HIV-1 elite controllers maintain undetectable levels of viral replication in the absence of antiretroviral therapy, but their underlying immunological and virological characteristics may vary. Here, we used a whole-genome transcriptional profiling approach to characterize gene expression signatures of CD4 T cells from an unselected cohort of elite controllers. In the majority of elite controllers, transcriptional profiles were similar to HAART-treated patients, while being different from HIV-1 negative persons. Yet, a smaller proportion of elite controllers showed an opposite gene expression pattern that was indistinguishable from HIV-1 negative persons, but different from HAART-treated individuals. Elite controllers with this gene expression signature had significantly higher CD4 T cell counts, smaller levels of HIV-1-specific CD8+ T cell responses and tended to have lower residual HIV-1 viremia as determined by ultra-sensitive single-digit PCR, but did not differ from other elite controllers in terms of HLA class I alleles, age or sex. Thus, these data identify a specific subgroup of elite controllers whose clinical, immunological and gene expression characteristics approximate those of HIV-1 negative persons.

PBMC from study persons were stained with monoclonal antibodies against CD3, CD4 and HLA-DR, and subsequently subjected to live sorting at 70 psi using an ARIA cell sorting device (Becton Dickinson) located in a specifically designated biosafety cabinet. Following mRNA extraction form the sorted cells (RNAeasy kit, Qiagen), whole genome transcriptional profiling was performed using WG-DASL microarrays (Illumina) according to standard protocols. We included an unselected cohort of elite controllers (n = 12) and two background populations of HIV-1 negative persons (n = 9) and HIV-1 infected persons effectively treated with HAART (n = 14). Four replicates were included in the study.