Questions about switching to dovato and probability of drug resistance

[frederick]

Hello guys. Would appreciate your inputs about my concerns. I'm planning to switch from my current drug regimen (Tenofovir DF, Lamivudine and Efavirenz) to Dolutegravir + Lamivudine (DOVATO) because of kidney issues.. I have the following questions:

1.) Is there a risk that I might not be able to go back to using tenofovir (TAF / TDF) and efavirenz in the future because of drug resistance? My ID says that there's a possibility but I've been reading that as long as one stays virologically suppressed then drug resistance is not possible.. Which one is true?

2.) I read that dovato should not be used with sorbitol and some other sugar alcohols since it can decrease the absorption of lamivudine. Does anyone know if this applies to erythritol as well?

3.) I'm taking my current regimen at 2am and plan to take dovato much earlier in the afternoon (say 2pm) since I read that it might cause insomnia for some. Would it be ok to take dovato 36 hours (instead of the usual 24 hours) after taking my current regimen? I'm thinking it should be fine but I just wanna be sure..

[Matths]

Hi Frederick, I have been taking Dovato since it came to market in the US and have been UD since then (with 100% compliance). I like the idea of fewer drugs achieving the same outcome as triple drug regimens which was my primary motivation at the time.

To answer your questions:

Ad 1) just recently there was a paper published showing that Dovato is as effective as triple therapy in suppressed patients. Here is the link: https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00100-4/fulltext?dgcid=raven_jbs_etoc_email

In your case being suppressed you will continue lamivudine with its excellent track record, plus dolutegravir with its high barrier to resistance. Assuming you have no resistance to the INSTI class you will be fine. In the unlikely event that Dovato doesn’t work for you, and given that you are concerned about kidney function, there are other options out there that are easy on the kidneys and work to keep you UD. But in my opinion, the switch to Dovato should result in a treatment with higher barrier to resistance than you already have and therefore should work very well.

Ad 3) given the half life time of the drugs you have been taking and the new regime, and therefore the assumption that the “old” drugs are at steady-state, you should be fine when doing the actual switch. I for myself take Dovato first thing in the morning always 24 hours apart and it works for me. I do it simply to not forget because middle of the day is usually busy and I may forget. But in any case, always take it at the same time whatever time works best for you.

Ad 2) I checked on the pharmacology of sugar alcohol and as long as you don’t take exorbitant amounts which cause diarrhea I don’t see a reason why this could interfere with the absorption of lamivudine or any other drug.

Hope this is helpful, best Matt

[leatherman]

as long as one stays virologically suppressed then drug resistance is not possible

resistance can develop when the amount of medication falls below the optimal level to keep the virus suppressed. Normally we take daily meds, which keeps the level of medication high enough to stop HIV from replicating. As we have reservoirs of HIV in our system which can occasionally activate, daily meds keep suppressing this HIV from gaining a foothold.

If however a person falls below 95% adherence, but continues to take some meds, the med level drops too low to be effective. Imagine someone simply stopping meds. At some point there aren't enough medications in their system to suppress HIV and it can once again begin to flourish. Most of the time, this doesn't result in resistance. However imagine someone skipping a day here, a couple days there, and that's where problems begin. With no meds HIV can flourish; but with some meds in their system, but at too low a level to be effective, HIV can mutate against the meds. That's resistance. From then on, even if the patient goes back to being 100% adherent, HIV isn't suppressed by that med anymore.

Changing meds, by going from successful adherence to one set of meds (resulting in undetectable) and switching to another regimen of meds (that one does not have resistance to) does not cause resistance because the level of meds in your system does not fall too low, but remains high enough to suppress HIV during the change.