Longitudinal comparison of monocytes from an HIV viremic vs avirmeic state - GSE5220

Longitudinal analysis of monocyte gene expressions patterns before and after cessation of HAART: understanding the impact of HIV viremia on the monocyte tranascritome. We used microarrays to detail the global program of gene expression underlying defects in monocytes from HIV infected patients during viremia..

Diminished Production of Monocyte Proinflammatory Cytokines During HIV Viremia is Mediated by Interferon-alpha: The in vivo effect of high-level HIV replication on the function of monocytes was investigated. HIV-positive patients had elevated spontaneous production of monocyte proinflammatory cytokines (IL-1?, IL-6, and TNF-?) compared to uninfected controls. These levels were highest in patients on-therapy and was diminished, in the context of viremia, following an interruption of therapy. Diminished production of proinflammatory cytokines during viremia was restored by culturing with autologous CD4+ T cells or monocytes from an on-therapy time point, or by the addition of lipopolysaccharide (LPS). Microarray analysis demonstrated that diminished monocyte production of proinflammatory cytokines was correlated with elevated levels of type I interferon-stimulated gene transcripts. Addition of exogenous IFN-?2A suppressed the spontaneous production of IL-1?, IL-6, and TNF-? but did not affect responses to LPS, recapitulating the changes observed in HIV viremic patients. These results suggest that high-level HIV viremia inhibits monocyte function through chronic stimulation by IFN-?. This effect of viremia on monocytes may play a role in diminished adaptive immune system functions in HIV-infected patients. Restoration of these functions may contribute to the partial immune reconstitution observed following therapy and may be involved in immune reconstitution and inflammatory syndrome seen in some patients.

A longitudinal study was performed on 8 HIV infected individuals looking at gene expression changes in monocytes as a result of rebound of HIV viral load following termination of HAART: 8 patients pre and post HAART cessation.