Antiretroviral drug therapy alters the profile of human immunodeficiency virus type 1-specific T-cell responses and shifts the immunodominant cytotoxic T-lymphocyte response from Gag to Pol

Abstract

Antiretroviral drug therapy and cytotoxic T lymphocytes (CTL) both exert selective pressures on human immunodeficiency virus type 1, which influence viral evolution. Compared to chronically infected, antiretroviral-untreated patients, most chronically infected, treated patients with detectable viremia lack a cellular immune response against the Gag 77-85(SL9) epitope but show a new immunodominant response against an epitope in protease PR 76-84. Hence, mutations induced by antiretroviral therapy likely alter the profile of epitopes presented to T cells and thus the direction of the response. The consequences of dual pressures from treatment and CTL need to be considered in monitoring of drug therapy.

FIG. 1.

Antiviral treatment alters the distribution of epitope recognition. Most chronically infected, antiretroviral-treated patients have gained a response targeting an epitope, which is under strong protease inhibitor-mediated drug pressure (PR 77-85). In contrast to the untreated chronically infected subjects, the treated individuals generally lack responses against the SL9 epitope. A sample was considered positive when the responses were at least two times the experimental background and above 0.05% IFN-γ- and TNF-α-positive CD8⁺ CD4⁻ CD3⁺ T cells. *, P < 0.01 (Fisher's exact test).