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Very high baseline HIV-1 RNA viral loads require potent and robust antiretroviral regimens to achieve virological suppression. The coformulated single tablet regimen of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) is recommended by the US Department of Health and Human Services for the treatment of HIV-1 in treatment-naive adults and adolescents regardless of baseline CD4(+) T-cell count and viral load. We report two cases of HIV-infected, treatment-naive patients, with baseline HIV-1 RNA viral loads >1,000,000 copies/ml who were initiated on the single tablet regimen EVG/COBI/FTC/TDF, but failed to attain viral load suppression and developed resistance to the components of EVG/COBI/FTC/TDF.
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http://dx.doi.org/10.3851/IMP2987 | DOI Listing |
Sci Signal
September 2025
Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
Replication of HIV-1 requires the coordinated action of host and viral transcription factors, most critically the viral transactivator Tat and the host nuclear factor κB (NF-κB). This activity is disrupted in infected cells that are cultured with extracellular vesicles (EVs) present in human semen, suggesting that they contain factors that could inform the development of new therapeutics. Here, we explored the contents of semen-derived EVs (SEVs) from uninfected donors and individuals with HIV-1 and identified host proteins that interacted with HIV Tat and the NF-κB subunit p65.
View Article and Find Full Text PDFPLoS Pathog
September 2025
INSERM UMR 1291, CNRS UMR 5051, Université de Toulouse, Toulouse Institute for Infectious and Inflammatory Diseases, Toulouse, France.
Vδ1 γδ T cells are key players in innate and adaptive immunity, particularly at mucosal interfaces such as the gut. An increase in circulating Vδ1 cells has long been observed in people with HIV-1, but remains poorly understood. We performed a comprehensive characterization of Vδ1 T cells in blood and duodenal intra-epithelial lymphocytes, obtained from endoscopic mucosal biopsies of 15 people with HIV-1 on antiretroviral therapy and 15 HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137).
View Article and Find Full Text PDFPLoS Biol
September 2025
Department of Virology, Immunology & Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States of America.
Despite the success of antiretroviral therapy in suppressing plasma viremia in people living with human immunodeficiency virus type-1 (HIV-1), persistent viral RNA expression in tissue reservoirs is observed and can contribute to HIV-1-induced immunopathology and comorbidities. Infection of long-lived innate immune cells, such as tissue-resident macrophages and microglia may contribute to persistent viral RNA production and chronic inflammation. We recently reported that de novo cytoplasmic expression of HIV-1 intron-containing RNA (icRNA) in macrophages and microglia leads to MDA5 and MAVS-dependent innate immune sensing and induction of type I IFN responses, demonstrating that HIV icRNA is a pathogen-associated molecular pattern (PAMP).
View Article and Find Full Text PDFFront Microbiol
August 2025
Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Introduction: Low-level viremia (LLV) in HIV infection, defined as detectable but low plasma viral load, is associated with an increased risk of virological failure (VF); however, the mechanisms underlying LLV remain unclear. Monocytes, as potential viral reservoirs, can migrate into tissues and differentiate into tissue-resident macrophage reservoirs, playing a critical role in viral dissemination and potentially driving persistent viremia.
Methods: This study aimed to analyze and compare the molecular characteristics of near-full-length HIV-1 proviral DNA quasispecies from monocytes in three distinct virological response groups: VF, LLV, and virological suppression (VS).
J Infect Public Health
September 2025
AP-HP, Hospital Bichat - Claude-Bernard, Infectious and Tropical Diseases Department, IAME UMR 1137 INSERM, Université Paris Cité, France; IMEA, Hospital Bichat-Claude Bernard, Paris, France.
Background: Polymedication and comorbidities are frequent in aging people with HIV (PWH) and often associated with elevated incidences of adverse events (AEs) and drug-drug interactions (DDIs). The objective of this study was to evaluate the efficacy, safety and practicality of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), an antiretroviral (ARV) therapy with limited DDIs, in an elderly virologically-controlled PWH population.
Materials And Methods: This study was prospective, multicentric, single-arm conducted in HIV-1 controlled PWH aged over 65 years who switched from a ritonavir- or cobicistat-boosted containing regimen to B/F/TAF.