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

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 () or after being ART-suppressed (). Here, we examine mechanisms producing 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 .

CONCLUSIONS

Our results suggest that in individuals with , ART stopped virus replication, but large pools of long-lived, HIV-infected macrophage continued to produce virus. This is mechanistically distinct from produced by CD4+ T cell clones. In addition, defects in independently accumulation in macrophage-tropic lineages found in three participants, suggesting that may impact survival of, or virus production from, HIV-infected macrophage.