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1. Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction

Author

Wood, Greta K., Sargent, Brendan F., Ahmad, Zain-Ul-Abideen, Tharmaratnam, Kukatharmini, Dunai, Cordelia, Egbe, Franklyn N., Martin, Naomi H., Facer, Bethany, Pendered, Sophie L., Rogers, Henry C., Hübel, Christopher, van Wamelen, Daniel J., Bethlehem, Richard A. I., Giunchiglia, Valentina, Hellyer, Peter J., Trender, William, Kalsi, Gursharan, Needham, Edward, Easton, Ava, Jackson, Thomas A., Cunningham, Colm, Upthegrove, Rachel, Pollak, Thomas A., Hotopf, Matthew, Solomon, Tom, Pett, Sarah L., Shaw, Pamela J., Wood, Nicholas, Harrison, Neil A., Miller, Karla L., Jezzard, Peter, Williams, Guy, Duff, Eugene P., Williams, Steven, Zelaya, Fernando, Smith, Stephen M., Keller, Simon, Broome, Matthew, Kingston, Nathalie, Husain, Masud, Vincent, Angela, Bradley, John, Chinnery, Patrick, Menon, David K., Aggleton, John P., Nicholson, Timothy R., Taylor, John-Paul, David, Anthony S., Carson, Alan, Bullmore, Ed, Breen, Gerome, Hampshire, Adam, Michael, Benedict D., Paddick, Stella-Maria, and Leek, E. Charles

Published
2024
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2. MAVMET trial: maraviroc and/or metformin for metabolic dysfunction associated fatty liver disease in adults with suppressed HIV

Author

McCabe, Leanne, Burns, James E., Latifoltojar, Arash, Post, Frank A., Fox, Julie, Pool, Erica, Waters, Anele, Santana, Beatriz, Garvey, Lucy, Johnson, Margaret, McGuinness, Ian, Chouhan, Manil, Edwards, Jonathan, Goodman, Anna L., Cooke, Graham, Murphy, Claire, Collaco-Moraes, Yolanda, Webb, Helen, Gregory, Adam, Mohamed, Fatima, Rauchenberger, Mary, Ryder, Stephen D., Sandford, Chris, Baker, Jason V., Angus, Brian, Boesecke, Christoph, Orkin, Chloe, Punwani, Shonit, Clark, Andrew, Gilson, Richard, Dunn, David, and Pett, Sarah L.

Published
2024
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3. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

Author

Group, The ITAC Study, Polizzotto, Mark N, Nordwall, Jacqueline, Babiker, Abdel G, Phillips, Andrew, Vock, David M, Eriobu, Nnakelu, Kwaghe, Vivian, Paredes, Roger, Mateu, Lourdes, Ramachandruni, Srikanth, Narang, Rajeev, Jain, Mamta K, Lazarte, Susana M, Baker, Jason V, Frosch, Anne EP, Poulakou, Garyfallia, Syrigos, Konstantinos N, Arnoczy, Gretchen S, McBride, Natalie A, Robinson, Philip A, Sarafian, Farjad, Bhagani, Sanjay, Taha, Hassan S, Benfield, Thomas, Liu, Sean TH, Antoniadou, Anastasia, Jensen, Jens Ulrik Stæhr, Kalomenidis, Ioannis, Susilo, Adityo, Hariadi, Prasetyo, Jensen, Tomas O, Morales-Rull, Jose Luis, Helleberg, Marie, Meegada, Sreenath, Johansen, Isik S, Canario, Daniel, Fernández-Cruz, Eduardo, Metallidis, Simeon, Shah, Amish, Sakurai, Aki, Koulouris, Nikolaos G, Trotman, Robin, Weintrob, Amy C, Podlekareva, Daria, Hadi, Usman, Lloyd, Kathryn M, Røge, Birgit Thorup, Saito, Sho, Sweerus, Kelly, Malin, Jakob J, Lübbert, Christoph, Muñoz, Jose, Cummings, Matthew J, Losso, Marcelo H, Turner, Dan, Shaw-Saliba, Kathryn, Dewar, Robin, Highbarger, Helene, Lallemand, Perrine, Rehman, Tauseef, Gerry, Norman, Arlinda, Dona, Chang, Christina C, Grund, Birgit, Holbrook, Michael R, Holley, Horace P, Hudson, Fleur, McNay, Laura A, Murray, Daniel D, Pett, Sarah L, Shaughnessy, Megan, Smolskis, Mary C, Touloumi, Giota, Wright, Mary E, Doyle, Mittie K, Popik, Sharon, Hall, Christine, Ramanathan, Roshan, Cao, Huyen, Mondou, Elsa, Willis, Todd, Thakuria, Joseph V, Yel, Leman, Higgs, Elizabeth, Kan, Virginia L, Lundgren, Jens D, Neaton, James D, and Lane, H Clifford

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Emerging Infectious Diseases, Clinical Research, Vaccine Related, Clinical Trials and Supportive Activities, Lung, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adenosine Monophosphate, Alanine, Antibodies, Neutralizing, Antiviral Agents, COVID-19, COVID-19 Vaccines, Double-Blind Method, Female, Hospitalization, Humans, Inpatients, Internationality, Male, Middle Aged, Treatment Outcome, Vaccines, Inactivated, ITAC (INSIGHT 013) Study Group, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPassive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited.MethodsIn this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581.FindingsFrom Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77-1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66-1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14-4·29); for patients who were antibody negative, the OR was 0·51 (0·29-0·90; pinteraction=0·001).InterpretationWhen administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry.FundingUS National Institutes of Health.

Published
2022

4. Bone turnover change after randomized switch from tenofovir disoproxil to tenofovir alafenamide fumarate in men with HIV

Author

Moore, Amelia E.B., Burns, James E., Sally, Deirdre, Milinkovic, Ana, Krokos, Georgios, John, Joemon, Rookyard, Christopher, Borca, Alessandro, Pool, Erica R.M., Tostevin, Anna, Harman, Alyss, Dulnoan, Dwight S., Gilson, Richard, Arenas-Pinto, Alejandro, Cook, Gary J.R., Saunders, John, Dunn, David, Blake, Glen M., and Pett, Sarah L.

Published
2024
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5. Cardiovascular disease risk in people of African ancestry with HIV in the United Kingdom.

Author

Ko, Stephanie, Dominguez‐Dominguez, Lourdes, Ottaway, Zoe, Campbell, Lucy, Fox, Julie, Burns, Fiona, Hamzah, Lisa, Ustianowski, Andrew, Clarke, Amanda, Kegg, Stephen, Schoeman, Sarah, Jones, Rachael, Pett, Sarah L., Hudson, Jonathan, and Post, Frank A.

