IMPROVED HEALTH OUTCOMES FOR PEOPLE LIVING WITH HIV
Grant number: 1042654 | Funding period: 2014 - 2017
Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected with hepatitis B virus (HBV)
Related publications (64)
Acceptability, motivation and the prospect of cure for people living with HIV and their healthcare providers in HIV cure-focused treatment interruption studies
Jillian SY Lau, Miranda Z Smith, Brent Allan, Cipriano Martinez, Jennifer Power, Sharon R Lewin, James H McMahon
BACKGROUND: Analytical treatment interruptions (ATI) are commonly used clinical endpoints to assess interventions aimed at curing ..
The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained and Reversed
Simin D Rezaei, Hao K Lu, J Judy Chang, Ajantha Rhodes, Sharon R Lewin, Paul U Cameron
HIV infection requires lifelong antiretroviral therapy because of the persistence of latently infected CD4+ T cells. The induction..
HIV latency reversing agents act through Tat post translational modifications
Georges Khoury, Talia M Mota, Shuang Li, Carolin Tumpach, Michelle Y Lee, Jonathan Jacobson, Leigh Harty, Jenny L Anderson, Sharon R Lewin, Damian FJ Purcell
BACKGROUND: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV ..
Modeling of Antilatency Treatment in HIV: What Is the Optimal Duration of Antiretroviral Therapy-Free HIV Remission?
Deborah Cromer, Mykola Pinkevych, Thomas A Rasmussen, Sharon R Lewin, Stephen J Kent, Miles P Davenport
A number of treatment strategies are currently being developed to promote antiretroviral therapy-free HIV cure or remission. While..
Plasma But Not Cerebrospinal Fluid Interleukin 7 and Interleukin 5 Levels Pre-Antiretroviral Therapy Commencement Predict Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome
Ngomu Akeem Akilimali, Christina C Chang, Daniel M Muema, Tarylee Reddy, Mahomed-Yunus S Moosa, Sharon R Lewin, Martyn A French, Thumbi Ndung'u
Background: Patients with human immunodeficiency virus/AIDS-associated cryptococcal meningitis (CM) frequently experience clinical..
Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy
Eunice E To, Ross Vlahos, Raymond Luong, Michelle L Halls, Patrick C Reading, Paul T King, Christopher Chan, Grant R Drummond, Christopher G Sobey, Brad RS Broughton, Malcolm R Starkey, Renee van der Sluis, Sharon R Lewin, Steven Bozinovski, Luke AJ O'Neill, Tim Quach, Christopher JH Porter, Doug A Brooks, John J O'Leary, Stavros Selemidis
The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target viral pathology irresp..
Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals
Kersten K Koelsch, Thomas A Rasmussen, William J Hey-Nguyen, Chester Pearson, Yin Xu, Michelle Bailey, Katherine H Marks, Sarah C Sasson, Mark S Taylor, Robyn Tantau, Solange Obeid, Brad Milner, Orla Morrissey, Angie N Pinto, Kazuo Suzuki, Michael P Busch, Sheila M Keating, Philipp Kaiser, Steven Yukl, Joseph K Wong
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV..
Human Immunodeficiency Virus Persistence and T-Cell Activation in Blood, Rectal, and Lymph Node Tissue in Human Immunodeficiency Virus-Infected Individuals Receiving Suppressive Antiretroviral Therapy
Gabriela Khoury, Remi Fromentin, Ajantha Solomon, Wendy Hartogensis, Marisela Killian, Rebecca Hoh, Ma Somsouk, Peter W Hunt, Valerie Girling, Elizabeth Sinclair, Peter Bacchetti, Jenny L Anderson, Frederick M Hecht, Steven G Deeks, Paul U Cameron, Nicolas Chomont, Sharon R Lewin
Background: Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)-infected individuals receivin..
Relationship of Human Immunodeficiency Virus Viral Load in Cerebrospinal Fluid and Plasma in Patients Co-infected With Cryptococcal Meningitis
Christina C Chang, Richard Kangethe, Saleha Omarjee, Keshni Hiramen, Bernadett Gosnell, Katlego Sojane, Mohamed-Yunus S Moosa, Sharon R Lewin, Martyn A French, Thumbi Ndung'u
We measured human immunodeficiency virus (HIV) ribonucleic acid (RNA) in paired cerebrospinal fluid (CSF) and plasma samples in a ..
Quantifying Adaptive and Innate Immune Responses in HIV-Infected Participants Using a Novel High Throughput Assay
Michelle K Yong, Paul U Cameron, Tim Spelman, Julian H Elliott, Christopher K Fairley, Jeffrey Boyle, Misato Miyamasu, Sharon R Lewin
OBJECTIVES: HIV infection is characterised by persistent immune dysfunction of both the adaptive and innate immune responses. The ..
