Alternately, what if homo erectus is able to make it to the Americas, giving the megafauna exposure to a less advanced hominid to adapt to before modern humans arrive??
There is one piece of evidence that hints at homo genus habitation in California ~150kya. Perhaps a Denisovan tribe came over, or maybe it was an early Human tribe if it was legitmate. These Denisovans were pretty big, I napkin-calculated them to 8ft off of a molar. There are American legends of very tall redheaded people, maybe we suppose these giant people domesticated select megafauna to build the megalithic base layer found at many archaeological sites in the Andes.
Maybe we can consider the Solutreans, and if they are accepted then the stress of the Younger Dryas could be supposed to cause a nucleus of civilization to develop, and their animal husbandry saves a portion of the megafauna. These Solutreans could dominate the Atlantic and Gulf of Mexico watersheds of North America, while Beringians the Pacific watershed of North America and some portion of the Caribbean and South America. Depending on the levels of development you subscribe to the Solutreans descendent people could have had Transatlantic trade. This would then mean more numerous worldwide plagues, but less severe consequences when the age of sail really knits the world together.
There were some really neat South American megafauna in recent geological history, but they died out from the Columbian Interchange before this takes place regrettably... and since geologic PODs are ASB that means no six fingered, long skulled Denisovan giants using leashed terrorbirds as hunting dogs... while riding on Gompotheres :-(