Nonsuppressible viremia during HIV-1 therapy meets molecular virology.

Ann Emery, Sarah B Joseph, Ronald Swanstrom

The Journal of clinical investigation 2023 Mar 15

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HIV-1 replication can be suppressed with antiretroviral therapy (ART), but individuals who stop taking ART soon become viremic again. Some people experience extended times of detectable viremia despite optimal adherence to ART. In this issue of the JCI, White, Wu, and coauthors elucidate a source of nonsuppressible viremia (NSV) in treatment-adherent patients - clonally expanded T cells harboring HIV-1 proviruses with small deletions or mutations in the 5'-leader, the UTR that includes the major splice donor site of viral RNA. These mutations altered viral RNA-splicing efficiency and RNA dimerization and packaging, yet still allowed production of detectable levels of noninfectious virus particles. These particles lacked the HIV-1 Env surface protein required for cell entry and failed to form the mature capsid cone required for infectivity. These studies improve our understanding of NSV and the regulation of viral functions in the 5'-leader with implications for rationalized care in individuals with NSV.

Citation

Ann Emery, Sarah B Joseph, Ronald Swanstrom. Nonsuppressible viremia during HIV-1 therapy meets molecular virology. The Journal of clinical investigation. 2023 Mar 15;133(6)