Time to Rethink Renal Dosing of Lamivudine?

Paul E. Sax, MD


November 18, 2019

This transcript has been edited for clarity.

Hello. This is Dr Paul Sax from Brigham and Women's Hospital and Harvard Medical School. Today I'd like to discuss renal dosing of lamivudine (3TC). This topic has recently become more important because of the results of the GEMINI and TANGO studies of the dolutegravir-lamivudine two-drug combination, where in initial therapy for GEMINI and switch therapy for TANGO, it was shown to be noninferior to triple therapy.

Why is renal dosing important? There will be people in whom you don't want to use tenofovir or abacavir. These are often older patients with renal comorbidities, who are exactly the sort of people in whom you would want to potentially use dolutegravir-lamivudine as a strategy.

I want to highlight a recent paper published in HIV Medicine, where 52 virologically stable patients (median age of 60 years) received the two-drug regimen of dolutegravir-lamivudine. The package insert recommends that the 300-mg dose be reduced when the creatinine clearance is < 50 mL/min. Many of the people in this study with creatinine clearance between 30 and 49 mL/min were dose-reduced to 150 mg daily.

Given the safety and tolerability of lamivudine, one might wonder whether such a dose reduction is actually required. And here I'd like to point out a different study. This was a 2018 paper published in Open Forum Infectious Diseases of 34 patients with impaired renal function who did not undergo the dose reductions that were required. Not surprisingly, the investigators found that they had higher levels of lamivudine because they did not excrete it as rapidly, but there were no significant toxicities associated with this. People whose creatinine clearance was between 30 and 49 mL/min received the full dose without any problems.

What do these studies mean for us clinicians? For the patient population in whom we probably want to use this two-drug combination the most—people with both renal and cardiovascular comorbidities—it is likely safe to go ahead and use the full dose of lamivudine, 300 mg daily, even in people who have a creatinine clearance between 30 and 49 mL/min. That's important because the coformulated tablet has 300 mg of lamivudine.

Recently I posed this question on Twitter, particularly to infectious diseases pharmacists, and there was essentially unanimity among them that dose reduction for creatinine clearance between 30 and 49 mL/min was not necessary. This is based not just on the study I cited but also on lots of clinical experience.

To summarize, I think that lamivudine is so safe that we can go ahead and not dose-reduce for people with mild to moderate impairment of renal function. I hope the package insert will eventually change so that this can become an official recommendation.

And I have one more question for you: Why is lamivudine abbreviated as 3TC? It's a mystery. See if you can figure it out and put it in the comments. Thanks very much.

Paul E. Sax, MD, is a professor of medicine at Harvard Medical School and clinical director of the division of infectious diseases at Brigham and Women's Hospital. His research interests include antiretroviral therapies, the cost-effectiveness of HIV management strategies, and complications of antiretroviral treatment. He blogs at HIV and ID Observations and has been a Medscape contributor since 2008.

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