27 results on '"Huang, Kuan-Hsiang Gary"'
Search Results
2. Qualitative and psychometric evaluation of the PROMIS®-Fatigue SF-7a scale to assess fatigue in patients with moderately to severely active inflammatory bowel disease
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Feagan, Brian G., Sandborn, William J., Sands, Bruce E., Liu, Yan, Vetter, Marion, Mathias, Susan D., Huang, Kuan-Hsiang Gary, Johanns, Jewel, Germinaro, Matthew, and Han, Chenglong
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- 2023
- Full Text
- View/download PDF
3. The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study
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Emery, Paul, Tanaka, Yoshiya, Bykerk, Vivian P., Bingham, Clifton O., Huizinga, Thomas W. J., Citera, Gustavo, Huang, Kuan-Hsiang Gary, Wu, Chun, Connolly, Sean E., Elbez, Yedid, Wong, Robert, Lozenski, Karissa, and Fleischmann, Roy
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- 2023
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4. Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis
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Emery, Paul, Tanaka, Yoshiya, Bykerk, Vivian P., Huizinga, Thomas W. J., Citera, Gustavo, Bingham, 3rd, Clifton O., Banerjee, Subhashis, Soule, Benjamin P., Nys, Marleen, Connolly, Sean E., Lozenski, Karissa L., Zhuo, Joe, Wong, Robert, Huang, Kuan-Hsiang Gary, and Fleischmann, Roy
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- 2023
- Full Text
- View/download PDF
5. Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study
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Abrahamovych, Orest, Afanasieva, Halyna, Aitova, Lilia, Altintas, Engin, Altwegg, Romain, Andreev, Pavel, Aomatsu, Kazuki, Augustyn, Monika, Balestrieri, Paola, Begun, Jakob, Brunatto, Luciana, Bulgheroni, Diego, Bunkova, Elena, Cabello, Mercedes, Cao, Qian, Caprioli, Flavio, Cerqueira, Rute, Chen, Baili, Chen, Chou-Chen, Chen, Chou-Pin, Chiu, Cheng-Tang, Choi, Chang Hwan, Cicala, Michele, Datsenko, Olena, Dewint, Pieter, Domenech, Eugeni, Dutré, Joris, Duvall, George, Fernandez, Juan, Filip, Rafal, Fogel, Ronald, Fowler, Sharyle, Fujii, Toshimitsu, Fukata, Masayuki, Furumoto, Yohei, Gasbarrini, Antonio, Gawdis-Wojnarska, Beata, Gilletta, Cyrielle, Gionchetti, Paolo, Goldin, Eran, Golovchenko, Oleksandr, Gonciarz, Maciej, Gonen, Can, Segura, Gaston Gonzalez, Gridnyev, Oleksii, Gyokeres, Tibor, Hébuterne, Xavier, Hedin, Charlotte, Hellström, Per, Hilmi, Ida Normiha, Horný, Ivo, Horvat, Gyula, Hoshi, Namiko, Hrdlicka, Ludek, Ishihara, Shunji, Ivanishyn, Olha, Jang, Byung Ik, Junior, Odery, Kagaya, Takashi, Kanmura, Shuji, Karakina, Marina, Katsuhiko, Nakai, Kierkus, Jaroslaw, Kim, Hyo Jong, Kim, Tae-Oh, Kim, Young-Ho, Kiss, Gyula G., Klaus, Jochen, Kleczkowski, Dariusz, Klopocka, Maria, Kobayashi, Taku, Kobielusz-Gembala, Iwona, Koo, Ja Seol, Kopon, Adam, Kravchenko, Tetiana, Kudo, Masatoshi, Kwon, Kwang An, Lago, Paula, Laharie, David, Lawrance, Ian, Leszczyszyn, Jaroslaw, Li, Yan, Lukas, Milan, Maaser, Christian, Maemoto, Atsuo, Marusawa, Hiroyuki, McBride, Matthew, Mendu, Shoba, Miheller, Pal, Miyabayashi, Hideharu, Mohl, Wolfgang, Moore, Gregory, Motoya, Satoshi, Murali, Narayanachar, Naem, Mohammed, Nakajima, Koichi, Nakamoto, Yasunari, Nancey, Stéphane, Neto, Joaquim, Onizawa, Michio, Ono, Yohei, Osada, Taro, Osipenko, Marina, Owczarek, Danuta, Patel, Bhaktasharan, Patel, Kamal, Petrova, Elina, Poroshina, Elena, Portela, Francisco, Prystupa, Lyudmyla, Rivero, Monserrat, Roblin, Xavier, Romatowski, Jacek, Rydzewska, Grazyna, Saibeni, Simone, Sakuraba, Hirotake, Samaan, Mark, Schultz, Michael, Schulze, Joerg, Sedghi, Shahriar, Seidler, Ursula, Shin, Sung Jae, Stanislavchuk, Mykola, Stokesberry, David, Suzuki, Takayoshi, Taguchi, Hiroki, Tankova, Lyudmila, Thin, Lena, Tkachev, Alexander, Torrealba, Leyanira, Tsarynna, Nataliia, Tulassay, Zsolt, Ueo, Tetsuya, Valuyskikh, Ekaterina, Vasilevskaya, Olga, Viamonte, Manuel, Wei, Shu-Chen, Weisshof, Roni, Wojcik, Katarzyna, Ye, Byong Duk, Yen, Hsu-Heng, Yoon, Hyuk, Yoshida, Kosuke, Yurkiv, Andriy, Zaha, Osamu, Zhan, Qiang, Peyrin-Biroulet, Laurent, Allegretti, Jessica R., Rubin, David T., Bressler, Brian, Germinaro, Matthew, Huang, Kuan-Hsiang (Gary), Shipitofsky, Nicole, Zhang, Hongyan, Wilson, Rebbecca, Han, Chenglong, Feagan, Brian G., Sandborn, William J., Panés, Julian, Hisamatsu, Tadakazu, Lichtenstein, Gary R., Sands, Bruce E., and Dignass, Axel
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- 2023
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6. Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study
