Steven Deeks
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Articles by Steven Deeks
SIV reservoir depletion and clearance from neonatal macaques following transient CCR5 depletion
Abstract Antiretroviral therapy (ART) suppresses viraemia in people with human immunodeficiency virus (HIV), but HIV provirus persists indefinitely in CD4-expressing cells. Cells containing active provirus express viral proteins and have been successfully targeted using broadly neutralizing antibodies (bnAbs). In contrast, cells containing latent provirus cannot be specifically targeted without latency reactivation.
SARS-CoV-2-specific monoclonal antibody AER002 in Long COVID: an exploratory randomized phase 2a mechanistic trial
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Abstract Persistence of SARS-CoV-2 has been proposed as a biological driver of Long COVID, a disabling chronic illness with no proven treatments. We conducted an exploratory, placebo-controlled, double-blind, 2:1 randomized mechanistic trial (NCT05877508) of the SARS-CoV-2-specific monoclonal antibody AER002 in 36 participants who met the World Health Organization case definition of Long COVID. After baseline characterization, participants received a single infusion and were followed for 360 days.
By Michael J Peluso, Dylan Ryder, Thomas Dalhuisen, Antonio Rodriguez, Antonio Rodríguez Verified, Brian LaFranchi, Joanna R. Vinden, Emily A. Fehrman, Beatrice Huang, Rebecca Hoh Verified, Mohammad Sofiqur Rahman, Mark Painter, E. John Wherry, Zoe Swank, Louise Hansen, David R. Walt, Yoshinori Fukazawa, Anisha Sekar, Prakash Bhuyan, Rajeev Venkayya, Robert R. Flavell, Henry F. VanBrocklin, J. Daniel Kelly, Priscilla Y. Hsue, Matthew S. Durstenfeld, Peter Hunt, Leonard Calabrese, Ma Somsouk, Jeffrey Martin, David Glidden, Amelia N. Deitchman, Timothy J. Henrich, Steven Deeks, Meghann C. Williams, Kofi A. Asare, Kathleen Bellon Pizarro, Emilio de Narvaez, Steven E. Bellan, Holly Tieu, Josephat Asiago
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Nature
Verified
Innate immune imprints shape HIV-1 reservoir cell persistence during long-term antiretroviral therapy
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Abstract Host immune responses that can target and eliminate HIV-1 reservoir cells during suppressive antiretroviral therapy are poorly understood. Here, analyzing over 6,000 proviral DNA amplicons from 104 individuals on long-term antiretroviral therapy, we found that carriers of HLA-C2 allotypes, which promote NK cell education via interactions with KIR2DL1, exhibited lower frequencies of intact proviruses.
By Toong Seng Tan, Weiwei Sun, Ce Gao, Mathias Viard, Lucy Walters, Melanie Lancien, Yuko Yuki, Xuan Guo, Rebecca Hoh Verified, David Haas, Nelson L. Michael, Gregory D. Kirk, George A Yendewa, Rajesh T. Gandhi, Seble Kassaye, Phyllis C Tien, Bruce Walker, Michael J Peluso, Jeffrey Jacobson, Steven Deeks, Mary Carrington, Xu Yu, Mathias Lichterfeld, Tram N. Van, Carlos Casquero
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Nature
Verified
Persistent cytolytic CD8 + T cells recognize SARS-CoV-2 and herpesvirus epitopes in long COVID
ArticleOnline now102946Open access Affiliations & Notes 1Gladstone Institutes, University of California, San Francisco, San Francisco, CA, United States of America 2Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America 3Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States of America 4Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San...
Multiomic analysis of ART-interruption cohorts identifies cell-extrinsic and -intrinsic mechanisms driving lymphocyte-mediated control of HIV rebound
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ArticleOnline nowOpen access Affiliations & Notes 1Gladstone Institutes, San Francisco, CA 94158, USA 2University of California, San Francisco, San Francisco, CA 94158, USA 3Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA 4Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA 5Leibniz Institute of Virology, Hamburg, Germany 6Institute of Infection Research and Vaccine Development, University Medical Center...
