Candidate human immunodeficiency virus (HIV)-1 vaccines that elicit cytotoxic T lymphocytes may modulate HIV infection, requiring a prototype evaluation to assess participants who become infected with HIV. Of 1497 participants in canarypox HIV-1 vaccine prime-boost trials, 28 (1.9%) acquired HIV-1 infection after vaccination. Median plasma HIV-1 RNA levels (vaccinees, 4.78 log10 copies/mL; placebo recipients, 4.27 log10 copies/mL) and CD4 cell counts (vaccinees, 552 cells/mm3; placebo recipients, 657 cells/mm3) before administration of antiretroviral therapy (ART) and time to a composite end point (plasma HIV-1 RNA level >55,000 copies/mL, CD4 cell count <350 cells/mm3, or initiation of ART) did not differ significantly between vaccinees and placebo recipients (P =.4, P =.1, and P =.7, respectively). Persons who acquire HIV-1 infection while enrolled in HIV-1 vaccine trials can be successfully followed after infection, to determine whether vaccines alter the course of HIV-1 infection.