136 results on '"Gelderblom, Huub C."'
Search Results
2. Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study
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Allagappen, Jon, Andriesen, Jessica, Ayres, Alison, Baral, Saman, Bekker, Linda-Gail, Besethi, Asiphe, Borremans, Caroline, Braams, Esmee, Brackett, Caroline, Brumskine, William, Chilengi, Roma, Choi, Rachel, Dubula, Thozama, Dumas, Jaiden Seongmi, Dunn, Brooke, Etikala, Radhika, Euler, Zelda, Everett, Sarah, Garrett, Nigel, Gelderblom, Huub, Gill, Katherine, Gillespie, Kevin, Goedhart, Dimitri, Goosmann, Erik, Grant, Shannon, Hands, Ellie, Haynes, Barton, Herringer, Bronwill, Hoosain, Zaheer, Hosseinipour, Mina, Hunidzarira, Portia, Hutter, Julia, Inambao, Mubiana, Innes, Craig, Keyes, Taylor, Kilembe, William, Kotze, Philippus, Kotze, Sheena, Laher, Fatima, Laszlo, Imre, Lazarus, Erica, Liao, Hua-Xin, Lin, Yong, Lu, Helen, Lucas, Judith, Malahleha, Mookho, McNair, Tara, Meerts, Peter, Mgaga, Zinhle, Montlha, Mahlodi, Mosito, Boitumelo, Moultrie, Andrew, Mudrak, Sarah, Oriol-Mathieu, Valérie, Sarzotti-Kelsoe, Marcella, Mathebula, Matson Tso, Matoga, Mitch, McClennen, Rachael, Mda, Pamela, Naicker, Vimla, Naidoo, Logashvari, Okkers, Cindy-Ann, Omarjee, Saleha, Pasmans, Hella, Philip, Tricia, Pinter, Abraham, Pitsi, Annah, Ramos, Ornelia, Randhawa, April, Roels, Sanne, Rohith, Shamiska, Rutten, Lucy, Sadoff, Jerald, Salinas, Gabriela, Salzgeber, Yvonne, Scheppler, Lorenz, Schwedhelm, Katharine, Schuller, Nicolette, Sharak, Angelina, Stanfield-Oakley, Sherry, Sopher, Carrie, Tafatatha, Terence, Takuva, Simbarashe G., Tang, Chan, Vandebosch, An, Viegas, Edna, Voillet, Valentin, Wegmann, Frank, Weijtens, Mo, Wilcox, Stephany, Williams, Anthony, Yu, Chenchen, Yu, Pei-Chun, Yuan, Olive, Zhang, Xuehan, Kenny, Avi, van Duijn, Janine, Dintwe, One, Heptinstall, Jack, Burnham, Randy, Sawant, Sheetal, Zhang, Lu, Mielke, Dieter, Khuzwayo, Sharon, Omar, Faatima Laher, Goodman, Derrick, Fong, Youyi, Benkeser, David, Zou, Rodger, Hural, John, Hyrien, Ollivier, Juraska, Michal, Luedtke, Alex, van der Laan, Lars, Giorgi, Elena E., Magaret, Craig, Carpp, Lindsay N., Pattacini, Laura, van de Kerkhof, Tom, Korber, Bette, Willems, Wouter, Fisher, Leigh H., Schuitemaker, Hanneke, Swann, Edith, Kublin, James G., Pau, Maria G., Buchbinder, Susan, Tomaka, Frank, Nijs, Steven, Lavreys, Ludo, Gelderblom, Huub C., Corey, Lawrence, Mngadi, Kathryn, Gray, Glenda E., Borducchi, Erica, Hendriks, Jenny, Seaton, Kelly E., Zolla-Pazner, Susan, Barouch, Dan H., Ferrari, Guido, De Rosa, Stephen C., McElrath, M Juliana, Andersen-Nissen, Erica, Stieh, Daniel J., Tomaras, Georgia D., and Gilbert, Peter B.
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- 2024
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3. Application of the SLAPNAP statistical learning tool to broadly neutralizing antibody HIV prevention research
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Williamson, Brian D., Magaret, Craig A., Karuna, Shelly, Carpp, Lindsay N., Gelderblom, Huub C., Huang, Yunda, Benkeser, David, and Gilbert, Peter B.
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- 2023
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4. Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial
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Julg, Boris, Stephenson, Kathryn E., Wagh, Kshitij, Tan, Sabrina C., Zash, Rebecca, Walsh, Stephen, Ansel, Jessica, Kanjilal, Diane, Nkolola, Joseph, Walker-Sperling, Victoria E. K., Ophel, Jasper, Yanosick, Katherine, Borducchi, Erica N., Maxfield, Lori, Abbink, Peter, Peter, Lauren, Yates, Nicole L., Wesley, Martina S., Hassell, Tom, Gelderblom, Huub C., deCamp, Allen, Mayer, Bryan T., Sato, Alicia, Gerber, Monica W., Giorgi, Elena E., Gama, Lucio, Koup, Richard A., Mascola, John R., Monczor, Ana, Lupo, Sofia, Rolle, Charlotte-Paige, Arduino, Roberto, DeJesus, Edwin, Tomaras, Georgia D., Seaman, Michael S., Korber, Bette, and Barouch, Dan H.
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- 2022
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5. Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial
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Stephenson, Kathryn E., Julg, Boris, Tan, C. Sabrina, Zash, Rebecca, Walsh, Stephen R., Rolle, Charlotte-Paige, Monczor, Ana N., Lupo, Sofia, Gelderblom, Huub C., Ansel, Jessica L., Kanjilal, Diane G., Maxfield, Lori F., Nkolola, Joseph, Borducchi, Erica N., Abbink, Peter, Liu, Jinyan, Peter, Lauren, Chandrashekar, Abishek, Nityanandam, Ramya, Lin, Zijin, Setaro, Alessandra, Sapiente, Joseph, Chen, Zhilin, Sunner, Lisa, Cassidy, Tyler, Bennett, Chelsey, Sato, Alicia, Mayer, Bryan, Perelson, Alan S., deCamp, Allan, Priddy, Frances H., Wagh, Kshitij, Giorgi, Elena E., Yates, Nicole L., Arduino, Roberto C., DeJesus, Edwin, Tomaras, Georgia D., Seaman, Michael S., Korber, Bette, and Barouch, Dan H.
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- 2021
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6. Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.
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Mayer, Bryan T., Zhang, Lily, deCamp, Allan C., Yu, Chenchen, Sato, Alicia, Angier, Heather, Seaton, Kelly E., Yates, Nicole, Ledgerwood, Julie E., Mayer, Kenneth, Caskey, Marina, Nussenzweig, Michel, Stephenson, Kathryn, Julg, Boris, Barouch, Dan H., Sobieszczyk, Magdalena E., Edupuganti, Srilatha, Kelley, Colleen F., McElrath, M. Juliana, and Gelderblom, Huub C.
