slower replication speed, more difficulty infecting the host, requirement of much greater volume of replication to accomplish the same rate of infection.
think of it this way: every cool feature you add to a living thing has an overhead.
you want your little bacteria to have antibiotic resistance? fine.
but it'll need that much more energy to grow relative to the bacteria which don't have the added burden.
this means that unless there's the selective pressure of antibiotics in the environment, your little antibiotic resistant microbe won't stand a chance -- it's a fraction less efficient under normal conditions, so it's effectively out-competed when in the wild.
as far as massive adaptations like airborne spreading, that's not something that can just mutate overnight. HIV is fragile, so you'd need to engineer an entirely new viral envelope, or, more likely, an entirely new carrier particle that the virus can reconstruct on its own without impacting its infectivity. viruses like the flu have these adaptations by default. but once again, if you decide to turn the flu into HIV, it's going to be at a disadvantage in the wild.
not to say that it is impossible to make virions which are able to out-compete their wild-type cousins when infecting hosts in the real world. far from it. it's just not as easy to make it work as a quick look might find.