Subjects
CARDIOVASCULAR disease prevention, RISK assessment, CROSS-sectional method, PEARSON correlation (Statistics), CARDIOVASCULAR diseases, BODY mass index, GLYCOSYLATED hemoglobin, RESEARCH funding, HIV-positive persons, LOGISTIC regression analysis, HYPERTENSION, SEX distribution, SMOKING, POPULATION health, CARDIOVASCULAR diseases risk factors, DISEASE prevalence, AGE distribution, DESCRIPTIVE statistics, BLACK British, DIASTOLIC blood pressure, TRIGLYCERIDES, SYSTOLIC blood pressure, HEALTH promotion, TIME, DIABETES, OBESITY, COMORBIDITY
Abstract

Objectives: Our objective was to describe the prevalence of cardiovascular disease (CVD) risk factors in people of African ancestry with HIV in the UK. Methods: We conducted a cross‐sectional analysis of CVD risk factors in Black people with HIV aged ≥40 years and estimated the 10‐year CVD risk using QRISK®3‐2018. Correlations between body mass index (BMI) and CVD risk factors were described using Pearson correlation coefficients, and factors associated with 10‐year CVD risk ≥5% were described using logistic regression. Results: We included 833 Black people with HIV and a median age of 54 years; 54% were female, 50% were living with obesity (BMI ≥30 kg/m2), 61% had hypertension, and 19% had diabetes mellitus. CVD risk >5% ranged from 2% in female participants aged 40–49 years to 99% in men aged ≥60 years, and use of statins ranged from 7% in those with CVD risk <2.5% to 64% in those with CVD risk ≥20%. BMI was correlated (R2 0.1–0.2) with triglycerides and diastolic blood pressure in women and with glycated haemoglobin, systolic and diastolic blood pressure, and total:high‐density lipoprotein (HDL) cholesterol ratio in men. In both female and male participants, older age, blood pressure, diabetes mellitus, and kidney disease were strongly associated with CVD risk ≥5%, whereas obesity, total:HDL cholesterol, triglycerides, and smoking status were variably associated with CVD risk ≥5%. Conclusions: We report a high burden of CVD risk factors, including obesity, hypertension, and diabetes mellitus, in people of African ancestry with HIV in the UK. BMI‐focused interventions in these populations may improve CVD risk while also addressing other important health issues. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

Author

Polizzotto, Mark N., Nordwall, Jacqueline, Babiker, Abdel G., Phillips, Andrew, Vock, David M., Eriobu, Nnakelu, Kwaghe, Vivian, Paredes, Roger, Mateu, Lourdes, Ramachandruni, Srikanth, Narang, Rajeev, Jain, Mamta K., Lazarte, Susana M., Baker, Jason V., Frosch, Anne E.P., Poulakou, Garyfallia, Syrigos, Konstantinos N., Arnoczy, Gretchen S., McBride, Natalie A., Robinson, Philip A., Sarafian, Farjad, Bhagani, Sanjay, Taha, Hassan S., Benfield, Thomas, Liu, Sean T.H., Antoniadou, Anastasia, Jensen, Jens Ulrik Stæhr, Kalomenidis, Ioannis, Susilo, Adityo, Hariadi, Prasetyo, Jensen MD, Tomas O., Morales-Rull, Jose Luis, Helleberg, Marie, Meegada, Sreenath, Johansen, Isik S., Canario, Daniel, Fernández-Cruz, Eduardo, Metallidis, Simeon, Shah, Amish, Sakurai, Aki, Koulouris, Nikolaos G., Trotman, Robin, Weintrob, Amy C., Podlekareva, Daria, Hadi, Usman, Lloyd, Kathryn M., Røge, Birgit Thorup, Saito, Sho, Sweerus, Kelly, Malin, Jakob J., Lübbert, Christoph, Muñoz, Jose, Cummings, Matthew J., Losso, Marcelo H., Turner, Dan, Shaw-Saliba, Kathryn, Dewar, Robin, Highbarger, Helene, Lallemand, Perrine, Rehman, Tauseef, Gerry, Norman, Arlinda, Dona, Chang, Christina C., Grund, Birgit, Holbrook, Michael R., Holley, Horace P., Hudson, Fleur, McNay, Laura A., Murray, Daniel D., Pett, Sarah L., Shaughnessy, Megan, Smolskis, Mary C., Touloumi, Giota, Wright, Mary E., Doyle, Mittie K., Popik, Sharon, Hall, Christine, Ramanathan, Roshan, Cao, Huyen, Mondou, Elsa, Willis, Todd, Thakuria, Joseph V., Yel, Leman, Higgs, Elizabeth, Kan, Virginia L., Lundgren, Jens D., Neaton, James D., and Lane, H. Clifford

Published
2022
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7. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Author

Allen, Claire, Archibald, Neil, Arkell, James, Arthur-Farraj, Peter, Baker, Mark, Ball, Harriet, Bradley-Barker, Verity, Brown, Zoe, Bruno, Stefania, Carey, Lois, Carswell, Christopher, Chakrabarti, Annie, Choulerton, James, Daher, Mazen, Davies, Ruth, Di Marco Barros, Rafael, Dima, Sofia, Dunley, Rachel, Dutta, Dipankar, Ellis, Richard, Everitt, Alex, Fady, Joseph, Fearon, Patricia, Fisniku, Leonora, Gbinigie, Ivie, Gemski, Alan, Gillies, Emma, Gkrania-Klotsas, Effrossyni, Grigg, Julie, Hamdalla, Hisham, Hubbett, Jack, Hunter, Neil, Huys, Anne-Catherine, Ihmoda, Ihmoda, Ispoglou, Sissi, Jha, Ashwani, Joussi, Ramzi, Kalladka, Dheeraj, Khalifeh, Hind, Kooij, Sander, Kumar, Guru, Kyaw, Sandar, Li, Lucia, Littleton, Edward, Macleod, Malcolm, Macleod, Mary Joan, Madigan, Barbara, Mahadasa, Vikram, Manoharan, Manonmani, Marigold, Richard, Marks, Isaac, Matthews, Paul, Mccormick, Michael, Mcinnes, Caroline, Metastasio, Antonio, Milburn-McNulty, Philip, Mitchell, Clinton, Mitchell, Duncan, Morgans, Clare, Morris, Huw, Morrow, Jasper, Mubarak Mohamed, Ahmed, Mulvenna, Paula, Murphy, Louis, Namushi, Robert, Newman, Edward, Phillips, Wendy, Pinto, Ashwin, Price, David Ashley, Proschel, Harald, Quinn, Terry, Ramsey, Deborah, Roffe, Christine, Ross Russell, Amy, Samarasekera, Neshika, Sawcer, Stephen, Sayed, Walee, Sekaran, Lakshmanan, Serra-Mestres, Jordi, Snowdon, Victoria, Strike, Gayle, Sun, James, Tang, Christina, Vrana, Mark, Wade, Ryckie, Wharton, Chris, Wiblin, Lou, Boubriak, Iryna, Herman, Katie, Plant, Gordon, Varatharaj, Aravinthan, Thomas, Naomi, Ellul, Mark A, Davies, Nicholas W S, Pollak, Thomas A, Tenorio, Elizabeth L, Sultan, Mustafa, Easton, Ava, Breen, Gerome, Zandi, Michael, Coles, Jonathan P, Manji, Hadi, Al-Shahi Salman, Rustam, Menon, David K, Nicholson, Timothy R, Benjamin, Laura A, Carson, Alan, Smith, Craig, Turner, Martin R, Solomon, Tom, Kneen, Rachel, Pett, Sarah L, Galea, Ian, Thomas, Rhys H, and Michael, Benedict D

Published
2020
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8. Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

