Emmanuel Guevara led team-mate Daniel Diaz by 17 seconds on the uphill finish at La Carolina, a climb which began 17km from the line.
That sees Diaz take control of the race, with overnight leader Michal Kwiatkowski (Omega Pharma-Quick Step) falling out of the top 10 following the 169.8km run from Juana Koslay.
BMC rider Tejay van Garderen is 17 seconds off the leader's pace with stage three winner Alex Diniz at 39 seconds.
The climbers will again dominate on stage six, which finishes at the summir of the Cat.1 Mirador del Sol.
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