Results from a Phase 2 clinical trial that lasted more than 4.5 years showed that Isentress is as safe and effective as Sustiva for long-term use in people with HIV who have not previously been treated with antiretrovirals.

In addition, participants taking Isentress (raltegravir) reported fewer side effects than those taking Sustiva (efavirenz).

“In this Phase 2 study, Isentress demonstrated comparable efficacy and tolerability to efavirenz [Sustiva] at 240 weeks in treatment-naïve adult patients with HIV-1,” said primary investigator Dr. Eduardo Gotuzzo in a press release. Dr. Gotuzzo presented the results last week at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2011).

He also noted that the effects of Isentress on cholesterol levels were minimal over the course of the study.

“Because physicians consider many factors when selecting antiretroviral therapy for adult HIV-1 patients new to treatment, the results seen in this Phase 2 study with Isentress in combination therapy showing a modest impact on LDL [“bad” cholesterol] and triglycerides provide important insights,” said Dr. Gotuzzo.

The antiretroviral Isentress is currently the only approved integrase inhibitor, although two other investigational integrase inhibitors – dolutegravir and elvitegravir – are currently in Phase 3 clinical trials.

Isentress is approved both for treatment-experienced adults with HIV and as a first-line treatment for people who have not previously taken antiretrovirals.

In this study, researchers compared the safety and efficacy of Isentress to those of Sustiva over an extended period to see how Isentress performed long-term.

Sustiva, in combination with Truvada (emtricitabine/tenofovir) in the form of Atripla (efavirenz/emtricitabine/tenofovir), is the most commonly prescribed first-line regimen for people with HIV.

Both Sustiva and Isentress, when taken with Truvada, are listed in HIV treatment guidelines as “preferred” regimens for people starting antiretroviral therapy for the first time.

The study included 198 treatment-naïve HIV-positive adults. Participants were initially randomly assigned to take either Sustiva or one of four different Isentress dosages, both in combination with Truvada. After 48 weeks, all 160 participants taking Isentress were moved to the 400 mg twice daily dosage; the remaining 38 participants continued to take Sustiva once daily. The trial lasted 240 weeks.

Results showed that at the end of the study, 69 percent of participants taking Isentress had successfully achieved and maintained an undetectable viral load (amount of HIV in the blood), compared to 63 percent of participants taking Sustiva.

In addition, participants taking Isentress had an average increase in CD4 (white blood cell) count of 302 cells per microliter over this period, versus an average increase of 276 cells per microliter in participants taking Sustiva.

The differences between the two study groups were not large enough to be considered significant.

Fewer patients taking Isentress reported side effects (55 percent) than those taking Sustiva (76 percent). Consistent with other clinical trials, participants taking Sustiva were more likely to report neuropsychiatric symptoms such as dizziness, headache, abnormal dreams, insomnia, and nightmares.

Participants in both groups experienced increases in cholesterol and triglycerides; however, the changes in the Sustiva group were larger than those in the Isentress group, particularly for overall cholesterol levels.

Other side effects, such as nausea and diarrhea, were similar between the two groups.

For more information, please see the study abstract or presentation (pptx) at the IAS 2011 conference website, or the Merck press release.