Article
Immunology
Matthew Pace, Ane Ogbe, Jacob Hurst, Nicola Robinson, Jodi Meyerowitz, Natalia Olejniczak, John P. Thornhill, Mathew Jones, Anele Waters, Julianne Lwanga, Kristen Kuldanek, Rebecca Hall, Panagiota Zacharopoulou, Genevieve E. Martin, Helen Brown, Nneka Nwokolo, Dimitra Peppa, Julie Fox, Sarah Fidler, John Frater
Summary: Natural Killer (NK) cells play a key role in controlling HIV replication and the effectiveness of antiretroviral therapy (ART). Primary HIV infection (PHI) disrupts NK cell function, but early ART can restore these functions. Different NK cell markers are associated with time to viral rebound and HIV DNA levels.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Fernando Real, Aiwei Zhu, Boxin Huang, Ania Belmellat, Alexis Sennepin, Thomas Vogl, Celine Ransy, Marc Revol, Riccardo Arrigucci, Anne Lombes, Johannes Roth, Maria Laura Gennaro, Frederic Bouillaud, Sarra Cristofari, Morgane Bomsel
Summary: This study found that tissue-resident macrophages contain active HIV-1 virus and can produce and release the virus upon stimulation with the endogenous factor S100A8. These findings have important implications for future HIV eradication strategies.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Basiel Cole, Laurens Lambrechts, Zoe Boyer, Ytse Noppe, Marie-Angelique De Scheerder, John-Sebastian Eden, Bram Vrancken, Timothy E. Schlub, Sherry McLaughlin, Lisa M. Frenkel, Sarah Palmer, Linos Vandekerckhove
Summary: This study extensively analyzes individuals undergoing ART treatment and highlights the role of HIV-infected cell clones in maintaining the replication-competent reservoir and contributing to viral rebound during ATI.
Article
Public, Environmental & Occupational Health
Christos Thomadakis, Constantin T. Yiannoutsos, Nikos Pantazis, Lameck Diero, Ann Mwangi, Beverly S. Musick, Kara Wools-Kaloustian, Giota Touloumi
Summary: This study compared the trends of CD4 cell count before and after the restart of antiretroviral therapy (ART) in HIV-infected individuals who had interrupted their care. The results showed that the increase in CD4 cell count after ART reinitiation was slower than before disengagement from care. This suggests that specific interventions targeted at better retention in care are urgently needed.
AMERICAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Microbiology
Yuta Hikichi, Rachel Van Duyne, Phuong Pham, Jennifer L. Groebner, Ann Wiegand, John W. Mellors, Mary F. Kearney, Eric O. Freed
Summary: The presence of mutations in the HIV-1 envelope glycoprotein (Env) can lead to reduced susceptibility to multiple classes of antiretroviral drugs (ARVs) and may contribute to virological failure in patients. The accumulation of Env mutations in individuals failing integrase inhibitor therapy suggests a possible mechanism for drug resistance development without mutations in target genes. Understanding how Env mutations affect drug resistance may influence therapeutic strategies for ARV-treated patients.
Article
Microbiology
Erin M. B. Scholz, Joseph N. Mwangi, Gabriela De la Cruz, Michael Nekorchuk, Chi Ngai Chan, Kathleen Busman-Sahay, Lourdes Adamson, Paul Luciw, Yuri Fedoriw, Jacob D. Estes, Elias P. Rosen, Angela D. M. Kashuba
Summary: Our study found that a significant portion of mesenteric lymph node tissue was not covered by any antiretroviral drugs, and a substantial amount of FDC-trapped virions and infected cells were not exposed to detected ARVs. While cumulative antiretroviral therapy coverage was high, a large portion of tissue coverage was from only one ARV, mainly maraviroc. Collagen deposition did not influence the heterogeneity of ARV distribution. Our findings suggest that ARV distribution, in addition to total-tissue drug concentration, is important when evaluating viral persistence in lymph nodes and other reservoir tissues.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Alfredo A. A. Hinay Jr, Kyosuke Kanai, Akeno Tsuneki-Tokunaga, Mizuki Komatsu, Elizabeth O. Telan, Seiji Kageyama
Summary: This study assessed the impact of high viral growth capability on the susceptibility of HIV isolates to antiretroviral drugs using an in vitro model. Results showed that HIV isolates with high growth capability exhibited reduced susceptibility to certain antiretroviral drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Steven A. Kemp, Oscar J. Charles, Anne Derache, Werner Smidt, Darren P. Martin, Collins Iwuji, John Adamson, Katya Govender, Tulio de Oliveira, Francois Dabis, Deenan Pillay, Richard A. Goldstein, Ravindra K. Gupta
Summary: This study analyzed the whole-genome sequences of chronically infected HIV-1-positive individuals failing 2nd-line regimens under non-suppressive antiretroviral therapy. The findings revealed dramatic changes in virus population structure and highlighted viral diversification, recombination, and haplotype competition during non-suppressive ART.
