Article
Pharmacology & Pharmacy
Soo-Yon Rhee, Neil Parkin, P. Richard Harrigan, Susan Holmes, Robert W. Shafer
Summary: This study reviewed the genetic mechanisms of resistance to Cabotegravir (CAB). The results showed that the most commonly selected mutations in patients developing virological failure while receiving CAB included Q148R, N155H, and E138K. The study also identified 14 drug resistance mutations significantly associated with reduced CAB susceptibility. The study highlights the importance of careful patient screening and close virological monitoring to prevent the emergence of drug resistance with the use of CAB.
ANTIVIRAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Yue Wang, Shuang-Xi Gu, Qiuqin He, Renhua Fan
Summary: The development history of HIV-1 IN strand transfer inhibitors (INSTIs) was briefly illustrated in the review. The currently approved INSTIs play a significant role in antiretroviral therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Horacio Gil, Elena Delgado, Sonia Benito, Maria Moreno-Lorenzo, Michael M. Thomson
Summary: This study analyzed the clinical, epidemiological, and virological features associated with INSTI resistance diagnosed in Spain. The results showed that INSTI resistance is uncommon and associated with long-term infections, older age, and additional resistance to other ARV drug classes. The study also found that INSTI resistance is rare in newly diagnosed HIV-1 infections.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Immunology
Ashima Pyngottu, Alexandra U. Scherrer, Roger Kouyos, Michael Huber, Hans Hirsch, Matthieu Perreau, Sabine Yerly, Alexandra Calmy, Matthias Cavassini, Marcel Stoeckle, Hansjakob Furrer, Pietro Vernazza, Enos Bernasconi, Huldrych F. Guenthard
Summary: This study examined factors associated with treatment failure in HIV patients on InSTI-based regimens, finding that high baseline viral load and AIDS-defining events were linked to failure. CD4 cell counts between 200-500 and >500 cells/μL were protective. Risk factors for treatment failure were similar to those for older treatments.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Chemistry, Medicinal
Jinglan Lai, Yuming Liu, Xiao Han, Aiqiong Huang, Jin Lin, Wen Ao, Hanhui Ye, Yahong Chen
Summary: The study found a low rate of INSTIs TDRM among therapy-naive HIV patients in Southeast China, making INSTIs suitable as a first-line regimen. However, special attention must still be paid to INSTIs TDRM in clinical practice.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Microbiology
Yun Lan, Linghua Li, Ruolei Xin, Xuemei Ling, Xizi Deng, Junbin Li, Liya Li, Weiping Cai, Feng Li, Fengyu Hu
Summary: The study revealed a comparatively low prevalence of INSTI-related drug resistance among HIV-1-infected patients in Guangdong province, China, with some ART-experienced individuals showing mutations conferring resistance to INSTIs. Therefore, surveillance should be reinforced before transitioning to INSTI-containing regimens.
Article
Immunology
Michael A. Leonard, Zinhle Cindi, Yuki Bradford, Kassem Bourgi, John Koethe, Megan Turner, Jamison Norwood, Beverly Woodward, Husamettin Erdem, Rebecca Basham, Paxton Baker, Peter F. Rebeiro, Timothy R. Sterling, Todd Hulgan, Eric S. Daar, Roy Gulick, Sharon A. Riddler, Phumla Sinxadi, Marylyn D. Ritchie, David W. Haas
Summary: The study utilized two cohorts to investigate the impact of pharmacogenetics on weight gain in patients switching from efavirenz to INSTI-based regimens. The results showed that CYP2B6 genotype was associated with weight gain after switching, potentially due to the withdrawal of the inhibitory effect of higher efavirenz concentrations. The association varied depending on the concomitant nucleoside analogue used.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Jane A. O'Halloran, John Sahrmann, Luis Parra-Rodriguez, Daniel T. Vo, Anne M. Butler, Margaret A. Olsen, William G. Powderly
Summary: The use of integrase strand transfer inhibitors (INSTIs) in treating HIV infection is associated with a 31% increased risk of new-onset diabetes mellitus/hyperglycemia in the 6 months following antiretroviral therapy initiation.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Nokuzola Mbhele, Michelle Gordon
Summary: This study investigated the impact of INSTI resistance-associated mutations on the structure of HIV-1C integrase, revealing that these mutations affect protein stability and weaken hydrogen bond interactions compared to the wild-type. Additionally, a double mutant in the 140's loop region was identified in South African HIV-1C isolates for the first time.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Genetics & Heredity
Weiguang Fan, Xiaodong Wang, Yuchen Zhang, Juan Meng, Miaomiao Su, Xuegang Yang, Haoxi Shi, Penghui Shi, Xinli Lu
Summary: This study investigated INSTI resistance mutations in newly diagnosed therapy-naive HIV-positive patients in Baoding City, China, and found a low resistance rate. Monitoring and research on HIV INSTI resistance should be strengthened in this area.