By Tongcui Ma, Ashley George, Reuben Thomas, Kailin Yin, Min-Gyoung Shin, Mauricio Montano, Yusuke Matsui, Manickam Ashokkumar, Kyrlia C. Young, Julia Prigann, Julie Frouard, Sabrina Leddy, Maisha Adiba, Christina Herrde, Ulrike C Lange, Cédric Feschotte, Douglas F Nixon, Nancie M. Archin, Jonathan Li, Davey Smith, Steven Deeks, Ole S. Søgaard, Martin Tolstrup, Sulggi A Lee, Satish Pillai, Mohamed Abdel-Mohsen, Katherine S. Pollard, Robert F. Siliciano, Melanie Ott, Nadia R. Roan, Zichong Li
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Cell Press
Verified
Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy - Nature Medicine
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Abstract Antiretroviral therapy (ART) suppresses HIV but does not eliminate the latent viral reservoir, which persists in programmed cell death protein 1 (PD-1)-expressing CD4+ T cells. Anti-PD-1 therapies have reduced the HIV reservoir in people living with HIV (PLWH) and cancer; however, the individuals who benefit and the mechanisms driving reservoir reduction remain unclear.
By Aarthi Talla, Muhammad Latif, Gabriela Sánchez Verified, Adam Pelletier, Sangeeta Kumari, Viviane Schuch, Khader Ghneim, Ajantha Rhodes, Frank Maldarelli, Robert Yarchoan, Kathryn Lurain, Ramya Ramaswami, Elad Sharon, Bruce Hess, Javier Martinez-Picado, Nicolas Chomont, Sharon Lewin, Steven Deeks, Steven Fling, Thomas Uldrick, Ashish Sharma, Rafick-Pierre Sekaly, Ana B. Enriquez, Saswat Kumar Bal, Leonard D’Amico, Martin A. Cheever
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Nature
Verified
Efficient mRNA delivery to resting T cells to reverse HIV latency - Nature Communications
Abstract A major hurdle to curing HIV is the persistence of integrated proviruses in resting CD4+ T cells that remain in a transcriptionally silent, latent state. One strategy to eradicate latent HIV is to activate viral transcription, followed by elimination of infected cells through virus-mediated cytotoxicity or immune-mediated clearance.
Mechanism for evolution of diverse autologous antibodies upon broadly neutralizing antibody therapy of people with HIV
Abstract Antiretroviral therapy (ART) inhibits Human Immunodeficiency Virus (HIV) replication to maintain undetectable viral loads in people living with HIV, but does not result in a cure. Due to the significant challenges of lifelong ART for many, there is strong interest in therapeutic strategies that result in cure.
Long COVID is associated with lower percentages of mature, cytotoxic NK cell phenotypes
Research LetterIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/JCI188182 Long COVID is associated with lower percentages of mature, cytotoxic NK cell phenotypes 1UCSF, San Francisco, United States of America Find articles by Tsao, T. in: JCI | PubMed | Google Scholar | 1UCSF, San Francisco, United States of America Find articles by Buck, A. in: JCI | PubMed | Google Scholar | 1UCSF, San Francisco, United States of America Find articles by Grimbert, L.
Cognate antigen engagement induces HIV-1 expression in latently infected CD4+ T cells from people on long-term antiretroviral therapy
Keywords HIV-1 persistence HIV-1 latent reservoir latency reversal antigenic stimulation dendritic cells CD4+ T cells cytomegalovirus Introduction Antiretroviral therapy (ART) effectively blocks viral replication, but HIV-1 persists in a small pool of latently infected resting CD4+ T cells harboring inducible, replication-competent proviruses.1,2,3 This reservoir was originally characterized with a quantitative viral outgrowth assay (QVOA) in which resting CD4+ T cells are stimulated with...
Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease - Nature Communications
Abstract Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells.
Early biological markers of post-acute sequelae of SARS-CoV-2 infection - Nature Communications
Abstract To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset.
HIV rebound in HIV controllers is associated with a specific fecal microbiome profile
Conflict of interest YC, LZ, CRdV, EV, DSG, and JJW are employees and stockholders of Gilead Sciences, Inc. OP was an employee and a stockholder of Gilead Sciences, Inc., during the execution of this study. SGD declares research support from Gilead Sciences, Inc.
HIV rebound in HIV controllers is associated with a specific fecal microbiome profile
Conflict of interest YC, LZ, CRdV, EV, DSG, and JJW are employees and stockholders of Gilead Sciences, Inc. OP was an employee and a stockholder of Gilead Sciences, Inc., during the execution of this study. SGD declares research support from Gilead Sciences, Inc.
Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2
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Abstract Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used ‘omic” assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation.
