UK switch to dolutegravir: do I still need 3TC/FTC or even 3 drugs?
Hi, I have been on Atripla for 7 years with an undetectable VL since soon after I started. According to my initial resistance test, I am resistant to both 3TC and FTC with the M184V mutation. I am also “susceptible” to abacavir, though it did not produce a “maximum response” on the original resistance test.
Currently, I still have full viral suppression, and never experienced any blips or serious side effects from Atripla. I am new to the UK and my new doctor recommended switching to TDF + FTC + dolutegravir to benefit from DTG’s benefits as a new drug, reduce the side effects of EFV, and prevent possible long term resistance.
My question is, given my resistance to 3TC/FTC, and the new research showing dolutegravir’s benefits and possible use in dual (or even mono) -therapies: why not just go for a dual therapy of TDF + dolutegravir?
Are there any benefits to keeping the FTC in the mix for someone who is resistant to it anyway?
Thanks for your question.
This example is really helpful to be able to post online – especially as this is in the UK where widespread access to some drugs is limited due to cost.
The first point is that your doctor is giving you particularly good care. You are being offered options that are not routinely available in some guidelines – but this is definitely a good thing for you.
The switch to dolutegravir might easily be better – even though you say you don’t currently have problems with side effects. Many people only become aware of side effects after switching.
Also, you are not being switched for cost. Changing to generic efavirenz would be much cheaper. Also, using dolutegravir with abacavir (with or without 3TC) would also cost less than using TDF/FTC. Your doctor might have other reasons for recommending TDF/FTC.
Your other questions are also important.
M184V resistance is a special mutation. Although it generates high level resistance to 3TC/FTC, it is still an active drug. This is because this mutation makes HIV less fit – much less HIV is produced.
Also, unlike most other mutations, continuing to take a drug doesn’t lead to more complicated patterns of mutations. Once you have M184V, it doesn’t seem linked to further resistance. It does seem to help by reducing the ability of HIV to replicate.
As 3TC and FTC have such low risks of side effects, continuing to use them is generally a good idea.
Your question about needing to use two, one or even on other drugs with dolutegravir is also very current.
Although several studies reported interesting and impressive results without any other drugs, it is too early to be trying this yet. Continuing to use dolutegravir with two other drugs is still recommended – especially as you can still use these other drugs. If you couldn’t use both abacavir and tenofovir DF for other reasons, this might be a reason to use dolutegravir just with either 3TC or FTC.
A large study looking at the two-drug conbimation of doulteravir + 3TC is already ongoing. The comparison group is using dolutegravir + TDF/FTC – so this study might find that TDF is not needed – but we need to see these results.
Although there have not been any studies looking at just dolutegravir + TDF, intuitively, this might be similar to dolutegravir + 3TC, but the side effect profile would be different.