Author

Aggarwal, Neil R, Nordwall, Jacquie, Braun, Dominique L, Chung, Lucy, Coslet, Jordan, Der, Tatyana, Eriobu, Nnakelu, Ginde, Adit A, Hayanga, Awori J, Highbarger, Helene, Holodniy, Mark, Horcajada, Juan P, Jain, Mamta K, Kim, Kami, Laverdure, Sylvain, Lundgren, Jens, Natarajan, Ven, Nguyen, Hien H, Pett, Sarah L, and Phillips, Andrew

Subjects
RISK assessment, VIRAL antibodies, SECONDARY analysis, RESPIRATORY therapy, DISEASE duration, HOSPITAL mortality, DESCRIPTIVE statistics, SEVERITY of illness index, RNA, VIRAL antigens, STATISTICS, ARTIFICIAL respiration, NASAL cannula, SOCIODEMOGRAPHIC factors, COVID-19, INTERLEUKINS, TIME, PROPORTIONAL hazards models, BIOMARKERS, VACCINATION status
Abstract

Background Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. Methods A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti–SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. Results Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29–3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09–5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29–6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06–3.22]; ≥4 L O2 [aHR, 4.41; 2.63–7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46–19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29–2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74–3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. Conclusions Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial

Author

Reduction of EArly mortaLITY in HIV-infected adults and children starting antiretroviral therapy (REALITY) Trial Team, Post, Frank A., Szubert, Alexander J., Prendergast, Andrew J., Johnston, Victoria, Lyall, Hermione, Fitzgerald, Felicity, Musiime, Victor, Musoro, Godfrey, Chepkorir, Priscilla, Agutu, Clara, Mallewa, Jane, Rajapakse, Chathurika, Wilkes, Helen, Hakim, James, Mugyenyi, Peter, Walker, A. Sarah, Gibb, Diana M., and Pett, Sarah L.

Published
2018

10. Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial

Author

Mugyenyi, Peter, Kityo, Cissy, Musiime, Victor, Wavamunno, Priscilla, Nambi, Esther, Ocitti, Paul, Ndigendawani, Milly, Kabahenda, Sheila, Kemigisa, Mable, Acen, Juliet, Olebo, David Francis, Mpamize, Gordon, Amone, Alex, Okweny, David, Mbonye, Andrew, Nambaziira, Florence, Rweyora, Angela, Kangah, Mary, Kabaswahili, Beatrice, Abach, James, Abongomera, George, Omongin, Joseph, Aciro, Irene, Philliam, Aleti, Arach, Beatrice, Ocung, Emmanuel, Amone, Geoffrey, Miles, Peter, Adong, Claudia, Tumsuiime, Constance, Kidega, Patrick, Otto, Ben, Apio, Florence, Baleeta, Keith, Mukuye, Andrew, Abwola, Mary, Ssennono, Fred, Baliruno, David, Tuhirwe, Stephen, Namisi, Ronald, Kigongo, Fredrick, Kikyonkyo, Dickson, Mushahara, Furaha, Tusiime, Julian, Musiime, Alex, Nankya, Agnes, Atwongyeire, Dickens, Sirikye, Sowal, Myalo, Sula, Noowe, Nelson, Lugemwa, Abbas, Kasozi, Mariam, Mwebe, Sandra, Atwine, Lorna, Senkindu, Tapson, Natuhurira, Ian, Katemba, Chrispus, Ninsiima, Emily, Acaku, Moses, Kyomuhangi, Joy, Ankunda, Rogers, Tukwasibwe, Deogratious, Ayesiga, Lillian, Hakim, James, Nathoo, Kusum, Bwakura-Dangarembizi, Mutsa, Reid, Andrew, Chidziva, Ennie, Mhute, Tawand, Tinago, Gloria, Bhiri, Joyline, Mudzingwa, Shepherd, Phiri, Misheck, Steamer, John, Nhema, Ruth, Warambwa, Colin, Musoro, Godfrey, Mutsai, Shirley, Nemasango, Beauty, Moyo, Columbus, Chitongo, Stuart, Rashirai, Kennias, Vhembo, Sydney, Mlambo, Brian, Nkomani, Sanele, Ndemera, Buxton, Willard, Marko, Berejena, Chipo, Musodza, Yeukai, Matiza, Patience, Mudenge, Boniface, Guti, Vongai, Etyang, Anthony, Agutu, Clara, Berkley, Jay, Maitland, Kathryn, Njuguna, Patricia, Mwaringa, Shalton, Etyang, Timothy, Awuondo, Ken, Wale, Stephen, Shangala, Jimmy, Kithunga, Jefwa, Mwarumba, Salim, Said Maitha, Salma, Mutai, Robert, Lozi Lewa, Margaret, Mwambingu, Gabriel, Mwanzu, Alfred, Kalama, Connie, Latham, Helen, Shikuku, Joyce, Fondo, Amos, Njogu, Anne, Khadenge, Connie, Mwakisha, Bryan, Siika, Abraham, Wools-Kaloustian, Kara, Nyandiko, Winston, Chepkorir-Cheruiyot, Priscilla, Sudoi, Allan, Wachira, Simon, Meli, Betty, Karoney, Mercy, Nzioka, Agnes, Tanui, Michael, Mokaya, Martha, Ekiru, Wilson, Mboya, Chris, Mwimali, Dorothy, Mengich, Cecilia, Choge, Julie, Injera, Wilfred, Njenga, Kennedy, Cherutich, Salinah, Anyango Orido, Millicent, Omondi Lwande, Gerald, Rutto, Peter, Mudogo, Alice, Kutto, Irene, Shali, Amina, Jaika, Linda, Jerotich, Hellen, Pierre, Mowlem, Mallewa, Jane, Kaunda, Symon, Van Oosterhout, Joep, O'Hare, Bernadette, Heydermann, Robert, Gonzalez, Carmen, Dzabala, Nettie, Kelly, Christine, Denis, Brigitte, Selemani, George, Nyondo- Mipando, Linda, Chirwa, Emmie, Banda, Peter, Mvula, Linley, Msuku, Harrison, Ziwoya, Milton, Manda, Yollam, Nicholas, Simon, Masesa, Clemens, Mwalukomo, Thandi, Makhaza, Lumbani, Sheha, Irene, Bwanali, Joseph, Limbuni, Molly, Gibb, Diana M, Thomason, Margaret J, Walker, Ann Sarah, Pett, Sarah L, Szubert, Alexander J, Griffiths, Anna, Wilkes, Helen, Rajapakse, Chathurika, Spyer, Moira J, Prendergast, Andrew J, Klein, Nigel, Rauchenberger, Mary, Van Looy, Nadine, Little, Emma, Fairbrother, Keith, Cowan, Frances, Seeley, Janet, Bernays, Sarah, Kawuma, Rachel, Mupambireyi, Zivai, Chepkorir, Priscilla, Melly, Betty, Walker, A Sarah, and Berkley, James A

Published
2018
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11. Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV‐negative controls: A cross‐sectional study nested within the POPPY cohort.

