Parenteral exposure to high HIV viremia leads to virus‐specific T cell priming without evidence of infection

AbstractPrevious studies on CTL responses in HIV‐exposed uninfected individuals assumed that the patients were exposed to replicating HIV, but the possibility that the immune responses detected were primed by exposure to a defective virus or viral antigen could not be excluded. Epidemiological and laboratory analysis of a nosocomial outbreak of acute hepatitis B unequivocally allowed the identification of an HIV‐1‐ and HBV‐co‐infected patient with high plasma levels of both viruses, as the source case of the epidemics. This clinical setting provided a natural model for testing the HIV‐specific T cell response in patients exposed to blood from a patient with highly replicating HIV. Parenteral exposure to both viruses led to acute hepatitis B in five subjects without evidence of HIV‐1 infection. Cryopreserved lymphocytes derived from three exposed patients were tested ex vivo in an ELISPOT assay for IFN‐γ release upon stimulation with peptides from structural and non‐structural HIV proteins; one of the patients was also tested with four HLA/class I tetramers. Circulating HIV‐specific CD8 cells were detected by tetramer staining and a high frequency of T cells were able to release IFN‐γ upon stimulation with HIV peptides, showing in vivo T cell priming by HIV. These results unequivocally demonstrate a HIV‐specific cell‐mediated immune response in the absence of infection after exposure to highly replicating HIV.