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Peyrin-Biroulet, Laurent, primary, Allegretti, Jessica R., additional, Rubin, David T., additional, Bressler, Brian, additional, Germinaro, Matthew, additional, Huang, Kuan-Hsiang (Gary), additional, Shipitofsky, Nicole, additional, Zhang, Hongyan, additional, Wilson, Rebbecca, additional, Han, Chenglong, additional, Feagan, Brian G., additional, Sandborn, William J., additional, Panés, Julian, additional, Hisamatsu, Tadakazu, additional, Lichtenstein, Gary R., additional, Sands, Bruce E., additional, Dignass, Axel, additional, Abrahamovych, Orest, additional, Afanasieva, Halyna, additional, Aitova, Lilia, additional, Altintas, Engin, additional, Altwegg, Romain, additional, Andreev, Pavel, additional, Aomatsu, Kazuki, additional, Augustyn, Monika, additional, Balestrieri, Paola, additional, Begun, Jakob, additional, Brunatto, Luciana, additional, Bulgheroni, Diego, additional, Bunkova, Elena, additional, Cabello, Mercedes, additional, Cao, Qian, additional, Caprioli, Flavio, additional, Cerqueira, Rute, additional, Chen, Baili, additional, Chen, Chou-Chen, additional, Chen, Chou-Pin, additional, Chiu, Cheng-Tang, additional, Choi, Chang Hwan, additional, Cicala, Michele, additional, Datsenko, Olena, additional, Dewint, Pieter, additional, Domenech, Eugeni, additional, Dutré, Joris, additional, Duvall, George, additional, Fernandez, Juan, additional, Filip, Rafal, additional, Fogel, Ronald, additional, Fowler, Sharyle, additional, Fujii, Toshimitsu, additional, Fukata, Masayuki, additional, Furumoto, Yohei, additional, Gasbarrini, Antonio, additional, Gawdis-Wojnarska, Beata, additional, Gilletta, Cyrielle, additional, Gionchetti, Paolo, additional, Goldin, Eran, additional, Golovchenko, Oleksandr, additional, Gonciarz, Maciej, additional, Gonen, Can, additional, Segura, Gaston Gonzalez, additional, Gridnyev, Oleksii, additional, Gyokeres, Tibor, additional, Hébuterne, Xavier, additional, Hedin, Charlotte, additional, Hellström, Per, additional, Hilmi, Ida Normiha, additional, Horný, Ivo, additional, Horvat, Gyula, additional, Hoshi, Namiko, additional, Hrdlicka, Ludek, additional, Ishihara, Shunji, additional, Ivanishyn, Olha, additional, Jang, Byung Ik, additional, Junior, Odery, additional, Kagaya, Takashi, additional, Kanmura, Shuji, additional, Karakina, Marina, additional, Katsuhiko, Nakai, additional, Kierkus, Jaroslaw, additional, Kim, Hyo Jong, additional, Kim, Tae-Oh, additional, Kim, Young-Ho, additional, Kiss, Gyula G., additional, Klaus, Jochen, additional, Kleczkowski, Dariusz, additional, Klopocka, Maria, additional, Kobayashi, Taku, additional, Kobielusz-Gembala, Iwona, additional, Koo, Ja Seol, additional, Kopon, Adam, additional, Kravchenko, Tetiana, additional, Kudo, Masatoshi, additional, Kwon, Kwang An, additional, Lago, Paula, additional, Laharie, David, additional, Lawrance, Ian, additional, Leszczyszyn, Jaroslaw, additional, Li, Yan, additional, Lukas, Milan, additional, Maaser, Christian, additional, Maemoto, Atsuo, additional, Marusawa, Hiroyuki, additional, McBride, Matthew, additional, Mendu, Shoba, additional, Miheller, Pal, additional, Miyabayashi, Hideharu, additional, Mohl, Wolfgang, additional, Moore, Gregory, additional, Motoya, Satoshi, additional, Murali, Narayanachar, additional, Naem, Mohammed, additional, Nakajima, Koichi, additional, Nakamoto, Yasunari, additional, Nancey, Stéphane, additional, Neto, Joaquim, additional, Onizawa, Michio, additional, Ono, Yohei, additional, Osada, Taro, additional, Osipenko, Marina, additional, Owczarek, Danuta, additional, Patel, Bhaktasharan, additional, Patel, Kamal, additional, Petrova, Elina, additional, Poroshina, Elena, additional, Portela, Francisco, additional, Prystupa, Lyudmyla, additional, Rivero, Monserrat, additional, Roblin, Xavier, additional, Romatowski, Jacek, additional, Rydzewska, Grazyna, additional, Saibeni, Simone, additional, Sakuraba, Hirotake, additional, Samaan, Mark, additional, Schultz, Michael, additional, Schulze, Joerg, additional, Sedghi, Shahriar, additional, Seidler, Ursula, additional, Shin, Sung Jae, additional, Stanislavchuk, Mykola, additional, Stokesberry, David, additional, Suzuki, Takayoshi, additional, Taguchi, Hiroki, additional, Tankova, Lyudmila, additional, Thin, Lena, additional, Tkachev, Alexander, additional, Torrealba, Leyanira, additional, Tsarynna, Nataliia, additional, Tulassay, Zsolt, additional, Ueo, Tetsuya, additional, Valuyskikh, Ekaterina, additional, Vasilevskaya, Olga, additional, Viamonte, Manuel, additional, Wei, Shu-Chen, additional, Weisshof, Roni, additional, Wojcik, Katarzyna, additional, Ye, Byong Duk, additional, Yen, Hsu-Heng, additional, Yoon, Hyuk, additional, Yoshida, Kosuke, additional, Yurkiv, Andriy, additional, Zaha, Osamu, additional, and Zhan, Qiang, additional