Author

Arenas‐Pinto, Alejandro, Bakewell, Nicholas, Milinkovic, Ana, Williams, Ian, Vera, Jaime, Post, Frank A., Anderson, Jane, Beynon, Michelle, O'Brien, Alastair, Doyle, Nicki, Gilson, Richard, Pett, Sarah L., Winston, Alan, and Sabin, Caroline A.

Subjects
HIV-positive persons, KRUSKAL-Wallis Test, ULTRASONIC imaging, CONFIDENCE intervals, FATTY liver, CROSS-sectional method, FISHER exact test, RISK assessment, COMPARATIVE studies, WAIST-hip ratio, RESEARCH funding, CHI-squared test, DESCRIPTIVE statistics, LOGISTIC regression analysis, ODDS ratio, DISEASE risk factors, ADULTS, MIDDLE age
Abstract

Background: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. Methods: Older (>50 years) and younger (<50 years) people with HIV and older HIV‐negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi‐squared/Fisher's exact/Kruskal–Wallis tests. Results: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV‐negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14–0.52) than controls, but male sex (OR 2.45; 95% CI 1.20–4.50) and high waist‐to‐hip ratio (OR 3.04; 95% CI 1.74–5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV‐related variables. Conclusions: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV‐related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study

Author

Pett, Sarah L, Kunisaki, Ken M, Wentworth, Deborah, Griffin, Timothy J, Kalomenidis, Ioannis, Nahra, Raquel, Montejano Sanchez, Rocio, Hodgson, Shane W, Ruxrungtham, Kiat, Dwyer, Dominic, Davey, Richard T, Wendt, Chris H, Lundgren, J, Jansson, P, Pearson, M, Aagaard, B, Hudson, F, Bennet, R, Pacciarini, F, Angus, B, Paton, N, Collaco Moraes, Y, Cooper, D, Pett, S, Emery, S, Courtney-Rogers, D, Robson, R, Gordin, F, Sanchez, A, Standridge, B, Vjecha, M, Moricz, A, Delfino, M, Belloso, W, Losso, M, Tillmann, K, Touloumi, G, Gioukari, V, Anagnostou, O, La Rosa, A, Saenz, M J, Lopez, P, Herrero, P, Portas, B, Avihingsanon, A, Ruxrungtham, K, Kaewon, P, Ubolyam, S, Brekke, K, Campbell, M, Denning, E, DuChene, A, Engen, N, George, M, Harrison, M, Neaton, J D, Nelson, R, Quan, S F, Schultz, T, Wentworth, D, Baxter, J, Brown, S, Hoover, M, Beigel, J, Davey, R T, Jr., Dewar, R, Gover, E, McConnell, R, Metcalf, J, Natarajan, V, Rehman, T, Voell, J, Dwyer, D E, Kok, J, Uyeki, T, Munroe, D, Paez, A, Bertrand, M, Temesgen, Z, Rizza, S, Wolfe, C, Carbonneau, J, Novak, R, Schwarber, M, Polenakovik, H, Clark, L, Patil, N, Riska, P, Omotosho, J, Faber, L, Markowitz, N, Glesby, M, Ham, K, Parenti, D, Simon, G, Baxter, J, Coburn, P, Freiberg, M, Koerbel, G, Dharan, N, Paez-Quinde, M, Gunter, J, Beilke, M, Lu, Z, Gunderson, E, Baker, J, Koletar, S, Harber, H, Hurt, C, Marcus, C, Allen, M, Cummins, S, Uslan, D, Bonam, T, Paez, A, Santiago, F, States, D, Gardner, E, DeHovitz, J, Holman, S, Watson, V, Nixon, D, Dwyer, D, Kabir, M, Pett, S, Kilkenny, F, Elliott, J, Garlick, J, McBride, J, Richmond, S, Barcan, L, Sanchez, M, Lopardo, G, Barcelona, L, Bonvehi, P, Temporiti, E R, Losso, M, Macias, L, Laplume, H, Daciuk, L, Warley, E, Tavella, S, Fernandez Cruz, E, Paño, J, Estrada, V, Lopetegui, P, Gimenez Julvez, T, Ryan, P, Sanz Moreno, J, Knobel, H, Soriano, V, Dalmau, D, Dockrell, D, Angus, B, Price, D, Newport, M, Chadwick, D, Østergaard, L, Yehdego, Y, Pedersen, C, Hergens, L, Joensen, Z, Aagaard, B, Kronborg, G, Collins, P, Nielsen, H, Gerstoft, J, Baadegaard, B, Koulouris, N, Antoniadou, A, Protopappas, K, Polixronopoulos, V, Diamantea, F, Sambatakou, H, Mariolis, I, Vassilopoulos, N, Gerogiannis, A, Pinedo Ramirez, Y, Cornelio Mauricio, E, Vega Bazalar, J, Castillo Cordova, R, Fãtkenhuerer, G, Thomas, E, Bergmann, F, Fõllmer, U, Rockstroh, J, Englehardt, A, Stephan, C, Thomas, E, Bogner, J, Brockmeyer, N, Klinker, H, Chetchotisakd, P, Jumpimai, T, Avihingsanon, A, Ruxrungtham, K, Clumeck, N, Kameya, K, Chu, M Y, Wu, T C, Horban, A, Bakowska, E, Burgmann, H, Tobudic, S, Maagaard, A, Wolff, M, and Allendes, G

Published
2018
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14. Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

Author

Flower, Barnaby, primary, Hung, Le Manh, additional, Mccabe, Leanne, additional, Ansari, M Azim, additional, Le Ngoc, Chau, additional, Vo Thi, Thu, additional, Vu Thi Kim, Hang, additional, Nguyen Thi Ngoc, Phuong, additional, Phuong, Le Thanh, additional, Quang, Vo Minh, additional, Dang Trong, Thuan, additional, Le Thi, Thao, additional, Nguyen Bao, Tran, additional, Kingsley, Cherry, additional, Smith, David, additional, Hoglund, Richard M, additional, Tarning, Joel, additional, Kestelyn, Evelyne, additional, Pett, Sarah L, additional, van Doorn, Rogier, additional, Van Nuil, Jennifer Ilo, additional, Turner, Hugo, additional, Thwaites, Guy E, additional, Barnes, Eleanor, additional, Rahman, Motiur, additional, Walker, Ann Sarah, additional, Day, Jeremy N, additional, Chau, Nguyen VV, additional, and Cooke, Graham S, additional

Published
2023
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15. Author response: Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

Author

Flower, Barnaby, primary, Hung, Le Manh, additional, Mccabe, Leanne, additional, Ansari, M Azim, additional, Le Ngoc, Chau, additional, Vo Thi, Thu, additional, Vu Thi Kim, Hang, additional, Nguyen Thi Ngoc, Phuong, additional, Phuong, Le Thanh, additional, Quang, Vo Minh, additional, Dang Trong, Thuan, additional, Le Thi, Thao, additional, Nguyen Bao, Tran, additional, Kingsley, Cherry, additional, Smith, David, additional, Hoglund, Richard M, additional, Tarning, Joel, additional, Kestelyn, Evelyne, additional, Pett, Sarah L, additional, van Doorn, Rogier, additional, Van Nuil, Jennifer Ilo, additional, Turner, Hugo, additional, Thwaites, Guy E, additional, Barnes, Eleanor, additional, Rahman, Motiur, additional, Walker, Ann Sarah, additional, Day, Jeremy N, additional, Chau, Nguyen VV, additional, and Cooke, Graham S, additional

