March 8, 2011
From CROI, March 2011: Isentress (raltegravir) is currently taken twice a day, the only drug that’s dosed that often as a preferred drug in the US Guidelines for people new to HIV treatment. Lab study of the drug has shown that taking it once a day may suppress HIV just as well. So, in an effort to simplify its dosing, the QDMRK study randomized nearly 800 people to take Isentress either once a day (800mg) or twice a day (400mg), together with Truvada.
None of the participants had taken HIV treatment before and all had viral loads >5,000 (2 out of 5 were >100,000), with no resistance to either drug in Truvada. A total of 382 people took Isentress once a day while 388 took it twice a day. Most were men and average age was 38. Average CD4 counts were just below 300, with about 1 out of 4 who were <200.
After 48 weeks, about 86% who took Isentress once a day and 91% who took it twice a day had viral loads <50 copies. However, when looking only at people with viral loads >100,000, 84% on twice-a-day and 74% on once-a-day were below 50 copies at week 48. As for those whose viral loads rebound above 50 copies, only 9 occurred on twice-a-day vs. 18 on once-a-day.
Although the overall results are generally good, and actually some of the best of recent HIV drug studies, they failed to meet a pre-specified viral load goal of the study which led to once-a-day not being “non-inferior” to twice a day dosing. This means it’s not as potent and failed to be equal to twice a day.
Side effects were similar between the two groups. Nine people in the first group and two in the second also developed resistant HIV to Isentress. Most of these cases developed in people who started at higher viral loads. Although Isentress dosed once a day had higher overall drug levels in blood, it fell lower in minimum blood drug levels (called trough concentration) compared to twice a day, which may be one reason why resistance had developed.
RESEARCH STUDY:
QDMRK, a phase III study of the safety and efficacy of once daily vs. twice daily RAL in combination therapy for treatment-naive HIV-infected patients. Eron J, et al. Poster #150LB.