By Kailin Yin, Michael J Peluso, Xiaoyu Luo, Reuben Thomas, Min-Gyoung Shin, Jason Neidleman, Alicer Andrew, Tongcui Ma, Rebecca Hoh Verified, Khamal Anglin, Beatrice Huang, Monica Lopez, Mónica López, Daisy Valdivieso, Kofi Asiamah Asare, Tyler-Marie Deveau, Sadie E. Munter, Rania A. Ibrahim, Ludger Ständker, Scott Lu, Sarah Goldberg, Sulggi A Lee, Kara Lynch, J. Daniel Kelly, Jeffrey Martin, Jan Münch, Steven Deeks, Timothy J. Henrich, Nadia R. Roan, Kyrlia C. Young, Urania Argueta
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Nature
Verified
Viral and host mediators of non-suppressible HIV-1 viremia - Nature Medicine
Abstract Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence.
Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence - Nature Communications
Abstract Persistence of HIV in people living with HIV (PWH) on suppressive antiretroviral therapy (ART) has been linked to physiological mechanisms of CD4+ T cells. Here, in the same 37 male PWH on ART we measure longitudinal kinetics of HIV DNA and cell turnover rates in five CD4 cell subsets: naïve (TN), stem-cell- (TSCM), central- (TCM), transitional- (TTM), and effector-memory (TEM). HIV decreases in TTM and TEM but not in less-differentiated subsets.
Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1
Co-immunoprecipitation (Co-IP) followed by western blotting Approximately 4 × 107 HEK 293T cells (from American Type Culture Collection) in two 150-mm dishes were transfected by plasmids (20 μg/dish) expressing FLAG-tagged BCL7C, KANSL2, or nothing. The following operations were all carried out at 4°C or on ice unless stated otherwise.
A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection - Nature
Abstract Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic1,2,3,4. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance.
Impact of misclassified defective proviruses on HIV reservoir measurements - Nature Communications
Human participants This study was approved by the institutional review board of the NIH National Institute of Allergy and Infectious Diseases and registered on ClinicalTrials.gov: NCT00039689. All study participants provided written informed consent, and leukapheresis products were collected in accordance with the protocol. All study participants were of male sex based on self-reporting. 5 participants were White, 3 Black and 2 Unknown/Hispanic-Latino.
Prevention, treatment and cure of HIV infection - Nature Reviews Microbiology
Authors and Affiliations Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles, CA, USA Raphael J. Landovitz Bridge HIV, San Francisco Department of Public Health, San Francisco, CA, USA Hyman Scott Division of HIV, Infectious Diseases & Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA Hyman Scott & Steven G. Deeks Contributions S.G.D. researched data for the article.
Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus - Nature Microbiology
Abstract HIV-1 persists as a latent reservoir in people receiving suppressive antiretroviral therapy (ART). When ART is interrupted (treatment interruption/TI), rebound virus re-initiates systemic infection in the lymphoid system. During TI, HIV-1 is also detected in cerebrospinal fluid (CSF), although the source of this rebound virus is unknown.
HIV silencing and cell survival signatures in infected T cell reservoirs - Nature
Abstract Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure1,2,3, but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA.
SARS‐CoV‐2 and Mitochondrial Proteins in Neural‐Derived Exosomes of COVID‐19
Research Article Abstract Objective As SARS-CoV-2 is known to invade neural cell mitochondria, a plasma system for quantifying central nervous system proteins in living humans was used to investigate neuropathogenic mechanisms of long-COVID-19.
First-in-human immunoPET imaging of HIV-1 infection using 89Zr-labeled VRC01 broadly neutralizing antibody - Nature Communications
Abstract A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed.
Early clues regarding the pathogenesis of long-COVID
Intense investigation into the predictors and determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), including ‘long COVID’, is underway. Recent studies provide clues to the mechanisms that might drive this condition, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse PASC. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to systemic symptoms, which in most people resolve within a few weeks.
Findings From Mayo Clinic’s Post-COVID Clinic: PASC Phenotypes Vary by Sex and Degree of IL-6 Elevation
A significant proportion of individuals suffer from persistent symptoms after acute infection with SARS-CoV-2. This syndrome, called long COVID by patient advocates, has been named post-acute sequelae of COVID-19 (PASC) by the National Institutes of Health.
Association between statin use, atherosclerosis, and mortality in HIV-infected adults
Loading metrics Open Access Peer-reviewed Research Article Binh An P. Phan , Yifei Ma, Rebecca Scherzer, Steven G. Deeks, Priscilla Y. Hsue Binh An P. Phan, Yifei Ma, Rebecca Scherzer, Steven G. Deeks, Priscilla Y. Hsue Published: April 30, 2020 https://doi.org/10.1371/journal.pone.0232636 Figures Abstract Background While HIV infection is associated with increased cardiovascular risk, benefit from statin is not well established in HIV-infected adults.