Published
2022
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17. Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for Hepatitis C: a single arm mechanistic pilot study

Author

Flower, Barnaby, primary, Hung, Le Manh, additional, McCabe, Leanne, additional, Ansari, M. Azim, additional, Le Ngoc, Chau, additional, Vo Thi, Thu, additional, Vu Thi Kim, Hang, additional, Nguyen Thi Ngoc, Phuong, additional, Phuong, Le Thanh, additional, Quang, Vo Minh, additional, Trong, Thuan Dang, additional, Le Thi, Thao, additional, Bao, Tran Nguyen, additional, Kingsley, Cherry, additional, Smith, David, additional, Hoglund, Richard M., additional, Tarning, Joel, additional, Kestelyn, Evelyne, additional, Pett, Sarah L, additional, van Doorn, Rogier, additional, van Nuil, Jennifer Ilo, additional, Turner, Hugo, additional, Thwaites, Guy, additional, Barnes, Eleanor, additional, Rahman, Motiur, additional, Walker, Ann Sarah, additional, Day, Jeremy, additional, Van Vinh Chau, Nguyen, additional, and Cooke, Graham S, additional

Published
2022
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21. Utility of a buccal swab point-of-care test for the IFNL4 genotype in the era of direct acting antivirals for hepatitis C virus.

Author

Sy, Aminata, McCabe, Leanne, Hudson, Emma, Ansari, Azim M., Pedergnana, Vincent, Lin, Shang-Kuan, Santana, S., Fiorino, Marzia, Ala, Aftab, Stone, Ben, Smith, M., Nelson, Mark, Barclay, Stephen T., McPherson, Stuart, Ryder, Stephen D., Collier, Jane, Barnes, Eleanor, Walker, Ann Sarah, Pett, Sarah L., and Cooke, Graham

Subjects
HEPATITIS C virus, GENOTYPES, POINT-of-care testing, ANTIVIRAL agents, HEPATITIS C, PLANT viruses
Abstract

Background: The CC genotype of the IFNL4 gene is known to be associated with increased Hepatitis C (HCV) cure rates with interferon-based therapy and may contribute to cure with direct acting antivirals. The Genedrive® IFNL4 is a CE marked Point of Care (PoC) molecular diagnostic test, designed for in vitro diagnostic use to provide rapid, real-time detection of IFNL4 genotype status for SNP rs12979860. Methods: 120 Participants were consented to a substudy comparing IFNL4 genotyping results from a buccal swab analysed on the Genedrive® platform with results generated using the Affymetix UK Biobank array considered to be the gold standard. Results: Buccal swabs were taken from 120 participants for PoC IFNL4 testing and a whole blood sample for genetic sequencing. Whole blood genotyping vs. buccal swab PoC testing identified 40 (33%), 65 (54%), and 15 (13%) had CC, CT and TT IFNL4 genotype respectively. The Buccal swab PoC identified 38 (32%) CC, 64 (53%) CT and 18 (15%) TT IFNL4 genotype respectively. The sensitivity and specificity of the buccal swab test to detect CC vs non-CC was 90% (95% CI 76–97%) and 98% (95% CI 91–100%) respectively. Conclusions: The buccal swab test was better at correctly identifying non-CC genotypes than CC genotypes. The high specificity of the Genedrive® assay prevents CT/TT genotypes being mistaken for CC, and could avoid patients being identified as potentially 'good responders' to interferon-based therapy. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial

Author

Kityo, Cissy, Szubert, Alexander J., Siika, Abraham, Heyderman, Robert, Bwakura-Dangarembizi, Mutsa, Lugemwa, Abbas, Mwaringa, Shalton, Griffiths, Anna, Nkanya, Immaculate, Kabahenda, Sheila, Wachira, Simon, Musoro, Godfrey, Rajapakse, Chatu, Etyang, Timothy, Abach, James, Spyer, Moira J., Wavamunno, Priscilla, Nyondo-Mipando, Linda, Chidziva, Ennie, Nathoo, Kusum, Klein, Nigel, Hakim, James, Gibb, Diana M., Walker, A. Sarah, and Pett, Sarah L.

Subjects
Raltegravir -- Testing, HIV infections -- Drug therapy, Biological sciences
Abstract

Background In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. Methods and findings In a 2x2x2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76-1.28], p = 0.91); in serious (aHR = 0.99 [0.81-1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71-1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63-1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76-1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. Conclusions Although 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals. Trial registration ClinicalTrials.gov NCT01825031. Trial registration International Standard Randomised Controlled Trials Number ISRCTN 43622374., Author(s): Cissy Kityo 1, Alexander J. Szubert 2, Abraham Siika 3, Robert Heyderman 4,5, Mutsa Bwakura-Dangarembizi 6, Abbas Lugemwa 7, Shalton Mwaringa 8, Anna Griffiths 2, Immaculate Nkanya 1, Sheila [...]

Published
2018
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25. High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study

Author

Flower, Barnaby, primary, McCabe, Leanne, additional, Le Ngoc, Chau, additional, Le Manh, Hung, additional, Le Thanh, Phuong, additional, Dang Trong, Thuan, additional, Vo Thi, Thu, additional, Vu Thi Kim, Hang, additional, Nguyen Tat, Thanh, additional, Phan Thi Hong, Dao, additional, Nguyen Thi Chau, An, additional, Dinh Thi, Tan, additional, Tran Thi Tuyet, Nga, additional, Tarning, Joel, additional, Kingsley, Cherry, additional, Kestelyn, Evelyne, additional, Pett, Sarah L, additional, Thwaites, Guy, additional, Nguyen Van, Vinh Chau, additional, Smith, David, additional, Barnes, Eleanor, additional, Ansari, M Azim, additional, Turner, Hugo, additional, Rahman, Motiur, additional, Walker, Ann Sarah, additional, Day, Jeremy, additional, and Cooke, Graham S, additional

Published
2021
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26. Prevalence of HIV/hepatitis B and HIV/hepatitis C coinfection among people of East, South, Central and West African ancestry in the United Kingdom

Author

Hung, Rachel, primary, Patel, Nisha, additional, Fox, Julie, additional, Cosgrove, Catherine, additional, Pett, Sarah L., additional, Burns, Fiona, additional, Ustianowski, Andrew, additional, Rosenvinge, Melanie, additional, Bhagani, Sanjay, additional, Dusheiko, Geoff, additional, Childs, Kate, additional, and Post, Frank A., additional

Published
2021
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27. Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial

Author

Mallewa, Jane, Szubert, Alexander J, Mugyenyi, Peter, Chidziva, Ennie, Thomason, Margaret J, Chepkorir, Priscilla, Abongomera, George, Baleeta, Keith, Etyang, Anthony, Warambwa, Colin, Melly, Betty, Mudzingwa, Shepherd, Kelly, Christine, Agutu, Clara, Wilkes, Helen, Nkomani, Sanele, Musiime, Victor, Lugemwa, Abbas, Pett, Sarah L, Bwakura-Dangarembizi, Mutsa, Prendergast, Andrew J, Gibb, Diana M, Walker, A Sarah, Berkley, James A., REALITY Trial Team, O'Hare, Bernadette, DiFDMRCWellcome Trust, University of St Andrews. School of Medicine, and University of St Andrews. Infection and Global Health Division

