Question on how resistance works

[CircularNatural]

Hello everyone, thanks for this great community.
I'm new to all is this, got my diagnosis and started meds (generic Dovato) recently.
Got tested for resistances first and luckily inherited none.
I'm concerned about this aspect of treatment, though. My doubt is the following:
Once (and if) you develop resistance to say, drug X, does this mean that you will now be permanently resistant to this X drug?
Does the virus make reservoirs of this resistant variant so that you can no longer undo that, or if you manage to "kill all the resistant virus" in circulation with a drug that it is sensitive to, you may be able to once again use those drugs that were no longer being an option?
Hope my question is understandable, otherwise I will try to rephrase it

Best regards to all

[leatherman]

here's some info I posted a little while ago in another thread about resistance:

Resistance (HIV mutating to resist a medication) mainly happens from not taking enough meds properly. The amount of virus has to drop to low levels, but not be totally absent, for the virus to mutate against the drug. In other words, someone who takes meds a few days, then skips a few, then takes it for a few more days sets themselves to have the levels of meds dip too low and HIV mutating before bringing the levels back up. Completely stopping meds usually doesn't cause resistance because the level of meds continue to drop well past any level to effect HIV before the HIV can mutate.



I took this chart from a site about antibiotics and edited it a little bit, so please ignore any weirdness there at the 2nd dose. The thing to take away is that any time adherence falls below the point (the red dashed line) of keeping the med level high enough (at least 95% adherence or higher*), resistance becomes possible.

Thankfully, the meds of today are much more effective. With a longer half-life (the amount of time the med is at the right level in your system), these meds stay in our systems longer, making incidents of non-adherence (skipping a dose) less likely to allow HIV to mutate. This is what allows a greater leeway (2-4 hrs) around the timing of each day's dose, or not developing resistance when missing a single dose in a month.

here's a good write-up about resistance from the San Fran AIDS foundation
https://www.sfaf.org/collections/beta/heres-what-you-need-to-know-about-hiv-drug-resistance/
and more info from poz.com
https://www.poz.com/basics/hiv-basics/hiv-drug-resistance

however as to you exact question, it depends on the drug and the mutation. For example, take drug XYZ. When HIV mutates to resist it, it could cause mutation AB that blocks a receptor or it could mutate ST so the transcriptase process doesn't happen. Mutation AB might be the more likely mutation and your HIV might always be resistant to medication XYZ --- and sometimes it might make your HIV resistant to ALL meds in the same classification as XYZ, and that's really bad as it would limit the classes of medications you could take. Or you might have the less likely mutation ST which simply causes the HIV to reproduce defective HIV copies that can't reproduce. Once all this damaged HIV dies off, the med XYZ could work again.

as to the second part of your question, if you developed a resistance, you would be switched to a different regimen (remember, almost all HIV treatments include 3-4 medications, even if combined into one pill) that your HIV is not resistant to. Eventually the free-floating resistant HIV would naturally die off or would be killed off by the new medications; but that would not change the rest of the HIV from always knowing this resistance mutation. Also because HIV  "hides" in latent reservoirs (which sometime activate, and why we have to take meds everyday to keep fighting the constantly renewing supply of HIV in our systems), some HIV might always remember this resistance mutation.

in the beginning days of HIV treatment, there were fewer meds and they were not as effective as more modern meds. It was easier to miss a dose or two and develop resistance... quite often the more severe resistance situation, wiping out the usage of a whole class of meds. However these days, resistance is much harder to happen (unless you're just a terribly non-adherent patient); but if it does occur, there are  quite a number of regimen changes that could be made to still keep a patient on an effective regimen.

TBH unless you royally screw up your adherence (and in that case, if you're going to be that off-n-on with taking your meds, you might as well just stop, and stop wasting your time with playing at treatment), you should be able to continue using whatever your current regimen is until they cure HIV and resistance should never be an issue you have to deal with.

[CircularNatural]

Thanks for your detailed and clear explanation. I consider myself an organised person so it's unlikely that I will skip doses. The only chance would be that I have to stop due to my meds not be available for external reasons (I hope it never happens). It's clear to me that in such a scenario I should stop "cold turkey" and wait a while until I get them back, maybe even get a new resistance testing.
I contracted HIV using a condom, so to be honest I no longer consider improbable scenarios improbable. I hope I have better luck with not developing resistance 🙏
I'm on Dovato (2-drug regimen) which supposedly is considered a safe option (I will keep updated on how this works long-term).
I hope a more permanent cure arrives for all of us in the not-so-far future.

Take care and keep healthy.
Best regards to all!