HIV
HIV infection Millions of people are infected with human immunodeficiency virus (HIV) globally. Antiretroviral therapy offers substantial benefit to those infected or at risk of infection — controlling viraemia and delaying the onset of acquired immune deficiency syndrome (AIDS). Here, the authors describe the basic and clinical research advances in this important global health issue. Steven G.
Beta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes
Abstract The pool of beta cell-specific CD8+ T cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell ‘multipotency index’ and found that beta cell-specific CD8+ T cells retained a stem-like epigenetic multipotency score.
Why and where an HIV cure is needed and how it might be achieved
Abstract Despite considerable global investment, only 60% of people who live with HIV currently receive antiretroviral therapy. The sustainability of current programmes remains unknown and key incidence rates are declining only modestly. Given the complexities and expenses associated with lifelong medication, developing an effective curative intervention is now a global priority. Here we review why and where a cure is needed, and how it might be achieved.
Author Correction: CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome
Access provided by Correction to: Nature Immunology https://doi.org/10.1038/s41590-019-0406-1, published online 17 June 2019. In the version of this article initially published, the right two labels along the horizontal axis of Fig. 8c (IntA and IntG) were in the incorrect order. The correct order is IntG (middle right) and IntA (far right). The error has been corrected in the HTML and PDF versions of the article.
CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome
Abstract Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS.
Liverpool and Chelsea target Ezequiel Lavezzi could be heading to Inter Milan
Liverpool and Chelsea target Ezequiel Lavezzi could be on his way to Inter Milan, according to reports. The Paris Saint Germain attacker has been tracked by a number of clubs across Europe and could now finally be on his way out of the French club. Liverpool boss Brendan Rodgers is unlikely to pursue his interest in the player after signing Mario Balotelli, while Chelsea boss Jose Mourinho has decided he has enough attacking options.
The end of HIV: Still a very long way to go, but progress continues
Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SD is an advisor to InnaVirVax, Bionor Pharma and Bryologix and receives grant support from Gilead, Merck and ViiV. SL’s institution has received funding for investigator-initiated industry-sponsored studies from Merck, Gilead, Viiv Healthcare and Tetralogic and has also acted on the advisory board for and as consultancy to Callimune, Tetralogic, and InnaVirVax.
CNN Africa - Timeline
See more of CNN Africa by logging into Facebook Message this Page, learn about upcoming events and more. If you don't have a Facebook account, you can create one to see more of this Page.
Cancer research could help the search towards an HIV cure
Nobel Laureate Françoise Barré-Sinoussi is the co-discoverer of HIV and immediate Past President of the International AIDS Society. Sharon Lewin is the Inaugural Director of the Peter Doherty Institute for Infection and Immunity, a joint venture of the University of Melbourne and Royal Melbourne Hospital, and Steven Deeks is Professor of Medicine in Residence at the University of California, San Francisco. The opinions expressed in this commentary are solely those of the authors.
RiseUpToHIV - Timeline | Facebook
RiseUpToHIV is excited to announce the launch of a new positive messaging video campaign called “My Positive Message.” In addition to the “No Shame About Being HIV+” storytelling campaign, this campaign will harness the power of video on social media to further tear down the walls of stigma, fear and shame. Take a minute to share your message of love, hope, strength about your experience living with or affected by HIV in order to encourage, educate, and empower others.
HIV and Hepatitis C-Coinfected Patients Have Lower Low‐Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent “PCSK9-Lipid Paradox”
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Methods and Results We studied 567 participants from a clinic‐based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL‐C level was 100 mg/dL (IQR 77–124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors.
By Payal Kohli, Peter Ganz, Yifei Ma, Rebecca Scherzer, Steven Deeks, Scott Wasserman, Rob Scott Verified, Sophia Hur, Bernard Weigel, Carl Grunfeld
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jaha.ahajournals.org
Video: West Ham fans fighting each other after Sunderland win
Even a win over Sunderland was not enough to put a smile on the faces of some West Ham fans at the weekend after they turned on each other. Angry Hammers supporters started throwing punches at one another before the police intervened and managed to bring the melee under control. It is not known what caused the fight but a rare win in 2015 was quickly forgotten as fans left Upton Park after the victory over the Black Cats.
Ex-Spurs boss Tim Sherwood favourite for Crystal Palace job
Former Tottenham manager Tim Sherwood is the favourite to take over at Crystal Palace after Neil Warnock was sacked earlier today. The former midfielder guided Spurs to a sixth place finish last season after taking over from Andre Villas-Boas before chairman Daniel Levy enacted a clause in his contract to end his spell.
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