Subjects
IMMUNE-ACTIVATION, Adult, Male, RZ Other systems of medicine, Adolescent, Arachis, Immunology, NDAS, HIV Infections, Article, Body Mass Index, INSECURITY, EFAVIRENZ, Young Adult, SDG 3 - Good Health and Well-being, Anti-Infective Agents, RA0421, RZ, RA0421 Public health. Hygiene. Preventive Medicine, Raltegravir Potassium, Humans, Micronutrients, SDG 2 - Zero Hunger, Child, Africa South of the Sahara, Aged, RISK, OUTCOMES, Science & Technology, Body Weight, ADULTS, ASSOCIATION, Middle Aged, Survival Analysis, Infectious Diseases, Treatment Outcome, Anti-Retroviral Agents, Child, Preschool, HIV/AIDS, Female, Life Sciences & Biomedicine, REALITY trial team, Diet Therapy
Abstract

Funding: Joint Global Health Trials Scheme (UK Medical Research Council, UK Department for International Development, and Wellcome Trust). BACKGROUND: In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only. METHODS: We did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5-12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] 0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious adverse events in both groups (p=0·81), and 181 had grade 4 adverse events in the RUSF group compared with 172 in the non-RUSF group (p=0·45). INTERPRETATION: In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised HIV-infected individuals starting ART is therefore not warranted at present. Publisher PDF Publisher PDF

Published
2018

29. Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status

Author

Pett, Sarah L., primary, Spyer, Moira, additional, Haddow, Lewis J., additional, Nhema, Ruth, additional, Benjamin, Laura A., additional, Najjuka, Grace, additional, Bilima, Sithembile, additional, Daud, Ibrahim, additional, Musoro, Godfrey, additional, Kitabalwa, Juliet, additional, Selemani, George, additional, Kandie, Salome, additional, Cornelius, K. Magut, additional, Katemba, Chrispus, additional, Berkley, Jay A., additional, Hassan, Amin S., additional, Kityo, Cissy, additional, Hakim, James, additional, Heyderman, Robert S., additional, Gibb, Diana M., additional, and Walker, Ann S., additional

Published
2020
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31. Characterising neuropsychiatric disorders in patients with COVID-19 – Authors' reply

Author

Varatharaj, Aravinthan, primary, Pollak, Thomas A, additional, Nicholson, Timothy R, additional, Coles, Jonathan P, additional, Benjamin, Laura A, additional, Carson, Alan, additional, Thomas, Rhys H, additional, Michael, Benedict D, additional, Davies, Nicholas WS, additional, Breen, Gerome, additional, Zandi, Michael, additional, Ellul, Mark A, additional, Thomas, Naomi, additional, Tenorio, Elizabeth L, additional, Sultan, Mustafa, additional, Easton, Ava, additional, Smith, Craig, additional, Kneen, Rachel, additional, Turner, Martin R, additional, Manji, Hadi, additional, Solomon, Tom, additional, Menon, David K, additional, Pett, Sarah L, additional, and Galea, Ian, additional

Published
2020
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32. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Author

Varatharaj, Aravinthan, primary, Thomas, Naomi, additional, Ellul, Mark A, additional, Davies, Nicholas W S, additional, Pollak, Thomas A, additional, Tenorio, Elizabeth L, additional, Sultan, Mustafa, additional, Easton, Ava, additional, Breen, Gerome, additional, Zandi, Michael, additional, Coles, Jonathan P, additional, Manji, Hadi, additional, Al-Shahi Salman, Rustam, additional, Menon, David K, additional, Nicholson, Timothy R, additional, Benjamin, Laura A, additional, Carson, Alan, additional, Smith, Craig, additional, Turner, Martin R, additional, Solomon, Tom, additional, Kneen, Rachel, additional, Pett, Sarah L, additional, Galea, Ian, additional, Thomas, Rhys H, additional, Michael, Benedict D, additional, Allen, Claire, additional, Archibald, Neil, additional, Arkell, James, additional, Arthur-Farraj, Peter, additional, Baker, Mark, additional, Ball, Harriet, additional, Bradley-Barker, Verity, additional, Brown, Zoe, additional, Bruno, Stefania, additional, Carey, Lois, additional, Carswell, Christopher, additional, Chakrabarti, Annie, additional, Choulerton, James, additional, Daher, Mazen, additional, Davies, Ruth, additional, Di Marco Barros, Rafael, additional, Dima, Sofia, additional, Dunley, Rachel, additional, Dutta, Dipankar, additional, Ellis, Richard, additional, Everitt, Alex, additional, Fady, Joseph, additional, Fearon, Patricia, additional, Fisniku, Leonora, additional, Gbinigie, Ivie, additional, Gemski, Alan, additional, Gillies, Emma, additional, Gkrania-Klotsas, Effrossyni, additional, Grigg, Julie, additional, Hamdalla, Hisham, additional, Hubbett, Jack, additional, Hunter, Neil, additional, Huys, Anne-Catherine, additional, Ihmoda, Ihmoda, additional, Ispoglou, Sissi, additional, Jha, Ashwani, additional, Joussi, Ramzi, additional, Kalladka, Dheeraj, additional, Khalifeh, Hind, additional, Kooij, Sander, additional, Kumar, Guru, additional, Kyaw, Sandar, additional, Li, Lucia, additional, Littleton, Edward, additional, Macleod, Malcolm, additional, Macleod, Mary Joan, additional, Madigan, Barbara, additional, Mahadasa, Vikram, additional, Manoharan, Manonmani, additional, Marigold, Richard, additional, Marks, Isaac, additional, Matthews, Paul, additional, Mccormick, Michael, additional, Mcinnes, Caroline, additional, Metastasio, Antonio, additional, Milburn-McNulty, Philip, additional, Mitchell, Clinton, additional, Mitchell, Duncan, additional, Morgans, Clare, additional, Morris, Huw, additional, Morrow, Jasper, additional, Mubarak Mohamed, Ahmed, additional, Mulvenna, Paula, additional, Murphy, Louis, additional, Namushi, Robert, additional, Newman, Edward, additional, Phillips, Wendy, additional, Pinto, Ashwin, additional, Price, David Ashley, additional, Proschel, Harald, additional, Quinn, Terry, additional, Ramsey, Deborah, additional, Roffe, Christine, additional, Ross Russell, Amy, additional, Samarasekera, Neshika, additional, Sawcer, Stephen, additional, Sayed, Walee, additional, Sekaran, Lakshmanan, additional, Serra-Mestres, Jordi, additional, Snowdon, Victoria, additional, Strike, Gayle, additional, Sun, James, additional, Tang, Christina, additional, Vrana, Mark, additional, Wade, Ryckie, additional, Wharton, Chris, additional, Wiblin, Lou, additional, Boubriak, Iryna, additional, Herman, Katie, additional, and Plant, Gordon, additional

Published
2020
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33. No overall impact on rate of weight gain with integrase inhibitor‐containing regimens in antiretroviral‐naïve adults.