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MONOCLONAL antibodies ,CLINICAL trials ,PHARMACOKINETICS ,MAXIMUM likelihood statistics ,HIV ,HIV antibodies - Abstract
Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial
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Priddy, Frances H, Lewis, David J M, Gelderblom, Huub C, Hassanin, Hana, Streatfield, Claire, LaBranche, Celia, Hare, Jonathan, Cox, Josephine H, Dally, Len, Bendel, Daryl, Montefiori, David, Sayeed, Eddy, Ackland, Jim, Gilmour, Jill, Schnepp, Bruce C, Wright, J Fraser, and Johnson, Philip
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- 2019
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8. Is HIV epidemic control by 2030 realistic?
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Beyrer, Chris, Tomaras, Georgia D, Gelderblom, Huub C, Gray, Glenda E, Janes, Holly E, Bekker, Linda-Gail, Millett, Gregorio, Pantaleo, Giuseppe, Buchbinder, Susan, and Corey, Lawrence
- Abstract
Rates of new HIV acquisition remain unacceptably high in most populations in low-income, middle-income, and high-income settings despite advances in treatment and prevention strategies. Although biomedical advances in primary prevention of new infections exist, systematic scale-up of these interventions has not occurred at the pace required to end AIDS by 2030. Low population coverage, adherence to oral pre-exposure prophylaxis in settings with high rates of HIV acquisition, and the fact that a significant proportion of new HIV infections occurs in populations not identified as high risk and are hence not targeted for prevention approaches impedes current prevention strategies. Although long-acting injectables and monoclonal antibodies are promising approaches to help reduce incidence, high cost and the need for high coverage rates mean that a vaccine or vaccine-like intervention still remains the most likely scenario to produce a population-level impact on HIV incidence, especially in countries with generalised epidemics. Current global efforts are not sufficient to meet 2030 HIV epidemic goals; acknowledgment of this issue is required to ensure persistent advocacy for population-based control of the ongoing HIV pandemic.
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- 2024
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9. Hepatitis B Virus Incidence and Risk Factors Among Human Immunodeficiency Virus-1 Negative Men Who Have Sex With Men in Kenya
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Wahome, Elizabeth, Ngetsa, Caroline, Mwambi, John, Gelderblom, Huub C., Manyonyi, Gloria Omosa, Micheni, Murugi, Hassan, Amin, Price, Matt A., Graham, Susan M., and Sanders, Eduard J.
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- 2017
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10. Cellular Immune Responses during High-Dose Interferon-α Induction Therapy for Hepatitis C Virus Infection
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Barnes, Eleanor, Gelderblom, Huub C., Humphreys, Isla, Semmo, Nasser, Reesink, Henk W., Beld, Marcel G. H. M., van Lier, René A. W., and Klenerman, Paul
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- 2009
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11. University students and HIV in Namibia: an HIV prevalence survey and a knowledge and attitude survey
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Beer, Ingrid H., Gelderblom, Huub C., Schellekens, Onno, Gaeb, Esegiel, Rooy, Gert, Mcnally, Alta, Wit, Ferdinand W., and Tobias, Rinke De Wit F.
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College students -- Beliefs, opinions and attitudes -- Health aspects ,HIV infection -- Risk factors -- Public opinion -- Demographic aspects ,Health - Abstract
Background: With an overall adult HIV prevalence of 15.3%, Namibia is facing one of the largest HIV epidemics in Africa. Young people aged 20 to 34 years constitute one of the groups at highest risk of HIV infection in Namibia. However, little is known about the impact of HIV on this group and its access to healthcare. The purpose of this study was to estimate HIV prevalence, to assess the knowledge of and attitudes towards HIV/AIDS, and to assess access to healthcare among university students in Namibia. Methods: We assessed HIV/AIDS knowledge and attitudes, HIV prevalence and access to healthcare among students at the Polytechnic of Namibia and the University of Namibia. HIV prevalence was tested through anonymous oral fluid‐based tests. Results: Half (n = 2790/5568) of the university students and 45% (n = 2807/6302) of the Polytechnic students participated in the knowledge and attitudes surveys. HIV/AIDS knowledge was reasonable, except for misperceptions about transmission. Awareness of one's own HIV status and risks was low. In all, 55% (n = 3055/5568) of university students and 58% (n = 3680/6302) of Polytechnic students participated in the HIV prevalence survey; 54 (1.8%) university students and 103 (2.8%) Polytechnic students tested HIV positive. Campus clinics were not the major providers of healthcare to the students. Conclusions: Meaningful strategies addressing the gap between knowledge, attitude and young people's perception of risk of HIV acquisition should be implemented. HIV prevalence among Namibian university students appears relatively low. Voluntary counselling and testing should be stimulated. Efforts should be made to increase access to healthcare through the campus clinics., Background Namibia in southern Africa has approximately 2.2 million inhabitants and is classified as a middle‐income country. The Namibian health system has both a public health service through the Ministry [...]
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- 2012
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12. Factor XIII Val34Leu mutation and liver fibrosis rate in viral hepatitis
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Dik, Kathelijne, de Bruijne, Joep, Takkenberg, Bart R., Roelofs, Joris J., Tempelmans, Marjan J., Dijkgraaf, Marcel G. W., Gelderblom, Huub C., Reesink, Henk W., Meijers, Joost C. M., Jansen, Peter L., and Levi, Marcel
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- 2012
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13. Factor XIII Val34Leu mutation accelerates the development of fibrosis in patients with chronic hepatitis B and C
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Dik, Kathelijne, de Bruijne, Joep, Takkenberg, Bart R., Roelofs, Joris J., Tempelmans, Marjan J., Dijkgraaf, Marcel G. W., Gelderblom, Huub C., Reesink, Henk W., Meijers, Joost C. M., Jansen, Peter L., and Levi, Marcel
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- 2012
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14. Warm flush at 37 °C following cold storage attenuates reperfusion injury in preserved rat livers
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van Wagensveld, Bart A., Reinders, Marcel E., van Gulik, Thomas M., Gelderblom, Huub C., Frederiks, Wilma M., Wanders, Ronald J. A., and Obertop, Huug
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- 1998
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15. Cellular immune responses during high-dose interferon-(alpha) induction therapy for hepatitis C virus infection
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Barnes, Eleanor, Gelderblom, Huub C., Humphreys, Isla, Semmo, Nasser, Reesink, Henk W., Beld, Marcel G.H.M., van Lier, Rene A.W., and Klenerman, Paul
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Cellular immunity -- Research ,Immune response -- Research ,Hepatitis C -- Care and treatment ,Hepatitis C -- Physiological aspects ,Hepatitis C -- Research ,Interferon alpha -- Dosage and administration ,Interferon alpha -- Research ,Health - Published
- 2009
16. High incidence of type 1 diabetes mellitus during or shortly after treatment with pegylated interferon α for chronic hepatitis C virus infection
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Schreuder, Tim C. M. A., Gelderblom, Huub C., Weegink, Christine J., Hamann, Dörte, Reesink, Henk W., DeVries, J. Hans, Hoekstra, Joost B. L., and Jansen, Peter L. M.
