To examine the possibility that transmitted/early HIV-1 strains with altered function could be inadvertently selected by antiretroviral-based microbicide prophylaxis, we assessed plasma RNA gag-protease and nef sequence and function for the earliest available time points (median 5 weeks following estimated date of infection) from participants who acquired infection during the CAPRISA 004 1% tenofovir gel microbicide trial [1]. This evidence concerns the gene S100B and infection.