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1. Effects of Food Insecurity on Hepatic Steatosis and Fibrosis in People With HIV

Author

Naggie, Susanna, Diehl, Anna Mae, Kopping, Mariko, Mangus, Rebecca, Chalasani, Naga, Cheek, Kaelea, Crandall, Holly, Cummings, Oscar W., Garcia, Nicole, Gawrieh, Samer, Releford, Montreca, Vilar-Gomez, Eduardo, Sulkowski, Mark, Brinkley, Sherilyn, Coleman, Daniel, Gilman, Lee, Mekhael, Sara, Moon, Juhi, Stelmash, Lauren, Williams, Quintara, Woreta, Tinsay, Heath, Sonya L., Goepfert, Paul A., Gray, Meagan, Hogue, Olivia, Lloyd, Audrey, Logan, Heather, Spraggins, Kristen, Tingle, William, Vereen, Latasha, Loomba, Rohit, Ajmera, Veeral, Cachay, Edward, Cervantes, Vanessa, Hernandez, Christie, Madamba, Egbert, Richards, Lisa, Tesfai, Kaleb, Tincopa, Monica, Price, Jennifer, Camberos, Rosaura, Laguardia, Yesenia, Luetkemeyer, Annie, McKinney, Jeffrey, Pearlman, Brittlyn, Stern, Sophie, Lake, Jordan E., Hernandez, Marisel Negret, Somasunderam, Anoma, Sterling, Richard, Devore, Megan, Nixon, Daniel, Kardashian, Ani, Sulkowski, Mark S., Wilson, Laura A., Sterling, Richard K., Heath, Sonya, Chalasani, Naga P., and Price, Jennifer C.

Published
2024
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2. Scipp: Scientific data handling with labeled multi-dimensional arrays for C++ and Python

Author

Heybrock, Simon, Arnold, Owen, Gudich, Igor, Nixon, Daniel, and Vaytet, Neil

Subjects
Computer Science - Mathematical Software, Physics - Data Analysis, Statistics and Probability, Physics - Instrumentation and Detectors
Abstract

Scipp is heavily inspired by the Python library xarray. It enriches raw NumPy-like multi-dimensional arrays of data by adding named dimensions and associated coordinates. Multiple arrays are combined into datasets. On top of this, scipp introduces (i) implicit handling of physical units, (ii) implicit propagation of uncertainties, (iii) support for histograms, i.e., bin-edge coordinate axes, which exceed the data's dimension extent by one, and (iv) support for event data. In conjunction these features enable a more natural and more concise user experience. The combination of named dimensions, coordinates, and units helps to drastically reduce the risk for programming errors. The core of scipp is written in C++ to open opportunities for performance improvements that a Python-based solution would not allow for. On top of the C++ core, scipp's Python components provide functionality for plotting and content representations, e.g., for use in Jupyter Notebooks. While none of scipp's concepts in isolation is novel per-se, we are not aware of any project combining all of these aspects in a single coherent software package., Comment: Proceedings of ICANS-XXIII, 13 pages, 5 figures

Published
2020
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3. Immunological determinants of clinical outcomes in COVID-19: A quantitative perspective

Author

Krieger, Elizabeth, Vissichelli, Nicole, Leichtle, Stefan, Kashioris, Markos, Sabo, Roy, Brophy, Don, Wang, Xiang-Yang, Kimbal, Pamela, Neale, Michael, Serrano, Myrna G., Buck, Gregory A., Roberts, Catherine, Qayyum, Rehan, Nixon, Daniel, Grossman, Steven, and Toor, Amir A.

Subjects
Quantitative Biology - Cell Behavior
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a variable clinical presentation that ranges from asymptomatic, to severe disease with cytokine storm. The mortality rates also differ across the globe, ranging from 0.5-13%. This variation is likely due to both pathogen and host factors. Host factors may include genetic differences in the immune response genes as well as variation in HLA and KIR allotypes. To better understand what impact these genetic variants in immune response genes may have in the differences observed in the immune response to SARS-CoV-2, a quantitative analysis of a dynamical systems model that considers both, the magnitude of viral growth, and the subsequent innate and adaptive response required to achieve control of infection is considered. Based on this broad quantitative framework it may be posited that the spectrum of symptomatic to severely symptomatic presentations of COVID19 represents the balance between innate and adaptive immune responses. In asymptomatic patients, prompt and adequate adaptive immune response quells infection, whereas in those with severe symptoms a slower inadequate adaptive response leads to a runaway cytokine cascade fueled by ongoing viral replication. Polymorphisms in the various components of the innate and adaptive immune response may cause altered immune response kinetics that would result in variable severity of illness. Understanding how this genetic variation may alter the response to SARS-CoV-2 infection is critical to develop successful treatment strategies., Comment: 36 pages, 1 table, 5 figures

