The Welsh region need a bonus point victory in Italy to keep their end of season play-off hopes alive.
Wales wing Williams still hasn’t recovered from a knee-injury he picked up in Wales’ Six Nations game against France while Byrne is also unavailable due to a knee injury.
Williams is expected to be fit for Wales’ first world cup warm-up game against the Barbarians on June 4th.
“Shane hasn’t made it,” said Holley
“We have tried but he just hasn’t made it for this week. If we are fortunate to make the play-offs, for whatever reason, then he maybe available for that.
“Lee has taken a bang on the knee and has a slight cartilage tear.
“That keeps him out for a couple of weeks but we don’t know the extent of that injury or whether he needs surgery yet.”
Former All Back Collins will miss the game due to a one game ban for three yellow cards in the Magners League this season.