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

作者：Matthew Moeser, Nathan Long, Laura P. Kincer, Ann M. Dennis, Joseph J. Eron, David A. Wohl, Claire E. Farel, Dirk P Dittmer, Linda Pluta, Julie A. Nelson, Abbas Mohammadi, Behzad Etemad, Jonathan Z. Li, Hugh McGann, Erasmus Smit, Meredith E. Clement, Tat S. Yau, Prema Menezes, Natalie M. Bowman, Shuntai Zhou, Sarah Joseph · 发表于：The Journal of Infectious Diseases · 年份：2026 · DOI：10.1093/infdis/jiag171 · 被引用次数：1 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、HIV-related health complications and treatments

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 on 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 four people on ART. Methods Blood samples were collected from four participants 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-1 drug resistance, genome intactness and genetic diversity. The ability of HIV-1 Envs to facilitate efficient entry into cells expressing low levels of CD4 (a proxy for macrophage tropism) was assessed. Results Before ART, the blood contained HIV-1 RNA genomes that were adapted to replication in CD4+ T cells and rapidly decayed after ART initiation. During ART, the blood contained HIV-1 genomes that were drug sensitive, genetically diverse, macrophage-tropic, not evolving and often had defects in vpr . 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...