Published
2020

4. Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial

Author

Fichtenbaum, Carl J, Ribaudo, Heather J, Leon-Cruz, Jorge, Overton, Edgar T, Zanni, Markella V, Malvestutto, Carlos D, Aberg, Judith A, Kileel, Emma M, Fitch, Kathleen V, Van Schalkwyk, Marije, Kumarasamy, Nagalingeswaran, Martinez, Esteban, Santos, Breno Riegel, Joseph, Yvetot, Lo, Janet, Siminski, Sue, Melbourne, Kathleen, Sponseller, Craig A, Desvigne-Nickens, Patrice, Bloomfield, Gerald S, Currier, Judith S, Hoffmann, Udo, Douglas, Pamela S, Grinspoon, Steven K, Curran, Adrian, Baranauskas, Adrienne, Wilkin, Aimee, Abrams-Downey, Alexandra J, Eckard, Allison Ross, Wurcel, Alysse G, González-Cordón, Ana, Paez, Armando, Sha, Beverly E, Santos, Breno, Yoshida, Carina Beppu, Rolle, Charlotte-Paige, Somboonwit, Charurut, Funk, Connie, Gómez-Ayerbe, Cristina, Frank, Cynthia, Nixon, Daniel E, Skiest, Daniel J, Choi, David, Mushatt, David M, Rial-Crestelo, David, Perez, Deborah K, Burke, Deirdre J, dos Santos, Desirée VG, Jayaweera, Dushyantha T, Gardner, Edward M, DeJesus, Edwin, Connick, Elizabeth, Lam, Emerline G, Hecker, Emily J, Kallas, Esper G, Waters, Evan, Rhame, Frank, Sattler, Fred R, Wang, Gary P, Enrile Seedhom, Helen May, Tavares, Isabel CF, Stapleton, Jack T, Bennet, Jaclyn, Brock, James B, Scott, James, Forcht, Janet, Lama, Javier R, Valencia, Javier, Brumfield, Jennifer K, Portilla, Joaquin, Kumar, Jonathan, Navarro, Jordi, Pinto, Jorge A, Castro, Jose G, Bernardino, Jose I, Casado, Jose L, Madruga, José Valdez, Baraiaetxaburu, Josu, Berenguer, Juan, Tashima, Karen T, Ho, Ken, Costa, Laura VL, Perez Latorre, Leire, Mohapi, Lerato, López-González, L, Fantry, Lori E, Domínguez-Domínguez, Lourdes, Martín-Carbonero, Luz, Cornelissen, Lynne M, Jain, Mamta K, Masiá, Mar, Lacerda, Marcus VG, Saumoy, Maria, Villalobos-Hernández, Marina, and Mall, Mark

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Research, HIV/AIDS, Clinical Trials and Supportive Activities, Prevention, Infectious Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, CD4-CD8 Ratio, Cross-Sectional Studies, Female, HIV Infections, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, HIV, statins, pitavastatin calcium, antiretroviral therapy, CD4 cell count, CD4/CD8 ratio, REPRIEVE, cardiovascular disease, REPRIEVE Investigators, Biological Sciences, Medical and Health Sciences, Microbiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPatterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.MethodsThe REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.ResultsA total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.ConclusionsThere were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.Clinical trials registrationNCT02344290.

Published
2020

9. Cytomegalovirus Antigenic Mimicry of Human Alloreactive Peptides: A Potential Trigger for Graft versus Host Disease

Author

Hall, Charles, Koparde, Vishal, Jameson-Lee, Max, Elnasseh, Abdelrhman, Scalora, Allison, Kobulnicky, Jared, Serrano, Myrna, Roberts, Catherine, Buck, Gregory, Neale, Micheal, Nixon, Daniel, and Toor, Amir

Subjects
Quantitative Biology - Genomics
Abstract

The association between human cytomegalovirus (hCMV) reactivation and the development of graft-versus-host-disease (GVHD) has been observed in stem cell transplantation (SCT). Seventy seven SCT donor-recipient pairs (DRP) (HLA matched unrelated donor (MUD), n=50; matched related donor (MRD), n=27) underwent whole exome sequencing to identify single nucleotide polymorphisms (SNPs) generating alloreactive peptide libraries for each DRP (9-mer peptide-HLA complexes); Human CMV CROSS (Cross-Reactive Open Source Sequence) Database was compiled from NCBI; HLA class I binding affinity for each DRPs HLA was calculated by NetMHCpan 2.8 and hCMV- derived 9-mers algorithmically compared to the alloreactive peptide-HLA complex libraries. Short consecutive (6 or greater) amino acid (AA) sequence homology matching hCMV to recipient peptides was considered for HLA-bound-peptide (IC50<500 nM) cross reactivity. Of the 70,686 hCMV 9-mers contained within the hCMV CROSS database, 29,658.8 +/- 9038.5 were found to match MRD DRP alloreactive peptides and 52,910.2 +/- 16121.8 matched MUD DRP peptides (Student's T-test, p<0.001). In silico analysis revealed multiple high affinity, immunogenic CMV-Human peptide matches (IC50<500 nM) expressed in GVHD-affected tissue-specific manner (proteins expressed at 10 RPKM or greater). hCMV+GVHD was found in 18 patients, 13 developing hCMV viremia before GVHD onset with a subset analysis of 7 instances of hCMV viremia prior to acute GVHD onset (n=3), chronic GVHD (n=2) and acute + chronic GVHD (n=2) indicating cross reactive peptide expression within affected organs. We propose that based on our analysis and preliminary clinical correlations that hCMV immune cross-reactivity may cause antigenic mimicry of human alloreactive peptides triggering GVHD., Comment: Pre-submission manuscript, 4 tables, 5 figures, 2 supplements & 2 Appendices-available upon request from first author

