COMMENTARY

What Doravirine Offers Patients With HIV

Paul E. Sax, MD

Disclosures

September 13, 2018

Hi. This is Dr Paul Sax from Brigham and Women's Hospital and Harvard Medical School.

Today I'd like to talk about a new HIV treatment that was just approved by the US Food and Drug Administration. I'm talking about doravirine. Doravirine is a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI), and it has several advantages over existing drugs in the class.

First, it has a novel resistance pathway, so it has activity versus, for example, K103N- or Y181C-containing viruses. Second, it has few drug-drug interactions. Third, it can be taken with or without food. And fourth, it has fewer central nervous system (CNS) side effects than efavirenz, which was demonstrated in a clinical trial.[1]

Why was the drug approved? The approval was based on the results of two pivotal phase 3 clinical trials.[1,2] In the first of these trials,[2] doravirine was compared with darunavir-ritonavir, both given in combination with either lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) or abacavir-3TC. In this clinical trial, the doravirine intervention was not inferior to ritonavir-darunavir at 48 weeks (primary endpoint), and at 96 weeks, it was superior, based largely on better tolerability.

The second clinical trial[1] was a bit different. It looked at a single-tablet formulation of doravirine TDF and 3TC, compared in a double-blind fashion with TDF-FTC efavirenz. In this study doravirine was found again to be noninferior overall to the TDF-FTC efavirenz arm, and also to have a better lipid profile and fewer CNS side effects. I should mention also that doravirine had a better lipid profile than darunavir-ritonavir.

You are probably thinking that it would be nice to find out how doravirine does in a head-to-head study versus an integrase-based regimen, but no such study has been done. That is obviously a knowledge gap with this particular agent.

However, the approval of doravirine and the approval of the single-tablet TDF-3TC doravirine treatment both offer new options to our patients that can be very useful. Why might that be? First, as you are aware, some patients don't tolerate integrase inhibitors, even though they are very effective and very well tolerated. Periodically, individuals have CNS or other side effects that make them unable to take drugs in this class. Second, it seems that doravirine has, in many ways, moved to the top of the NNRTI class, in that one doesn't have to worry (unlike with rilpivirine) about acid-reducing agents or taking it with food, or with efavirenz with the CNS side effects.

The third thing to mention is that the TDF-3TC doravirine single tablet is likely to have some pharmacoeconomic benefit because the other two components of the regimen are generic. Presumably, it will be priced very competitively.

That's a summary of some of the clinical trial data that we have on doravirine. Keep an eye out for it because it's likely to appear in your pharmacies very soon. Thanks very much for listening.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....