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Switching to dual therapy

Mar 11, 2017

Hi Dr Young

I am a 39 year old man from the UK and have been positive since 2006. I have been on therapy since 2009, starting with a combination of nevirapine and truvada. Unfortunately this combination failed to reduce my viral load to undetectable so I switched to maraviroc, 3tc, darunavir and ritonavir - a rather unconventional combination but one that did allow me to achieve undetectable status.

My doctor decided in June 2015 to switch me on to Triumeq, largely because he feels that dolutegravir is a superior integrase inhibitor but also because it would reduce my pill burden. After following my own research into current clinical trials, I came across the recent trail concerning dual therapy with just dolutegravir and Lamivudine (Lamidol) The results are impressive (97% viral suppression at 48 weeks) and therefore I have just today had a discussion with my doctor about changing my regimen, effectively knocking out Abacavir and taking dolutegravir and Lamivudine as dual therapy. My motivation for this is quite simple - if I can maintain an undetectable viral load with less drugs in my body then surely this is a sensible and wise route to go down, knowing that it is likely I will have many years of dosing ahead of me!

I am due to start the switch tomorrow (March 10th) and my viral load will be closely monitored over the next three months. I would really appreciate your view on this and if you have any strong feelings either way on dual therapy.

Regards

Daniel

Response from Dr. Young

Hello and thanks for posting from the UK.

Two-drug therapy is a very promising yet experimental approach to HIV therapy. Two drugs could lower risk of toxicity and side effects, and theoretically lower costs of medication.

While the dataset is growing and encouraging, it's limited in the regimens (most use dolutegravir), and the only powered studies (called SWORD -1 and -2) were restricted to individuals without prior history of treatment failure or drug resistance who had lengthy viral suppression before switching to dolutegravir with the non-nuke ripivirine. (Details of the study results were previously posted on TheBodyPro. It's anticipated that dolutegravir+rilpivirine will soon be available as a single pill combination that (because of rilpivirine) needs to be taken with food.

Two-drug regimens with dolutegravir and 3TC (sometimes called D3) have been generated a lot of interest because of the excellent tolerability of both drugs and (potentially), the availability of generic 3TC, limited drug-drug interactions and lack of dietary requirements. Several pilot studies have indeed shown impressive initial results, including the Argentine 40 patient treatment-naive PADDLE study and the French 110 patient switch Lamidol study. The Lamidol study also excluded individuals with previous drug resistance.

Based on the affirmative results of these pilot, early phase studies, several large phase 3 clinical trials of D3 are now under way, including several sponsored by ViiV Healthcare (the makers of dolutegravir and lamivudine), and a large NIH-sponsored ACTG study. It will likely take an additional 1-2 years before the main results of these studies will be presented.

Until then, I would not view D3 as a proven or recommended treatment for the general population of people living with HIV, nor for people who are living with drug-resistant virus. As such, I would currently recommend that two-drug therapy be restricted to people who don't have drug resistant virus, or have specific reasons where current 3-drug treatment poses significant problems (with tolerability or toxicity).

In your case, and in my opinion, because your virus might indeed harbor drug resistance, and because you're already tolerating Triumeq (dolutegravir+lamivudine+abacavir) without issues, I'd be reluctant to recommend switching from a well-tolerated, well-proven regimen to the experimental D3, unless it was in the confines of a scientifically- and ethically-monitored clinical trial.

I hope that this is helpful, and stay in touch, BY



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