Modeling of Experimental Data Supports HIV Reactivation from Latency after Treatment Interruption on Average Once Every 5-8 Days
Mykola Pinkevych, Stephen J Kent, Martin Tolstrup, Sharon R Lewin, David A Cooper, Ole S Sogaard, Thomas A Rasmussen, Anthony D Kelleher, Deborah Cromer, Miles P Davenport
CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies
LR Gray, D Cowley, C Welsh, HK Lu, BJ Brew, SR Lewin, SL Wesselingh, PR Gorry, MJ Churchill
Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to elimina..
Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells
Ruian Ke, Sharon R Lewin, Julian H Elliott, Alan S Perelson
Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents a..
The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4( ) T-cells
Nitasha A Kumar, Karey Cheong, David R Powell, Candida da Fonseca Pereira, Jenny Anderson, Vanessa A Evans, Sharon R Lewin, Paul U Cameron
BACKGROUND: Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infect..
HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days-Implications for HIV Remission
Mykola Pinkevych, Deborah Cromer, Martin Tolstrup, Andrew J Grimm, David A Cooper, Sharon R Lewin, Ole S Sogaard, Thomas A Rasmussen, Stephen J Kent, Anthony D Kelleher, Miles P Davenport
HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However therapy must be continued f..
The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals
Reena Rajasuriar, Yong Yean Kong, Reshika Nadarajah, Noor Kamila Abdullah, Tim Spelman, Muhamad Yazli Yuhana, Sasheela Ponampalavanar, Adeeba Kamarulzaman, Sharon R Lewin
BACKGROUND: HIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T ..
Comparison of Etests and Vitek 2 (R) to broth microdilution for the susceptibility testing of Cryptococcus neoformans
Yesholata Mahabeer, Christina C Chang, Dianithi Naidu, Afton Dorasamy, Sharon Lewin, Thumbi Ndung'u, Mohammed-Yunus Moosa, Martyn French, Koleka Mlisana, Yacoob Coovadia
We determined the susceptibility of 102 clinical isolates Cryptococcus neoformans from Durban, South Africa, to amphotericin B, fl..
No Difference in the Rate of Change in Telomere Length or Telomerase Activity in HIV-Infected Patients after Three Years of Darunavir/Ritonavir with and without Nucleoside Analogues in the MONET Trial
Ajantha Solomon, Surekha Tennakoon, Edwin Leeansyah, Jose Arribas, Andrew Hill, Yvon Van Delft, Christiane Moecklinghoff, Sharon R Lewin
OBJECTIVE: To determine whether nucleos(t)ide reverse transcriptase inhibitors (NRTI) contribute to an accelerated loss in telomer..
Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy
Julian H Elliott, Fiona Wightman, Ajantha Solomon, Khader Ghneim, Jeffrey Ahlers, Mark J Cameron, Miranda Z Smith, Tim Spelman, James McMahon, Pushparaj Velayudham, Gregor Brown, Janine Roney, Jo Watson, Miles H Prince, Jennifer F Hoy, Nicolas Chomont, Remi Fromentin, Francesco A Procopio, Joumana Zeidan, Sarah Palmer
UNLABELLED: Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier t..
Hepatitis C prevalence among HIV-infected patients in Guinea-Bissau: a descriptive cross-sectional study
Bo Langhoff Honge, Sanne Jespersen, Candida Medina, David da Silva Te, Zacarias Jose da Silva, Sharon R Lewin, Lars Ostergaard, Alex Lund Laursen, Henrik Krarup, Christian Erikstrup, Christian Wejse
OBJECTIVES: To estimate the prevalence and determine the clinical presentation of risk factors of hepatitis C virus (HCV) among HI..
Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial
Thomas A Rasmussen, Martin Tolstrup, Christel R Brinkmann, Rikke Olesen, Christian Erikstrup, Ajantha Solomon, Anni Winckelmann, Sarah Palmer, Charles Dinarello, Maria Buzon, Mathias Lichterfeld, Sharon R Lewin, Lars Ostergaard, Ole S Sogaard
BACKGROUND: Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability ..
Lipopolysaccharide, Immune Activation, and Liver Abnormalities in HIV/Hepatitis B Virus (HBV)-Coinfected Individuals Receiving HBV-Active Combination Antiretroviral Therapy
Megan Crane, Anchalee Avihingsanon, Reena Rajasuriar, Pushparaj Velayudham, David Iser, Ajantha Solomon, Baotuti Sebolao, Andrew Tran, Tim Spelman, Gail Matthews, Paul Cameron, Pisit Tangkijvanich, Gregory J Dore, Kiat Ruxrungtham, Sharon R Lewin
We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency v..
