Ace! That's exactly what I was missing. I had tried \G without success but hadn't thought to put it in an alternation. Adapting your solution to use a look-behind so that I'm not replacing something with itself gives us

#!/usr/local/bin/perl -l
#
use strict;
use warnings;

$_ = q{DFR7234C__A_B_C_Bonzo_Dog_D_B};
print;

s{(?:(?<=__)|\G)[A-Z]_}{}g;

print;
[download]

which produces the desired

DFR7234C__A_B_C_Bonzo_Dog_D_B
DFR7234C__Bonzo_Dog_D_B
[download]

Your solution doesn't require any messing about with pos() which is a plus, but I am still wondering whether such tinkering is possible.

Thank you,

JohnGG