Article
Infectious Diseases
Boris Revollo, Laura Vinuela, Lorena de la Mora, Federico Garcia, Marc Noguera-Julian, Mariona Parera, Roger Paredes, Josep M. Llibre
Summary: This article reports a case of integrase resistance in a patient treated with co-formulated dolutegravir/lamivudine. It highlights the importance of carefully considering and monitoring drug-drug interactions, even when they are regarded as having a low potential.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Medicine, General & Internal
Hendrik Streeck, Alvino Maestri, Daniel Habermann, Trevor A. Crowell, Allahna L. Esber, Gowoon Son, Leigh Anne Eller, Michael A. Eller, Ajay P. Parikh, Peter A. Horn, Lucas Maganga, Emmanuel Bahemana, Yakubu Adamu, Francis Kiweewa, Jonah Maswai, John Owuoth, Merlin L. Robb, Nelson L. Michael, Christina S. Polyak, Daniel Hoffmann, Julie A. Ake
Summary: Chronic immune activation in HIV-1 infection is influenced by factors such as HIV viral load, sex, age, region, and ART use. Predictors and associations among biomarkers and co-infections affect biomarkers associated with noncommunicable diseases.
Article
Biochemistry & Molecular Biology
Kathryn E. Stephenson, Boris Julg, C. Sabrina Tan, Rebecca Zash, Stephen R. Walsh, Charlotte-Paige Rolle, Ana N. Monczor, Sofia Lupo, Huub C. Gelderblom, Jessica L. Ansel, Diane G. Kanjilal, Lori F. Maxfield, Joseph Nkolola, Erica N. Borducchi, Peter Abbink, Jinyan Liu, Lauren Peter, Abishek Chandrashekar, Ramya Nityanandam, Zijin Lin, Alessandra Setaro, Joseph Sapiente, Zhilin Chen, Lisa Sunner, Tyler Cassidy, Chelsey Bennett, Alicia Sato, Bryan Mayer, Alan S. Perelson, Allan deCamp, Frances H. Priddy, Kshitij Wagh, Elena E. Giorgi, Nicole L. Yates, Roberto C. Arduino, Edwin DeJesus, Georgia D. Tomaras, Michael S. Seaman, Bette Korber, Dan H. Barouch
Summary: A study showed that a single dose of a broadly neutralizing, HIV-specific antibody PGT121 can transiently reduce viral load in some HIV-infected individuals and lead to durable virus suppression in certain cases. Further research is warranted to explore the potential of antibody-based therapeutic strategies for long-term HIV suppression.
Article
Biochemistry & Molecular Biology
Lucia Bailon, Anuska Llano, Samandhy Cedeno, Tuixent Escriba, Miriam Rosas-Umbert, Mariona Parera, Maria Casadella, Miriam Lopez, Francisco Perez, Bruna Oriol-Tordera, Marta Ruiz-Riol, Josep Coll, Felix Perez, Anne R. Leselbaum, Ian McGowan, Devi Sengupta, Edmund G. Wee, Tomas Hanke, Roger Paredes, Yovaninna Alarcon-Soto, Bonaventura Clotet, Marc Noguera-Julian, Christian Brander, Jose Molto, Beatriz Mothe, Angel Rivero
Summary: The HTI vaccines were able to induce strong, polyfunctional, and broad T-cell responses, but they did not prevent viral rebound. However, in some participants, these vaccines were associated with a longer time off antiretroviral treatment, suggesting that their immunogenicity may be beneficial for future cure approaches.
Article
Chemistry, Medicinal
Richard A. Hartz, Li Xu, Sing-Yuen Sit, Jie Chen, Brian L. Venables, Zeyu Lin, Sharon Zhang, Zhufang Li, Dawn Parker, Tara S. Simmons, Susan Jenkins, Umesh M. Hanumegowda, Ira Dicker, Mark Krystal, Nicholas A. Meanwell, Alicia Regueiro-Ren
Summary: This study investigated the structure-activity relationships of a series of HIV-1 maturation inhibitors based on GSK3640254 by incorporating novel C-17 amine substituents. The results showed that the modified compounds exhibited potent inhibition activity against both wild-type and variant viruses, with compound 26 showing the strongest activity and desirable overall profile. Pharmacokinetic studies also indicated that compound 26 had low clearance and good oral bioavailability in rats and dogs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Adam Akullian, Alain Vandormael, Joel C. Miller, Anna Bershteyn, Edward Wenger, Diego Cuadros, Dickman Gareta, Till Barnighausen, Kobus Herbst, Frank Tanser
Summary: In a hyper-epidemic region of KwaZulu-Natal, South Africa, the median age of HIV seroconversion increased in both men and women, suggesting a changing demographic of HIV risk with a focus on younger age groups. The decline in HIV incidence was more pronounced in young men and women, while older individuals showed stable or even lagging declines in incidence. These results provide direct epidemiological evidence of the impact of large-scale treatment and prevention interventions on the age distribution of HIV incidence in sub-Saharan Africa.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Chemistry, Medicinal
Wensheng Yu, Jian Liu, Dane Clausen, Younong Yu, Joseph L. Duffy, Ming Wang, Shouning Xu, Lin Deng, Takao Suzuki, Christine C. Chung, Robert W. Myers, Daniel J. Klein, James Fells, M. Katharine Holloway, Jin Wu, Guoxin Wu, Bonnie J. Howell, Richard J. O. Barnard, Joseph Kozlowski
Summary: The discovery of histone deacetylase (HDACs) 1, 2, and 3 inhibitors with ethyl ketone as the zinc-binding group is described. These inhibitors exhibit good enzymatic and cellular activity, high selectivity against hERG, minimized serum shift in cellular potency, and improved selectivity over HDACs 6 and 8. They contain a variety of substituted heterocycles on the imidazole or oxazole scaffold, with compounds 31 and 48 standing out for their potency, selectivity, reduced hERG activity, optimized serum shift, and good PK profiles in rats and dogs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Louise Kuhn, Maria Paximadis, Bianca Da Costa Dias, Yanhan Shen, Sizanani Mncube, Renate Strehlau, Stephanie Shiau, Faeezah Patel, Megan Burke, Karl-Gunter Technau, Gayle Sherman, Shayne Loubser, Elaine J. Abrams, Caroline T. Tiemessen
Summary: Early initiation of antiretroviral therapy, higher CD4+ T-cell percentage, lower viral load pre-ART, absence of maternal antenatal ART, and breastfeeding are associated with lower levels of HIV-1 DNA in treated infants.
