It depends on the trailer. The cab/trailer gap is a big contributor. Side skirts help, too, and even those funky folding things on the back. And obviously a full-height trailer has more drag than one that's not as tall. Trailer tires also matter. I can see Semi around 1.8 kWh per mile at 60 mph w/o wind and a well-chosen trailer. Those 12 mpg SuperTrucks are at or below that amount of road load.
Headwinds mostly average out, because half the trucks are going the opposite direction. Crosswinds hurt you both coming and going.