- Published
- 2023
- Full Text
- View/download PDF
7. The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients With Hematologic Malignancies Requiring Antibiotics
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Huang, Kuan-Hsiang Gary, Cluzet, Valerie, Hamilton, Keith, and Fadugba, Olajumoke
- Published
- 2018
8. The impact of host and therapy mediated selection on HIV-1 evolution
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Huang, Kuan-Hsiang Gary, Klenerman, Paul, and Frater, John
- Subjects
616.9 ,Immunology ,Infectious diseases ,Viruses ,virology ,viral evolution ,Cytotoxic T Cells ,B cells ,antibodies ,highly active antiretroviral therapy ,molecular epidemiology - Abstract
The Human immunodeficiency virus (HIV) pandemic has resulted in a heavy global disease burden, and clinically causes Acquired Immuno-Deficiency Syndrome (AIDS). The development of highly active antiretroviral therapy (HAART) has achieved remarkable control of the rapidly evolving HIV. However, HIV remains neither curable nor preventable by vaccine, and in the developing regions worst affected by HIV, HAART remains inaccessible to most patients. Furthermore, the change in both immunology and viral evolution during chronic HIV infection and its relation to AIDS pathogenesis remains unknown. Following the failure of recent HIV vaccines, it is believed that a better understanding of host-pathogen interaction is vital to advance therapeutic (vaccine and drug) design. In this thesis, I have performed an investigation of viral adaptation in response to different selection forces during advanced HIV infection and AIDS. The thesis first examined a case study that reveals the potential role of B cell-mediated neutralising antibody (NAb) in chronic HIV infection through the unexpected effect of B cell depletion agent, anti-CD20 (Rituximab). Here, longitudinal results have shown that viral load (VL), env gene diversity, and NAb sensitive strains increased during B cell and NAb depletion as a result of Rituximab administration, and reversed as B cells recovered. The study provides preliminary evidence to support the idea that NAb may be effective at suppressing HIV. The rest of the thesis focused on the cross-sectional cohort at Bloemfontein, South Africa (n=1491), a resource-limited region affected by the pandemic. Here, we used methods that include molecular and pretherapy drug resistance epidemiology, mathematical modelling, phylogenetically adjusted bioinformatics analysis and in vitro viral replication capacity (VRC) assay to study materials including cohort demography, plasma samples, CD4 cell count, VL, viral genetic sequences and host human leukocyte antigen (HLA) tissue types. Our analysis was further augmented by the additional data kindly contributed by our neighbouring Durban cohort collaborators (n=775), which also includes an IFN! ELISPOT assay that measures cytotoxic T lymphocyte (CTL) responses. Using the HIV pol sequencing data and phylogenetic analysis we confirmed that the local molecular epidemiology is similar to the circulating strains documented in the regional database. However, the pretherapy drug resistance mutation screening results have revealed an unexpected high incidence of drug-induced viral mutants in the AIDS patients with CD4 counts <100 cells/μl. According to mathematical modelling, this finding is attributable to additional sources of antiretroviral therapy exposure, which warrants public health caution. The investigation then focused on studying the changes in HLA class I mediated CTL selection and viral evolution as CD4 counts are reduced in AIDS. Interestingly we have noted evidence that suggest weakening CTL immune selection against gag during AIDS is associated with increased viral fitness (measured by VRC) and reversion of previous immune-escape mutations which conferred high fitness costs. In conclusion, this thesis compared different sources of host and drug mediated HIV selection and its implication for viral evolution. The identification of more bottleneck sites conferring high fitness costs to the selection of escape mutants is expected to be helpful in the design of future therapeutics (via vaccine, drug, immune therapy, or public health strategy). As we have learnt from the principle of combinational ARV, it would be desirable for a vaccine to select HIV at multiple sites of high escape-mutation fitness cost, hence offering protective effect.