Published
2016

12. Comparison of the Metabolic Effects of Ritonavir-Boosted Darunavir or Atazanavir Versus Raltegravir, and the Impact of Ritonavir Plasma Exposure: ACTG 5257

Author

Ofotokun, Ighovwerha, Na, Lumine H, Landovitz, Raphael J, Ribaudo, Heather J, McComsey, Grace A, Godfrey, Catherine, Aweeka, Francesca, Cohn, Susan E, Sagar, Manish, Kuritzkes, Daniel R, Brown, Todd T, Patterson, Kristine B, Para, Michael F, Leavitt, Randi Y, Villasis-Keever, Angelina, Baugh, Bryan P, Lennox, Jeffrey L, Currier, Judith S, Team, for the AIDS Clinical Trials Group A5257, Saemann, Michelle, Baer, Jennifer, Koletar, Susan, Meixner, Linda, Seefried, Edward, Bailey, Vicki, Basham, Rebecca, Currin, David, Chicurel-Bayard, Miriam, Spitz, Teresa, Frain, Judy, Lindsey, Elizabeth, James, Tamara, Putnam, Beverly, Basler, Cathi, Dube, Michael P, Santos, Bartolo, Daar, Eric, Shaik, Sadia, Tebas, Pablo, Thomas, Aleshia, Bedimo, Roger, Mba, Michelle, Cohn, David, Moran, Fran, Bagur, Jorge L Santana, Dueño, Ileana Boneta, Taiwo, Babafemi, Berzins, Baiba, Chang, Emery, Palmer, Maria, Adams, Mary, Hurley, Christine, Lane, Timothy, Van Dam, Cornelius, Tashima, Karen, Patterson, Helen, del Rio, Carlos, Patrick, Ericka, Markowitz, Norman, Brar, Indira, Arduino, Roberto C, Martinez, Maria Laura, Kim, Rose, Smith, Yolanda, Bolivar, Hector, Fischl, Margaret A, Telzak, Edward, Cindrich, Richard, Sax, Paul, Keenan, Cheryl, Whitely, Kim, Davis, Traci, MacArthur, Rodger D, Farrough, Marti, Aberg, Judith A, Cespedes, Michelle S, Dunaway, Shelia, Storey, Sheryl, Gallant, Joel, Wiggins, Ilene, Sha, Beverly, Navarro, Veronica, Watson, Vicky, Nixon, Daniel, Luetkemeyer, Annie, Dwyer, Jay, Allen, Kristen, Walton, Patricia, Kumar, Princy, Timpone, Joseph, McKellar, Mehri, Granholm, Jacquelin, Yin, Michael T, Torres, Madeline, Valle, Sandra, Slamowitz, Debbie, Davis, Charles E, Blattner, William A, Linus, Benjamin, and Albrecht, Mary

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Adult, Anti-HIV Agents, Atazanavir Sulfate, Blood Glucose, Darunavir, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Lipids, Male, Raltegravir Potassium, Ritonavir, HIV/AIDS, cART, lipids, metabolic syndrome, AIDS Clinical Trials Group (ACTG) A5257 Team, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundMetabolic effects following combination antiretroviral therapy (cART) vary by regimen type. Changes in metabolic effects were assessed following cART in the AIDS Clinical Trials Group (ACTG) A5257 study, and correlated with plasma ritonavir trough concentrations (C24).MethodsTreatment-naive adult subjects were randomized to ritonavir-boosted atazanavir or darunavir, or raltegravir-based cART. Changes in lipids and other metabolic outcomes over time were estimated. Differences between arms were estimated with 97.5% confidence intervals and compared using pairwise Student t tests. Associations between ritonavir C24 and lipid changes at week 48 were evaluated via linear regression.ResultsAnalyses included 1797 subjects with baseline fasting data. Baseline lipid profiles and metabolic syndrome rates (approximately 21%) were similar across arms. Comparable increases occurred in total cholesterol, triglycerides, and low-density lipoprotein cholesterol with the boosted protease inhibitors (PIs); each PI had greater increases relative to raltegravir (all P ≤ .001 at week 96). Metabolic syndrome incident rates by week 96 (approximately 22%) were not different across arms. Ritonavir C24 was not different by arm (P = .89) (median, 69 ng/mL and 74 ng/mL in the atazanavir and darunavir arms, respectively) and were not associated with changes in lipid measures (all P > .1).ConclusionsRaltegravir produced the most favorable lipid profile. Metabolic syndrome rates were high at baseline and increased to the same degree in all arms. Ritonavir C24 was not different in the PI arms and had no relationship with the modest but comparable increases in lipids observed with either atazanavir or darunavir. The long-term clinical significance of the lipid changes noted with the PIs relative to raltegravir deserves further evaluation.Clinical trials registrationNCT 00811954.

