney transplant recipients, we assessed the impact of CMV DNAemia on the overall graft survival and the incidence of moderate-to-severe interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 36 months. CMV DNAemia was stratified by viral load in whole blood...
January 16, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28085003/prevalence-of-sofosbuvir-resistance-associated-variants-in-brazilian-and-worldwide-ns5b-sequences-of-genotype-1-hcv
#14
Allan Peres-da-Silva, Carlos Eduardo Brandão-Mello, Elisabeth Lampe
BACKGROUND: The prevalence of natural polymorphisms associated with resistance to NS5B NI sofosbuvir is distinct in different geographical regions. In Brazil, direct acting anti-HCV therapy has recently changed by the introduction of IFN-free regimens with sofosbuvir and the presence of resistant variants on clinical outcomes remains unknown. The aim of this study was to assess the natural polymorphisms associated with resistance to the NS5B NI sofosbuvir in Brazilian HCV-1 isolates and to compare it with that from other geographic regions...
January 13, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28085002/hcv-intergenotype-2k-1b-recombinant-detected-in-a-daa-treated-patient-in-italy
#15
Stefania Paolucci, Marta Premoli, Serena Ludovisi, Mario U Mondelli, Fausto Baldanti
Direct acting antiviral (DAA) combinations are potent and effective drugs currently recommended for treatment of chronic HCV infection. Difficult to treat genotypes are the most important predictors of treatment failure. We report a case of DAA treatment failure in a HCV infected patient carrying a recombinant genotype 2k/1b. This strain first isolated from a Russian patient in 2002, has now been observed for the first time in Italy.
January 13, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28076335/infrequent-development-of-drug-resistance-in-hiv-1-infected-treatment-naive-subjects-after-96-weeks-of-treatment-with-elvitegravir-cobicistat-emtricitabine-tenofovir-alafenamide-or-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate
#16
Nicolas Margot, Stephanie Cox, Moupali Das, Scott McCallister, Michael D Miller, Christian Callebaut
BACKGROUND: Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide RT inhibitor (NtRTI) tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) composed of elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/mL at week 48, and maintained through week 96...
January 11, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28067632/hcv-genotype-1-subtypes-and-resistance-associated-substitutions-in-drug-naive-and-in-direct-acting-antiviral-treatment-failure-patients
#17
Yael Gozlan, Ziv Ben-Ari, Roy Moscona, Rachel Shirazi, Avia Rakovsky, Arij Kabat, Ella Veizman, Tania Berdichevski, Peretz Weiss, Oranit Cohen-Ezra, Yoav Lurie, Inna Gafanovich, Marius Braun, Michal Cohen-Naftaly, Amir Shlomai, Oren Shibolet, Ehud Zigmond, Eli Zuckerman, Michal Carmiel-Haggai, Assy Nimer, Rawi Hazzan, Yaakov Maor, Yona Kitay-Cohen, Yonat Shemer, Zipi Kra-Oz, Lisita Schreiber, Ofer Peleg, Ella Mendelson, Orna Mor
BACKGROUND: Direct-acting antiviral (DAA) treatment regimens and response rates of patients with hepatitis C virus (HCV) genotype 1 (GT1) are currently considered subtype-dependent. Identification of clinically relevant resistance-associated substitutions (RASs) in the NS3 and NS5A proteins at baseline and in DAA failures, may also impact clinical decisions. METHODS: In a multicenter cohort study (n=308), NS3 or NS5B sequencing (n=248) was used to discriminate between GT1 subtypes...
January 9, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28054933/association-of-hiv-infection-with-biomarkers-of-kidney-injury-and-fibrosis-in-the-multicenter-aids-cohort-study
#18
Vasantha Jotwani, Rebecca Scherzer, Michelle M Estrella, Lisa P Jacobson, Mallory D Witt, Frank Palella, Ken Ho, Michael Bennett, Chirag R Parikh, Joachim H Ix, Michael Shlipak
BACKGROUND: Chronic kidney disease (CKD) is common among HIV-infected individuals, but serum creatinine is insensitive for detecting kidney damage at early stages. We hypothesized that HIV infection would be associated with elevations in subclinical markers of kidney injury and fibrosis in a contemporary cohort of men. METHODS: In this cross-sectional study, we measured urine levels of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), pro-collagen type III N-terminal pro-peptide (PIIINP), and albumin-creatinine ratio (ACR) in 813 HIV-infected and 331 uninfected men enrolled in the Multicenter AIDS Cohort Study...
January 5, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28054932/hiv-infection-rather-than-concurrent-opportunistic-infections-drives-most-systemic-procoagulant-vascular-and-damage-responses-a-prospective-cohort-study-in-central-africa
#19
Saskia Janssen, Michaela Am Huson, Kara K Osbak, Elie-Gide Rossatanga, Abraham Alabi, René Lutter, Martin P Grobusch, Tom van der Poll
BACKGROUND: HIV infection is accompanied by various systemic host responses, including activation of coagulation and the vascular endothelium. We sought to determine the impact of opportunistic co-infections in a Central-African setting. METHODS: This prospective study included 98 HIV-infected individuals in Gabon initiating combination antiretroviral therapy (cART) and followed them up for 6 months. Patients were stratified according to the presence of active tuberculosis (TB; n=19), mucocutaneous opportunistic infection (n=9), or no opportunistic infection (n=70)...
January 5, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28054931/life-expectancy-after-initiation-of-combination-antiretroviral-therapy-in-thailand
#20
Sirinya Teeraananchai, Suchada Chaivooth, Stephen J Kerr, Sorakij Bhakeecheep, Anchalee Avihingsanon, Achara Teeraratkul, Petchsri Sirinirund, Matthew G Law, Kiat Ruxrungtham
BACKGROUND: Access to combination antiretroviral therapy (cART) has decreased mortality in HIV positive people. We aimed to estimate the expected additional years of life in HIV-positive Thai people after starting cART through the National AIDS Program (NAP), administered by the Thai National Health Security Office (NHSO). METHODS: The NHSO database collects characteristics of all Thai HIV-infected patients through the National AIDS Program, including linkage with the National Death Registry for vital status...
January 5, 2017: Antiviral Therapy
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