The Role of Triumeq in HIV Treatment
August 25, 2014
The approval of Triumeq, the single-tablet coformulation of abacavir, lamivudine and the integrase inhibitor dolutegravir, is an important step forward for antiretroviral therapy. All of the previously approved single-tablet regimens (STRs) -- Atripla, Complera and Stribild -- contain tenofovir (Viread), which some people can't take, usually because of kidney disease. Since Triumeq contains abacavir rather than tenofovir, it will not affect kidney function.
Another plus for Triumeq is dolutegravir, marketed by itself as Tivicay. Dolutegravir has done extremely well in every trial it's been tested in. In the SINGLE study, the combination of dolutegravir plus Epzicom (the same combination of drugs in Triumeq) was the first regimen to show one-year superiority over Atripla. Dolutegravir was also superior to darunavir/ritonavir (Prezista/Norvir) -- another first -- in the FLAMINGO trial. In both studies, superiority was based on better tolerability with less dropout due to side effects.
In the SAILING study, treatment-experienced patients who had drug resistance -- but no resistance to integrase inhibitors -- did better on dolutegravir than on raltegravir (Isentress). Dolutegravir seems to have a higher barrier to resistance than the other two integrase inhibitors, raltegravir and elvitegravir (the latter of which is contained in Stribild); to date, no resistance has been seen in people starting dolutegravir as an initial regimen. Only time will tell whether its barrier is as high as that of boosted protease inhibitors (PIs), where we never see resistance in people who didn't have PI resistance to begin with. Dolutegravir is also well tolerated and has relatively few drug interactions -- just a few more than raltegravir.
Despite its many attributes, Triumeq is not for everyone. While dolutegravir itself has no discernable disadvantages, the pairing with abacavir can be a deal breaker in some cases. Pre-treatment HLA-B*5701 testing is required, and those who test positive can't take it because of the high risk of the abacavir hypersensitivity reaction.
We've worried about using abacavir in people with high viral loads, because in the large ACTG 5202 trial tenofovir/emtricitabine (Truvada) was superior to abacavir/lamivudine (Epzicom) when combined with either efavirenz (Sustiva) or atazanavir/ritonavir (Reyataz/Norvir) in people with baseline viral loads above 100,000. Fortunately, that doesn't seem to be an issue when abacavir/lamivudine is combined with dolutegravir, so in contrast to other abacavir-based regimens, Triumeq is recommended for initial therapy regardless of viral load.
Finally, there's still a lingering concern about a possible association between abacavir and risk of myocardial infarction (MI, a.k.a. heart attack), which has been seen in a number of studies, but not in others. We are eagerly awaiting the analysis from the large NA-ACCORD cohort, which may serve as the final "tie-breaker." If NA-ACCORD shows the same association as D:A:D and other cohorts, we'll be forced to accept the risk and look harder for a cause. But if there's no link between abacavir and MI, I suspect we'll put this controversy to rest and move on. In the meantime, U.S. treatment guidelines recommend that abacavir, including Triumeq, be avoided in people with multiple cardiac risk factors, which include smoking, high blood pressure, high cholesterol, diabetes and a family history of MI.
There's a growing recognition, based on multiple clinical trials, that starting therapy with integrase inhibitors may be the best way to go for most people, and there are now two integrase inhibitor-based STRs to choose from: Stribild and Triumeq. Both are excellent choices. Stribild has the advantage of being combined with tenofovir/emtricitabine, which has been our nucleoside backbone of choice for many years based on potency and tolerability. Triumeq has fewer drug interactions, a higher barrier to resistance and is an option for people who can't take tenofovir. With the approval of Triumeq, an even great number of HIV-positive people will be candidates for easy single-tablet regimens.
Joel Gallant, M.D., M.P.H., is the associate medical director of specialty services at Southwest CARE Center in New Mexico. You can ask him a question directly on his Tumblr page, Ask Dr. Joel.
Copyright © 2014 Remedy Health Media, LLC. All rights reserved.
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