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
Virology
Claudia R. de Andrade Arrais, Kledoaldo Lima, Marta Barreiros, Jessyca K. F. Rodrigues, Nilviane P. S. Sousa, Daniel D. Costa, Francisco D. R. P. Santos, Gerson F. M. Pereira, Antonia I. e Silva Viana, Allan K. Barros, Elcio Leal
Summary: This study evaluated the genetic characterization of 132 HIV-1 pol sequences from children and adolescents undergoing antiretroviral therapy in Northeast Brazil. Most individuals harbored HIV-1 B and BF recombinants, with an overall antiretroviral resistance rate of 47%. The study highlighted the importance of surveillance of resistance mutations, with key mutations including M184V and K103N.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Microbiology
Bin Zhao, Wei Song, Mingming Kang, Xue Dong, Xin Li, Lu Wang, Jianmin Liu, Haibo Ding, Zhenxing Chu, Lin Wang, Yu Qiu, Hong Shang, Xiaoxu Han
Summary: This study describes the prevalence of transmitted drug resistance (TDR) among newly diagnosed HIV-infected patients in Shenyang, China between 2016 and 2019. The results show a moderate prevalence of TDR (5-15%) in Shenyang, and TDR strains are mainly transmitted among men who have sex with men (MSM).
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ping Gao, Shu Song, Zhao Wang, Lin Sun, Jian Zhang, Christophe Pannecouque, Erik De Clercq, Peng Zhan, Xinyong Liu
Summary: Novel diarylpyrimidine derivatives designed and synthesized in the study demonstrated strong anti-HIV activity, with compounds IVB-5-4 and IVB-5-8 showing superior activity against HIV-1(IIIB). These compounds not only exhibited potent inhibition against wide-type HIV-1 strain, but also showed low nanomole activity against some mutant strains.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Tommaso Clemente, Roberta Caccia, Laura Galli, Andrea Galli, Andrea Poli, Giulia Carla Marchetti, Alessandra Bandera, Maurizio Zazzi, Maria Mercedes Santoro, Paola Cinque, Antonella Castagna, Vincenzo Spagnuolo
Summary: This study measured inflammation, immune activation, and microbial translocation biomarkers in four-class drug-resistant (4DR) people living with HIV (PLWH). The results showed that 4DR-PLWH with detectable viremia had the highest biomarker concentrations. The study also found an association between viremia and increased expression of CD38/HLA-DR and PD-1 on CD4+ and CD8+ cells. Therefore, therapeutic approaches to reduce inflammation and T-cell exhaustion in 4DR-PLWH need to be investigated.
JOURNAL OF INFECTION
(2023)
Article
Virology
Vlad Novitsky, Winstone Nyandiko, Rachel Vreeman, Allison K. DeLong, Mark Howison, Akarsh Manne, Josephine Aluoch, Ashley Chory, Festus Sang, Celestine Ashimosi, Eslyne Jepkemboi, Millicent Orido, Joseph W. Hogan, Rami Kantor
Summary: Drug resistance is still a global challenge for children and adolescents living with HIV. Next generation sequencing can provide information about resistance evolution and potentially improve care for ART-experienced CALWH in resource-limited settings. A study conducted in Kenya found that resistance evolution was detected in 93% of participants, and minority resistance variants also evolved under drug selection pressure. The study suggests that NGS can help us better understand the dynamics of drug resistance evolution and improve care.