FRONTIERS IN GENETICS
(2022)
Article
Immunology
Emma M. Kileel, Carlos D. Malvestutto, Janet Lo, Kathleen Fitch, Carl J. Fichtenbaum, Judith A. Aberg, Markella Zanni, Esteban Martinez, Nwora Lance Okeke, Princy Kumar, Esau Joao, Sara H. Bares, Daniel Berrner, Marek Smieja, Jhoanna C. Roa, Sara McCallum, Pamela S. Douglas, Heather J. Ribaudo, Steven K. Grinspoon
Summary: Over a 2-year follow-up period, the use of integrase strand transfer inhibitors (INSTIs) was associated with weight gain among patients who had been using INSTIs for less than 2 years at the start of the study (+0.27 kg/m(2)/year; 95% CI, .22 to .33), but not among those who had been using INSTIs for more than 2 years. The difference in weight gain between the two groups was statistically significant (P = .01).
CLINICAL INFECTIOUS DISEASES
(2023)
Review
Virology
Clemence Richetta, Nhat Quang Tu, Olivier Delelis
Summary: This review discusses the mode of action of INSTIs and summarizes the resistance mutations, as well as the role of unintegrated viral DNA in conferring resistance. It provides a more detailed understanding of HIV resistance to these inhibitors and contributes to the development of new INSTIs in the future.
Article
Immunology
Nan Wang, Xia Xiong, Zhiqi Liu, Ruixian Zhang, Sha Luo, Hongying Zhang, Xuping Wu
Summary: This study investigated the prevalence of integrase inhibitor resistance-related mutations and other drug resistance-related mutations among newly diagnosed ART-naive HIV-positive patients in Nanjing, China. It was found that a few patients had major integrase resistance-related mutations and others had accessory resistance-related mutations. These results highlight the importance of further molecular surveillance-based monitoring of the HIV epidemic in Nanjing.
MICROBIAL PATHOGENESIS
(2023)
Review
Biochemistry & Molecular Biology
Gioele Renzi, Fabrizio Carta, Claudiu T. Supuran
Summary: Integration of viral RNA into host genomes is a crucial step in retroviral replication, catalyzed by the conserved virus-encoded enzyme Integrase (IN). The authors discuss the discoveries and advances in developing targeted inhibitors for HIV-IN as therapeutic applications. The accumulated knowledge serves as a valuable resource for designing effective antiretroviral drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Michal S. Barski, Teresa Vanzo, Xue Zhi Zhao, Steven J. Smith, Allison Ballandras-Colas, Nora B. Cronin, Valerie E. Pye, Stephen H. Hughes, Terrence R. Burke, Peter Cherepanov, Goedele N. Maertens
Summary: Researchers identified a compound named XZ450 as the most effective against HTLV-1 and visualized its binding mechanism to the HTLV-1 intasome through structural studies. This provides support for the potential use of this compound for pre-exposure prophylaxis and treatment of HTLV-1 infection.
