[Genetic barrier to antiretroviral drug-resistance. Focus on raltegravir, the first integrase inhibitor].

The genetic barrier for the antiretroviral describes the ability to select resistant viruses to this antiretroviral when the viral replication is not controlled. This includes combining several concepts: (1) the number of nucleotide changes required for a resistance mutation, (2) the impact of this mutation on the level of susceptibility to antiretroviral (3) the impact of this mutation on viral replication capacity; all theses conditions influencing the level of resistant variants. The antiretroviral concentration impact also the emergence of resistance. Finally, combine with other molecules, the selection of resistance mutations ton an antiretroviral may differ from one treatment to another. It is recognized that the genetic barrier to lamivudine/emtricitabine, efavirenz and nevirapine is low, and is intermediate for nucleoside such as zidovudine and tenofovir. However, ritonavir boosted protease inhibitor with high plasma concentration have a high genetic barrier. For integrase inhibitors such as raltegravir, the emergence of resistance is certainly faster than the ritonavir boosted protease inhibitors, but seems slower and less systematic than for efavirenz or lamivudine. Many factors could influence the raltegravir resistance such as the level of viral load and replication duration, genetic polymorphism of HIV (integrase gene and other, viral subtype) and the plasma and/or intra- cellular raltegravir concentration.