- Published
- 2010
9. Mapping the drivers of within-host pathogen evolution using massive data sets
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Palmer, Duncan S., Turner, Isaac, Fidler, Sarah, Frater, John, Goedhals, Dominique, Goulder, Philip, Huang, Kuan-Hsiang Gary, Oxenius, Annette, Phillips, Rodney, Shapiro, Roger, Vuuren, Cloete van, McLean, Angela R., and McVean, Gil
- Published
- 2019
- Full Text
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10. Mapping the drivers of within-host pathogen evolution using massive data sets
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Palmer, Duncan S., primary, Turner, Isaac, additional, Fidler, Sarah, additional, Frater, John, additional, Goulder, Philip, additional, Goedhals, Dominique, additional, Huang, Kuan-Hsiang Gary, additional, Oxenius, Annette, additional, Phillips, Rodney, additional, Shapiro, Roger, additional, van Vuuren, Cloete, additional, McLean, Angela R., additional, and McVean, Gil, additional
- Published
- 2017
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11. Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection
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Adland, Emily, primary, Paioni, Paolo, additional, Thobakgale, Christina, additional, Laker, Leana, additional, Mori, Luisa, additional, Muenchhoff, Maximilian, additional, Csala, Anna, additional, Clapson, Margaret, additional, Flynn, Jacquie, additional, Novelli, Vas, additional, Hurst, Jacob, additional, Naidoo, Vanessa, additional, Shapiro, Roger, additional, Huang, Kuan-Hsiang Gary, additional, Frater, John, additional, Prendergast, Andrew, additional, Prado, Julia G., additional, Ndung’u, Thumbi, additional, Walker, Bruce D., additional, Carrington, Mary, additional, Jooste, Pieter, additional, and Goulder, Philip J. R., additional
- Published
- 2015
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12. Dipstick proteinuria is an independent predictor of high on treatment platelet reactivity in patients on clopidogrel, but not aspirin, admitted for major adverse cardiovascular events.
- Author
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Davila, Carlos D, Vargas, Fernando, Huang, Kuan-Hsiang Gary, Monaco, Thomas, Dimou, Anastasios, Rangaswami, Janani, Figueredo, M.D., Vincent M, Davila, Carlos D, Vargas, Fernando, Huang, Kuan-Hsiang Gary, Monaco, Thomas, Dimou, Anastasios, Rangaswami, Janani, and Figueredo, M.D., Vincent M
- Abstract
The effectiveness of aspirin and clopidogrel in patients with chronic kidney disease (CKD) suffering from acute cardiovascular events is unclear. High on treatment platelet reactivity (HTPR) has been associated with worse outcomes. Here, we assessed the association of dipstick proteinuria (DP) and renal function on HTPR and clinical outcomes. Retrospective cohort analysis of 261 consecutive, non-dialysis patients admitted for Major Adverse Cardiovascular Events (MACE) that had VerifyNow P2Y12 and VerifyNow Aspirin assays performed. HTPR was defined as P2Y12 reactivity unit (PRU) > 208 for clopidogrel and aspirin reaction units (ARU) > 550 for aspirin. Renal function was classified based on the estimated glomerular filtration rate (eGFR), and dipstick proteinuria was defined as ≥30 mg/dl of albumin detected on a spot analysis. All cause mortality, readmissions, and cardiac catheterizations were reviewed over 520 days. In patients on clopidogrel (n = 106), DP was associated with HTPR, independent of eGFR, diabetes mellitus, smoking or use of proton pump inhibitor (AOR = 4.76, p = 0.03). In patients with acute coronary syndromes, HTPR was associated with more cardiac catheterizations (p = 0.009) and readmissions (p = 0.032), but no differences in in-stent thrombosis or re-stenosis were noted in this cohort. In patients on aspirin (n = 155), no associations were seen between DP and HTPR. However, all cause mortality was significantly higher with HTPR in this group (p = 0.038). In this cohort, DP is an independent predictor of HTPR in patients on clopidogrel, but not aspirin, admitted to the hospital for MACE.
