Based on HIV-1 breakthrough infections in the RV144 trial sequenced at the time of HIV-1 diagnosis, a sieve analysis that focused on the V1/V2 region of Env identified two sites in the V2 loop (HXB2 amino acids Env 169 and 181) at which the level of efficacy of the vaccine significantly differed depending on whether the genome of the infecting HIV-1 virus matched the vaccine immunogen sequence at the site [7]. Here, ERVW-1 is linked to infection.