Weak anti-HIV CD8(+) T-cell effector activity in HIV primary infection

HIV-specific CD8(+) T cells play a major role in the control of virus durin g HIV primary infection (PI) but do not completely prevent viral replicatio n. We used IFN-gamma enzyme-linked immunospot assay and intracellular stain ing to characterize the ex vivo CD8(+) T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV- specific responses in 71% of subjects. Gag and Nef peptides were more frequ ently recognized than Env and Pol peptides. The number of peptides recogniz ed was low (median 2, range 0-6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were respo nders with a median of 5 peptides recognized (range 1-13). The frequency of HIV-specific CD8(+) T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8(+)CD 28(-) terminally differentiated T cells was much lower in PI than at the ch ronic stage of infection. The weakness of the immune response during HN PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establi shing the goals for effective vaccination.