CD4+ T cell targeting of human immunodeficiency virus type 1 (HIV-1) peptide sequences present in vivo during chronic, progressive HIV-1 disease

We previously detected HIV-1 Gag-specific CD4+ T cells recognizing reference strain viral epitopes in subjects with progressive, chronic infection. To test whether these CD4+ T cells persist in vivo by failing to recognize autologous HIV-1 epitopes, we compared autologous plasma HIV-1 p24 nucleotide sequences with targeted HXB.2 strain Gag p24 CD4+ T cell epitopes in nine chronically infected, untreated subjects. In five responding subjects, 10 of 26 HXB.2 strain p24 peptides targeted by CD4+ T cells exactly matched autologous plasma viral sequences. Four subjects with plasma viral loads > 100,000 copies/mL had no measurable p24-specific CD4+ T cell responses despite carrying HIV-1 strains that matched HXB.2 sequences at predicted epitopes. These results show that HIV-1-specific CD4+ T cells can persist in chronic HIV-1 infection despite recognition of epitopes present in vivo. However, with high-level in vivo HIV-1 replication, CD4+ T cells targeting autologous HIV-1 may be non-responsive or absent.