The main downside is that you won't be a medical student. If you want to be a clinician and pursue a PhD, it is likely you will regret your decision. Do you plan to pursue an MD after this? If so, your training will be longer, not be fully funded, and you will have more years off between PhD and re-initiating research.
Another option you did not list would be to apply MD to additional programs (or simply to many more MD/PhD programs). You could then do a straight MD (possibly with a year off for research) and pursue research during/after residency, which is what MD/PhD's will do anyways who want to stay in research. You also have the possibility to apply for the PhD internally during M1/M2.
If you really want training at places with big names, do it during fellowship/post-doc. Where you pursue PhD training has less bearing than who you train with. Don't limit yourself to top PhD places over similarly good MD/PhD programs. I would have chosen an MD/PhD at all MSTP's and most MD/PhD programs over a #1 PhD program in a heartbeat, and I assume most current/former MD/PhD students would at least agree with the sentiment (at least those who intend to practice medicine).
I have personally seen top MD/PhD applicants rejected everywhere because of the sole focus on top PhD training, which IMO is short-sighted. You can get excellent training at many places- and when the top lab/institution matters most is during post-doc.
If you have no interviews by November and you are a reasonably competitive applicant, suck it up, improve your application, and apply MD/PhD again next year. (If you applied late, some programs continue to extend interview invites into February).