Author

Burns, James E., Stirrup, Oliver, Waters, Laura, Dunn, David, Gilson, Richard, and Pett, Sarah L.

Subjects
HIV infections, HIV-positive persons, RALTEGRAVIR, HIV integrase inhibitors, PROTEASE inhibitors, CONFIDENCE intervals, VIRAL load, RETROSPECTIVE studies, WEIGHT gain, DESCRIPTIVE statistics
Abstract

Objectives: Integrase strand transfer inhibitors (INSTIs) are commonplace in modern antiretroviral therapy (ART). Increased weight gain with their use is increasingly scrutinized. We evaluated weight changes in treatment‐naïve adults with HIV‐1 attending a UK centre who started regimens including raltegravir or dolutegravir. Methods: A retrospective cohort study of adults prescribed an INSTI between January 2015 and March 2020 were categorized as having started an ART regimen containing raltegravir, dolutegravir, a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Individuals with one or more weight measurement ≤ 5 years both pre‐ and post‐ART initiation, who started a three‐drug regimen with ≥ 6 months duration and achieved virological suppression (< 50 copies/mL) within 6 months were included. A random effects model with linear slope pre‐ and post‐ART was used, adjusting for age, gender, ethnicity, ART regimen, backbone and year of initiation. Results: The cohort included 390 adults; 88.7% were male, 66.4% were of white ethnicity, their median age was 40 years, there was a median of six weight measurements, 2.2 years from diagnosis to ART initiation, 2.9 years from ART to the last weight measurement, and weight and body mass index at initiation were 75 kg and 24.1 kg/m2 respectively. Of these, 254 (65%) started an INSTI. The average pre‐ART rate of weight gain was 0.44 kg/year [95% confidence interval (CI): 0.19–0.70], increasing to 0.88 kg/year (0.63–1.10, p = 0.04) after ART initiation. Our adjusted model found no evidence of an association between ART regimen and rate of weight gain. Conclusions: Weight increased in the cohort both pre‐ and post‐ART. We found no evidence of a higher rate of weight gain following ART initiation with an INSTI compared with other regimens. [ABSTRACT FROM AUTHOR]

Published
2022
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40. Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study

Author

Pett, Sarah L. Kunisaki, Ken M. Wentworth, Deborah Griffin, Timothy J. Kalomenidis, Ioannis Nahra, Raquel Montejano Sanchez, Rocio Hodgson, Shane W. Ruxrungtham, Kiat Dwyer, Dominic Davey, Richard T. Wendt, Chris H. INSIGHT FLU003 Plus Study Grp

Abstract

Background. Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods. We performed a case-control (1: 2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1) pdm09 with protocol-defined disease progression (diedtransferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. Results. We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mMM; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P = .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mMM). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90). Conclusions. High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1) pdm09. The clinical utility of this biomarker in this setting merits further exploration.

Published
2018

42. Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status.

Author

Pett, Sarah L., Spyer, Moira, Haddow, Lewis J., Nhema, Ruth, Benjamin, Laura A., Najjuka, Grace, Bilima, Sithembile, Daud, Ibrahim, Musoro, Godfrey, Kitabalwa, Juliet, Selemani, George, Kandie, Salome, Cornelius, K. Magut, Katemba, Chrispus, Berkley, Jay A., Hassan, Amin S., Kityo, Cissy, Hakim, James, Heyderman, Robert S., and Gibb, Diana M.

Published
2021
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43. Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa

Author

Hakim, James, Musiime, Victor, Szubert, Alex J., Mallewa, Jane, Siika, Abraham, Agutu, Clara, Walker, Simon, Pett, Sarah L., Bwakura-Dangarembizi, Mutsa, Lugemwa, Abbas, Kaunda, Symon, Karoney, Mercy, Musoro, Godfrey, Kabahenda, Sheila, Nathoo, Kusum, Maitland, Kathryn, Griffiths, Anna, Thomason, Margaret J., Kityo, Cissy, Mugyenyi, Peter, Prendergast, Andrew J., Walker, A. Sarah, Gibb, Diana M., REALITY Trial Team, O'Hare, Bernadette Ann-Marie, DiFDMRCWellcome Trust, University of St Andrews. School of Medicine, and University of St Andrews. Infection and Global Health Division

Subjects
Male, REALITY Trial Team, 0301 basic medicine, Placebo-controlled study, CHILDREN, HIV Infections, Kaplan-Meier Estimate, law.invention, DOUBLE-BLIND, 0302 clinical medicine, Anti-Infective Agents, Randomized controlled trial, WORLDWIDE, law, Medicine, 030212 general & internal medicine, Child, 11 Medical and Health Sciences, Medicine(all), education.field_of_study, Mortality rate, Pyridoxine, General Medicine, Middle Aged, OPEN-LABEL, 3. Good health, Anti-Retroviral Agents, Chemoprophylaxis, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, Tuberculosis, Adolescent, 030106 microbiology, Population, NDAS, R Medicine, TUBERCULOSIS, Article, Young Adult, 03 medical and health sciences, Medicine, General & Internal, Pharmacotherapy, SDG 3 - Good Health and Well-being, PEOPLE, General & Internal Medicine, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, Isoniazid, Humans, Intensive care medicine, education, Africa South of the Sahara, Aged, Science & Technology, AIDS-Related Opportunistic Infections, business.industry, MORTALITY, ADULTS, Raltegravir, medicine.disease, CD4 Lymphocyte Count, HIV-1, business, CRYPTOCOCCAL MENINGITIS
Abstract

Supported by the Joint Global Health Trials Scheme of the Medical Research Council (MRC), the U.K. Department for International Development, and the Wellcome Trust through a grant (G1100693),with additional support from the PENTA Foundation. The MRC Clinical Trials Unit at University College London is supported by grants from the MRC (MC-UU-12023/23 and MC-UU-12023/26). Dr. Prendergast is funded by a grant (108065/Z/15/Z) from the Wellcome Trust, which also funds the Malawi–Liverpool–Wellcome Trust Clinical Research Program at the University of Malawi College of Medicine through a grant (101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)–Wellcome Trust Research Program through a grant (077092). Background: In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. Methods: In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. Results: A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P = 0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P = 0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P = 0.02), cryptococcal infection (P = 0.01), oral or esophageal candidiasis (P = 0.02), death of unknown cause (P = 0.03), and new hospitalization (P = 0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P = 0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P = 0.08 and P = 0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups. Conclusions: Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects. Publisher PDF

Published
2017

44. The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct-acting antiviral hepatitis C treatment strategies in Vietnam.

Author

McCabe, Leanne, White, Ian R., Chau, Nguyen Van Vinh, Barnes, Eleanor, Pett, Sarah L., Cooke, Graham S., Walker, A. Sarah, on behalf of SEARCH investigators, Day, Jeremy N., Dung, Nguyen Thanh, Flower, Barnaby, Hallett, Tim, Hung, Le Manh, Kestelyn, Evelyne, Khoa, Dao Bach, Phuong, Le Thanh, Rahman, Motiur, Tarning, Joel, Turner, Hugo C., and Thwaites, Guy E.

