Incomplete functional T-cell reconstitution in immunological non-responders at one year after initiation of antiretroviral therapy possibly predisposes them to infectious diseases

摘要

Background Immunological non-responders (INR) represent a unique category of HIV-infected patients on antiretroviral therapy. These patients have suppressed viremia but a suboptimal increase in CD4 cell count, which might have opposing effects on functional immune reconstitution. Hence, the extent of immune reconstitution in INR patients was investigated in order to determine their susceptibility to opportunistic infections. Methods Twenty-three INR patients (CD4 increase 50 cells/mmsup3/sup, viral load 40 copies/ml), 40 age-, sex-, and baseline CD4 count-matched responders (CD4 increase 100 cells/mmsup3/sup, viral load 40 copies/ml), and 18 treatment failures defined as per the national guidelines were enrolled at 1?year of antiretroviral therapy. The following examinations were performed: haemogram, phenotypic characterization by flow cytometry, and assessment of functional immune status by ELISPOT and intracellular cytokine assays. Results A higher percentage of INR patients had clinically symptomatic infections than the responders. CD8sup+/sup activation and innate immune parameters, including the absolute neutrophil count and natural killer (NK) cell frequency and functionality, were restored in the INR patients. They had significantly higher non-HIV antigen-specific T-cell responses and activated CD4sup+/sup cells, but significantly compromised T-cell functionality, as assessed after anti-CD3 stimulation, and lower CD31sup+/sup and CD62Lsup+/supCD4sup+/sup cells. Conclusions INR patients showed lower thymic output, incomplete functional T-cell reconstitution, higher responses to HIV co-pathogens, and higher symptomatic events, indicating the need for close monitoring and intervention strategies to overcome their continuing immunocompromised status.