CLINICAL INFECTIOUS DISEASES
(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
Microbiology
Johan Lombaard, Francis Ssali, Puthanakit Thanyawee, Jan Fourie, Simon Vanveggel, Cornelia Linthicum, Veerle Van Eygen, Rodica Van Solingen-Ristea
Summary: This study examined the long-term safety and efficacy of RPV plus NRTIs in HIV-1-infected adolescents. The results showed that participants with higher adherence and lower baseline viral load had better virologic response. However, treatment-emergent RPV resistance and NRTI resistance were observed in some participants.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Immunology
Aude Christelle Ka'e, Aubin Joseph Nanfack, Georgia Ambada, Maria Mercedes Santoro, Desire Takou, Ezechiel Ngoufack Jagni Semengue, Alex Durand Nka, Marie Laure Mpouel Bala, Orphelie Ndoh Endougou, Elise Elong, Grace Beloumou, Sandrine Djupsa, Davy Hyacinthe Gouissi, Nadine Fainguem, Michel Carlos Tommo Tchouaket, Samuel Martin Sosso, Daniel Kesseng, Francis Ateba Ndongo, Nelson Sonela, Arnaud Cedric Lacmago Kamta, Hyppolite K. Tchidjou, Therese Ndomgue, Suzie Tetang Moyo Ndiang, Anne Esther Njom Nlend, Celine Nguefeu Nkenfou, Carla Montesano, Gregory Edie Halle-Ekane, Giulia Cappelli, Caroline T. Tiemessen, Vittorio Colizzi, Francesca Ceccherini-Silberstein, Carlo-Federico Perno, Joseph Fokam
Summary: Antiretroviral therapy (ART) has improved the lifespan of people living with HIV, but their immune system remains in a state of sustained activation/inflammation. This study investigated the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Calixte Ida Penda, Magaly Moukoko Mbonjo, Joseph Fokam, Armando Blondel Djiyou Djeuda, Ngondi Grace, Francis Ateba Ndongo, Serge Bilong, Bertrand Eyoum Bille, Paul Koki Ndombo, Avelin Aghokeng, Alexis Ndjolo, Carole Else Eboumbou Moukoko
Summary: This study aimed to investigate the rates of virological failure (VF) and HIV drug resistance (HIVDR) among adolescents with HIV on antiretroviral therapy (ART) in Cameroon. The study found that higher rates of VF were associated with suboptimal adherence, older age, living outside the city where they received ART, severe immunocompromise, and starting ART in infancy. The overall rate of HIVDR was high among participants who underwent genotyping resistance testing.
Article
Virology
Elena Bruzzesi, Arianna Gabrieli, Davide Bernasconi, Giulia Marchetti, Andrea Calcagno, Diego Ripamonti, Andrea Antinori, Nicola Squillace, Antonella Cingolani, Antonio Muscatello, Alessandra Bandera, Andrea Gori, Stefano Rusconi, Silvia Nozza, INACTION Study Grp
Summary: The introduction of antiretroviral therapy (ART) during primary HIV-1 infection (PHI) can restrict the establishment of HIV reservoirs. This study aimed to assess the effect of three different ART regimens on HIV-DNA load in individuals living with HIV (PLWH) who started ART in PHI. The results showed that regardless of the treatment regimen, the HIV-DNA load in PLWH decreased during the treatment period.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Medicine, Research & Experimental
Gabriel Duette, Bonnie Hiener, Hannah Morgan, Fernando G. Mazur, Vennila Mathivanan, Bethany A. Horsburgh, Katie Fisher, Orion Tong, Eunok Lee, Haelee Ahn, Ansari Shaik, Remi Fromentin, Rebecca Hoh, Charline Bacchus-Souffan, Najla Nasr, Anthony L. Cunningham, Peter W. Hunt, Nicolas Chomont, Stuart G. Turville, Steven G. Deeks, Anthony D. Kelleher, Timothy E. Schlub, Sarah Palmer
Summary: Through studying CD4(+) T cells of HIV-1 patients, the importance of effector memory T cells in the persistence of HIV-1 has been identified, and Nef has been suggested as a potential therapeutic target.
JOURNAL OF CLINICAL INVESTIGATION
(2022)