Published
2015

17. Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1–infected individuals with low-density lipoprotein cholesterol

Author

Bergstrom, Katherine, Boone, Linda, Myers, Laurie, Meres, Debra, Shin, Katherine, Aweeka, Francesca, Cavanagh, Karen, Medvik, Kathleen A., Hovind, Laura, Shaw, Karl, Zadzilla, Amanda, Nixon, Daniel E., Bosch, Ronald J., Chan, Ellen S., Funderburg, Nicholas T., Hodder, Sally, Lake, Jordan E., Lederman, Michael M., Klingman, Karin L., and Aberg, Judith A.

Published
2017
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18. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial

Author

Kunisaki, Ken M, Niewoehner, Dennis E, Collins, Gary, Aagaard, Bitten, Atako, Nafisah B, Bakowska, Elzbieta, Clarke, Amanda, Corbelli, Giulio Maria, Ekong, Ernest, Emery, Sean, Finley, Elizabeth B, Florence, Eric, Infante, Rosa M, Kityo, Cissy M, Madero, Juan Sierra, Nixon, Daniel E, Tedaldi, Ellen, Vestbo, Jørgen, Wood, Robin, and Connett, John E

Published
2016
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23. Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period: 2009–2015

Author

Dwyer, Dominic E, Lynfield, Ruth, Losso, Marcelo H, Davey, Richard T, Cozzi-Lepri, Alessandro, Wentworth, Deborah, Uyeki, Timothy M, Gordin, Fred, Angus, Brian, Qvist, Tavs, Emery, Sean, Lundgren, Jens, Neaton, James D, Aagaard, Bitten, Borges, Álvaro H D, Cozzi-Lepri, Alessandro, Eid, Marius, Jansson, Per O, Jeppesen, Marianne, Joensen, Zillah Maria, Pedersen, Ruth Kjærgaard, Lundgren, Jens, Nielsen, Birgit Riis, Pearson, Mary, Peters, Lars, Qvist, Tavs, Angus, Brian, Babiker, Abdel, Bennett, Rachel, Braimah, Nafisah, Collaco-Moraes, Yolanda, Cursley, Adam, Hudson, Fleur, Pett, Sarah, Russell, Charlotte, Webb, Helen, Carey, Dianne, Courtney-Rodgers, David, Emery, Sean, Shaw, Pamela, Gordin, Fred, Sanchez, Adriana, Standridge, Barbara, Vjecha, Michael, Brekke, Kate, Campbell, Megan, Denning, Eileen, DuChene, Alain, Engen, Nicole, George, Michelle, Harrison, Merrie, Neaton, James D, Nelson, Ray, Quan, Siu-Fun, Schultz, Terri, Wentworth, Deborah, Baxter, John, Brown, Shawn, Hoover, Marie, Beigel, John, Davey, Richard T, Jr., Dewar, Robin, Gover, Erin, McConnell, Rose, Metcalf, Julia, Natarajan, Ven, Rehman, Tauseef, Voell, Jocelyn, Dwyer, Dominic E, Kok, Jen, Uyeki, Timothy M, Munroe, David, Aguila, Damian, Alzogaray, Maria Fernanda, Ballesteros, Maria Fernanda, Barcan, Laura, Barcelona, Laura, Belloso, Waldo, Berdiñas, Veronica, Bonvehi, Pablo, Caeiro, Juan Pablo, Cisneros, Veronica, Crinejo, Ana, David, Daniel, Doldan, Luz, Ebenrstejin, Juan, Lipari, Flavio, Lopardo, Ana, Lopardo, Gustavo, Losso, Marcelo, Lucchetti, Pablo, Lupo, Sergio, Macias, Laura Moreno, de Tesco, Alejandra Moricz, Mykietiuk, Analia, Nannini, Estaban, Nieto, Gabriel, Nieto, Laura, Peroni, Luciana, Retta, Ignacio, Rodriguez, Patricia, Sanchez, Marisa, Sanchez, Pablo, de Paz Sierra, Mariana, Tavella, Silvina, Temporiti, Elena, Trape, Liliana, Vieni, Ines, Warley, Eduardo, Yahni, Diego, Zarate, Abel Humberto, Avihingsanon, Anchalee, Charoentonpuban, Kanlaya, Chetchotisakd, Ploenchan, Kaewon, Peeraporn, Laopraynak, Naphassanant, Manosuthi, Weerawat, Pussadee, Kanitta, Putcharoen, Opass, Ruxrungtham, Kiat, Suwanpimonkul, Gompol, Ubolyam, Sasiwimol, Arduino, Roberto, Atkinson, Barbara, Aulicino, Taryn M, Baker, Jason V, Bardascino, Cindy, Bass, Caitlin, Baxter, John D, Beilke, Mark, Bentley, Beverly D, Lee Bertrand, Mary, Brown, Ann B, Carbonneau, June, Cindrich, Richard, Coburn, Patty, Cohen, Calvin J, Clark, Linda, Cummins, Shirley, Dassow, Paul, DeHovitz, Jack A, Dharan, Nila