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To investigate the origin and spatiotemporal dynamics of dissemination of the HIV-1 CRF06_cpx clade in western Africa.A total of 180 HIV-1 CRF06_cpx-like pol sequences isolated from 12 different countries from west and west-central Africa over a period of 16 years (1995–2010) were analyzed.Evolutionary, phylogeographic and demographic parameters were jointly estimated from sequence data using a Bayesian coalescent-based method and combined with molecular epidemiology and spatial accessibility data.The CRF06_cpx most probably emerged in Burkina Faso in 1979 (1970–1985). From Burkina Faso, the virus was first disseminated to Mali and Nigeria during the 1980s and later to other countries from west and west-central Africa. Demographic reconstruction indicates that the CRF06_cpx epidemic grew exponentially during the 1980s, with a median growth rate of 0.82 year−1 (0.60–1.09 year−1), and after stabilize. We found a negative correlation between CRF06_cpx prevalence and the geographical distance to Burkina Faso's capital. Regional accessibility information agrees with the overall geographical range of the CRF06_cpx, but not fully explains the highly heterogeneous distribution pattern of this CRF at regional level.The CRF06_cpx epidemic in western Africa probably emerged at the late 1970s and grew during the 1980s at a rate comparable to the HIV-1 epidemics in the United States and Europe. Burkina Faso seems to be the most important epicenter of dissemination of the HIV-1 CRF06_cpx strain at regional level. The explanation for the current geographical distribution of CRF06_cpx is probably multifactorial.