Transmission dynamics of the M184V drug resistance mutation in primary HIV infection.

OBJECTIVES: M184V in HIV-1 reverse transcriptase is among the most common mutations in patients failing antiretroviral therapy but is found only rarely in cases of transmitted drug resistance. METHODS: To investigate this apparent paradox, we developed an allele-specific real-time PCR (AS-PCR) assay to determine the transmission of M184V in newly infected individuals. RESULTS: M184V transmission may occur to a greater extent than previously thought. Persistence of M184V may commonly involve linkage to other drug resistance mutations. The presence of M184V as a single substitution in newly infected individuals was shown to wane over time, as a likely consequence of reversion and overgrowth by more fit wild-type viruses. CONCLUSIONS: The M184V mutation can be documented in newly infected individuals, and the alternative hypothesis that this substitution might impact on the ability of HIV to be transmitted is unfounded.