BMS-626529 is a new antiretroviral of the entry inhibitors class. It inhibits attachment of the virus through interaction with the HIV-1 envelope glycoprotein gp120, blocking binding between gp120 and CD4 receptor, thereby avoiding viral entry into target cells. The drug is administered as an oral phosphonooxymethyl prodrug, BMS-663068. In phase 1 study, after 8 days of monotherpay, there was a very high variability in plasma HIV-1 RNA decrease, the maximum decrease being 1.46 log10 copies/ml. This variable response is only related to a high variation in in vitro susceptibility of HIV-1 isolates to BMS-626529. Virologic response is not affected by co-recptor tropism, antiretroviral treatment experience, nor plasma HIV- 1 RNA level or CD4 cells count. In vitro selection study have shown that the M426L gp120 primary substitution was the one associated with non response to BMS-663068. After 8 days of BMS-663068 monotherapy, there was no emergence of resistance to BMS-626529 by standard genotypic and phenotypic sequencing.