Fixed-Dose Combination HIV Therapies

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The HCPLive Peer Exchange “Optimizing Outcomes in HIV Treatment” features insight and opinion on the latest developments in HIV research, diagnosis, and management from leading physician specialists.

This Peer Exchange is moderated by Paul Doghramji, MD, who is a family physician at Collegeville Family Practice in Collegeville, PA, and Medical Director of health services at Ursinus College, also in Collegeville, PA.

The panelists are:

• Alfred A. DeLuca, MD, Infectious Disease Specialist at CentraState Healthcare System in Manalapan, NJ
• Ian Frank, MD, Director of Anti-Retroviral Clinical Research and Director of Clinical Core at Penn Center for AIDS Research, and Professor of Medicine at the Hospital of the University of Pennsylvania in Philadelphia, PA
• Paul Sax, MD, Associate Professor of Medicine at Harvard Medical School and Clinical Director of the Division of Infectious Diseases and the HIV Program at Brigham and Women's Hospital, in Boston, MA

This segment focuses on fixed-dose combination therapies for treating HIV, highlighting the recently approved fixed-dose medication Triumeq (dolutegravir abacavir lamivudine) and the arguments for and against its adoption. The panel also discusses how these medications can be administered to patients who have difficulty swallowing pills.

Triumeq is a fixed-dose combination product that contains abacavir, dolutegravir, and lamivudine, and is administered as a single pill once a day. “The study results with dolutegravir in naïve patient populations have been nothing short of remarkable,” says Frank. In head-to-head studies of dolutegravir-inclusive combination regimens, “dolutegravir has always done as well or better than the comparator,” sometimes in terms of tolerability, sometimes in terms of efficacy. “So dolutegravir, I think, is arguably the most potent integrase inhibitor that we have available,” he says.

With a fairly recent approval in August 2014, it remains to be seen how widely Triumeq will be adopted as a treatment option. “Because of the fact that it containsabacavir,” which is associated with hypersensitivity reactions and cardiovascular risk, Sax says, “I don’t feel like its use will be quite as broad as some of the other fixed-dose one-pill regimens.” Cost may balance out that equation though, as Triumeq is significantly less expensive than the other fixed-dose integrase inhibitor—based treatments, which will be an advantage from the payor perspective, according to Sax. This neutral pricing may also help offset its novelty, which can be an issue because “any time there’s something new it almost always raises red flags among payors.”

Because “we do struggle occasionally” with patients who have difficulty swallowing pills, Sax says that“there’s a liquid protease inhibitor combination called lopinavir/ritonavir (Kaletra),” but “it doesn’t taste very good” and it actually contains a considerable amount of alcohol, which can be problematic for patients with abuse issues. There are also two injectable products — zidovudine and enfuviritide – although “injectable enfuviritide is not practical because it’s a twice-daily injection with large injection site reactions,” he says.

Crushing the tablets is another possibility to overcome swallowing problems. “Rilpivirine, which is a non-nucleoside reverse transcriptase inhibitor that’s a component of Complera, will dissolve in water,” Frank says, allowing for the option of crushing it and mixing it into water to drink. So there are a few alternative ways to administer these medications to patients who have difficulty swallowing pills.