Transmission of drug-resistant HIV-1 variants has been increasingly documented. The most commonly observed resistance-associated mutations are thymidine analogue mutations as well as non-nucleoside reverse transcriptase inhibitor mutations. We report on a case of secondary transmission of a protease inhibitor (PI) primary mutation from an infected untreated subject to his sexual partner. Sequences isolated from the 2 patients showed a high level of identity (>99%), both carrying the major IAS PI mutation M46I. The latter mutation persisted in the bloodstream of the female partner 1 year after its first detection.