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Ever since its discovery, human immunodeficiency virus type 1 (HIV-1) infection has remained a significant public health concern. The number of HIV-1 seropositive individuals currently stands at 40.1 million, yet definitive treatment for the virus is still unavailable on the market. Vaccination has proven to be a potent tool in combating infectious diseases, as evidenced by its success against other pathogens. However, despite ongoing efforts and research, the unique viral characteristics have prevented the development of an effective anti-HIV-1 vaccine. In this review, we aim to provide an historical overview of the various approaches attempted to create an effective anti-HIV-1 vaccine. Our objective is to explore the reasons why specific methods have failed to induce a protective immune response and to analyze the different modalities of immunogen presentation. This trial is registered with NCT05414786, NCT05471076, NCT04224701, and NCT01937455.
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http://dx.doi.org/10.1155/2024/2147912 | DOI Listing |
Curr HIV Res
August 2025
U.S. Mil-itary HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Reports of HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) medi-ating a potential 'vaccinal effect' implicate passively transferred bNAbs in promoting endoge-nous anti-HIV-1 immune responses. To date, three clinical trials have reported either increased anti-HIV-1 neutralizing antibodies or T cell responses following bNAb administration to people living with HIV. Despite strong enthusiasm for this hypothesis, motivated in large part by its potential application to HIV-1 therapeutic strategies, the mechanism(s) underlying a vaccinal ef-fect remain unclear.
View Article and Find Full Text PDFActa Pharm Sin B
August 2025
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound demonstrated exceptional efficacy against both WT HIV-1 (EC = 1.
View Article and Find Full Text PDFViruses
August 2025
State Key Laboratory of Virology and Biosafety, Department of Infectious Diseases, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2025
State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Sichuan, Chengdu 610041, China.. Electronic address:
In this work, we describe the design, synthesis, and biological evaluation of a series of novel dual-target prodrugs that simultaneously target HIV-1 viral infection factors (Vif) and reverse transcriptase (RT). Among them, the two most effective compounds, A1 and A7, were found to inhibit HIV-1IIIB at nanomolar concentrations (EC = 8.1 nM, EC = 9.
View Article and Find Full Text PDFJ Med Chem
August 2025
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong 250012, P.R. China.
To develop effective non-nucleoside reverse transcriptase inhibitors (NNRTIs) with improved antidrug resistance profiles and drug-like properties, a series of novel diarylpyrimidine derivatives targeting the hydrophobic domain of the NNRTI-binding pocket was strategically designed, synthesized, and evaluated. Following structural optimization, (EC = 5.06-54.
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