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- 2008
17. A003 Protocol - A Phase 1, randomized, blinded, dose-escalation study of rAAV1-PG9DP recombinant AAV vector coding for PG9 antibody in healthy male adults
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Priddy, Frances H., Lewis, David J. M., Gelderblom, Huub C., Hassanin, Hanaa A., Streatfield, Claire, LaBranche, Celia, Hare, Jonathan, Cox, Josephine H., Dally, Len, Bendel, Daryl, Montefiori, David, Sayeed, Eddy, Ackland, Jim, Gilmour, Jill, Schnepp, Bruce C., Wright, Fraser, and Johnson, Philip
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110309 Infectious Diseases ,FOS: Health sciences - Abstract
Clinical Trial protocol for a Phase 1, randomized, blinded, dose-escalation study of rAAV1-PG9DP recombinant AAV vector coding for PG9 antibody in healthy male adults
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- 2019
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18. Monocyte-derived dendritic cells from chronic HCV patients are not infected but show an immature phenotype and aberrant cytokine profile
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Gelderblom, Huub C., Nijhuis, Laurens E. J., de Jong, Esther C., te Velde, Anje A., Pajkrt, Dasja, Reesink, Henk W., Beld, Marcel G. H. M., van Deventer, Sander J. H., and Jansen, Peter L. M.
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- 2007
19. Viral complementation allows HIV-1 replication without integration
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Bristol Gregory C, Lawrie Steven D, Burke Sean A, Vatakis Dimitrios N, Gelderblom Huub C, and Levy David N
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background The integration of HIV-1 DNA into cellular chromatin is required for high levels of viral gene expression and for the production of new virions. However, the majority of HIV-1 DNA remains unintegrated and is generally considered a replicative dead-end. A limited amount of early gene expression from unintegrated DNA has been reported, but viral replication does not proceed further in cells which contain only unintegrated DNA. Multiple infection of cells is common, and cells that are productively infected with an integrated provirus frequently also contain unintegrated HIV-1 DNA. Here we examine the influence of an integrated provirus on unintegrated HIV-1 DNA (uDNA). Results We employed reporter viruses and quantitative real time PCR to examine gene expression and virus replication during coinfection with integrating and non-integrating HIV-1. Most cells which contained only uDNA displayed no detected expression from fluorescent reporter genes inserted into early (Rev-independent) and late (Rev-dependent) locations in the HIV-1 genome. Coinfection with an integrated provirus resulted in a several fold increase in the number of cells displaying uDNA early gene expression and efficiently drove uDNA into late gene expression. We found that coinfection generates virions which package and deliver uDNA-derived genomes into cells; in this way uDNA completes its replication cycle by viral complementation. uDNA-derived genomes undergo recombination with the integrated provirus-derived genomes during second round infection. Conclusion This novel mode of retroviral replication allows survival of viruses which would otherwise be lost because of a failure to integrate, amplifies the effective amount of cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the opportunity for diversification through errors of polymerization and recombination.
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- 2008
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20. OUTCOMES OF AHI SCREENING AND IMMEDIATE ART INITIATION IN COASTAL KENYA
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Sanders, Eduard, Chirro, Oscar, Oduor, Clifford, Juma Mangi, Wahome, Elizabeth, Price, Matt A., Gelderblom, Huub C., Elst, Elisabeth M. Van Der, and Graham, Susan M.
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- 2017
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21. Acceptability and tolerability of repeated intramuscular electroporation of Multi-antigenic HIV (HIVMAG) DNA vaccine among healthy African participants in a phase 1 randomized controlled trial.
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Mpendo, Juliet, Mutua, Gaudensia, Nanvubya, Annet, Anzala, Omu, Nyombayire, Julien, Karita, Etienne, Dally, Len, Hannaman, Drew, Price, Matt, Fast, Patricia E., Priddy, Frances, Gelderblom, Huub C., and Hills, Nancy K.
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ELECTROPORATION ,DNA vaccines ,AIDS vaccines ,MUSCLE contraction ,AFRICANA studies - Abstract
Introduction: Intramuscular electroporation (IM/EP) is a vaccine delivery technique that improves the immunogenicity of DNA vaccines. We evaluated the acceptability and tolerability of electroporation among healthy African study participants. Methods: Forty-five participants were administered a DNA vaccine (HIV-MAG) or placebo by electroporation at three visits occurring at four week-intervals. At the end of each visit, participants were asked to rate pain at four times: (1) when the device was placed on the skin and vaccine injected, before the electrical stimulation, (2) at the time of electrical stimulation and muscle contraction, and (3) at 10 minutes and (4) 30 minutes after the procedure was completed. For analyses, pain level was dichotomized as either "acceptable" (none/slight/uncomfortable) or "too much" (Intense, severe, and very severe) and examined over time using repeated measures models. Optional brief comments made by participants were summarized anecdotally. Results: All 45 participants completed all three vaccination visits; none withdrew from the study due to the electroporation procedure. Most (76%) reported pain levels as acceptable at every time point across all vaccination visits. The majority of "unacceptable" pain was reported at the time of electrical stimulation. The majority of the participants (97%) commented that they preferred electroporation to standard injection. Conclusion: Repeated intramuscular electroporation for vaccine delivery was found to be acceptable and feasible among healthy African HIV vaccine trial participants. The majority of participants reported an acceptable pain level at all vaccination time points. Further investigation may be warranted into the value of EP to improve immunization outcomes. ClinicalTrials.gov NCT01496989 [ABSTRACT FROM AUTHOR]
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- 2020
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22. University students and HIV in Namibia: an HIV prevalence survey and a knowledge and attitude survey
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de Beer, Ingrid H., Gelderblom, Huub C., Schellekens, Onno, Gaeb, Esegiel, van Rooy, Gert, McNally, Alta, Wit, Ferdinand W., and Tobias, Rinke de Wit F.
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HIV (Viruses) -- Statistics -- Demographic aspects -- Care and treatment -- Surveys ,College students -- Surveys -- Health aspects ,Health education -- Surveys ,Highly active antiretroviral therapy -- Usage -- Health aspects ,Health - Abstract
Background With an overall adult HIV prevalence of 15.3%, Namibia is facing one of the largest HIV epidemics in Africa. Young people aged 20 to 34 years constitute one of the groups at highest risk of HIV infection in Namibia. However, little is known about the impact of HIV on this group and its access to healthcare. The purpose of this study was to estimate HIV prevalence, to assess the knowledge of and attitudes towards HIV/AIDS, and to assess access to healthcare among university students in Namibia. Methods We assessed HIV/AIDS knowledge and attitudes, HIV prevalence and access to healthcare among students at the Polytechnic of Namibia and the University of Namibia. HIV prevalence was tested through anonymous oral fluid-based tests. Results Half (n = 2790/5568) of the university students and 45% (n = 2807/6302) of the Polytechnic students participated in the knowledge and attitudes surveys. HIV/AIDS knowledge was reasonable, except for misperceptions about transmission. Awareness of one's own HIV status and risks was low. In all, 55% (n = 3055/5568) of university students and 58% (n = 3680/6302) of Polytechnic students participated in the HIV prevalence survey; 54 (1.8%) university students and 103 (2.8%) Polytechnic students tested HIV positive. Campus clinics were not the major providers of healthcare to the students. Conclusions Meaningful strategies addressing the gap between knowledge, attitude and young people's perception of risk of HIV acquisition should be implemented. HIV prevalence among Namibian university students appears relatively low. Voluntary counselling and testing should be stimulated. Efforts should be made to increase access to healthcare through the campus clinics., Authors: Ingrid H de Beer (corresponding author) (equal contributor) [1]; Huub C Gelderblom (equal contributor) [2,3,4]; Onno Schellekens [5]; Esegiel Gaeb [6]; Gert van Rooy [7]; Alta McNally [8]; Ferdinand [...]