NATURE COMMUNICATIONS
(2021)
Article
Public, Environmental & Occupational Health
Sotirios Roussos, Dimitrios Paraskevis, Meni Malliori, Angelos Hatzakis, Vana Sypsa
Summary: Estimating the population size of PWID based on community-based program data yields estimates 2.1 times higher than official estimates based on drug treatment data, indicating the need for re-evaluation of resources for harm reduction and elimination of HIV and hepatitis C in PWID.
Article
Immunology
Nuria Climent, Juan Ambrosioni, Tania Gonzalez, Cristina Xufre, Maria Casadella, Marc Noguera-Julian, Roger Paredes, Montserrat Plana, Judith Grau-Exposito, Josep Mallolas, Jose Alcami, Sonsoles Sanchez-Palomino, Jose M. Miro
Summary: This study reports a case of a highly controlled HIV infection individual who maintained undetectable viral loads for 15 years after stopping antiretroviral therapy. The researchers found that the high activity of NK cells and CD8 T cells were associated with the control of viral replication.
Article
Immunology
Adolfo de Salazar, Laura Vinuela, Ana Fuentes, Elisa Teyssou, Charlotte Charpentier, Sidonie Lambert-Niclot, Esther Serrano-Conde, Marta Pingarilho, Lavinia Fabeni, Anne De Monte, Karl Stefic, Carlo Federico Perno, Antonio Aguilera, Iker Falces, Rafael Delgado, Sandra Fernandes, Isabel Diogo, Perpetua Gomes, Dimitrios Paraskevis, Maria-Mercedes Santoro, Francesca Ceccherini-Silberstein, Anne-Genevieve Marcelin, Federico Garcia
Summary: The prevalence of transmitted drug resistance to INSTIs and NRTIs and clinically relevant resistance was evaluated in newly diagnosed HIV patients naive to ART in Europe. The results showed low prevalence rates of INSTI-SDRMs (0.30%), NRTI-SDRMs (5.77%), INSTI-CRR (2.33%), and first-line NRTI-CRR (1.74-2.29%) during 2018-2021.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Deniz Gokengin, Dominik Bursa, Agata Skrzat-Klapaczynska, Ivailo Alexiev, Elena Arsikj, Tatevik Balayan, Josip Begovac, Alma Cicic, Gordana Dragovic, Arjan Harxhi, Kerstin Aimla, Botond Lakatos, Raimonda Matulionyte, Velida Mulabdic, Cristiana Oprea, Antonios Papadopoulos, Nino Rukhadze, Dalibor Sedlacek, Lubomir Sojak, Janez Tomazic, Anna Vassilenko, Marta Vasylyev, Antonija Verhaz, Nina Yancheva, Oleg Yurin, Justyna Kowalska
Summary: This study aimed to assess the current situation and challenges for pre- and post-exposure prophylaxis (PrEP and PEP) in Central and Eastern Europe (CEE), with a response rate of 91.6%. The results showed that PrEP was licensed in 68.2% of the centers, with an estimated 9000 individuals on PrEP. It was available in daily, on-demand, or both forms, with an access rate ranging from less than 1% to 80%. Major barriers for access included lack of knowledge/awareness among those in need, reimbursement restrictions, and low perception of HIV risk.
Article
Infectious Diseases
Annabel Rector, Mandy Bloemen, Gilberte Schiettekatte, Piet Maes, Marc Van Ranst, Elke Wollants
Summary: This study evaluated the possibility of extracting viral nucleic acids for genetic analysis from archived rapid antigen detection tests (Ag-RDTs). The results showed that SARS-CoV-2 nucleic acids as well as other viruses can be successfully extracted and sequenced from Ag-RDTs. The buffer of the Ag-RDTs had a significant impact on the efficiency of viral RNA extraction and sequencing.