Subjects
EXPERIMENTAL design, HEPATITIS C, RIBAVIRIN
Abstract

Background: Eliminating hepatitis C is hampered by the costs of direct-acting antiviral treatment and the need to treat hard-to-reach populations. Access could be widened by shortening or simplifying treatment, but limited research means it is unclear which approaches could achieve sufficiently high cure rates to be acceptable. We present the statistical aspects of a multi-arm trial designed to test multiple strategies simultaneously and a monitoring mechanism to detect and stop individual randomly assigned groups with unacceptably low cure rates quickly.Methods: The VIETNARMS trial will factorially randomly assign patients to two drug regimens, three treatment-shortening strategies or control, and adjunctive ribavirin or no adjunctive ribavirin with shortening strategies (14 randomly assigned groups). We will use Bayesian monitoring at interim analyses to detect and stop recruitment into unsuccessful strategies, defined by more than 0.95 posterior probability that the true cure rate is less than 90% for the individual randomly assigned group (non-comparative). Final comparisons will be non-inferiority for regimens (margin 5%) and strategies (margin 10%) and superiority for adjunctive ribavirin. Here, we tested the operating characteristics of the stopping guideline for individual randomly assigned groups, planned interim analysis timings and explored power at the final analysis.Results: A beta (4.5, 0.5) prior for the true cure rate produces less than 0.05 probability of incorrectly stopping an individual randomly assigned group with a true cure rate of more than 90%. Groups with very low cure rates (<60%) are very likely (>0.9 probability) to stop after about 25% of patients are recruited. Groups with moderately low cure rates (80%) are likely to stop (0.7 probability) before overall recruitment finishes. Interim analyses 7, 10, 13 and 18 months after recruitment commences provide good probabilities of stopping inferior individual randomly assigned groups. For an overall true cure rate of 95%, power is more than 90% to confirm non-inferiority in the regimen and strategy comparisons, regardless of the control cure rate, and to detect a 5% absolute difference in the ribavirin comparison.Conclusions: The operating characteristics of the stopping guideline are appropriate, and interim analyses can be timed to detect individual randomly assigned groups that are highly likely to have suboptimal performance at various stages. Therefore, our design is suitable for evaluating treatment-shortening or -simplifying strategies.Trial Registration: ISRCTN registry: ISRCTN61522291. Registered on 4 October 2019. [ABSTRACT FROM AUTHOR]

Published
2020
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45. Markers of Inflammation, Coagulation, and Renal Function Are Elevated in Adults with HIV Infection

Author

Neuhaus, Jacqueline, Jacobs, David R., Baker, Jason V., Calmy, Alexandra, Duprez, Daniel, La Rosa, Alberto, Kuller, Lewis H., Pett, Sarah L., Ristola, Matti, Ross, Michael J., Shlipak, Michael G., Tracy, Russell, Neaton, James D., Neuhaus, Jacqueline, Jacobs, David R., Baker, Jason V., Calmy, Alexandra, Duprez, Daniel, La Rosa, Alberto, Kuller, Lewis H., Pett, Sarah L., Ristola, Matti, Ross, Michael J., Shlipak, Michael G., Tracy, Russell, and Neaton, James D.

Abstract

(See the article by Kalayjian et al, on pages 1796-1805, and the editorial commentary by Dubé and Sattler, on pages 1783-1785.) Background. Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection. Methods. For persons 45-76 years of age, levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, D-dimer, and cystatin C were compared in 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study and 5386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study. For persons 33-44 years of age, hsCRP and IL-6 levels were compared in 287 participants in the SMART study and 3231 participants in the Coronary Artery Development in Young Adults (CARDIA) study. Results. hsCRP and IL-6 levels were 55% (P<.001) and 62% (P<.001) higher among HIV-infected participants than among CARDIA study participants. Compared with levels noted in MESA study participants, hsCRP, IL-6, D-dimer, and cystatin C levels were 50%, 152%, 94%, and 27% higher, respectively (P<.001 , for each), among HIV-infected participants. HIV-infected participants receiving antiretroviral therapy who had HIV RNA levels ≤400 copies/mL had levels higher (by 21% to 60%) (P<.001) than those in the general population, for all biomarkers. Conclusions. hsCRP, IL-6, D-dimer, and cystatin C levels are elevated in persons with HIV infection and remain so even after HIV RNA levels are suppressed with antiretroviral therapy. Additional research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways, to guide potential interventions

Published
2017

46. Characterising neuropsychiatric disorders in patients with COVID-19 – Authors' reply

Author

Davies, Nicholas WS, Breen, Gerome, Zandi, Michael, Ellul, Mark A, Thomas, Naomi, Tenorio, Elizabeth L, Sultan, Mustafa, Easton, Ava, Smith, Craig, Kneen, Rachel, Turner, Martin R, Manji, Hadi, Solomon, Tom, Menon, David K, Pett, Sarah L, Galea, Ian, Varatharaj, Aravinthan, Pollak, Thomas A, Nicholson, Timothy R, Coles, Jonathan P, Benjamin, Laura A, Carson, Alan, Thomas, Rhys H, and Michael, Benedict D

Published
2020
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47. Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa

Author

Hakim, James, primary, Musiime, Victor, additional, Szubert, Alex J., additional, Mallewa, Jane, additional, Siika, Abraham, additional, Agutu, Clara, additional, Walker, Simon, additional, Pett, Sarah L., additional, Bwakura-Dangarembizi, Mutsa, additional, Lugemwa, Abbas, additional, Kaunda, Symon, additional, Karoney, Mercy, additional, Musoro, Godfrey, additional, Kabahenda, Sheila, additional, Nathoo, Kusum, additional, Maitland, Kathryn, additional, Griffiths, Anna, additional, Thomason, Margaret J., additional, Kityo, Cissy, additional, Mugyenyi, Peter, additional, Prendergast, Andrew J., additional, Walker, A. Sarah, additional, and Gibb, Diana M., additional

Published
2017
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49. The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies

Author

Davey, Richard T, Lynfield, Ruth, Dwyer, Dominic E, Losso, Marcello H, Cozzi-Lepri, Alessandro, Wentworth, Deborah, Lane, H Clifford, Dewar, Robin, Rupert, Adam, Metcalf, Julia A, Pett, Sarah L, Uyeki, Timothy M, Bruguera, Jose Maria, Angus, Brian, Cummins, Nathan, Lundgren, Jens, Neaton, James D, The INSIGHT FLU 002 & 003 Study Groups, and Newport, Melanie

Subjects
RC0251
Abstract

BACKGROUND\ud \ud Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies.\ud \ud METHODS\ud \ud Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p

Published
2013

50. Biomarkers and bacterial pneumonia risk in patients with treated HIV infection: a case-control study

Author

Bjerk, Sonja M., Baker, Jason V., Emery, Sean, Neuhaus, Jacqueline, Angus, Brian, Gordin, Fred M., Pett, Sarah L., Stephan, Christoph, Kunisaki, Ken M., Bjerk, Sonja M., Baker, Jason V., Emery, Sean, Neuhaus, Jacqueline, Angus, Brian, Gordin, Fred M., Pett, Sarah L., Stephan, Christoph, and Kunisaki, Ken M.

Abstract

Background: Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist. Methods: We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1:1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Results: Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). Conclusions: In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.

Published
2013

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