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- 2012
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23. Clinical Performance of the New Roche Cobas® Taqman HCV Test and High Pure System for Extraction, Detection and Quantitation of HCV RNA in Plasma and Serum
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Gelderblom, Huub C., Menting, Sandra, Beld, Marcel G., Medical Microbiology and Infection Prevention, and KIT: Biomedical Research
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Pharmacology ,Infectious Diseases ,virus diseases ,Pharmacology (medical) ,digestive system diseases - Abstract
We evaluated the Roche COBAS® TaqMan HCV Test For Use With The High Pure System (TaqMan HPS; Roche Diagnostics), for the extraction, detection and quantitation of hepatitis C virus (HCV) RNA in serum or plasma of HCV-infected individuals. The TaqMan HPS is a real-time PCR assay with a reported linear dynamic range of 3.0x101 to 2.0x108 HCV RNA IU/ml, and a reported lower limit of detection (LLD) of 10 IU/ml. Calculation of the HCV RNA titre is based upon an external standard curve in the presence of an internal control. Intra-assay and inter-assay variation were small in reference panel members with HCV RNA ≥100 IU/ml. Genotype performance and quantitative correlation between the TaqMan HPS and the bDNA (VERSANT® HCV 3.0 assay; Bayer Diagnostics), assessed in 59 patient samples, were good for HCV genotype 1 but poor for genotypes 2, 3 and 4. For genotypes 2, 3 and 4, values obtained from the TaqMan HPS were in general 0.5 log lower than those from the bDNA. Sensitivity was poor in low viral titre samples of genotypes 1, 2, 3 and 4. The LLD (95%) was estimated at 41 HCV RNA IU/ml for genotype 4. The TaqMan HPS underestimates HCV RNA at all levels in plasma and serum from HCV-infected individuals, and the LLD should be reconsidered. This is clinically relevant because underestimation of HCV RNA levels during therapy may lead physicians into making incorrect treatment decisions.
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- 2006
24. HIV virologic failure and its predictors among HIV-infected adults on antiretroviral therapy in the African Cohort Study.
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Kiweewa, Francis, Esber, Allahna, Musingye, Ezra, Reed, Domonique, Crowell, Trevor A., Cham, Fatim, Semwogerere, Michael, Namagembe, Rosemary, Nambuya, Alice, Kafeero, Cate, Tindikahwa, Allan, Eller, Leigh Anne, Millard, Monica, Gelderblom, Huub C., Keshinro, Babajide, Adamu, Yakubu, Maswai, Jonah, Owuoth, John, Sing’oei, Valentine Chepkorir, and Maganga, Lucas
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HIV-positive persons ,ANTIRETROVIRAL agents ,VIROLOGY ,VIREMIA ,IMMUNODEFICIENCY ,RETROVIRUSES - Abstract
Introduction: The 2016 WHO consolidated guidelines on the use of antiretroviral drugs defines HIV virologic failure for low and middle income countries (LMIC) as plasma HIV-RNA ≥ 1000 copies/mL. We evaluated virologic failure and predictors in four African countries. Materials and methods: We included HIV-infected participants on a WHO recommended antiretroviral therapy (ART) regimen and enrolled in the African Cohort Study between January 2013 and October 2017. Studied outcomes were virologic failure (plasma HIV-RNA ≥ 1000 copies/mL at the most recent visit), viraemia (plasma HIV-RNA ≥ 50 copies/mL at the most recent visit); and persistent viraemia (plasma HIV-RNA ≥ 50 copies/mL at two consecutive visits). Generalized linear models were used to estimate relative risks with their 95% confidence intervals. Results: 2054 participants were included in this analysis. Viraemia, persistent viraemia and virologic failure were observed in 396 (19.3%), 160 (7.8%) and 184 (9%) participants respectively. Of the participants with persistent viraemia, only 57.5% (92/160) had confirmed virologic failure. In the multivariate analysis, attending clinical care site other than the Uganda sitebeing on 2
nd line ART (aRR 1.8, 95% CI 1·28–2·66); other ART combinations not first line and not second line (aRR 3.8, 95% CI 1.18–11.9), a history of fever in the past week (aRR 3.7, 95% CI 1.69–8.05), low CD4 count (aRR 6.9, 95% CI 4.7–10.2) and missing any day of ART (aRR 1·8, 95% CI 1·27–2.57) increased the risk of virologic failure. Being on 2nd line therapy, the site where one receives care and CD4 count < 500 predicted viraemia, persistent viraemia and virologic failure. Conclusion: In conclusion, these findings demonstrate that HIV-infected patients established on ART for more than six months in the African setting frequently experienced viraemia while continuing to be on ART. The findings also show that being on second line, low CD4 count, missing any day of ART and history of fever in the past week remain important predictors of virologic failure that should trigger intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, clinical care sites are different calling for further analyses to elucidate on the unique features of these sites. [ABSTRACT FROM AUTHOR]- Published
- 2019
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25. Towards optimal treatment for chronic hepatitis C infection
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Gelderblom, Huub C., Jansen, Peter L. M., Beld, Marcellinus G. H. M., Reesink, Hendrik W., and Medical Microbiology
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- 2008
26. High incidence of type 1 diabetes mellitus during or shortly after treatment with pegylated interferon alpha for chronic hepatitis C virus infection
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Schreuder, Tim C. M. A., Gelderblom, Huub C., Weegink, Christine J., Hamann, Dörte, Reesink, Henk W., DeVries, J. Hans, Hoekstra, Joost B. L., Jansen, Peter L. M., Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, Landsteiner Laboratory, Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Amsterdam Cardiovascular Sciences, and General Internal Medicine
- Abstract
BACKGROUND: Development of diabetes mellitus (DM) during or shortly after treatment with interferon alpha (IFN-alpha) in patients with chronic hepatitis C virus (HCV) infection has been reported sporadically. We prospectively screened for DM during and after IFN-alpha therapy for chronic HCV infection. METHODS: Blood glucose levels of patients with chronic HCV infection were routinely assessed at all outpatient visits during and after treatment with pegylated-IFN-alpha (Peg-IFN-alpha) and ribavirin (Riba). RESULTS: Between December 2002 and October 2005, 189 non-diabetic patients were treated with Peg-IFN-alpha/Riba, of whom five developed type 1 DM (2.6%), three type 2 DM (1.6%) and one an indeterminate type of DM. Classical symptoms of DM were present in three patients who developed DM shortly after cessation of Peg-IFN-alpha/Riba. In the other patients, symptoms of DM were either indistinguishable from side effects caused by Peg-IFN-alpha/Riba or absent. CONCLUSION: Our study showed a high incidence of type 1 DM during Peg-IFN-alpha/Riba therapy for chronic HCV infection. Symptoms of DM may be absent or mistaken for Peg-IFN-alpha/Riba-associated side effects. To diagnose DM without delay, we propose routine assessment of blood glucose at all outpatient visits during and after Peg-IFN-alpha/Riba treatment in chronic HCV patients
- Published
- 2008
27. Low-level HCV viraemia after initial response during antiviral therapy: transcription-mediated amplification predicts treatment failure
