Dolutegravir: A New Option in HIV Therapy

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

Today I would like to discuss the latest approved antiretroviral agent, which is dolutegravir. Dolutegravir is a once-daily integrase inhibitor, and it has been studied in several phase 3 clinical trials; two of these were in treatment-naive patients and showed that dolutegravir was extremely active and very well tolerated. Let me give you a bit more detail.

In one of the studies,^[1] dolutegravir was compared with raltegravir along with nucleosides of choice, and it was clearly just as effective, meeting noninferiority criteria, and was also extremely well tolerated. In the second study,^[2] which had a novel design, the combination of abacavir, lamivudine, plus dolutegravir was compared with the fixed-dose combination of tenofovir/FTC (emtricitabine)/efavirenz. In that study, which is called the SINGLE study, dolutegravir was actually superior to the single pill of tenofovir/FTC/efavirenz. Superiority was driven largely by lower rates of drug discontinuation in those receiving abacavir, lamivudine, and dolutegravir.

A third treatment-naive study is currently in the works; that study compares dolutegravir with boosted darunavir.^[3] We expect to see results of that study, which is called FLAMINGO, by the end of this year.

Dolutegravir has also been studied in treatment-experienced patients, including in the SAILING study,^[4] which showed that, in patients with varying degrees of prior treatment history but without extensive resistance, dolutegravir once daily was superior to raltegravir twice daily in patients who also received an optimized background regimen.

The strength of this finding was greatly bolstered by the fact that those with the highest baseline HIV viral loads before entering the study actually had a bigger difference between dolutegravir and raltegravir and in the study overall.

Another area where dolutegravir looks very promising is in that small group of patients who have resistance to both raltegravir and elvitegravir, our 2 approved integrase inhibitors. The VIKING studies^[5,6] showed that dolutegravir remains active against many of these viruses but not all of them. Of course, it is always important, when you have a patient who is failing an integrase-based regimen, to do a genotype to establish their degree of resistance.

Now we have a once-daily integrase inhibitor that does not require boosting: dolutegravir. The dosing for patients without integrase resistance is 50 mg once a day; the dosing for patients with integrase resistance is 50 mg twice a day. The only thing missing so far is a fixed-dose combination. There is one planned with abacavir, lamivudine, and dolutegravir, and one can envision others in the future because the milligram dose is so small.

So, there you have it -- a summary of dolutegravir, now approved by the FDA for use in the treatment of HIV. Thank you very much.