A long-term follow-up of an HIV type 1-infected patient reveals a coincidence of Nef-directed cytotoxic T lymphocyte effectors and high incidence of epitope-deleted variants

Cytotoxic T lymphocytes (CTL) play a critical role in controlling human imm unodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) infec tions. However, in spite of developing a strong CTL response most HIV-1-inf ected patients eventually progress to AIDS. Amino acid changes in CTL epito pe have been previously described and may permit HIV to escape from CTL imm une responses. The importance of CTL selection pressure in controlling the course of viral evolution in HIV-infected patient remains debatable. For ov er a 10-year period, we longitudinally followed a patient for bulk unstimul ated effector (eCTL) and stimulated memory CTL responses (mCTL) against the viral proteins Gag, Pol, and Nef. The patient showed a strong CTL response against Nef in unstimulated peripheral blood mononuclear cells with a peak during Month 40 of the follow-up. The mCTL response was also higher agains t Nef than Gag and Pol. PCR amplification and nucleotide sequencing of the plasma viral variants showed a viral variant with the epitope deletion that was detected early during the follow-up and essentially replaced the wild- type virus during the peak eCTL response. These studies support the importa nce of Nef epitope deletion as a mechanism for HIV-1 escape from CTL immune pressure.