- Author
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Gelderblom, Huub C., Reesink, Henk W., Beld, Marcel G. H. M., Weegink, Christine J., Jansen, Peter L. M., Dijkgraaf, Marcel G. W., Zaaijer, Hans L., Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Public Health, Epidemiology and Data Science, and Amsterdam institute for Infection and Immunity
- Subjects
virus diseases ,digestive system diseases - Abstract
BACKGROUND: In chronic hepatitis C patients with an initial virological response (IVR) during antiviral therapy (that is, HCV RNA becomes negative before week 16 of treatment) the significance of reappearing viraemia below the detection limit of PCR is not known. We studied this phenomenon in subsets of patients. METHODS: We assessed HCV RNA at weeks 16 and 20 of therapy by PCR and by more sensitive transcription-mediated amplification (TMA) in 23 patients with breakthrough or relapse and in 34 patients with sustained virological response (SVR). All patients participated in a high-dose-interferon induction study for difficult-to-treat patients. Therapy consisted of amantadine hydrochloride and ribavirin, combined with interferon-alpha2b induction during the first 6 weeks and thereafter combined with weekly pegylated interferon-alpha2b. RESULTS: Among the 57 IVR patients, we detected transient or persistent reappearance of low levels of HCV RNA in 10 of the 23 (43%) patients with eventual breakthrough or relapse; but in none of the 34 SVR patients. In 5 of 10 patients reappearing HCV RNA was only detectable by TMA. CONCLUSION: Reappearance of low levels of HCV RNA in patients with IVR predicts treatment failure
- Published
- 2007
28. Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 Point-of-Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in Durban, South Africa.
- Author
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Jaggernath, Manjeetha, Naicker, Rumallen, Madurai, Savathree, Brockman, Mark A., Ndung’u, Thumbi, and Gelderblom, Huub C.
- Subjects
POINT-of-care testing ,HEMOGLOBINS ,COMMUNITY health services ,MEDICAL research ,BIOLOGICAL assay - Abstract
In South Africa, various point-of-care hemoglobin meters are used. However, the regulatory framework for approval, implementation and oversight of use of point-of-care hemoglobin meters is suboptimal. We assessed the diagnostic accuracy of the HemoCue Hb 301, STAT-Site M
Hgb and URIT-12 point-of-care hemoglobin meters, compared to a central laboratory based reference assay, in a central laboratory and a community based clinic in Durban, South Africa. Differences in performance of the point-of-care assays, compared to the reference assay, were more pronounced in the community based clinic. Results were reasonable for the HemoCue Hb 301, but poor for the STAT-Site MHgb and the URIT-12. Poor test performance of point-of-care hemoglobin meters, and inadequate evaluations and oversight in South Africa, leads to suboptimal clinical care and clinical research, and increased costs. There is a need for proper evaluation and quality assurance of point-of-care tests, the results of which should be made widely available to key stakeholders. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
29. Mass Drug Administration for Trachoma: How Long Is Not Long Enough?
- Author
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Jimenez, Violeta, Gelderblom, Huub C., Mann Flueckiger, Rebecca, Emerson, Paul M., and Haddad, Danny
- Subjects
- *
TRACHOMA , *DRUG administration , *INFECTIOUS disease transmission , *SYMPTOMS , *LOGISTIC regression analysis - Abstract
Background: Blinding trachoma is targeted for elimination by 2020 using the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements). Annual mass drug administration (MDA) with azithromycin is a cornerstone of this strategy. If baseline prevalence of clinical signs of trachomatous inflammation – follicular among 1-9 year-olds (TF1-9) is ≥10% but <30%, the World Health Organization guidelines are for at least 3 annual MDAs; if ≥30%, 5. We assessed the likelihood of achieving the global elimination target of TF1-9 <5% at 3 and 5 year evaluations using program reports. Methodology/Principal Findings: We used the International Trachoma Initiative's prevalence and treatment database. Of 283 cross-sectional survey pairs with baseline and follow-up data, MDA was conducted in 170 districts. Linear and logistic regression modeling was applied to these to investigate the effect of MDA on baseline prevalence. Reduction to <5% was less likely, though not impossible, at higher baseline TF1-9 prevalences. Increased number of annual MDAs, as well as no skipped MDAs, were significant predictors of reduced TF1-9 at follow-up. The probability of achieving the <5% target was <50% for areas with ≥30% TF1-9 prevalence at baseline, even with 7 or more continuous annual MDAs. Conclusions: Number of annual MDAs alone appears insufficient to predict program progress; more information on the effects of baseline prevalence, coverage, and underlying environmental and hygienic conditions is needed. Programs should not skip MDAs, and at prevalences >30%, 7 or more annual MDAs may be required to achieve the target. There are five years left before the 2020 deadline to eliminate blinding trachoma. Low endemic settings are poised to succeed in their elimination goals. However, newly-identified high prevalence districts warrant immediate inclusion in the global program. Intensified application of the SAFE strategy is needed in order to guarantee blinding trachoma elimination by 2020. Author Summary: Trachoma, the world's leading infectious cause of blindness, is scheduled for elimination by 2020. Reaching this elimination target depends on successful implementation of the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements). Annual mass antibiotic distributions are key to breaking the cycle of transmission in a community. However, it is not clear how many annual mass treatments need to be carried out in order to achieve elimination. Our study analyzes the effect of mass antibiotic distribution on different baseline prevalence levels of trachoma, in order to assess factors that affect the success of reaching elimination goals. We find that the prevailing belief, which suggests that 3 annual mass treatments can achieve local elimination of trachoma at prevalences between 10–30%, and 5 annual mass treatments for districts above this benchmark, is probably incorrect. In fact, much longer intervals may be required with "business as usual" programmatic strategies, which often include skipped years of treatment. Districts with high prevalence levels may require more intense treatment strategies to eliminate trachoma. Intensified recommendations must be implemented without delay in order to reach the 2020 elimination deadline. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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30. Integrating Data and Resources on Neglected Tropical Diseases for Better Planning: The NTD Mapping Tool (NTDmap.org).
- Author
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Flueckiger, Rebecca M., Nikolay, Birgit, Gelderblom, Huub C., Smith, Jennifer L., Haddad, Danny, Tack, Wesley, Hendrickx, Guy, Addiss, David, Cano, Jorge, Hatcher, Danny R., Hopkins, Adrian, Pullan, Rachel L., Pavluck, Alex, Ottesen, Eric, and Brooker, Simon J.
