February 15, 2009
In a poster presentation at CROI 2009 in Montreal, Canada, the STARTMRK study results show that the first-in-class integrase inhibitor Isentress (raltegravir) works at least as well as Sustiva (efavirenz) at suppressing HIV levels. It also showed that using Isentress resulted in higher CD4 counts.
STARTMRK included 563 people who had never been on HIV therapy. Half received Isentress (400mg, 2x a day) or Sustiva (600m, 1x a day) with Truvada (tenofovir/Viread + emtricitabine/Emtriva). At study entry, none showed resistance to Sustiva or Truvada, all had viral loads above 5,000 with more than half above 100,000, and nearly half had CD4 counts below 200.
The study included 19% women and 58% people of color, while the average age was 37 years. Nearly 1 in 5 had a type of HIV different from subtype B, a common type found in the US. The study assessed the number of people who had undetectable HIV and the rate of change in CD4s. Side effects were also studied, including effects on the central nervous system (CNS) and changes in fats/cholesterol levels (called lipid levels).
After 48 weeks on therapy, Isentress suppressed HIV as well as Sustiva. Isentress increased CD4 counts higher than Sustiva, but it's not clear if this increase was statistically meaningful. Isentress was, in general, better tolerated. Fewer overall side effects occurred with Isentress than Sustiva and notably there were fewer CNS affects with Isentress. As for effects on the liver in those with or without hepatitis B or C, both drugs performed similarly.
Isentress was developed and approved for use in treatment experienced individuals. However, this study is one of many that are looking at its effectiveness when used in first line therapy. Here, compared against the most widely used NNRTI, Isentress seems to be an equal choice for people starting therapy for the first time.
The decision to choose one strategy over the other would likely come down to concerns about side effects. From this and other studies, Isentress seems well tolerated, but since it's a very new drug we don't know its possible side effects over the long-term. On the other hand, Sustiva has been well studied and its effects on the CNS are well documented and have long been a concern for many. These include sleep disturbances, unusual dreams and trouble concentrating as well as rash, dizziness and diarrhea. Some people tolerate Sustiva very well; many others experience at least some degree of side effects which may affect their adherence. At this point, it may just come down to which drug is better tolerated by a given individual and what side effects a person is willing to live with.