- Published
- 2014
13. Dipstick proteinuria is an independent predictor of high on treatment platelet reactivity in patients on clopidogrel, but not aspirin, admitted for major adverse cardiovascular events
- Author
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Davila, Carlos D., primary, Vargas, Fernando, additional, Huang, Kuan-Hsiang Gary, additional, Monaco, Thomas, additional, Dimou, Anastasios, additional, Rangaswami, Janani, additional, and Figueredo, Vincent M., additional
- Published
- 2014
- Full Text
- View/download PDF
14. PROTEINURIA IS INDEPENDENTLY ASSOCIATED WITH HIGH ON TREATMENT PLATELET REACTIVITY IN PATIENTS ON CLOPIDOGREL BUT NOT ASPIRIN FOR THE TREATMENT OF MAJOR ADVERSE CARDIOVASCULAR EVENTS
- Author
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Davila, Carlos D., primary, Vargas, Fernando M., additional, Huang, Kuan-Hsiang Gary, additional, Monaco, Thomas, additional, Dimou, Anastasios, additional, Rangaswami, Janani, additional, and Figueredo, Vincent, additional
- Published
- 2014
- Full Text
- View/download PDF
15. HIV control through a single nucleotide on the HLA-B locus
- Author
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Kløverpris, Henrik N, Harndahl, Mikkel, Leslie, Alasdair J, Carlson, Jonathan M, Ismail, Nasreen, van der Stok, Mary, Huang, Kuan-Hsiang Gary, Chen, Fabian, Riddell, Lynn, Steyn, Dewald, Goedhals, Dominique, van Vuuren, Cloete, Frater, John, Walker, Bruce D, Carrington, Mary, Ndung'u, Thumbi, Buus, Søren, Goulder, Philip, Kløverpris, Henrik N, Harndahl, Mikkel, Leslie, Alasdair J, Carlson, Jonathan M, Ismail, Nasreen, van der Stok, Mary, Huang, Kuan-Hsiang Gary, Chen, Fabian, Riddell, Lynn, Steyn, Dewald, Goedhals, Dominique, van Vuuren, Cloete, Frater, John, Walker, Bruce D, Carrington, Mary, Ndung'u, Thumbi, Buus, Søren, and Goulder, Philip
- Abstract
Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and strong linkage disequilibrium between HLA class I alleles complicates the discrimination of individual HLA allelic effects from those of other HLA and non-HLA alleles on the same haplotype. Here, we exploit an experiment of nature involving two recently diverged HLA alleles, HLA-B*42:01 and HLA-B*42:02, which differ by only a single amino acid. Crucially, they occur primarily on identical HLA class I haplotypes and, as Bw6 alleles, do not act as NK cell ligands and are therefore largely unconfounded by other genetic factors. We show that in an outbred cohort (n = 2,093) of HIV C-clade-infected individuals, a single amino acid change at position 9 of the HLA-B molecule critically affects peptide binding and significantly alters the cytotoxic T lymphocyte (CTL) epitopes targeted, measured directly ex vivo by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay (P = 2 × 10(-10)) and functionally through CTL escape mutation (P = 2 × 10(-8)). HLA-B*42:01, which presents multiple Gag epitopes, is associated with a 0.52 log(10) lower viral-load set point than HLA-B*42:02 (P = 0.02), which presents no p24 Gag epitopes. The magnitude of this effect from a single amino acid difference in the HLA-A*30:01/B*42/Cw*17:01 haplotype is equivalent to 75% of that of HLA-B*57:03, the most protective HLA class I allele in this population. This naturally controlled experiment represents perhaps the clearest demonstration of the direct impact of a particular HIV-specific CTL on disease control.