- Subjects
NEGLECTED diseases - Abstract
This article discusses the importance of mapping neglected tropical diseases (NTDs) to effectively plan interventions. It highlights various resources that provide detailed information on the geographical distribution of NTDs and emphasizes the need for accessible tools for policymakers and program staff. The article introduces an innovative online tool that allows users to visualize and manipulate geographical data for NTD programs. The tool has been developed based on the needs and feedback of NTD control programs and includes features such as overlaying map layers, combining data sources, and viewing multiple variables. It has been piloted and refined based on user feedback and will continue to be developed further. Overall, the tool is a valuable resource for planning, implementing, and evaluating NTD control activities. [Extracted from the article]
- Published
- 2015
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31. COVID-19 vaccine roll-out in South Africa: The added value of wastewater surveillance for SARS-CoV-2.
- Author
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Street, Renée A., Mathee, Angela, Johnson, Rabia, Muller, Christo J. F., Louw, Johan, Mdhluli, Mongezi, Gelderblom, Huub C., and Gray, Glenda E.
- Published
- 2021
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32. Inflammatory markers neopterin and alanine aminotransferase in HCV patients treated with HCV NS3•4A protease inhibitor telaprevir (VX-950) and/or peginterferon alfa-2a.
- Author
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Gelderblom, Huub C., Zeuzem, Stefan, Weegink, Christine J., Forestier, Nicole, Mcnair, Lindsay, Purdy, Susan, Dijkgraaf, Marcel G. W., Jansen, Peter L. M., and Reesink, Henk W.
- Subjects
- *
LIVER cells , *NEOPTERIN , *ALANINE aminotransferase , *HEPATITIS C virus , *MONOCYTES , *PLACEBOS , *INFLAMMATION - Abstract
Objective. Neopterin is a marker of monocyte/macrophage activity. Alanine aminotransferase (ALAT) is a marker of hepatocyte injury. The aim of this study was to determine changes in neopterin and ALAT levels, as markers of inflammation, in two ancillary studies during two-phase 1b trials of hepatitis C virus (HCV) NS3•4A protease inhibitor telaprevir (VX-950), with or without peginterferon alfa-2a (Peg-IFN). Material and methods. Fifty-four chronic hepatitis C patients (genotype 1) received placebo or telaprevir, with or without Peg-IFN, for 14 days in two multiple-dose studies. Results. During administration of telaprevir, every patient demonstrated a >2-log decrease in HCV RNA. Mean neopterin and ALAT levels decreased in all four groups receiving telaprevir alone. In contrast, mean neopterin levels increased and ALAT levels decreased in the Peg-IFN plus telaprevir and Peg-IFN plus placebo groups. Conclusions. These data suggest that treatment of chronic hepatitis C patients with an HCV NS3•4A protease inhibitor ameliorates inflammation. The increase in neopterin levels and the decrease in ALAT levels during administration of Peg-IFN with or without telaprevir are in accordance with earlier observations showing that IFN reduces hepatocyte injury but increases monocyte/macrophage activity. The IFN-mediated immunomodulatory effects appear to remain intact when IFN is combined with telaprevir. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
33. Prediction of virologic response in difficult-to-treat chronic hepatitis C patients during high-dose interferon induction therapy.
- Author
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Gelderblom, Huub C., Zaaijer, Hans L., Dijkgraaf, Marcel G. W., Van Der Meer, Jan, Weegink, Christine J., Jansen, Peter L. M., Beld, Marcel G. H. M., and Reesink, Henk W.
- Subjects
- *
HEPATITIS C , *INTERFERONS , *AMANTADINE , *RIBAVIRIN , *RNA , *PATIENTS , *THERAPEUTICS - Abstract
Objective. To determine (i) whether early viral kinetics or other markers during a modified treatment regimen are predictors of treatment outcome and (ii) whether fast responders can be treated for 24 weeks, without compromising the sustained virologic response (SVR) rate. Material and methods. One hundred “difficult-to-treat” chronic hepatitis C patients (46 previous non-responders/relapsers (any genotype), 54 treatment-naive patients genotypes 1 and 4) were treated with triple antiviral induction therapy: amantadine hydrochloride and ribavirin, combined with 6 weeks interferon alfa-2b induction (weeks 1-2: 18 MU/day, weeks 3-4: 9 MU/day, weeks 5-6: 6 MU/day), thereafter combined with weekly peginterferon alfa-2b. Fast responders (≥3 log10 HCV RNA decline at week 4) were randomized to 24 or 48 weeks. Slow responders (<3 log10 HCV RNA decline at week 4) were treated for 48 weeks. Treatment was stopped in patients with detectable HCV RNA at week 24. Results. Thirty-six patients achieved SVR: 28 of 60 fast responders (47%) versus 8 of 32 slow responders (25%, p<0.05). Relapse rates among fast responders treated for 24 or 48 weeks were 27% and 20%, respectively (p=NS). SVR in fast responders was independent of baseline HCV RNA ≥ or <600,000 IU/mL. All treatment-naive patients with HCV RNA <5 IU/mL at week 1 or 2 achieved SVR; all treatment-naive patients with HCV RNA ≥5 IU/mL at week 16 became non-SVR. In previous non-responders/relapsers, the predictive value for SVR was 83% if HCV RNA was <5 IU/mL at week 2; all previous non-responders/relapsers with HCV RNA ≥5 IU/mL at week 8 became non-SVR. Conclusions. With high-dose interferon induction, SVR and non-SVR can be predicted reliably within 16 weeks. Fast responders can be treated for 24 weeks, and SVR is independent of baseline viral load in fast responders. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
34. Viral complementation allows HIV-1 replication without integration.
- Author
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Gelderblom, Huub C., Vatakis, Dimitrios N., Burke, Sean A., Lawrie, Steven D., Bristol, Gregory C., and Levy, David N.
- Subjects
- *
VIRAL replication , *HIV , *GENE expression , *GENOMES , *DNA - Abstract
Background: The integration of HIV-1 DNA into cellular chromatin is required for high levels of viral gene expression and for the production of new virions. However, the majority of HIV-1 DNA remains unintegrated and is generally considered a replicative dead-end. A limited amount of early gene expression from unintegrated DNA has been reported, but viral replication does not proceed further in cells which contain only unintegrated DNA. Multiple infection of cells is common, and cells that are productively infected with an integrated provirus frequently also contain unintegrated HIV-1 DNA. Here we examine the influence of an integrated provirus on unintegrated HIV-1 DNA (uDNA). Results: We employed reporter viruses and quantitative real time PCR to examine gene expression and virus replication during coinfection with integrating and non-integrating HIV-1. Most cells which contained only uDNA displayed no detected expression from fluorescent reporter genes inserted into early (Rev-independent) and late (Rev-dependent) locations in the HIV-1 genome. Coinfection with an integrated provirus resulted in a several fold increase in the number of cells displaying uDNA early gene expression and efficiently drove uDNA into late gene expression. We found that coinfection generates virions which package and deliver uDNA-derived genomes into cells; in this way uDNA completes its replication cycle by viral complementation. uDNA-derived genomes undergo recombination with the integrated provirus-derived genomes during second round infection. Conclusion: This novel mode of retroviral replication allows survival of viruses which would otherwise be lost because of a failure to integrate, amplifies the effective amount of cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the opportunity for diversification through errors of polymerization and recombination. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
35. Continuous or Intermittent Vascular Clamping during Hemihepatectomy in Pigs: Hyaluronic Acid Kinetics in the Assessment of Early Microvascular Liver Damage.