J, Faber, Leslie, Farrough, Marti, Freiberg, Matthew, Gardner, Edward, Jo Garrett, Kimberly, Geisler, Christiane, Glesby, Marshall, Green, Julia, Grenade, Joanne, Gunderson, Edie, Gunter, John, Ham, Kirsis, Holman, Susan, Hughes, Valery, Hurt, Christopher, Johnson, Mary, Koerbel, Glory, Koletar, Susan, Lan, Audrey, MacArthur, Rodger, Marcus, Cheryl, Markowitz, Norm, Martinez, Maria Laura, McLaughlin, Karen, Nahra, Raquel, Nettles, Mary Jane, Nixon, Daniel, Novak, Richard, Nuffer, Kathleen, Olivet, Hannah B, Omotosho, Bola, Paez, Armando P, Paez-Quinde, Marta, Parker, Sonija, Patil, Namrata, Polenakovik, Hari, Powell, Sandra, Prosser, Rachel A, Reilly, Nancy A, Riska, Paul F, Rizza, Stacey, Schooley, Robert, Schwarber, Marla, Scott, James, Simon, Gary L, Sivoravong, Jon, Skiest, Daniel J, Solorzano, Clemencia, Sondengam, Rita, Swanson, Nicole, Tedaldi, Ellen, Temesgen, Zelalem, Thomas, Doug, Thron, Bill, Traverse, Colleen, Uddin, David E, Uslan, Daniel Z, Vasco, Marina, Vaughan, William M, Vecino, Isabel, Wade, Barbara, Walker, Catrice, Watson, Kathy, Watson, Vicky, Wohl, David, Wolfe, Cameron R, Andry, Leslie, Bielen, Mireille, Clumeck, Nathan, Florence, Eric, Kabeya, Kabamba, Sagaer, Jolanthe, Weckx, Jozef, Anagnostou, Olga, Antoniadou, Anastasia, Daikos, George, Gioukari, Vicky, Kalomenidis, Ioannis, Kantzanou, Maria, Koratzanis, Georgios, Koulouris, Nikolaos, Maltezos, Efstratios, Metallidis, Symeon, Polixronopoulos, Vlassis, Sambatakou, Helen, Skoutelis, Athanasios, Touloumi, Giota, Vasilopoulos, Nikolaos, Bloch, Mark, Cunningham, Nicky, Dwyer, Dominic E, Edwards, Sian, Elliott, Julian, Garlick, Jill, Habel, Philip, Kilkenny, Fiona, Lau, Helen, MacRae, Karen, McBride, John, Moore, Richard, Prone, Isabel, Ram, Ristila, Richmond, Sue, Roth, Norm, Meng Soo, Tuck, Jo-Anne, Thompson, Vincent, Trina, Vlakahis, Emanuel, Woolstencroft, Rachel, Chadwick, David, Clarke, Tristan, Democratis, Jane, Dockrell, David, Heyderman, Robert, Jeffs, Ben, Kutter, Stefan, Llewelyn, Martin, Minton, Jane, Newport, Melanie, Price, Ashley, Benites, Carlos, Castillo, Raul, Chinchay, Romina, Cornelio, Eva, Guevara, Maria, Gutierrez, Luis, Hidalgo, Jose, La Rosa, Alberto, Pinedo, Yvett, Saenz, Maria, Vega, Juan, Baadegaard, Bente, Bach, Karen, Collins, Philippa, Gerstoft, Jan, Hergens, Lene, Jensen, Lene Pors, Joensen, Zillah Maria, Kronborg, Gitte, Loftheim, Iben Rose, Nielsen, Henrik, Oestergaard, Lars, Pedersen, Court, Stauning Pedersen, Jens Aage, Yehdego, Yordanos, Bergmann, Frank, Boesecke, Christoph, Bogner, Johannes R, Brockmeyer, Norbert, Czaja-Harder, Christine, Draenert, Rika, Fätkenheuer, Gerd, Klinker, Hartwig, Kümmerle, Tim, Lehmann, Clara, Müller, Vera, Plettenberg, Andreas, Rockstroh, Jürgen, Schlabe, Stefan, E Schmidt, Wolfgang, Schürmann, Dirk, Schüttfort, Gundolf, Seybold, Ulrich, Stephan, Christoph, Stoehr, Albrecht, Tillmann, Klaus, Wiebecke, Susanne, Wolf, Timo, Arribas, Jose, Carbone, Javier, Fernández Cruz, Eduardo, Dalmau, David, Estrada, Vincente, Herrero, Patricia, Knobel, Hernando, López, Paco, Montejano, Rocío, Sans Moreno, José, Ramón Paño, José, Portas, Begoña, Rodrigo, Maria, Romero, Pilar, Sánchez-Sendín, Domingo, Soriano, Vincente, Bakowska, Elzbieta, Horban, Andrzej Jerzy, Knysz, Brygida, Kowalska, Karolina Pyziak, Zubkiewicz-Zarebska, Anna, Kase, Kerstin, Mülle, Helen, Zilmer, Kai, Allendes, Gladys, Flores, Jimena, Northland, Rebeka, Perez, Carlos, Velasco, Isabel, Wolff, Marcelo, Chu, Man-Yee, Wu, Tak-chiu, Burgmann, Heinz, Tobudic, Selma, Imahashi, Mayumi, Imamura, Junji, Iwatani, Yasumasa, Kogure, Ayumi, Nakahata, Masashi, Sugiura, Wataru, Yokomaku, Yoshiyuki, and Maagaard, Anne