- Published
- 2012
16. HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703
- Author
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Matthews, Philippa C, Adland, Emily, Listgarten, Jennifer, Leslie, Alasdair, Mkhwanazi, Nompumelelo, Carlson, Jonathan M, Harndahl, Mikkel, Buus, Anette Stryhn, Payne, Rebecca P, Ogwu, Anthony, Huang, Kuan-Hsiang Gary, Frater, John, Paioni, Paolo, Kloverpris, Henrik, Jooste, Pieter, Goedhals, Dominique, van Vuuren, Cloete, Steyn, Dewald, Riddell, Lynn, Chen, Fabian, Luzzi, Graz, Balachandran, Thambiah, Ndung'u, Thumbi, Buus, Søren, Carrington, Mary, Shapiro, Roger, Heckerman, David, Goulder, Philip J R, Matthews, Philippa C, Adland, Emily, Listgarten, Jennifer, Leslie, Alasdair, Mkhwanazi, Nompumelelo, Carlson, Jonathan M, Harndahl, Mikkel, Buus, Anette Stryhn, Payne, Rebecca P, Ogwu, Anthony, Huang, Kuan-Hsiang Gary, Frater, John, Paioni, Paolo, Kloverpris, Henrik, Jooste, Pieter, Goedhals, Dominique, van Vuuren, Cloete, Steyn, Dewald, Riddell, Lynn, Chen, Fabian, Luzzi, Graz, Balachandran, Thambiah, Ndung'u, Thumbi, Buus, Søren, Carrington, Mary, Shapiro, Roger, Heckerman, David, and Goulder, Philip J R
- Abstract
The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703.
- Published
- 2011
17. Abstract 172: The Effects of Renal Function on Platelet Reactivity in Patients Treated with Clopidogrel and Admitted for Major Adverse Cardiovascular Events in a Community Setting
- Author
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Davila, Carlos, primary, Vargas, Fernando, additional, Monaco, Thomas, additional, Huang, Kuan-Hsiang Gary, additional, Morris, D L, additional, Figueredo, Vincent M, additional, and Christian, Witzke, additional
- Published
- 2013
- Full Text
- View/download PDF
18. Dipstick proteinuria is an independent predictor of high on treatment platelet reactivity in patients on clopidogrel, but not aspirin, admitted for major adverse cardiovascular events.
- Author
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Davila, Carlos D., Vargas, Fernando, Huang, Kuan-Hsiang Gary, Monaco, Thomas, Dimou, Anastasios, Rangaswami, Janani, and Figueredo, Vincent M.
- Subjects
CARDIOVASCULAR system abnormalities ,CLOPIDOGREL ,PROTEINURIA ,KIDNEY diseases ,ASPIRIN ,ADVERSE health care events ,BLOOD platelets ,PROTON pump inhibitors ,PATIENTS - Abstract
The effectiveness of aspirin and clopidogrel in patients with chronic kidney disease (CKD) suffering from acute cardiovascular events is unclear. High on treatment platelet reactivity (HTPR) has been associated with worse outcomes. Here, we assessed the association of dipstick proteinuria (DP) and renal function on HTPR and clinical outcomes. Retrospective cohort analysis of 261 consecutive, non-dialysis patients admitted for Major Adverse Cardiovascular Events (MACE) that had VerifyNow P2Y12 and VerifyNow Aspirin assays performed. HTPR was defined as P2Y12 reactivity unit (PRU) > 208 for clopidogrel and aspirin reaction units (ARU) > 550 for aspirin. Renal function was classified based on the estimated glomerular filtration rate (eGFR), and dipstick proteinuria was defined as ≥30 mg/dl of albumin detected on a spot analysis. All cause mortality, readmissions, and cardiac catheterizations were reviewed over 520 days. In patients on clopidogrel (n = 106), DP was associated with HTPR, independent of eGFR, diabetes mellitus, smoking or use of proton pump inhibitor (AOR = 4.76,p = 0.03). In patients with acute coronary syndromes, HTPR was associated with more cardiac catheterizations (p = 0.009) and readmissions (p = 0.032), but no differences in in-stent thrombosis or re-stenosis were noted in this cohort. In patients on aspirin (n = 155), no associations were seen between DP and HTPR. However, all cause mortality was significantly higher with HTPR in this group (p = 0.038). In this cohort, DP is an independent predictor of HTPR in patients on clopidogrel, but not aspirin, admitted to the hospital for MACE. [ABSTRACT FROM PUBLISHER]
- Published
- 2015
- Full Text
- View/download PDF
19. HIV Control through a Single Nucleotide on the HLA-B Locus
- Author
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Kløverpris, Henrik N., primary, Harndahl, Mikkel, additional, Leslie, Alasdair J., additional, Carlson, Jonathan M., additional, Ismail, Nasreen, additional, van der Stok, Mary, additional, Huang, Kuan-Hsiang Gary, additional, Chen, Fabian, additional, Riddell, Lynn, additional, Steyn, Dewald, additional, Goedhals, Dominique, additional, van Vuuren, Cloete, additional, Frater, John, additional, Walker, Bruce D., additional, Carrington, Mary, additional, Ndung'u, Thumbi, additional, Buus, Søren, additional, and Goulder, Philip, additional
- Published
- 2012
- Full Text
- View/download PDF
20. Co-Operative Additive Effects between HLA Alleles in Control of HIV-1
- Author
