Several reports have attempted to correlate Nef sequence polymorphisms with clinical outcome [12,13], with mixed results; however, relatively few studies have assessed potential functional impairment of Nef in the context of progressive or non-progressive HIV-1 infection using patient-derived sequences [14,15,16,17], and each of these reports examined only a small number of individuals. The gene discussed is S100B; the disease is HIV-1 infection.