A New Type of Nonsuppressible Viremia Produced by HIV-Infected Macrophage

Authors

• Matthew J. Moeser, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Olivia D. Council, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Nathan Long, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Laura Kincer, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Ann M. Dennis, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Joseph Eron, University of North Carolina at Chapel Hill, Chapel Hill, NC
• David Wohl, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Claire E. Farel, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Dirk P. Dittmer, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Linda Pluta, Lineberger Comprehensive Cancer Center, Chapel Hill, NC
• Julie Nelson, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Abbas Mohammadi, Brigham and Women's Hospital, Boston, MA
• Behzad Etemad, Brigham and Women's Hospital, Boston, MA
• Jonathan Z. Li, Brigham and Women's Hospital, Boston, MA
• Hugh McGann, Waikato Hospital, Hamilton, New Zealand
• Erasmus Smit, Waikato Hospital, Hamilton, New Zealand
• Meredith Clement, LSU Health Sciences Center - New OrleansFollow
• Tat Yau, LSU Health Sciences Center - New OrleansFollow
• Prema Menezes, UNC Center for AIDS Research, Chapel Hill, North Carolina
• Natalie M. Bowman, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Shuntai Zhou, University of North Carolina at Chapel Hill, Chapel Hill, NC
• Sarah B. Joseph, University of North Carolina at Chapel Hill, Chapel Hill, NC

Document Type

Article

Publication Date

4-22-2026

Publication Title

The Journal of Infectious Diseases

Abstract

BACKGROUND: HIV-1 RNA typically declines rapidly after initiation of antiretroviral therapy (ART), often reaching undetectable levels within a few weeks and remaining undetectable by standard assays. However, some patients receiving ART have persistent nonsuppressible viremia (NSV) that does not respond to treatment optimization or intensification. NSV can emerge at the time of ART initiation (primary NSV) or after being ART suppressed (secondary NSV). Here, we examine mechanisms producing primary NSV in 4 people undergoing ART. METHODS: Blood samples were collected from 4 participants with advanced immunodeficiency who, despite being adherent to ART, required approximately a year or more to become virologically suppressed. Viral RNA and proviral DNA genomes were sequenced to examine HIV drug resistance, genome intactness, and genetic diversity. The ability of HIV Envs to facilitate efficient entry into cells expressing low levels of CD4, a proxy for macrophage tropism, was also assessed. RESULTS: Before ART, blood contained HIV RNA genomes that were adapted to replication in CD4+ T cells and rapidly decayed after ART initiation. During ART, blood contained HIV genomes that were drug sensitive, genetically diverse, and macrophage tropic; moreover, they were not evolving and often had vpr defects. CONCLUSIONS: Our results suggest that in individuals with primary NSV, ART stopped virus replication, but large pools of long-lived HIV-infected macrophage continued to produce virus. This is mechanistically distinct from secondary NSV produced by CD4+ T-cell clones. Defects in vpr independently accumulated in macrophage-tropic lineages found in 3 participants, suggesting that vpr may affect survival or virus production from HIV-infected macrophage.

First Page

1005

Last Page

1014

PubMed ID

42018762

Volume

233

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Recommended Citation

Moeser, Matthew J.; Council, Olivia D.; Long, Nathan; Kincer, Laura; Dennis, Ann M.; Eron, Joseph; Wohl, David; Farel, Claire E.; Dittmer, Dirk P.; Pluta, Linda; Nelson, Julie; Mohammadi, Abbas; Etemad, Behzad; Li, Jonathan Z.; McGann, Hugh; Smit, Erasmus; Clement, Meredith; Yau, Tat; Menezes, Prema; Bowman, Natalie M.; Zhou, Shuntai; and Joseph, Sarah B., "A New Type of Nonsuppressible Viremia Produced by HIV-Infected Macrophage" (2026). School of Medicine Faculty Publications. 4728.
https://digitalscholar.lsuhsc.edu/som_facpubs/4728
10.1093/infdis/jiag171