Published
2017
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24. A Systematic Review of Handgrip Strength Measurement in Clinical and Epidemiological Studies of Kidney Disease: Toward a Standardized Approach

Author

Wilkinson, Thomas J., primary, Gabrys, Iwona, additional, Lightfoot, Courtney J., additional, Lambert, Kelly, additional, Baker, Luke A., additional, Billany, Roseanne E., additional, Kanavaki, Archontissa, additional, Palmer, Jared, additional, Robinson, Katherine A., additional, Nixon, Daniel, additional, Watson, Emma L., additional, and Smith, Alice C., additional

Published
2022
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25. Cytomegalovirus viremia and risk of disease progression and death in HIV-positive patients starting antiretroviral therapy

Author

Levi, Laura I., Sharma, Shweta, Schleiss, Mark R., Furrer, Hansjakob, Nixon, Daniel E., Blackstad, Mark, Hernandez-Alvarado, Nelmary, Dwyer, Dominic E., Borges, Alvaro H., Lane, H. Clifford, Lundgren, Jens, Neaton, James D., Molina, Jean Michel, Levi, Laura I., Sharma, Shweta, Schleiss, Mark R., Furrer, Hansjakob, Nixon, Daniel E., Blackstad, Mark, Hernandez-Alvarado, Nelmary, Dwyer, Dominic E., Borges, Alvaro H., Lane, H. Clifford, Lundgren, Jens, Neaton, James D., and Molina, Jean Michel

Abstract

Objective: The aim of this study was to assess the prevalence of cytomegalovirus (CMV) viremia in HIV-positive patients starting antiretroviral therapy (ART) and to evaluate its impact on clinical outcomes. Design: A retrospective analysis of four clinical trials (INSIGHT FIRST, SMART, START, and ANRS REFLATE TB). Methods: Stored plasma samples from participants were used to measure CMV viremia at baseline prior to initiating ART and at visits through 1 year of follow-up after ART initiation. CMV viremia was measured centrally using a quantitative PCR assay. Within FIRST, associations of CMV viremia at baseline and through 8 months of ART were examined with a composite clinical outcome of AIDS, serious non-AIDS events, or death using Cox proportional hazards regression. Results: Samples from a total of 3176 participants, 1169 from FIRST, 137 from ANRS REFLATE TB, 54 from SMART, and 1816 from START were available with baseline CMV viremia prevalence of 17, 26, 0, and 1%, respectively. Pooled across trials, baseline CMV viremia was associated with low CD4+T-cell counts and high HIV RNA levels. In FIRST, CMV viremia was detected in only 5% of participants between baseline and month 8. After adjustment for CD4+T-cell count and HIV RNA levels, hazard ratios for risk of clinical outcomes was 1.15 (0.86-1.54) and 2.58 (1.68-3.98) in FIRST participants with baseline and follow-up CMV viremia, respectively. Conclusion: Baseline CMV viremia in HIV-positive patients starting ART is associated with advanced infection and only persistent CMV viremia after ART initiation is associated with a higher risk of morbidity and mortality.

Published
2022

26. Evaluating the effect of atorvastatin exposure and vitamin D levels on lipid outcomes in people with HIV‐1 with suppressed HIV‐1 RNA and LDL cholesterol <130 mg/dL.

