To determine the interaction between response to PR inhibitor therapy and development of drug resistance in PR, we selected three children for detailed genetic analysis of HIV-1 PR before and during therapy with PR inhibitors. The children were representative of each response group to the Phase 1/11 studies of ritonavir or indinavir (Fig. 5). Patient A was a 14-year-old hemophiliac (Centers for Disease Control [CDC] stage A3) who responded to ritonavir therapy with sustained suppression of plasma virus below the levels of detection for almost 1 year and an increase of about 200 CD4 T cells (Fig. 5A). Patient B was a 6.7-year-old, CDC stage C3 child who was infected by maternal transmission. Patient B had a 2 log increase in CD4 T cells over the course of 1 year of ritonavir therapy, but displayed only a transient decline in virus levels (Fig. 5B). Patient D was a 14-year-old, peri-natally infected adolescent with advanced disease (CDC C3) who experienced no sustained increase in CD4 T cells or suppression of virus levels (Fig. 5C).
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