A health care worker (HCW) was infected via needlestick with human immunodeficiency virus (HIV) type 1 from a subject with AIDS who harbored a zidovudine-resistant, syncytium-inducing (SI) HIV strain. The phenotypic characteristics of the HIV-1 isolates obtained from the HCW and markers of virus load were followed for 20 months. Although the HCW was initially infected with an SI strain, within 75 days of infection the isolate became non-SI and remained so for > or = 635 days. Even though the AIDS patient had a zidovudine-resistant virus, the HCW was infected with a zidovudine-sensitive virus. Plasma RNA levels peaked 20 days after infection, declined rapidly within 2 weeks, and remained stable for the duration of follow-up. Similarly, the HCW's CD4 lymphocyte count remained stable throughout the study. Thus, selection for non-SI and zidovudine-sensitive virus occurred in the HCW, who, after initial symptomatic infection associated with high levels of plasma HIV-1 RNA, developed low plasma RNA copy numbers and stable CD4 lymphocyte counts.