October 26, 2008
A study presented at the joint 2008 ICAAC / IDSA in Washington, DC found that Isentress (raltegravir) was equally potent and better tolerated than Sustiva (efavirenz) when used as part of a person's first HIV regimen. While it's unlikely to greatly change prescribing practices, this study adds to the list of impressive results for Merck's first-in-class integrase inhibitor.
The STARTMRK trial randomized 563 people who had never taken HIV treatment to take either Isentress or Sustiva, both combined with Truvada (tenofovir + emtricitabine). The study was designed to compare the proportion of people with CD4 counts below 50 and the rates of adverse events (side effects). Data were presented after 48 weeks.
Overall, similar proportions of people in both groups had CD4 counts below 50: 86% for Isentress vs. 82% for Sustiva. More people (12.4% vs. 8.5%) stopped taking Sustiva during the study, which is considered a good measure of a drug's tolerability. As seen in other studies, people taking Isentress saw their HIV levels decline more quickly than those on Sustiva.
People taking Isentress had somewhat larger increases in CD4 counts as well, averaging 189 cells compared to 163 for Sustiva. This difference is considered statistically significant (meaning it is unlikely to be from chance), but the impact of such a difference on HIV disease progression or other health outcomes is unclear.
People taking Sustiva in this study were more likely to experience side effects. 77% of people taking Sustiva reported drug-related side effects, compared to 44% of people on Isentress. Central nervous system effects, like dizziness and sleep disturbances, along with rash made up most of the difference.
While this study shows that Isentress is equally potent and better tolerated than Sustiva when either is taken with Truvada as part of first line therapy, it may be unlikely to significantly change prescribing practices. Isentress is taken twice a day while Sustiva is once daily. Research shows some preference on the part of patients for once-a-day treatment. Merck is studying the potential to give Isentress once daily, but those results are not yet available.
Also, Sustiva + Truvada are sold together in the very popular once-a-day pill Atripla. The simplicity and potency of this regimen has led it to be the most prescribed combination for first line treatment in the US.
Lastly, Sustiva has been on the market for many years now and has built up a large amount of safety information. At a meeting Project Inform held just before ICCAC, one widely respected HIV doctor and researcher cautioned those in attendance against what he sees as Americans' tendency to jump on the newest thing, reminding everyone that there is no substitute for real world experience when it comes to understanding the safety of a drug. "How many side effects did we learn about only after a drug was approved?" he reminded us.
While this study might not unseat Atripla as the market leader for first line treatment, it helps support the use of Isentress earlier in the course of HIV disease. Isentress was studied initially for use in people with extensive HIV treatment, where it has worked quite well. This study suggests that Isentress can be successfully used as part of earlier HIV drug combinations as well.