Author

Rahman, Farah, Brates, Irena, Aweeka, Francesca, Bosch, Ronald J., Deitchman, Amelia, Nixon, Daniel, and Aberg, Judith A.

Subjects
PROTEASE inhibitors, ATORVASTATIN, LDL cholesterol, CARDIOVASCULAR diseases, VITAMIN D, TREATMENT effectiveness, RANDOMIZED controlled trials, HIGHLY active antiretroviral therapy, PRE-tests & post-tests, BLIND experiment, STATISTICAL sampling, CROSSOVER trials, LIPIDS, HIV
Abstract

Introduction: Cardiovascular disease (CVD) has become a leading cause of morbidity and mortality among people with HIV. Atorvastatin is known to reduce cardiovascular risk. We (1) compared atorvastatin concentrations between different boosted protease inhibitors (PIs) and with lipid outcomes and (2) compared pre‐atorvastatin 25‐OH vitamin D levels with atorvastatin concentrations and with lipid outcomes, in people with HIV with suppressed HIV‐1 RNA and low‐density lipoprotein cholesterol (LDL‐C) <130 mg/dL. Methods: A5275 was a randomized, double‐blind, placebo‐controlled crossover study of atorvastatin in virally suppressed people with HIV with fasting LDL‐C <130 mg/dL. We analyzed results over the 20 weeks of active atorvastatin treatment. Atorvastatin was initiated at 10 mg daily and increased to 20 mg daily after 4 weeks if there were no findings of toxicity. Atorvastatin trough concentrations were measured at week 20. Participants took combination antiretroviral therapy (ART) that included a boosted PI throughout. Results: Overall (n = 67), 70% of participants were male, and the median age was 51 years. There was no apparent association between atorvastatin trough concentrations and pre‐atorvastatin vitamin D levels (r = 0.01, p = 0.9) or by boosted PI (p = 0.20). Median pre‐ to post‐atorvastatin change was −39.0 mg/dL in fasting total cholesterol, −40.4 ng/mL in lipoprotein‐associated phospholipase A2 (LP‐PLA2), and −13.8 U/L in oxidized LDL, with all changes negatively correlated with atorvastatin trough concentrations (r = −0.19, −0.09, −0.21; p ≥ 0.096). Conclusions: No apparent associations between pre‐atorvastatin vitamin D levels and outcomes were observed (all p > 0.70). In virologically suppressed people with HIV, higher atorvastatin concentrations were marginally associated with greater decreases in lipid outcomes. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Cytomegalovirus viremia and risk of disease progression and death in HIV-positive patients starting antiretroviral therapy

Author

Levi, Laura I, Sharma, Shweta, Schleiss, Mark R, Furrer, Hansjakob, Nixon, Daniel E, Blackstad, Mark, Hernandez-Alvarado, Nelmary, Dwyer, Dominic E, Borges, Alvaro H, Lane, H Clifford, Lundgren, Jens, Neaton, James D, and Molina, Jean-Michel

Subjects
Immunology, Cytomegalovirus, virus diseases, 610 Medicine & health, HIV Infections, Article, CD4 Lymphocyte Count, Infectious Diseases, HIV Seropositivity, Cytomegalovirus Infections, Disease Progression, HIV-1, Immunology and Allergy, RNA, Humans, Viremia, 610 Medizin und Gesundheit, Retrospective Studies
Abstract

OBJECTIVE To assess the prevalence of CMV viremia in HIV-positive patients starting antiretroviral therapy (ART) and to evaluate its impact on clinical outcomes. DESIGN Retrospective analysis of four clinical trials (INSIGHT FIRST, SMART, START, and ANRS REFLATE TB). METHODS Stored plasma samples from participants were used to measure CMV viremia at baseline prior to initiating ART and at visits through one year of follow-up after ART initiation. CMV viremia was measured centrally using a quantitative PCR assay. Within FIRST, associations of CMV viremia at baseline and through eight months of ART were examined with a composite clinical outcome of AIDS, serious non-AIDS events, or death using Cox proportional hazards regression. RESULTS Samples from a total of 3176 participants, 1169 from FIRST, 137 from ANRS REFLATE TB, 54 from SMART, and 1816 from START were available with baseline CMV viremia prevalence of 17%, 26%, 0% and 1%, respectively. Pooled across trials, baseline CMV viremia was associated with low CD4+ T-cell counts and high HIV RNA levels. In FIRST, CMV viremia was detected in only 5% of participants between baseline and month 8. After adjustment for CD4+ T-cell count and HIV RNA levels, hazard ratios (HR) for risk of clinical outcomes was 1.15 (0.86-1.54) and 2.58 (1.68 - 3.98) in FIRST participants with baseline and follow-up CMV viremia, respectively. CONCLUSION Baseline CMV viremia in HIV-positive patients starting ART is associated with advanced infection and only persistent CMV viremia after ART initiation is associated with a higher risk of morbidity and mortality.