Targets for intervention to improve virological outcomes for patients receiving free antiretroviral therapy in Tamil Nadu, India
James H McMahon, Anand Manoharan, Christine Wanke, Shoba Mammen, Hepsibah Jose, Thabeetha Malini, Tony Kadavanu, Michael R Jordan, Julian H Elliott, Sharon R Lewin, Dilip Mathai
Operational research to identify factors predicting poor clinical outcomes is critical to maximize patient care and prolong first-..
Short Communication: CD4 T Cell Declines Occurring During Suppressive Antiretroviral Therapy Reflect Continued Production of Casp8p41
Nathan W Cummins, Jacqueline Neuhaus, Amy M Sainski, Michael A Strausbauch, Peter J Wettstein, Sharon R Lewin, Montserrat Plana, Stacey A Rizza, Zelalem Temesgen, Giota Touloumi, Matthew Freiberg, James Neaton, Andrew D Badley
Most patients on suppressive antiretroviral therapy (ART) experience improvements in CD4 T cell count. However, some patients with..
Compartmentalization of innate immune responses in the central nervous system during cryptococcal meningitis/HIV coinfection
Vivek Naranbhai, Christina C Chang, Raveshni Durgiah, Saleha Omarjee, Andrew Lim, Mahomed-Yunus S Moosa, Julian H Elliot, Thumbi Ndung'u, Sharon R Lewin, Martyn A French, William H Carr
OBJECTIVE: The role of innate immunity in the pathogenesis of cryptococcal meningitis is unclear. We hypothesized that natural kil..
Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV- positive individuals
Clare LV Westhorpe, Anna Maisa, Tim Spelman, Jennifer F Hoy, Elizabeth M Dewar, Sofie Karapanagiotidis, Anna C Hearps, Wan-Jung Cheng, Janine Trevillyan, Sharon R Lewin, Dmitri Sviridov, Julian H Elliott, Anthony Jaworowski, Anthony M Dart, Suzanne M Crowe
Chronic HIV infection is associated with increased risk of cardiovascular disease (CVD), including in patients with virological su..
Increased glucose metabolic activity is associated with CD4 R T-cell activation and depletion during chronic HIV infection
Clovis S Palmer, Matias Ostrowski, Maelenn Gouillou, Louis Tsai, Di Yu, Jingling Zhou, Darren C Henstridge, Anna Maisa, Anna C Hearps, Sharon R Lewin, Alan Landay, Anthony Jaworowski, Joseph M McCune, Suzanne M Crowe
OBJECTIVES: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells...
Decline in serum 25 hydroxyvitamin D levels in HIV-HBV-coinfected patients after long-term antiretroviral therapy
Anchalee Avihingsanon, Tanakorn Apornpong, Reshmie A Ramautarsing, Sasiwimol Ubolyam, Pisit Tangkijvanich, Jintanat Ananworanich, Joep MA Lange, Gail Matthews, Sharon R Lewin, Kiat Ruxrungtham
BACKGROUND: Vitamin D insufficiency plays an important role in the development of fibrosis in chronic liver disease. METHODS: This..
HIV-1 envelope-receptor interactions required for macrophage infection and implications for current HIV-1 cure strategies
Paul R Gorry, Nicholas Francella, Sharon R Lewin, Ronald G Collman
Myeloid cells residing in the CNS and lymphoid tissues are targets for productive HIV-1 replication, and their infection contribut..
An In-Depth Comparison of Latent HIV-1 Reactivation in Multiple Cell Model Systems and Resting CD4 T Cells from Aviremic Patients
Celsa A Spina, Jenny Anderson, Nancie M Archin, Alberto Bosque, Jonathan Chan, Marylinda Famiglietti, Warner C Greene, Angela Kashuba, Sharon R Lewin, David M Margolis, Matthew Mau, Debbie Ruelas, Suha Saleh, Kotaro Shirakawa, Robert F Siliciano, Akul Singhania, Paula C Soto, Valeri H Terry, Eric Verdin, Christopher Woelk
The possibility of HIV-1 eradication has been limited by the existence of latently infected cellular reservoirs. Studies to examin..
HIV and co-infections
Christina C Chang, Megan Crane, JingLing Zhou, Michael Mina, Jeffrey J Post, Barbara A Cameron, Andrew R Lloyd, Anthony Jaworowski, Martyn A French, Sharon R Lewin
Despite significant reductions in morbidity and mortality secondary to availability of effective combination anti-retroviral thera..