Article
Immunology
Chi-Chuan Wang, Chi-Hao Shao, Hsing-Jung Li, Wang-Huei Sheng
Summary: This study explored the initial ART use patterns and ART persistence in patients starting HIV treatment in Taiwan. It found a rapid increase in INI-based regimens and a decrease in PI-based regimens. The persistence of ART was influenced by treatment guidelines and government policies.
JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION
(2022)
Article
Microbiology
Jennillee Wallace, Hemil Gonzalez, Reshma Rajan, Srinivas D. Narasipura, Amber K. Virdi, Arnold Z. Olali, Ankur Naqib, Zarema Arbieva, Mark Maienschein-Cline, Lena Al-Harthi
Summary: Combination antiretroviral therapy (cART) has significantly improved the treatment of HIV/AIDS, but it may also affect cell dysregulation and increase susceptibility to comorbidities in persons living with HIV (PLWH).
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Virology
Xiaolei Wang, Huanbin Xu
Summary: Although antiretroviral therapy (ART) has significantly suppressed human immunodeficiency virus (HIV) replication and rendered the virus undetectable, a small number of residual replicable HIV proviruses can still persist, leading to viral rebound after treatment interruption. With current treatments unable to eradicate HIV proviral reservoirs, developing new therapeutic strategies to eliminate these reservoirs is crucial for achieving ART-free HIV remission.
Article
Virology
Christian Gaebler, Shane D. Falcinelli, Elina Stoffel, Jenna Read, Ross Murtagh, Thiago Y. Oliveira, Victor Ramos, Julio C. C. Lorenzi, Jennifer Kirchherr, Katherine S. James, Brigitte Allard, Caroline Baker, JoAnn D. Kuruc, Marina Caskey, Nancie M. Archin, Robert F. Siliciano, David M. Margolis, Michel C. Nussenzweig
Summary: The study compared two novel assays, IPDA and Q4PCR, for measuring intact HIV proviral DNA in samples from 39 ART-suppressed people living with HIV, showing a 19-fold difference in frequencies of intact proviral DNA. This disparity may be partially due to inefficiencies in long-distance PCR amplification and the presence of intact proviruses with defects in other parts of the genome. The head-to-head comparison provides context for interpreting the results of the assays and highlights the importance of both methods in accurately quantifying the replication-competent HIV reservoir.
JOURNAL OF VIROLOGY
(2021)
Review
Medicine, General & Internal
Jun-Jie Xu, Meng-Jie Han, Yong-Jun Jiang, Hai-Bo Ding, Xi Li, Xiao-Xu Han, Fan Lv, Qing-Feng Chen, Zi-Ning Zhang, Hua-Lu Cui, Wen-Qing Geng, Jing Zhang, Qi Wang, Jing Kang, Xiao-Lin Li, Hong Sun, Ya-Jing Fu, Ming-Hui An, Qing-Hai Hu, Zhen-Xing Chu, Ying-Jie Liu, Hong Shang
Summary: China has made progress in combating HIV/AIDS, including measures such as legislation and widespread nucleic acid testing to prevent infections and providing free ART treatment. In the future, efforts should focus on controlling the spread through sexual transmission, closing the gap in identifying HIV cases, and ensuring the long-term effectiveness and safety of ART.
CHINESE MEDICAL JOURNAL
(2021)
Article
Microbiology
Michael T. Pyne, Keith E. Simmon, Melanie A. Mallory, Weston C. Hymas, Jeffery Stevenson, Adam P. Barker, David R. Hillyard
Summary: HIV-1 antiretroviral therapy management requires sequencing of different portions of the HIV-1 pol gene. Traditional Sanger sequencing has limited ability to detect minor variants. Next generation sequencing enables detection of variants at frequencies as low as 1%, allowing for earlier detection of resistance. However, implementation of NGS in the clinical laboratory is hindered by complicated design and analysis.
