Persistence of lamivudine-sensitive HIV-1 quasispecies in the presence of lamivudine in vitro and in vivo.

The establishment of persistent infection is one of the major obstacles facing the eradication of HIV-1. To improve our understanding of the mechanisms of viral persistence, we investigated the fate of defined viral quasispecies under conditions that might favor their eradication. We retrospectively analyzed changes in viral populations in HIV-1-infected patients treated with zidovudine/lamivudine and subsequently failing therapy within months in the years 1996 to 1997. Furthermore, we developed an in vitro model based on simultaneous infection of T cells with 2 or more different viral variants. Changes in minority quasispecies of drug-sensitive and drug-resistant HIV-1 variants based on lamivudine and the corresponding lamivudine-resistant viruses carrying the M184I or M184V mutation were investigated using an allele-specific real-time polymerase chain reaction assay. We demonstrate that lamivudine-sensitive and lamivudine-resistant HIV-1 variants are able to persist despite highly unfavorable conditions in vivo and in vitro and that selective advantages of viral variants can vary depending on the complexity of other simultaneously replicating viral variants.