- Author
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van Wagensveld, Bart A., van Gulik, Thomas M., Gelderblom, Huub C., Scheepers, Joris J. G., Bosma, Anne, Endert, Erik, Obertop, Huug, and Gouma, Dirk J.
- Subjects
HYALURONIC acid ,MICROCIRCULATION disorders ,HEPATECTOMY - Abstract
Objective: To assess the uptake of hyaluronic acid (HA) as a marker of microvascular damage in a model of hemihepatectomy in pigs having continuous or intermittent vascular inflow occlusion. Design: Prospective, animal study. Setting: Laboratory for experimental surgery, University hospital, The Netherlands. Interventions: Total liver ischaemia was achieved during 90 minutes by continuous (n = 5) or intermittent (n = 5) occlusion of the portal vein and hepatic artery followed by 120 minutes of reperfusion. In a second series of pigs (n = 8) a left hemihepatectomy was added to the protocol. Main outcome measures: Uptake of exogenous HA was assessed before ischaemia and after 120 minutes of reperfusion, together with the galactose elimination capacity. Plasma activities of aspartate aminotransferase (AST), alanine amino transferase, and lactate dehydrogenase were measured and specimens of liver were obtained for histopathological examination. Results: HA uptake was slightly reduced after reperfusion in unresected livers compared with uptake before ischaemia. After hemihepatectomy HA uptake after reperfusion was significantly reduced after both continuous and intermittent occlusion, but more HA was taken up after continuous occlusion (p = 0.02). Release of AST after reperfusion was increased only after hemihepatectomy. Conclusions: Microvascular damage, as assessed by HA uptake capacity, significantly contributed to normothermic ischaemia and reperfusion injury in porcine liver. Vascular inflow occlusion during 90 minutes in combination with hemihepatectomy resulted in less liver damage when vascular occlusion was continuous rather than intermittent. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
36. Warm flush at 37°C following cold storage attenuates reperfusion injury in preserved rat livers.
- Author
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Wagensveld, Bart A., Reinders, Marcel E., Gulik, Thomas M., Gelderblom, Huub C., Frederiks, Wilma M., Wanders, Ronald J. A., and Obertop, Huug
- Published
- 1998
- Full Text
- View/download PDF
37. Hepatitis C virus RNA quantification by the COBAS ® AmpliPrep ®/COBAS ® TaqMan ® System: Averages do not tell the whole story
- Author
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Gelderblom, Huub C. and Beld, Marcel G.H.M.
- Published
- 2007
- Full Text
- View/download PDF
38. Reply from the authors.
- Author
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Dik, Kathelijne, de Bruijne, Joep, Takkenberg, R. Bart, Roelofs, Joris J., Tempelmans, Marjan J., Dijkgraaf, Marcel G. W., Gelderblom, Huub C., Reesink, Henk W., Meijers, Joost C. M., Jansen, Peter L., and Levi, Marcel
- Subjects
LETTERS to the editor ,FIBROSIS ,VIRAL hepatitis ,ANTIVIRAL agents ,THROMBOSIS ,PHOSPHOLIPID antibodies - Published
- 2012
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- View/download PDF
39. Transient reappearance of serum hepatitis C virus RNA observed by real-time PCR during antiviral therapy with peginterferon and ribavirin: Reappearance of references published in 2005–2009
- Author
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Gelderblom, Huub C. and Beld, Marcel G.H.M.
- Published
- 2010
- Full Text
- View/download PDF
40. Hepatitis C virus RNA quantification by the COBAS® AmpliPrep®/COBAS® TaqMan® System: Averages do not tell the whole story
- Author
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Gelderblom, Huub C. and Beld, Marcel G.H.M.
- Published
- 2007
- Full Text
- View/download PDF
41. Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.
- Author
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Kenny A, van Duijn J, Dintwe O, Heptinstall J, Burnham R, Sawant S, Zhang L, Mielke D, Khuzwayo S, Omar FL, Stanfield-Oakley S, Keyes T, Dunn B, Goodman D, Fong Y, Benkeser D, Zou R, Hural J, Hyrien O, Juraska M, Luedtke A, van der Laan L, Giorgi EE, Magaret C, Carpp LN, Pattacini L, van de Kerkhof T, Korber B, Willems W, Fisher LH, Schuitemaker H, Swann E, Kublin JG, Pau MG, Buchbinder S, Tomaka F, Nijs S, Lavreys L, Gelderblom HC, Corey L, Mngadi K, Gray GE, Borducchi E, Hendriks J, Seaton KE, Zolla-Pazner S, Barouch DH, Ferrari G, De Rosa SC, McElrath MJ, Andersen-Nissen E, Stieh DJ, Tomaras GD, and Gilbert PB
- Subjects
- Humans, Female, Case-Control Studies, Male, Adult, Vaccine Efficacy, HIV Antibodies blood, HIV Antibodies immunology, Immunoglobulin G blood, Immunoglobulin G immunology, env Gene Products, Human Immunodeficiency Virus immunology, Africa, Southern, Young Adult, Southern African People, AIDS Vaccines immunology, AIDS Vaccines administration & dosage, HIV Infections immunology, HIV Infections prevention & control, HIV Infections virology, HIV-1 immunology
- Abstract
Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models., Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions., Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker., Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen., Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV., Competing Interests: Declaration of interests TvdK has a patent application with Johnson & Johnson and has stocks in Johnson & Johnson. BK received internal support for the present manuscript from her employer (Los Alamos National Laboratory). In the past 36 months, she received support for attending meetings and/or travel from NIH NIAID and from the Gates foundation. Her institution (LANL) had a patent on this work, although she did not receive any personal funds through this patent and was not involved with the licensing of the design to Johnson & Johnson. DHB has a patent on the mosaic HIV vaccine, but no royalties. FT was an employee of Janssen/Johnson & Johnson at the time the work was conducted and owns stock in Johnson & Johnson. LL received support from Janssen Infectious Diseases BV, Beerse, Belgium for travel expenses to attend HIV conferences and has stock or stock options in Johnson & Johnson. JvD, MGP, WW, TvdK and JHen are employees of Janssen/Johnson & Johnson and hold stock or stock options in Johnson & Johnson. WW has a patent planned, issued, or pending with Johnson & Johnson. SCDR had contracts in the past 36 months to perform immunogenicity testing for Janssen, Sanofi, and Moderna. HS and DJS were employees of Janssen Vaccines & Prevention BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. SN was an employee of Janssen Infectious Diseases BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. LP was an employee of Janssen Vaccines & Prevention BV at the time the work was conducted. GDT has received consulting fees for a scientific consulting session. All other authors have no potential competing interests to disclose. Funding for the Imbokodo Study and Correlates Group is the same as listed in “Acknowledgments” for the current work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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- View/download PDF
42. Hepatitis B Virus Incidence and Risk Factors Among Human Immunodeficiency Virus-1 Negative Men Who Have Sex With Men in Kenya.