Letter
Immunology
Marc Van Ranst, York Zoellner, Joerg Schelling, Bram Palache
EXPERT REVIEW OF VACCINES
(2023)
Article
Biochemistry & Molecular Biology
Nikolaos I. Vlachogiannis, Panagiotis A. Ntouros, Maria Pappa, Evrydiki Kravvariti, Evangelia Georgia Kostaki, Georgios E. Fragoulis, Christina Papanikolaou, Dimitra Mavroeidi, Vasiliki-Kalliopi Bournia, Stylianos Panopoulos, Katerina Laskari, Aikaterini Arida, Vassilis G. Gorgoulis, Maria G. Tektonidou, Dimitrios Paraskevis, Petros P. Sfikakis, Vassilis L. Souliotis
Summary: Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, affecting organ function and leading to chronic diseases. In this study, the relationship between chronological age and DNA damage response (DDR) signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals was investigated. The results showed that DNA damage levels in PBMCs were only marginally correlated with age until 50 years, but a linear relationship was observed after 50 years. Furthermore, individuals older than 50 years exhibited higher levels of endogenous double-strand breaks (DSBs), oxidative stress, apurinic/apyrimidinic sites, and decreased DSBs repair capacity compared to those younger than 50 years. Prospective studies are needed to confirm DNA damage accumulation as a biomarker of aging and determine the relevant age threshold.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Annabel Rector, Mandy Bloemen, Marijn Thijssen, Leen Delang, Joren Raymenants, Jonathan Thibaut, Bram Pussig, Lore Fondu, Bert Aertgeerts, Marc Van Ranst, Chris Van Geet, Jef Arnout, Elke Wollants
Summary: Wastewater surveillance is crucial in managing the global COVID-19 pandemic, serving as an early warning system for outbreaks and a tool to track the circulation of specific variants. This study used various wastewater collection points in Leuven to investigate the application of wastewater surveillance. Wastewater samples were collected and analyzed using RT-qPCR to quantify SARS-CoV-2 RNA, and specific mutations were detected to identify circulating variants. The study found that wastewater SARS-CoV-2 concentration preceded peaks in positive cases and detected the presence of different variants simultaneously during the transition period. Wastewater-based surveillance is a valuable tool for monitoring virus circulation and variants in larger populations.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Clinical Neurology
Matteo Riva, Roxanne Wouters, David Nittner, Jolien Ceusters, Edmond Sterpin, Roberto Giovannoni, Uwe Himmelreich, Willy Gsell, Marc Van Ranst, An Coosemans
Summary: This study aimed to analyze the effects of optimizing radiotherapy schedules in combination with radioimmunotherapy on the tumor microenvironment of experimental high-grade gliomas. The results showed that radiation dosage and fractionation significantly influenced the survival, tumor immunity, and glioma stem cells in experimental high-grade gliomas. These findings should be considered when designing more synergistic and effective radioimmunotherapy combinations.
JOURNAL OF NEUROSURGICAL SCIENCES
(2023)
Article
Virology
Kassiani Mellou, Kyriaki Tryfinopoulou, Styliani Pappa, Kassiani Gkolfinopoulou, Sofia Papanikou, Georgia Papadopoulou, Evangelia Vassou, Evangelia-Georgia Kostaki, Kalliopi Papadima, Elissavet Mouratidou, Maria Tsintziloni, Nikolaos Siafakas, Zoi Florou, Antigoni Katsoulidou, Spyros Sapounas, George Sourvinos, Spyridon Pournaras, Efthymia Petinaki, Maria Goula, Vassilios Paparizos, Anna Papa, Theoklis Zaoutis, Dimitrios Paraskevis
Summary: In May 2022, multiple cases of mpox were reported in non-endemic countries for the first time. Greece confirmed its first case on June 8, 2022, and a total of 88 cases were reported in the country until April 2023. The Greek National Public Health Organization established a multidisciplinary response team to monitor and manage the situation.