JOURNAL OF CLINICAL MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Ann Emery, Sarah B. Joseph, Ronald Swanstrom
Summary: The study found that despite optimal adherence to ART, some treatment-adherent patients still experience extended times of detectable viremia. This is due to clonally expanded T cells carrying HIV-1 proviruses with small deletions or mutations in the 5 '-leader, which affect viral RNA-splicing efficiency and packaging. These mutations result in the production of noninfectious virus particles without the required surface protein and mature capsid cone for cell entry and infectivity. This research enhances our understanding of nonsuppressible viremia and provides implications for improved care in individuals with this condition.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Immunology
Bethany A. Horsburgh, Eunok Lee, Bonnie Hiener, John-Sebastian Eden, Timothy E. Schlub, Susanne von Stockenstrom, Lina Odevall, Jeffrey M. Milush, Teri Liegler, Elizabeth Sinclair, Rebecca Hoh, Eli A. Boritz, Daniel C. Douek, Remi Fromentin, Nicolas Chomont, Steven G. Deeks, Frederick M. Hecht, Sarah Palmer
Article
Virology
Michael Roche, Carolin Tumpach, Jori Symons, Matthew Gartner, Jenny L. Anderson, Gabriela Khoury, Kieran Cashin, Paul U. Cameron, Melissa J. Churchill, Steven G. Deeks, Paul R. Gorry, Sharon R. Lewin
JOURNAL OF VIROLOGY
(2020)
Article
Immunology
Yetao Wang, Lawrence Lifshitz, Kyle Gellatly, Carol L. Vinton, Kathleen Busman-Sahay, Sean McCauley, Pranitha Vangala, Kyusik Kim, Alan Derr, Smita Jaiswal, Alper Kucukural, Patrick McDonel, Peter W. Hunt, Thomas Greenough, JeanMarie Houghton, Ma Somsouk, Jacob D. Estes, Jason M. Brenchley, Manuel Garber, Steven G. Deeks, Jeremy Luban
Review
Microbiology
Lillian B. Cohn, Nicolas Chomont, Steven G. Deeks
CELL HOST & MICROBE
(2020)
Article
Immunology
Sulggi A. Lee, Sushama Telwatte, Hiroyu Hatano, Angela D. M. Kashuba, Mackenzie L. Cottrell, Rebecca Hoh, Teri J. Liegler, Sophie Stephenson, Ma Somsouk, Peter W. Hunt, Steven G. Deeks, Steven Yukl, Radojka M. Savic
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2020)
Article
Infectious Diseases
Sabina Herrera, Borja M. Fernandez-Felix, Peter W. Hunt, Steven G. Deeks, Talia Sainz, Sonya L. Heath, Chad J. Achenbach, Benigno Rodriguez, Christopher Mathews, Katerina Christopoulos, Kenneth Mayer, Sonia Napravnik, Santiago Moreno, Sergio Serrano-Villar
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2020)
Article
Virology
Valerie F. Boltz, Cristina Ceriani, Jason W. Rausch, Wei Shao, Michael J. Bale, Brandon F. Keele, Rebecca Hoh, Jeffrey M. Milush, Steve G. Deeks, Frank Maldarelli, Mary F. Kearney, John M. Coffin
Summary: Researchers investigated the relationship between latent HIV-1 infection and genome methylation, finding no support for the proposition that latent HIV infection is associated with methylation of the HIV 5' LTR promoter.
Article
Cell Biology
Guorui Xie, Xiaoyu Luo, Tongcui Ma, Julie Frouard, Jason Neidleman, Rebecca Hoh, Steven G. Deeks, Warner C. Greene, Nadia R. Roan
Summary: Using mass cytometry analysis, the study reveals different features of HIV-susceptible cells in vivo and in vitro. In vivo, Th17 and alpha 4 beta 1(+) cells are preferentially targeted, while in vitro, Tem, Ttm, Th1, and Th1/Th17 subsets are targeted. HIV remodels cells to a T follicular helper phenotype.