- Author
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Wahome E, Ngetsa C, Mwambi J, Gelderblom HC, Manyonyi GO, Micheni M, Hassan A, Price MA, Graham SM, and Sanders EJ
- Abstract
No data exist on hepatitis B virus (HBV) incidence among African men who have sex with men (MSM). We tested plasma samples archived between 2005 and 2014 for HBV core antibody or surface antigen seroconversion in a cohort of 312 initially human immunodeficiency virus (HIV)-1-negative MSM with no evidence of prior HBV infection. Hepatitis B virus incidence was 6.0/100 person-years (95% confidence interval [CI], 3.9-9.1). Hepatitis B virus acquisition was associated with being uncircumcised (adjusted incidence rate ratio [aIRR], 5.0; 95% CI, 1.5-16.8), recent HIV-1 acquisition (aIRR, 2.9; 95% CI, 1.1-7.7), rape (aIRR, 5.0; 95% CI, 1.2-20.4), and any tertiary education (aIRR, 3.2; 95% CI, 1.1-9.7). African MSM have a substantial risk of HBV acquisition and require vaccination urgently.
- Published
- 2016
- Full Text
- View/download PDF
43. Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 Point-of-Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in Durban, South Africa.
- Author
-
Jaggernath M, Naicker R, Madurai S, Brockman MA, Ndung'u T, and Gelderblom HC
- Subjects
- Adolescent, Adult, Humans, Male, Middle Aged, South Africa epidemiology, Anemia blood, Anemia diagnosis, Hemoglobins metabolism, Hospitals, Community, Point-of-Care Systems
- Abstract
In South Africa, various point-of-care hemoglobin meters are used. However, the regulatory framework for approval, implementation and oversight of use of point-of-care hemoglobin meters is suboptimal. We assessed the diagnostic accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 point-of-care hemoglobin meters, compared to a central laboratory based reference assay, in a central laboratory and a community based clinic in Durban, South Africa. Differences in performance of the point-of-care assays, compared to the reference assay, were more pronounced in the community based clinic. Results were reasonable for the HemoCue Hb 301, but poor for the STAT-Site MHgb and the URIT-12. Poor test performance of point-of-care hemoglobin meters, and inadequate evaluations and oversight in South Africa, leads to suboptimal clinical care and clinical research, and increased costs. There is a need for proper evaluation and quality assurance of point-of-care tests, the results of which should be made widely available to key stakeholders.
- Published
- 2016
- Full Text
- View/download PDF
44. High incidence of type 1 diabetes mellitus during or shortly after treatment with pegylated interferon alpha for chronic hepatitis C virus infection.
- Author
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Schreuder TC, Gelderblom HC, Weegink CJ, Hamann D, Reesink HW, Devries JH, Hoekstra JB, and Jansen PL
- Subjects
- Blood Glucose analysis, C-Peptide blood, DNA Probes, HLA, Female, Humans, Interferon alpha-2, Interferon-alpha therapeutic use, Male, Polyethylene Glycols therapeutic use, Recombinant Proteins, Ribavirin therapeutic use, Diabetes Mellitus, Type 1 etiology, Hepatitis C, Chronic drug therapy, Interferon-alpha adverse effects, Polyethylene Glycols adverse effects, Ribavirin adverse effects
- Abstract
Background: Development of diabetes mellitus (DM) during or shortly after treatment with interferon alpha (IFN-alpha) in patients with chronic hepatitis C virus (HCV) infection has been reported sporadically. We prospectively screened for DM during and after IFN-alpha therapy for chronic HCV infection., Methods: Blood glucose levels of patients with chronic HCV infection were routinely assessed at all outpatient visits during and after treatment with pegylated-IFN-alpha (Peg-IFN-alpha) and ribavirin (Riba)., Results: Between December 2002 and October 2005, 189 non-diabetic patients were treated with Peg-IFN-alpha/Riba, of whom five developed type 1 DM (2.6%), three type 2 DM (1.6%) and one an indeterminate type of DM. Classical symptoms of DM were present in three patients who developed DM shortly after cessation of Peg-IFN-alpha/Riba. In the other patients, symptoms of DM were either indistinguishable from side effects caused by Peg-IFN-alpha/Riba or absent., Conclusion: Our study showed a high incidence of type 1 DM during Peg-IFN-alpha/Riba therapy for chronic HCV infection. Symptoms of DM may be absent or mistaken for Peg-IFN-alpha/Riba-associated side effects. To diagnose DM without delay, we propose routine assessment of blood glucose at all outpatient visits during and after Peg-IFN-alpha/Riba treatment in chronic HCV patients.
- Published
- 2008
- Full Text
- View/download PDF
45. Low-level HCV viraemia after initial response during antiviral therapy: transcription-mediated amplification predicts treatment failure.
- Author
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Gelderblom HC, Reesink HW, Beld MG, Weegink CJ, Jansen PL, Dijkgraaf MG, and Zaaijer HL
- Subjects
- Adult, Aged, Biomarkers, Drug Therapy, Combination, Female, Hepacivirus genetics, Hepatitis C, Chronic diagnosis, Hepatitis C, Chronic virology, Humans, Male, Middle Aged, Polymerase Chain Reaction, Predictive Value of Tests, RNA, Viral blood, Sensitivity and Specificity, Species Specificity, Treatment Failure, Viremia diagnosis, Antiviral Agents therapeutic use, Hepacivirus isolation & purification, Hepatitis C, Chronic drug therapy, Nucleic Acid Amplification Techniques
- Abstract
Background: In chronic hepatitis C patients with an initial virological response (IVR) during antiviral therapy (that is, HCV RNA becomes negative before week 16 of treatment) the significance of reappearing viraemia below the detection limit of PCR is not known. We studied this phenomenon in subsets of patients., Methods: We assessed HCV RNA at weeks 16 and 20 of therapy by PCR and by more sensitive transcription-mediated amplification (TMA) in 23 patients with breakthrough or relapse and in 34 patients with sustained virological response (SVR). All patients participated in a high-dose-interferon induction study for difficult-to-treat patients. Therapy consisted of amantadine hydrochloride and ribavirin, combined with interferon-alpha2b induction during the first 6 weeks and thereafter combined with weekly pegylated interferon-alpha2b., Results: Among the 57 IVR patients, we detected transient or persistent reappearance of low levels of HCV RNA in 10 of the 23 (43%) patients with eventual breakthrough or relapse; but in none of the 34 SVR patients. In 5 of 10 patients reappearing HCV RNA was only detectable by TMA., Conclusion: Reappearance of low levels of HCV RNA in patients with IVR predicts treatment failure.
- Published
- 2007
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