Article
Microbiology
Syed Hani Abidi, George Makau Nduva, Dilsha Siddiqui, Wardah Rafaqat, Syed Faisal Mahmood, Amna Rehana Siddiqui, Apsara Ali Nathwani, Aneeta Hotwani, Sharaf Ali Shah, Sikander Memon, Saqib Ali Sheikh, Palwasha Khan, Joakim Esbjoernsson, Rashida Abbas Ferrand, Fatima Mir
Summary: The study on the HIV-1 outbreak in Larkana, Pakistan, revealed that it was a multi-source outbreak rather than a single-source one as previously thought. Poor infection prevention control practices may have led to the introduction of the Larkana strain into the general population. This underscores the importance of scaling up HIV-1 prevention programs among key population groups and improving infection prevention control in Pakistan.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Infectious Diseases
Francesca Lombardi, Andrea Giacomelli, Daniele Armenia, Alessia Lai, Alex Dusina, Antonia Bezenchek, Laura Timelli, Francesco Saladini, Francesca Vichi, Paola Corsi, Grazia Colao, Bianca Bruzzone, Roberta Gagliardini, Annapaola Callegaro, Antonella Castagna, Maria Mercedes Santoro
Summary: This study found that HIV-1 drug resistance has remained stable since 2011, although HIV-MDR still exists at a lower rate, emphasizing the need for continuous monitoring and accurate management of ART-experienced patients with HIV.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Infectious Diseases
Alexandra Duhant, Byabene Kusinza, Claire Tantet, Basimane Bisimwa, Mathilde Gare, Bihehe Masemo, Chakib Alloui, Mukanire Ntakwinjan, Frederic Mechai, Minh Patrick Le, Athenais Gerber, Balthazar Muhigirwa, Gilles Peytavin, Emmanuel Gordien, Segolene Brichler, Mukengere Mukwege, Frederic Le Gal
Summary: The Panzi General Reference Hospital in the Democratic Republic of Congo treats many patients living with HIV-1. However, data on antiretroviral resistance levels and dosage in this region are lacking. The study found a high level of resistance to antiretroviral therapy, mainly due to poor treatment compliance. Closer patient monitoring, viral load testing, and therapeutic education management tools are necessary to adapt the current treatment regimen in this region.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
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
Multidisciplinary Sciences
Abhimanyu K. Singh, Brent De Wijngaert, Marc Bijnens, Kris Uyttersprot, Hoai Nguyen, Sergio E. Martinez, Dominique Schols, Piet Herdewijn, Christophe Pannecouque, Eddy Arnold, Kalyan Das
Summary: A protocol for rapid structure determination of HIV-1 reverse transcriptase (RT) complexes by cryo-electron microscopy (cryo-EM) has been optimized. Six structures of RT complexes with nonnucleoside inhibitors were determined, revealing important differences in structure and conformation. These differences have implications for understanding drug resistance mechanisms and drug design.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Kirsten L. White, Nathan Osman, Ernesto Cuadra-Foy, Bluma G. Brenner, Devleena Shivakumar, Federico Campigotto, Manuel Tsiang, Philip A. Morganelli, Nikolai Novikov, Scott E. Lazerwith, Haolun Jin, Anita Niedziela-Majka
Summary: The HIV integrase strand transfer inhibitor bictegravir has a longer dissociation half-life and more durable antiviral activity against wild-type HIV compared to other drugs like dolutegravir, raltegravir, and elvitegravir. Bictegravir makes more contacts with the IN-DNA complex than dolutegravir, contributing to its prolonged residence time and resilience against many resistance mutations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Natasha O. Moraka, Wonderful T. Choga, Marea N. Pema, Moses Kudzai Chawawa, Irene Gobe, Margaret Mokomane, Ontlametse T. Bareng, Lynette Bhebhe, Nametso Kelentse, Graceful Mulenga, Molly Pretorius Holme, Terence Mohammed, Catherine K. Koofhethile, Joseph M. Makhema, Roger Shapiro, Shahin Lockman, Sikhulile Moyo, Simani Gaseitsiwe
Summary: In this study, we used HIV-1C sequences to predict resistance to known broadly neutralizing antibodies and evaluate the impact of different HIV-1 Env characteristics on virus neutralization. Our results support the use of sequence data and machine learning tools to predict the best broadly neutralizing antibodies to use within populations.
SCIENTIFIC REPORTS
(2023)
Article
Virology
Charlotte Charpentier, Quentin Le Hingrat, Valentine Marie Ferre, Florence Damond, Diane Descamps
Summary: The use of antiretroviral drugs with low genetic barrier to resistance in low- and middle-income countries, combined with limited viral load testing, has led to higher rates of acquired drug resistance, sustaining the rate of transmitted drug resistance. Injectable long-acting forms of ARV drugs are being developed, with requirements for new ARV drugs including no transmitted drug resistance, no cross-resistance, and high genetic barrier to resistance. The WHO has set ambitious goals for HIV testing, treatment, and viral suppression, but reaching these goals requires widespread implementation and use of close virological monitoring in LMICs.
Article
Multidisciplinary Sciences
Abhimanyu K. Singh, Sergio E. Martinez, Weijie Gu, Hoai Nguyen, Dominique Schols, Piet Herdewijn, Steven De Jonghe, Kalyan Das
Summary: The authors discovered a transient P-pocket created by HIV reverse transcriptase while sliding over a DNA substrate and developed a cryo-EM platform for lead optimization. By screening 300 drug-like fragments, they identified two leads that bind to the P-pocket, which is resilient to drug-resistance mutations and composed of structural elements from polymerase active site, primer grip, and template-primer. An engineered RT/DNA aptamer complex was utilized to trap the transient P-pocket and structures of the RT/DNA complex in the presence of an inhibitory fragment were determined.
NATURE COMMUNICATIONS
(2021)