The diversity of HIV-1 and human genetics complicates our ability to determine the impact of treatment during primary HIV-1 infection on disease outcome. Here, we show, in a small group infected with virtually identical HIV-1 strains and treated during primary HIV-1 infection, that patients expressing protective human leucocyte antigen alleles had lower viral loads following treatment discontinuation. These data suggest that genetic factors play an important role in the outcome of HIV-1 infection despite early therapy.