5 results on '"Vera Holzmayer"'
Search Results
2. Analysis of HBsAg Immunocomplexes and cccDNA Activity During and Persisting After NAP‐Based Therapy
- Author
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Michel Bazinet, Pavlina Jimbei, Valentina Smeşnoi, Liviu Iarovoi, Mark S. Anderson, Gavin Cloherty, Andrew Vaillant, Ulf Dittmer, Tatina Musteata, Iurie Moscalu, Jeff Gersch, Valentin Cebotarescu, Victor Pântea, Vera Holzmayer, Alina Jucov, Lilia Cojuhari, Mary C. Kuhns, and Gheorghe Plăcintă
- Subjects
Adult ,Male ,Hepatitis B virus ,HBsAg ,Polymers ,Medizin ,RC799-869 ,Antiviral Agents ,Virus ,Hepatitis B, Chronic ,Antigen ,Pegylated interferon ,Nucleic Acids ,Humans ,Medicine ,Seroconversion ,Tenofovir ,Cross-Over Studies ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,virus diseases ,Alanine Transaminase ,Original Articles ,cccDNA ,Diseases of the digestive system. Gastroenterology ,Hepatitis B ,medicine.disease ,Hepatitis B Core Antigens ,Virology ,digestive system diseases ,Nap ,Treatment Outcome ,RNA, Viral ,Virus Inactivation ,Drug Therapy, Combination ,Female ,Original Article ,Interferons ,DNA, Circular ,business ,medicine.drug - Abstract
CA Extern Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use–only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core-related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead-in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti-HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow-up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti-HBs-independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP-based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.
- Published
- 2021
3. Hepatitis B Virus Serum DNA andRNA Levels in Nucleos(t)ide Analog‐Treated or Untreated Patients During Chronic and Acute Infection
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Mary C. Kuhns, Maria De Medina, Jeffrey Gersch, Eugene R. Schiff, Vera Holzmayer, Gavin Cloherty, Anne L. McNamara, Ka Cheung Luk, and Emily K. Butler
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0301 basic medicine ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Humans ,Seroconversion ,Hepatitis B virus ,Hepatology ,DNA synthesis ,business.industry ,virus diseases ,Nucleosides ,Viral Load ,Hepatitis B ,medicine.disease ,Virology ,digestive system diseases ,030104 developmental biology ,Real-time polymerase chain reaction ,chemistry ,Lamivudine ,DNA, Viral ,Nucleic acid ,RNA, Viral ,030211 gastroenterology & hepatology ,business ,Viral load ,Biomarkers ,DNA - Abstract
Treatment of chronic hepatitis B (CHB) patients with nucleos(t)ide analogs (NAs) suppresses hepatitis B virus (HBV) DNA synthesis but does not affect synthesis of HBV pregenomic RNA (pgRNA). Hepatitis B virus pgRNA is detectable in the serum during NA treatment and has been proposed as a marker of HBV covalently closed circular DNA activity within the infected hepatocyte. We developed an automated assay for the quantification of serum HBV pgRNA using a dual-target real-time quantitative PCR approach on the Abbott m2000sp/rt system. We demonstrate accurate detection and quantification of serum HBV RNA. Hepatitis B virus DNA was quantified using the Abbott RealTime HBV viral load assay. We further compared serum nucleic acid levels and kinetics in HBV-positive populations. Samples included on-therapy CHB samples (n = 16), samples (n = 89) from 10 treatment naïve CHB subjects receiving 12 weeks of NA treatment with 8-week follow-up, hepatitis B surface antigen-positive blood donor samples (n = 102), and three seroconversion series from plasmapheresis donors (n = 79 samples). Conclusion: During NA treatment of CHB subjects, we observed low correlation of HBV DNA to pgRNA levels; pgRNA concentration was generally higher than HBV DNA concentrations. In contrast, when NA treatment was absent we observed serum pgRNA at concentrations that correlated to HBV DNA and were approximately 2 log lower than HBV DNA. Importantly, we observe this trend in untreated subject samples from both chronic infections and throughout seroconversion during acute infection. Results demonstrate that the presence of pgRNA in serum is part of the HBV lifecycle; constant relative detection of pgRNA and HBV DNA in the serum is suggestive of a linked mechanism for egress for HBV DNA or pgRNA containing virions.
- Published
- 2018
4. The Prevalence of Diverse HIV-1 Strains Was Stable in Cameroonian Blood Donors From 1996 to 2004
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Julie Yamaguchi, Sushil G. Devare, Charlotte Ngansop, Pierre Bodelle, Priscilla Swanson, Lazare Kaptue, Catherine A. Brennan, Florence Makamche, Lutz G. Gürtler, Ruthie Coffey, John Hackett, Gerald Schochetman, Nicaise Ndembi, Vera Holzmayer, Leopold Zekeng, Alan Golden, Dora Mbanya, Ana Vallari, Barbara J. Harris, and Ka-Cheung Luk
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Time Factors ,Molecular Sequence Data ,Population ,Blood Donors ,HIV Infections ,Gp41 ,Virus ,law.invention ,law ,Prevalence ,Humans ,Pharmacology (medical) ,Cameroon ,education ,Phylogeny ,education.field_of_study ,biology ,Phylogenetic tree ,Strain (biology) ,virus diseases ,biology.organism_classification ,Virology ,Integrase ,Infectious Diseases ,Lentivirus ,HIV-1 ,Recombinant DNA ,biology.protein - Abstract
Objective: The HIV epidemic in Cameroon is characterized by a high level of strain diversity despite a relatively low prevalence of infection. In this study, HIV strains infecting blood donors in Cameroon were characterized to determine the prevalence of subtypes and intersubtype recombinants and if strain prevalence was changing over time. Methods: From 1996 through 2004, 676 HIV-infected blood donations were collected at blood banks in Douala and Yaounde, Cameroon. A subset of the HIV-1 group M strains (n = 574) were classified based on phylogenetic analysis of viral sequences from the gag p24, pol integrase, and env gp41 regions. Results: HIV-1 group M accounted for 97.3% (n = 658) of infections, whereas group O was present in 2.2% (n = 15) and HIV-2 in 0.4% (n = 3). Within the group M infections, 14 subtypes and circulating recombinant forms (CRFs) and unique recombinant forms (URFs) were identified. Overall, CRF02_AG accounted for 58.2% of infections, URFs 14.8%, and levels of subtypes, A, B, C, D, F2, and G, and CRFs, 01, 06, 09, 11, 13, 22, and 37, varied from 0.2% to 6.1%. Evaluation of HIV strains present in the donor population over this 9-year period showed no substantial changes in the proportion of infections caused by each subtype and CRF, the percentage of intersubtype recombinants, or the strain composition of the URFs. Conclusions: HIV-1 strain diversity in Cameroon did not significantly change, suggesting a mature and relatively stable epidemic.
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- 2008
5. The Challenge of HIV-1 Genetic Diversity: Discordant CD4+ T-Cell Count and Viral Load in an Untreated Patient Infected With a Subtype F Strain
- Author
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Hector Bolivar, Wai-Bing Mak, Klara Abravaya, John Hackett, Gabriel Manzi, Margaret A. Fischl, Vera Holzmayer, and Rebeca Geffin
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Genetic diversity ,Cd4 t cell ,Strain (biology) ,Human immunodeficiency virus (HIV) ,Biology ,medicine.disease_cause ,Virology ,Article ,Infectious Diseases ,Genetic variation ,Immunology ,medicine ,Pharmacology (medical) ,Viral load - Published
- 2009
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