Broad, intense anti-human immunodeficiency virus (HIV) ex vivo CD8(+) responses in HIV type 1-infected patients: Comparison with anti-Epstein-Barr virus responses and changes during antiretroviral therapy

The ex vivo antiviral CD8(+) repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4(+) T-cell counts and virus lo ads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patien ts recognized many HIV peptides, with markedly high frequencies, in associa tion with all the HLA class I molecules tested. We found no correlation bet ween the intensity of anti-HIV CD8(+) responses and the CD4(+) counts or vi rus load, In contrast, the polyclonality of anti-HIV CD8(+) responses was p ositively correlated with the CD4(+) counts. The anti-EBV responses were si gnificantly less intense than the anti-HIV responses and were positively co rrelated with the CD4(+) counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8(+) resp onses in two patients with stable CD4(+) counts, while both antiviral respo nses decreased in two patients with obvious progression toward disease. Las t, highly active antiretroviral therapy induced marked decreases in the num ber of anti-HIV CD8(+) T cells, while the anti-EBV responses increased. The se findings emphasize the magnitude of the ex vivo HIV-specific CD8(+) resp onses at all stages of HIV infection and suggest that the CD8(+) hyperlymph ocytosis commonly observed in HIV infection is driven mainly by virus repli cation, through intense, continuous activation of HIV-specific CD8(+) T cel ls until ultimate progression toward disease. Nevertheless, highly polyclon al anti-HIV CD8(+) responses may be associated with a better clinical statu s. Our data also suggest that a decrease of anti-EBV CD8(+) responses may o ccur with depletion of CD4(+) T cells, but this could be restored by highly active antiretroviral treatment.