Circulating Heat Shock Protein 60 Levels Are Elevated in HIV Patients and Are Reduced by Anti-Retroviral Therapy
Itaru Anraku, Reena Rajasuriar, Caroline Dobbin, Richard Brown, Sharon R Lewin, Andreas Suhrbier
Circulating heat shock protein 60 (Hsp60) and heat shock protein 10 (Hsp10) have been associated with pro- and anti-inflammatory a..
Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation
Gregor F Lichtfuss, Wan-Jung Cheng, Yagmur Farsakoglu, Geza Paukovics, Reena Rajasuriar, Pushparaj Velayudham, Marit Kramski, Anna C Hearps, Paul U Cameron, Sharon R Lewin, Suzanne M Crowe, Anthony Jaworowski
FcRγ is an ITAM-containing adaptor required for CD16 signaling and function in NK cells. We have previously shown that NK cells fr..
HIV replication is associated with increased severity of liver biopsy changes in HIV-HBV and HIV-HCV co-infection
Jennifer Audsley, Philipp du Cros, Zachary Goodman, Catriona McLean, Anne Mijch, Sharon R Lewin, Joe Sasadeusz
Histological parameters were assessed in liver biopsies (n = 48) performed in patients co-infected with human immunodeficiency vir..
Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand
Anchalee Avihingsanon, Gail V Matthews, Sharon R Lewin, Pip Marks, Jose Sasadeusz, David A Cooper, Scott Bowden, Stephen Locarnini, Greg J Dore, Kiat Ruxrungtham
BACKGROUND: Hepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals ..
The role of SNPs in the alpha-chain of the IL-7R gene in CD4 T-cell recovery in HIV-infected African patients receiving suppressive cART
R Rajasuriar, DR Booth, M Gouillou, T Spelman, I James, A Solomon, K Chua, G Stewart, S Deeks, DR Bangsberg, C Muzoora, PU Cameron, P Hunt, J Martin, SR Lewin
We previously found an association between faster CD4+ T-cell recovery in HIV-infected patients receiving combination antiretrovir..
HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry
Michael Roche, Martin R Jakobsen, Anne Ellett, Hamid Salimiseyedabad, Becky Jubb, Mike Westby, Benhur Lee, Sharon R Lewin, Melissa J Churchill, Paul R Gorry
BACKGROUND: Maraviroc (MVC) and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5..
Factors Associated with Elevated ALT in an International HIV/HBV Co-Infected Cohort on Long-Term HAART
Jennifer Audsley, Eric C Seaberg, Joe Sasadeusz, Gail V Matthews, Anchalee Avihingsanon, Kiat Ruxrungtham, Kit Fairley, Robert Finlayson, Hyon S Hwang, Margaret Littlejohn, Stephen Locarnini, Gregory J Dore, Chloe L Thio, Sharon R Lewin
BACKGROUND: Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV..
Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database
Reena Rajasuriar, Maelenn Gouillou, Tim Spelman, Tim Read, Jennifer Hoy, Matthew Law, Paul U Cameron, Kathy Petoumenos, Sharon R Lewin
BACKGROUND: A small but significant number of patients do not achieve CD4 T-cell counts >500 cells/µl despite years of suppressive..
Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals
Emma Tippett, Wan-Jung Cheng, Clare Westhorpe, Paul U Cameron, Bruce J Brew, Sharon R Lewin, Anthony Jaworowski, Suzanne M Crowe
CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of ..
Decreased NK Cell FcR gamma in HIV-1 Infected Individuals Receiving Combination Antiretroviral Therapy: a Cross Sectional Study
Edwin Leeansyah, Jingling Zhou, Geza Paukovics, Sharon R Lewin, Suzanne M Crowe, Anthony Jaworowski
BACKGROUND: FcRgamma is an immunoreceptor tyrosine-based activation motif (ITAM)-signalling protein essential for immunoreceptor s..
Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy
LQ Zhang, SR Lewin, M Markowitz, HH Lin, E Skulsky, R Karanicolas, YX He, X Jin, S Tuttleton, M Vesanen, H Spiegel, R Kost, J van Lunzen, HJ Stellbrink, S Wolinsky, W Borkowsky, P Palumbo, LG Kostrikis, DD Ho
The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigra..
Dramatic rise in plasma viremia after CD8( ) T cell depletion in simian immunodeficiency virus-infected macaques
X Jin, DE Bauer, SE Tuttleton, S Lewin, A Gettie, J Blanchard, CE Irwin, JT Safrit, J Mittler, L Weinberger, LG Kostrikis, LQ Zhang, AS Perelson, DD Ho
To determine the role of CD8(+) T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the ef..