We find that people with non-suppressible human immunodeficiency virus (HIV) viremia despite antiretroviral therapy (ART) exhibit several distinguishing features. These include expanded CD4+ T cell clones containing HIV proviruses integrated into transcriptionally permissive regions, the presence of certain proviral defects or human leukocyte antigen (HLA)-escape mutations, enhanced survival signatures, and muted interferon and cytotoxic CD8+ T cell responses.
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References
Halvas, E. K. et al. HIV-1 viremia not suppressible by antiretroviral therapy can originate from large T cell clones producing infectious virus. J. Clin. Investig. 130, 5847–5857 (2020). This study demonstrated that clusters of HIV-1-infected cells can lead to NSV.
Podsadecki, T. J., Vrijens, B. C., Tousset, E. P., Rode, R. A. & Hanna, G. J. Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia. J. Infect. Dis. 196, 1773–1778 (2007). This study showed that patients with low-level viremia do not always experience virologic failure or develop drug resistance.
Vancoillie, L. et al. Longitudinal sequencing of HIV-1 infected patients with low-level viremia for years while on ART shows no indications for genetic evolution of the virus. Virology 510, 185–193 (2017). This study revealed that in some patients with persistent low-level viremia, there may be no evidence of viral evolution, indicating the absence of active virus replication.
White, J. A. et al. Clonally expanded HIV-1 proviruses with 5′-leader defects can give rise to nonsuppressible residual viremia. J. Clin. Investig. 133, e165245 (2023). This study showed that proviruses exhibiting 5′-leader sequence deletions can be found in patients with NSV and may lead to the production of envelope-deficient viruses.
Palmer, S. et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc. Natl. Acad. Sci. USA 105, 3879–3884 (2008). This study indicated that highly sensitive HIV-1 viral load assays can identify very low levels of HIV-1 viremia, even in PWH who appear to have successfully suppressed the virus through ART.
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This is a summary of: Mohammadi, A. et al. Viral and host mediators of non-suppressible HIV-1 viremia. Nat. Med. https://doi.org/10.1038/s41591-023-02611-1 (2023).
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Viral, cellular and immune aspects of non-suppressible HIV-1 viremia. Nat Med 29, 3016–3017 (2023). https://doi.org/10.1038/s41591-023-02688-8
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DOI: https://doi.org/10.1038/s41591-023-02688-8
