Dynamics of HIV variants and specific cytotoxic T-cell recognition in nonprogressors and progressors

Infection with the human immunodeficiency virus (HIV) results in a disease characterized by a rapid viral replication, immunodeficiency and chronic immune activation. The vigorous polyspecific cytotoxic T-cell (CTL) response directed against multiple HIV epitopes reduces HIV-infected cell numbers, although unable to eradicate the virus. The plasticity of the specific CTL repertoire ensures adaptation to the high rate of viral variation that can be found in CTL epitopes of several HIV-1 proteins. However, viral persistence occurs despite continous CTL recognition and although functional importance of conserved sites in the different HIV proteins may impose constraints to viral variation. In the reverse transcriptase (RT) which is a major target for antiretroviral therapy, the impact of the continous pressure of drug therapy is more obvious than that of the CTLs. Shifts in immunodominant RT regions seem to allow the maintenance of the HIV-1 RT CTL recognition with disease progression and antiretroviral therapy. In respect to new highly active drug combinations, understanding the capacity of virus-specific CTLs to control residual viral variants seems very important and may allow development of efficient immunotherapies to prevent drug-induced viral resistance. (C) 1997 Elsevier Science B.V.