Hilton found the end zone on a 75-yard punt return in the first quarter and the Colts (7-4) never trailed after that, winning for the fifth time in six games following a one-sided loss to New England last week.
Andrew Luck passed for 240 yards on 20-of-37 efficiency with one interception as Indianapolis remained without consecutive losses in the current season.
The Bills (4-7), meanwhile, fell for the fourth time in five games as Ryan Fitzpatrick was held to 180 yards on 17-of-33 passing.
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