Coverage of 2008
International AIDS Conference

August 3–8, 2008, Mexico City, Mexico

Isentress gets another good grade

by Paul Dalton, August 4, 2008

Data were presented today at the International AIDS Conference in Mexico City on a head-to-head study comparing the integrase inhibitor Isentress (raltegravir) to Sustiva (efavirenz) in people taking HIV drugs for the first time. The study found that Isentress proved equally potent and durable to Sustiva, the most widely used drug in first line treatment.

Marty Markowitz presented 96-week results from a phase II, dose-ranging study of Isentress. In the earlier phase of the study, volunteers were randomly assigned to take 1 of 4 doses of Isentress (100, 200, 400 or 800mg, twice daily) or Sustiva, each along with Truvada (tenofovir + emtricitabine). After 48 weeks, everyone taking Isentress was moved to the 400mg group, which was the dose chosen to move forward.

Earlier study data showed that Isentress performed equally to Sustiva. The results presented today showed that Isentress is comparable to Sustiva over almost 2 years of use. These results agree with preliminary data from a similar, but larger head-to-head study of Isentress vs. Sustiva.

After 96 weeks of treatment, 84% of people taking either Isentress or Sustiva had HIV levels below 400 copies/mL. Similar numbers were seen when looking at the percentage of people with HIV levels below 50 copies (83% for Isentress vs. 84 % for Sustiva). Both groups experienced an increase in CD4 cells of about 200.

The major difference was in the frequency of adverse events, with 51% of people taking Isentress reporting any adverse events, vs. 74% on Sustiva. Most of the difference was due to the neuro-psychiatric side effects associate with Sustiva. Isentress also had less of an effect on lipids than did Sustiva.

One audience member questioned why the 400mg dose was chosen over the others, given that earlier reports had shown little difference in overall reductions in HIV levels. Markowitz cautioned that he was not speaking on behalf of Merck, who makes Isentress, but reported that the dose was chosen based on ‘extensive pharmacokinetic studies,’ which found a high degree of variability in people taking Isentress. He mentioned that there was talk of studying Isentress as a once a day treatment, for people taking HIV drugs for the first time.

As mentioned earlier, this smaller study confirms what has been preliminarily reported from an ongoing larger study of Isentress vs. Sustiva in people taking first line therapy. There is intense interest in Isentress, which has shown some interesting, and possibly unique, characteristics. A quick look at www.clinicaltirals.gov — a central repository of clinical research — shows over 50 ongoing studies involving Isentress, from drug interaction studies to intensification and substitution studies.

While these results show that Isentress is comparable to Sustiva in people on first line therapy, it’s unlikely to result in any significant changes in the way Isentress is used. For one thing, Isentress is only FDA approved for use by treatment experienced people, and this study will not change that. Also, as a panelist in an earlier talk pointed out, using either Isentress or Selzentry (maraviroc) — another new HIV treatment — would result in doubling the cost of treatment. With little data, and the increasingly tight budgets for programs like Medicare, Medicaid and ADAP, it is unlikely that many people will switch from cheaper, more studied first line options like Sustiva and Kaletra (lopinavir + ritonavir) any time soon.

Nonetheless, these results should be seen as more good news for Isentress, and for people living with HIV. The more drugs that are shown to be effective and well tolerated the better.