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Matthews, Philippa C., primary, Listgarten, Jennifer, additional, Carlson, Jonathan M., additional, Payne, Rebecca, additional, Huang, Kuan-Hsiang Gary, additional, Frater, John, additional, Goedhals, Dominique, additional, Steyn, Dewald, additional, van Vuuren, Cloete, additional, Paioni, Paolo, additional, Jooste, Pieter, additional, Ogwu, Anthony, additional, Shapiro, Roger, additional, Mncube, Zenele, additional, Ndung'u, Thumbi, additional, Walker, Bruce D., additional, Heckerman, David, additional, and Goulder, Philip J. R., additional
- Published
- 2012
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- View/download PDF
21. Steroid Induced Diabetes And Acute Exacerbation Of Chronic Obstructive Pulmonary Disease (AECOPD)
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Lai, JULIE YU KUANG, primary, Nguyen, Ha, additional, Huang, Kuan Hsiang Gary, additional, Braitman, Leonard, additional, and Eiger, Glenn, additional
- Published
- 2012
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22. A Molecular Assay for Sensitive Detection of Pathogen-Specific T-Cells
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Kasprowicz, Victoria O., primary, Mitchell, Jessica E., additional, Chetty, Shivan, additional, Govender, Pamla, additional, Huang, Kuan-Hsiang Gary, additional, Fletcher, Helen A., additional, Webster, Daniel P., additional, Brown, Sebastian, additional, Kasmar, Anne, additional, Millington, Kerry, additional, Day, Cheryl L., additional, Mkhwanazi, Nompumelelo, additional, McClurg, Cheryl, additional, Chonco, Fundisiwe, additional, Lalvani, Ajit, additional, Walker, Bruce D., additional, Ndung'u, Thumbi, additional, and Klenerman, Paul, additional
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- 2011
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23. HLA-A*7401–Mediated Control of HIV Viremia Is Independent of Its Linkage Disequilibrium with HLA-B*5703
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Matthews, Philippa C., primary, Adland, Emily, additional, Listgarten, Jennifer, additional, Leslie, Alasdair, additional, Mkhwanazi, Nompumelelo, additional, Carlson, Jonathan M., additional, Harndahl, Mikkel, additional, Stryhn, Anette, additional, Payne, Rebecca P., additional, Ogwu, Anthony, additional, Huang, Kuan-Hsiang Gary, additional, Frater, John, additional, Paioni, Paolo, additional, Kloverpris, Henrik, additional, Jooste, Pieter, additional, Goedhals, Dominique, additional, van Vuuren, Cloete, additional, Steyn, Dewald, additional, Riddell, Lynn, additional, Chen, Fabian, additional, Luzzi, Graz, additional, Balachandran, Thambiah, additional, Ndung’u, Thumbi, additional, Buus, Søren, additional, Carrington, Mary, additional, Shapiro, Roger, additional, Heckerman, David, additional, and Goulder, Philip J. R., additional
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- 2011
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24. Full-Length Characterization of Hepatitis C Virus Subtype 3a Reveals Novel Hypervariable Regions under Positive Selection during Acute Infection
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Humphreys, Isla, primary, Fleming, Vicki, additional, Fabris, Paolo, additional, Parker, Joe, additional, Schulenberg, Bodo, additional, Brown, Anthony, additional, Demetriou, Charis, additional, Gaudieri, Silvana, additional, Pfafferott, Katja, additional, Lucas, Michaela, additional, Collier, Jane, additional, Huang, Kuan-Hsiang Gary, additional, Pybus, Oliver G., additional, Klenerman, Paul, additional, and Barnes, Eleanor, additional
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- 2010
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25. Full-Length Characterization of Hepatitis C Virus Subtype 3a Reveals Novel Hypervariable Regions under Positive Selection during Acute Infection
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Humphreys, Isla, primary, Fleming, Vicki, additional, Fabris, Paolo, additional, Parker, Joe, additional, Schulenberg, Bodo, additional, Brown, Anthony, additional, Demetriou, Charis, additional, Gaudieri, Silvana, additional, Pfafferott, Katja, additional, Lucas, Michaela, additional, Collier, Jane, additional, Huang, Kuan-Hsiang Gary, additional, Pybus, Oliver G., additional, Klenerman, Paul, additional, and Barnes, Eleanor, additional
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- 2009
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26. Prevalence of HIV type-1 drug-associated mutations in pre-therapy patients in the Free State, South Africa
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Huang, Kuan-Hsiang Gary, Goedhals, Dominique, Fryer, Helen, van Vuuren, Cloete, Katzourakis, Aris, Oliveira, Tulio De, Brown, Helen, Cassol, Sharon, Seebregts, Chris, McLean, Angela, Klenerman, Paul, Phillips, Rodney, and Frater, John
- Abstract
