Derdeyn CA, Kilby JM, Miralles GD, Sfakianos G, Saag M, Hockett RD, Bucy RP; University of Alabama, Birmingham.
Combination antiretroviral therapy given to Human Immunodeficiency Virus type 1 (HIV-1) infected patients can result in sustained suppression of viral replication. However, recent studies have shown that a reservoir of latently infected T cells exists. We investigated whether a population of transcriptionally active cells is also present in vivo despite effective viral suppression. We distinguished between transcriptionally active and latently infected cells using a novel in situ hybridization approach to detect viral RNA before and after in vitro T cell activation. Here we show that two distinct populations of infected cells (inducible and transcriptionally active) were detected in peripheral blood mononuclear cells (PBMC) from HIV-1 infected subjects with active in vivo viral replication or effective viral suppression. The frequencies of these two cell populations were correlated with the plasma viral load of the subject. However, neither the transcriptionally active cell frequency nor the inducible cell frequency decreased with increased duration of viral suppression. In addition, a approximate 2 log10 excess of total vDNA compared to the frequency of latently infected cells was observed. Finally, the frequency of transcriptionally active cells after in vitro activation was highly correlated with the frequency of cells that could produce infectious virus in a coculture assay. Thus, we report for the first time the detection of an infectious cell reservoir in PBMC from HIV-1 infected subjects undergoing effective antiretroviral therapy that includes both latent and transcriptionally active infected cells.
Keywords: AEGIS, HIV-1, RNA, Viral, Viral Load, Virus Replication, Anti-HIV Agents, Transcription, Genetic, HIV Protease Inhibitors, Reverse Transcriptase Inhibitors, In Situ Hybridization, Human, in vitro, therapy, virology, genetics, drug therapy, AIDS