Published
2022
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36. Additional file 1 of Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population

Author

Wilkinson, Thomas J., Nixon, Daniel G. D., Palmer, Jared, Lightfoot, Courtney J., and Smith, Alice C.

Abstract

Additional file 1: Supplementary Material 1: Missing symptom data. Supplementary Material 2: Frequency of symptoms reported across groups. Supplementary Material 3: Breakdown of responses in top three symptoms across groups. Supplementary Material 4: Odds ratio of having a symptom present across groups.

Published
2021
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39. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection

Author

Kuller, Lewis H., Tracy, Russell, Belloso, Waldo, De Wit, Stephane, Drummond, Fraser, Lane, H. Clifford, Ledergerber, Bruno, Lundgren, Jens, Neuhaus, Jacqueline, Nixon, Daniel, Paton, Nicholas I., and Neaton, James D.

Subjects
Biological sciences
Abstract

Background In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]). We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis. Methods and Findings Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1+2. Two studies were conducted: (1) a nested case-control study for studying biomarker associations with mortality, and (2) a study to compare DC and VS participants for biomarker changes. For (1), markers were determined at study entry and before death (latest level) for 85 deaths and for two controls (n = 170) matched on country, age, sex, and date of randomization. Odds ratios (ORs) were estimated with logistic regression. For each biomarker, each of the three upper quartiles was compared to the lowest quartile. For (2), the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following randomization. Higher levels of hsCRP, IL-6, and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality. Unadjusted ORs (highest versus lowest quartile) were 2.0 (95% confidence interval [CI], 1.0-4.1; p = 0.05), 8.3 (95% CI, 3.3-20.8; p < 0.0001), and 12.4 (95% CI, 4.2-37.0; p < 0.0001), respectively. Associations were significant after adjustment, when the DC and VS groups were analyzed separately, and when latest levels were assessed. IL-6 and D-dimer increased at 1 mo by 30% and 16% in the DC group and by 0% and 5% in the VS group (p < 0.0001 for treatment difference for both biomarkers); increases in the DC group were related to HIV-RNA levels at 1 mo (p < 0.0001). In an expanded case-control analysis (four controls per case), the OR (DC/VS) for mortality was reduced from 1.8 (95% CI, 1.1-3.1; p = 0.02) to 1.5 (95% CI, 0.8-2.8) and 1.4 (95% CI, 0.8-2.5) after adjustment for latest levels of IL-6 and D-dimer, respectively. Conclusions IL-6 and D-dimer were strongly related to all-cause mortality. Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels. Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation. Trial Registration: ClinicalTrials.gov (NCT00027352). doi:10.1371/journal.pmed.0050203, Introduction The Strategies for Management of Anti-Retroviral Therapy (SMART) trial compared episodic use of antiretroviral treatment (ART) guided by CD4+ count with the current practice of continuous ART. Risk of [...]

Published
2008

43. The role of dietary supplements during cancer therapy

Author

Norman, Helen A., Butrum, Ritva R., Feldman, Elaine, Heber, David, Nixon, Daniel, Picciano, Mary Frances, Rivlin, Richard, Simopoulos, Artemis, Wargovich, Michael J., Weisburger, Elizabeth K., and Zeisel, Steven H.

Subjects
Diet therapy, Cancer -- Care and treatment, Food/cooking/nutrition
Abstract

This guide was compiled after recommendations by the American Institute for Cancer Research (AICR) Cancer Resource Advisory Council. It encompasses the AICR position on current issues in nutrition for cancer survivors during treatment and is intended to provide advice about dietary supplements for cancer survivors who are still being treated. Current scientific findings about the safety and effectiveness of some commonly used dietary antioxidants and nonantioxidant supplements during chemotherapy are presented and assessed. Use of dietary supplements during cancer treatment remains controversial. Patients are cautioned that vitamin and mineral supplements as therapies are not substitutes for established medicine. The current recommendation for cancer patients is to only take moderate doses of supplements because evidence from human clinical studies that confirm their safety and benefits is limited. A daily multivitamin containing supplements at the levels of the Dietary Reference Intakes can be used safely as part of a program of healthy nutrition. In addition, the AICR Cancer Resource Advisory Council concluded that further scientific research is needed to provide a set of firm guidelines for the use of vitamin and mineral supplements by cancer patients during treatment. KEY WORDS: * dietary antioxidant * dietary supplement * micronutrient * chemotherapy

Published
2003

45. A fluid-based soft-object model

Author

Nixon, Daniel and Lobb, Richard

Subjects
Modeling, Animation software, Fluid mechanics -- Models, Computer graphics -- Research, Computer animation -- Models, Image processing equipment industry -- Research
Published
2002

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