Signature genes associated with immunological non-responsiveness to anti-retroviral therapy in HIV-1 subtype-c infection

Objective HIV-infected individuals undergoing therapy may show an immunological-discordant response to therapy, with poor CD4 + T cells recovery, despite viral suppression below the detection limit. The present study was carried out to delineate the underlying molecular mechanisms of immunological non-responsiveness to HIV therapy. Design We conducted microarray-based whole gene expression profiles of 30 subjects infected with HIV-1 subtype C, in peripheral blood to discern the signature genes associated with immunological non-responsiveness. After a thorough analysis and comparison of gene-expression profiles, microarray data was validated via qRT-PCR approach. Results Overall, we found 10 genes significantly up-regulated and 60 genes down-regulated (≥2-fold change) in immunological non-responders as compared to responders. Based on these results and pathway analysis of the protein-protein interaction, 20 genes were shortlisted for validation in human infected cases. We found statistically significant differences in expression levels of twelve genes IL-1α , IL-1β , IL-7R , TNF-α , FoxP3 , PDCD5 , COX7B , SOCS1 , SOCS3 , RPL9 , RPL23 , and LRRN3 respectively among immunological non-responders compared to therapy responders, confirming their an intimate relationship with immunological responsiveness to therapy. Conclusions Altogether, microarray and qRT-PCR validation results indicated that the aberrant expression of key genes involved in the regulation of T cell homeostasis, immune activation, inflammatory cytokine production, apoptosis, and immune-regulatory processes are possibly associated with immunological non-responsiveness in HIV-1 C infected individuals on ART.