Article
Virology
Ivailo Alexiev, Anupama Shankar, Yi Pan, Lyubomira Grigorova, Alexandra Partsuneva, Reneta Dimitrova, Anna Gancheva, Asya Kostadinova, Ivaylo Elenkov, Nina Yancheva, Rusina Grozdeva, Dimitar Strashimirov, Mariana Stoycheva, Ivan Baltadzhiev, Tsetsa Doichinova, Lilia Pekova, Minas Kosmidis, Radoslava Emilova, Maria Nikolova, William M. Switzer
Summary: The prevalence of transmitted HIV drug resistance and genetic diversity in Bulgaria between 2012 and 2020 was investigated. The study found a low prevalence of drug resistance mutations in ART-naive patients, but high HIV-1 genetic diversity. Most drug resistance mutations were present in transmission clusters involving male-to-male sexual contact. This study provides valuable information for the development of enhanced prevention strategies to end the HIV epidemic.
Article
Immunology
Dimitrios Paraskevis, Maria Gkova, Kassiani Mellou, Gerasimos Gerolymatos, Naya Psalida, Kassiani Gkolfinopoulou, Evangelia-Georgia Kostaki, Stylianos Loukides, Anastasia Kotanidou, Athanasios Skoutelis, Eleftherios Thiraios, Georgios Saroglou, Dimitrios Zografopoulos, Dimitrios Filippou, Elias Mossialos, Theoklis Zaoutis, Mina Gaga, Sotirios Tsiodras, Anastasia Antoniadou
Summary: This retrospective cohort study evaluated the effectiveness of molnupiravir and nirmatrelvir/ritonavir in highly vulnerable patients with SARS-CoV-2. The results showed that both drugs significantly reduced the risk of hospitalization and death among these patients. The risk reduction was most pronounced in elderly patients (≥75 years old) and those with high levels of drug adherence.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Isabel Leroux-Roels, Marc Van Ranst, Corinne Vandermeulen, Carline Vanden Abeele, Nathalie De Schrevel, Bruno Salaun, Celine Verheust, Marie-Pierre David, Shady Kotb, Veronica Hulstrom
Summary: This study evaluated the safety and immune responses of a third dose of an investigational vaccine against respiratory syncytial virus (RSV) in older adults aged 60-80 years. The results showed that the third dose of the vaccine was well tolerated and induced a good immune response in older adults.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Virology
Marta Giovanetti, Eleonora Cella, Ivan Ivanov, Lyubomira Grigorova, Ivan Stoikov, Deyan Donchev, Reneta Dimitrova, Svetoslav Nanev Slavov, Carla Mavian, Vagner Fonseca, Fabio Scarpa, Alessandra Borsetti, Neli Korsun, Ivelina Trifonova, Veselin Dobrinov, Todor Kantardjiev, Iva Christova, Massimo Ciccozzi, Ivailo Alexiev
Summary: This study provides a comprehensive analysis of the genomic epidemiology and lineage dynamics of SARS-CoV-2 in Bulgaria over a three-year period. The findings shed light on the virus evolution, emergence of variants of concern, and their impact on the pandemic trajectory. Understanding the genomic epidemiology is crucial for targeted public health strategies and managing future outbreaks.
Article
Microbiology
Ivailo Alexiev, Ivan Ivanov, Marta Giovanetti, Eleonora Cella, Ivan Stoikov, Deyan Donchev, Lyubomira Grigorova, Anna Gancheva, Reneta Dimitrova, Fabio Scarpa, Neli Korsun, Ivelina Trifonova, Veselin Dobrinov, Todor Kantardjiev, Iva Christova, Massimo Ciccozzi
Summary: The first recombinant SARS-CoV-2 variants were identified in 2022, causing public health concerns. The importance of recombinant variants has increased especially since the WHO designated the recombinant variant XBB and its lineages as subvariants that require monitoring on 20 November 2022. In this study, we provide the first insights into the new SARS-CoV-2 variant named XAN, a recombinant composed of Omicron sub-lineages BA.2 and BA.5. To our knowledge, this is the first report on the recombinant SARS-CoV-2 XAN variant identified in Bulgaria.