Top 10 HIV/AIDS-Related Clinical Developments of 2011

6. No Go Isentress QD

For once-a-day Isentress, the story is less one of audacity than of hope. Twice-a-day regimens are now considered by most providers and many patients to be one dose too many, and there was a real desire to see otherwise-user-friendly Isentress join the other preferred ranks by becoming once a day. Pharmacologic data from Merck, the maker of the drug, suggested that the business end of Isentress was intracellular and that plasma levels were not the best indicator of what this integrase inhibitor could do. Therefore, it was with confidence that the QDMRK trial was launched.¹⁴

In this placebo-controlled study, 775 treatment-naive patients were randomized to Isentress once a day versus twice a day, both in combination with Truvada. At baseline, 39 percent of the treated patients had viral loads of more than 100,000 copies/mL and 24 percent had CD4+ cell counts of fewer than 200 cells/µL. Of the once-daily group, 83 percent had virological response, versus 89 percent in the twice-daily group (difference: -5.7 percent, 95% CI: -10.7 to -0.83; P = .044). Therefore, once-daily dosing of Isentress was inferior to twice-daily dosing of the drug. The difference in responses was even greater among those with baseline viral loads over 100,000 copies/mL: 74 percent versus 84 percent in the once-daily and twice-daily arms, respectively (difference: -9.9 percent, 95% CI -19 to -0.8). A similar splay was seen in those with CD4+ cell counts below 200 cells/µL at entry.

Of the 53 recipients of once-daily Isentress with virological failure, 22 (42 percent) never responded and 31 (58 percent) had viral rebound. Of the 35 recipients of twice-daily Isentress with virological failure, 14 (40 percent) never responded and 21 (60 percent) had viral rebound. Integrase mutations were more commonly seen in the once-daily arm, as was resistance to Emtriva (emtricitabine, FTC).

Serious adverse events were reported in 7 percent of the once-daily recipients and 10 percent of the twice-daily recipients, and adverse events leading to discontinuation occurred in four patients (1 percent) in each group.

The Bottom Line

If wishing alone had mattered, the results of this study would have been different. But it was not to be. Again, it is not that once-a-day Isentress was awful. Rather, it was not as good as twice-a-day dosing of the drug. For those with baseline viral loads of over 100,000 copies/mL or CD4+ cell counts below 200 cells/µL, there was a more substantial difference, which would preclude most use of once-daily Isentress in such patients.