Background We aimed to characterize the molecular epidemiology of HIV type-1 (HIV-1) and the prevalence of drug- associated mutations prior to initiating highly active antiretroviral therapy (HAART) in the Free State province, South Africa. The Free State has a population of 3 million, an antenatal HIV prevalence of approximately 34% and a well established infrastucture for antiretroviral (ARV) provision.Methods HIV-1 polymerase genes were sequenced from 425 HAART-naive HIV-1-positive patients at voluntary primary healthcare HIV testing centres, who were subsequently attending district centres for assessment for commencing ARVs. Patients (>18 years) were sampled randomly with no exclusion for gender or clinical criteria. Sequences were analysed according to phylogeny and drug resistance.Results Phylogenetic clustering within the cohort was suggestive of multiple introductions of subtype C virus into the region. Drug resistance mutations (according to the International AIDS Society-USA classification) were distributed randomly across the cohort phylogeny with an overall prevalence of 2.3% in the sampled patients. When stratified according to CD4+T-cell count, the prevalence of resistance was 3.6%, 0.9% and 1.2% for CD4+T-cell counts <100, 200-350 and >500 cells/µ l, respectively, and was most common for non-nucleoside reverse transcriptase inhibitor resistance (3.1% in patients with CD4+T-cell count <100 cells/µ l). We surveyed all drug-selected mutations and found further significant clustering among patients with low CD4+T-cell counts (P=0.003), suggesting unrecognized exposure to ARVs.Conclusions In the Free State population, there was a statistical association between low CD4+T-cell counts and drug-associated viral polymorphisms. Our data advocate the benefit of detailed history taking from patients starting HAART at low CD4+T-cell counts with close follow-up of the virological response.
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- 2009
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27. Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations.
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Huang KH, Goedhals D, Carlson JM, Brockman MA, Mishra S, Brumme ZL, Hickling S, Tang CS, Miura T, Seebregts C, Heckerman D, Ndung'u T, Walker B, Klenerman P, Steyn D, Goulder P, Phillips R, van Vuuren C, and Frater J
- Subjects
- CD4 Lymphocyte Count, Disease Progression, Enzyme-Linked Immunospot Assay, Histocompatibility Antigens Class I genetics, Humans, Mutation genetics, Polymorphism, Genetic genetics, South Africa, gag Gene Products, Human Immunodeficiency Virus genetics, nef Gene Products, Human Immunodeficiency Virus genetics, pol Gene Products, Human Immunodeficiency Virus genetics, Acquired Immunodeficiency Syndrome genetics, Acquired Immunodeficiency Syndrome virology
- Abstract
We lack the understanding of why HIV-infected individuals in South Africa progress to AIDS. We hypothesised that in end-stage disease there is a shifting dynamic between T cell imposed immunity and viral immune escape, which, through both compensatory and reverting viral mutations, results in increased viral fitness, elevated plasma viral loads and disease progression. We explored how T cell responses, viral adaptation and viral fitness inter-relate in South African cohorts recruited from Bloemfontein, the Free State (n = 278) and Durban, KwaZulu-Natal (n = 775). Immune responses were measured by γ-interferon ELISPOT assays. HLA-associated viral polymorphisms were determined using phylogenetically corrected techniques, and viral replication capacity (VRC) was measured by comparing the growth rate of gag-protease recombinant viruses against recombinant NL4-3 viruses. We report that in advanced disease (CD4 counts <100 cells/µl), T cell responses narrow, with a relative decline in Gag-directed responses (p<0.0001). This is associated with preserved selection pressure at specific viral amino acids (e.g., the T242N polymorphism within the HLA-B*57/5801 restricted TW10 epitope), but with reversion at other sites (e.g., the T186S polymorphism within the HLA-B*8101 restricted TL9 epitope), most notably in Gag and suggestive of "immune relaxation". The median VRC from patients with CD4 counts <100 cells/µl was higher than from patients with CD4 counts ≥ 500 cells/µl (91.15% versus 85.19%, p = 0.0004), potentially explaining the rise in viral load associated with disease progression. Mutations at HIV Gag T186S and T242N reduced VRC, however, in advanced disease only the T242N mutants demonstrated increasing VRC, and were associated with compensatory mutations (p = 0.013). These data provide novel insights into the mechanisms of HIV disease progression in South Africa. Restoration of fitness correlates with loss of viral control in late disease, with evidence for both preserved and relaxed selection pressure across the HIV genome. Interventions that maintain viral fitness costs could potentially slow progression.
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- 2011
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