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Background: Understanding factors affecting the size and the evolution of the HIV reservoir is essential for the development of curative strategies. This study aimed to assess the impact of antiretroviral therapy (ART) initiated during primary infection (PHI) chronic infection (CHI) on the levels and dynamics of integrated HIV-1 DNA, a biomarker of viral persistence.
Methods: Integrated and total HIV-1-DNA were measured in the blood of 92 patients treated during PHI (early group) and 41 during CHI (deferred group), at diagnosis, ART initiation, and 12-24 months on treatment.
Results: On ART, detectable (>1.78 log copies/10 PBMCs) integrated HIV-1 DNA levels were significantly lower in the early deferred group (2.99 log 3.29 log = 0.005). The proportion of undetectable integrated HIV-1 DNA tended to be higher in the early group deferred group (61 % 46 %; p = 0.133).
Conclusion: Treatment initiated at PHI limits the levels of integrated HIV-1 DNA in blood. However, initiating treatment at CHI does not allow reaching such low levels in most patients, probably because the stable proviruses at that stage are present in the less prone to elimination long-lived cells. Thus, early ART could provide an opportunity to preparing for functional cure and eradication strategies.
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http://dx.doi.org/10.1016/j.jve.2023.100357 | DOI Listing |
Front 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).
Biochemistry
September 2025
Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida 32306, United States.
Islatravir (ISL, EFdA) is a nucleoside analog that inhibits HIV-1 reverse transcriptase (RT) translocation during viral replication. Its high potency stems from unique structural features: a 4'-ethynyl group that interacts with the hydrophobic pocket (containing A114, Y115, F160, M184, and D185) in HIV-1 RT, hindering translocation, and a 3'-hydroxyl group that mimics natural nucleosides for efficient incorporation. Recent phase 3 clinical trials, combining ISL with Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor, show that it is noninferior to existing treatments, offering a unique advantage due to their distinct resistance profiles.
View Article and Find Full Text PDFJACS Au
August 2025
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom.
The ability to selectively control DNA conformation using light as an external stimulus offers unique opportunities to control specific DNA sequences in biological settings and to develop nucleotide-based nanodevices. We describe a duplex/G-quadruplex (G4) junction-binding chemotype derived from a cyclic azobenzene core that reversibly photoswitches between and isomers, mediated exclusively by visible light under physiological conditions. We demonstrate the selective binding of the elongated conformation, with over 50-fold higher affinity, toward LTR-III G4 (an important HIV-1 sequence), and show that binding and dissociation from the LTR-III G4 can be controlled reversibly by alternate irradiation with low-intensity blue and green light.
View Article and Find Full Text PDFSci Rep
August 2025
Sorbonne University, INSERM, Pierre Louis Institute of Epidemiology and Public Health, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Laboratoire de Virologie, Paris, 75013, France.
Antibodies to programmed cell death 1 (PD-1), Programmed death-ligand 1 (PDL-1) and Cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4) can revert HIV latency and enhance anti-HIV cytotoxic response but their impact on HIV proviral sequences and integration landscape in people with HIV (PWH) remain to be studied. Two PWH treated with PD-1/PDL-1 and one with PD-1/CTLA4 were studied among the ANRS-CO-24 OncoVIHAC cohort study. Matched integration site and proviral sequencing were performed pre- and post-treatment.
View Article and Find Full Text PDFViruses
August 2025
Andevir, University Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France.
Integrase is a key protein during HIV-1 replication as it catalyzes the integration of viral DNA into the host DNA. After several decades of research, highly potent and selective active site inhibitors have emerged. The new challenge is now to develop molecules with an original mode of action, targeting integrase out of its catalytic site.
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