Article
Cardiac & Cardiovascular Systems
Anjali B. Thakkar, Yifei Ma, Mark Dela Cruz, Yuaner Wu, Victor Arechiga, Shreya Swaminathan, Peter Ganz, Alan H. B. Wu, Rebecca Scherzer, Steven Deeks, Priscilla Y. Hsue
Summary: HIV infection affects the balance between levels of ANG1 and ANG2, leading to endothelial dysfunction. Treatment status may alter this balance, and HIV promotes endothelial dysfunction through microvascular impairment.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Immunology
Jeffrey A. Tomalka, Mehul S. Suthar, Steven G. Deeks, Rafick Pierre Sekaly
Summary: Host genetic and environmental factors play a significant role in vaccine-induced immune responses. Understanding and accounting for these factors are crucial for the development of effective vaccines against SARS-CoV-2.
Article
Medicine, Research & Experimental
Akif Altinbas, Jacinta A. Holmes, Shadi Salloum, Anna Lidofsky, Nadia Alatrakchi, Ma Somsouk, Peter Hunt, Steven Deeks, Kara W. Chew, Georg Lauer, Annie Kruger, Wenyu Lin, Raymond T. Chung
Summary: This study assessed the relationship between LOXL-2 and TNC-C levels and fibrosis severity in HIV and/or HCV-infected individuals. The study found that LOXL-2 and TNC-C levels were significantly higher in individuals with intermediate fibrosis in HCV and HCV/HIV co-infected individuals.
BIOMARKERS IN MEDICINE
(2022)
Article
Microbiology
Laura P. Kincer, Sarah Beth Joseph, Maria M. Gilleece, Blake M. Hauser, Sabrina Sizemore, Shuntai Zhou, Clara Di Germanio, Henrik Zetterberg, Dietmar Fuchs, Steven G. Deeks, Serena Spudich, Magnus Gisslen, Richard W. Price, Ronald Swanstrom
Summary: HIV-1 can persist in a latent reservoir in individuals receiving antiretroviral therapy, and rebound virus can be detected in the cerebrospinal fluid during treatment interruption. In this study, we found that high viral loads and clonally amplified viral lineages in the cerebrospinal fluid were correlated with the influx of white blood cells. Additionally, we did not observe rebound macrophage-tropic virus in the cerebrospinal fluid, indicating that the CNS may not be a source of this virus. We propose a model in which R5 T cell-tropic virus is released from infected T cells in the CNS during treatment interruption.
NATURE MICROBIOLOGY
(2023)
Review
Microbiology
Raphael J. Landovitz, Hyman Scott, Steven G. Deeks
Summary: In this Review, the authors explore the current state of HIV prevention and treatment, highlighting unmet needs and emerging tools. They discuss the combination of different approaches to achieve better outcomes, and describe recent progress in pre-exposure prophylaxis, vaccines, treatment, and cure. They emphasize the need for continued efforts to develop effective preventative vaccines and scalable cures, as the limitations of antiretroviral drugs become more apparent.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Christian Gaebler, Thiago Y. Oliveira, Michael J. Peluso, Joshua T. Schiffer, Lillian B. Cohn, Steven G. Deeks, Michel C. Nussenzweig
Summary: Most proviruses in people living with HIV are defective, but intact proviruses can lead to viral rebound. The two-probe intact proviral DNA assay (IPDA) found 40-fold more intact proviruses compared to the near full length (nfl) Q4PCR. Both assays showed that defective proviruses did not decay over 10 years. However, the average half-lives of intact proviruses were different: 108 months for IPDA and 65 months for Q4PCR. Misclassified defective proviruses and very long-lived intact proviruses could explain this difference.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Charline Bacchus-Souffan, Mark Fitch, Mohamed Abdel-Mohsen, Rebecca Hoh, Haelee Ahn, Mars Stone, Frederick Hecht, Jeffrey Martin, Steven G. Deeks, Marc K. Hellerstein, Joseph M. McCune, Joshua T. Schiffer, Peter W. Hunt
Summary: The persistence of HIV in people on suppressive antiretroviral therapy is linked to physiological mechanisms of CD4+ T cells. This study investigates the longitudinal kinetics of HIV DNA and cell turnover rates in different CD4 cell subsets. The results indicate that HIV clears faster in more proliferative/differentiated CD4 cell subsets and therapies targeting proliferation and differentiation may reduce HIV DNA levels.
NATURE COMMUNICATIONS
(2023)
