ANTIVIRAL PRESSURE EXERTED BY HIV-1-SPECIFIC CYTOTOXIC T-LYMPHOCYTES (CTLS) DURING PRIMARY INFECTION DEMONSTRATED BY RAPID SELECTION OF CTLESCAPE VIRUS

The HIV-1-specific cytotoxic T lymphocyte (CTL) response is temporally associated with the decline in viremia during primary HIV-1 infection , but definitive evidence that it is of importance in virus containmen t has been lacking. Here we show that in a patient whose early CTL res ponse was focused on a highly immunodominant epitope in gp160, there w as rapid elimination of the transmitted virus strain and selection for a virus population bearing amino acid changes at a single residue wit hin this epitope, which conferred escape from recognition by epitope-s pecific CTL. The magnitude (>100-fold), kinetics (30-72 days from onse t of symptoms) and genetic pathways of virus escape from CTL pressure were comparable to virus escape from antiretroviral therapy, indicatin g the biological significance of the CTL response in vivo. One aim of HIV-1 vaccines should thus be to elicit strong CTL responses against m ultiple codominant viral epitopes.