Recently Approved Combination Products for HIV

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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

In this segment, the panelists offer their opinions on several recently approved combination HIV medications.

Dr. Sax noted there are 4 single-tablet options now for patients with HIV. The drug Complera combines tenofovir, emtricitabine, and rilpivirine, and is an effective, well-tolerated, once-a-day option that should be taken with food to ensure optimal absorption. However, according to Dr. Sax, “it doesn’t seem to be quite as effective at controlling the virus in patients who have a very high amount of virus in their blood or a very low CD4 cell count.”

Dr. DeLuca said Stribild, which contains an integrase strand inhibitor known as elvitegravir that must be boosted with the boosting agent, cobicistat, was originally known as the “quad pill.” His experience with it has been positive, with good results and feedback from patients.

Triumeq (dolutegravir abacavir lamivudine) is the newest of the fixed-dose combination medications for HIV. Dr. Frank noted that abacavir “is associated with a hypersensitivity reaction, so providers who prescribe Triumeq should get an HLA-B*5701 test” for their patients. He also said there’s an issue with abacavir and cardiovascular risk that should be considered when selecting treatment options. Overall, Dr. Frank said Triumeq is “a very effective combination.”

Enfuvirtide was the first fusion inhibitor approved for HIV treatment. Raltegravir was the first integrase inhibitor to be approved. Tivicay is the newest member of this class. According to Dr. Sax, raltegravir (and the integrase inhibitor class as a whole) was “a real leap forward” that works by blocking the process by which viral HIV DNA is incorporated into the host DNA. He said the integrase inhibitors are well tolerated and extremely potent, and produce rapid decreases in HIV viral load. “Many people actually have commented that pretty much everyone starting treatment these days should be on an integrase-based regimen,” either as a fixed-dose combination or separately, said Dr. Sax. He also mentioned that he often prescribes Truvada for pre-exposure prophylaxis. Dr. Frank added that one of the chief advantages of integrase inhibitors is that they have a low potential for metabolic complications and are not generally associated with GI intolerance.

In clinical trials, Stribild was not associated with higher discontinuation rates than the comparator medication (the fixed-dose combination drug Atripla). According to Dr. Sax, patients in the Stribild arm of the trial experienced slightly higher rates of nausea, whereas patients treated with Atripla experienced more central nervous system side effects. He also mentioned that because cobicistat inhibits the tubular secretion of creatinine, patients on Stribild can experience a rise in their levels, which “can be tricky to sort out.” He said dolutegravir is also associated with this phenomenon.

Dr. Sax said Stribild “works very well in patients with high viral loads, low viral loads, high T cells, low T cells. However, he noted that there relatively little information on the use of any of the newer HIV drugs “in the types of patients who we see in the hospital with newly diagnosed opportunistic infections‑‑the really sick AIDS patients—who are usually there because they either never engaged in care or diagnosed late.”

Tivicay (dolutegravir), an integrase inhibitor that received FDA approval in 2013, “has a rapid decrease in plasma viremia as well as a robust CD4 response, with fewer side effects than many of its comparators and a high genetic barrier to resistance,” according to Dr. DeLuca. He also said it is well tolerated with few drug interactions. Dr. Sax said dolutegravir has been studied in treatment-naive patients and in patients switching from complex regimens to single pill regimens. It’s also been studied in treatment-experienced patients who have failed other regimens. “Dolutegravir has a very broad indication. It can be used in treatment-naive patients and in treatment-experienced patients. It’s the only integrase inhibitor that can be actually used after one of the first integrase inhibitors (raltegravir or elvitegravir) has been used,” he said.