Interim results from a Phase 3 clinical trial show that the investigational integrase inhibitor elvitegravir, taken once daily, may be as effective and safe as twice-daily Isentress in treatment-experienced HIV-positive adults.

“[Patients] could use elvitegravir [once daily] instead of Isentress [twice daily] in combination with a boosted protease inhibitor with the same efficacy and safety,” said Dr. Jean-Michel Molina, a researcher at the Hôpital Saint Louis and University of Paris and lead author of the study.

The study authors noted that once daily dosing as opposed to twice daily dosing might improve patients’ adherence to treatment.

Investigators previously presented the results of the study in July at the International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (see related AIDS Beacon news).

Elvitegravir, which is being developed by Gilead Sciences, and Isentress (raltegravir) are both integrase inhibitors, a relatively new class of antiretroviral. Currently, Isentress is the only approved integrase inhibitor.

In this clinical trial, researchers compared the safety and efficacy of elvitegravir to that of Isentress in 702 HIV-positive adults who had previously been treated for HIV. Two-thirds of the participants had resistance to two or more classes of antiretroviral drugs.

Half of the participants were randomly assigned to receive elvitegravir once daily and the other half Isentress twice daily. Placebo pills were used to ensure that all participants received the same number of pills daily.

All patients also took a Norvir (ritonavir)-boosted protease inhibitor and a third antiretroviral, which was either a nucleoside reverse transcriptase inhibitor, Intelence (etravirine), Selzentry (maraviroc), or Fuzeon (enfuvirtide). The most commonly used protease inhibitor was Prezista (darunavir).

Results showed that after 48 weeks, 59 percent of patients in the elvitegravir group achieved and maintained undetectable viral loads (amount of HIV in the blood), compared to 58 percent of patients in the Isentress group.

Increases in CD4 (white blood cell) counts were also similar between the two groups: an average increase of 119 of cells per microliter in participants taking elvitegravir versus 127 cells per microliter in participants taking Isentress.

Drug adherence up to week 48 of the study was determined by pill counts at every visit during the study. Adherence was similar (95 percent) in both groups.

Rates and types of side effects were similar between the two groups. The most common side effects in participants taking elvitegravir were diarrhea (12 percent of participants), upper respiratory tract infection (6 percent), bronchitis (5 percent), back pain (5 percent), depression (5 percent), sinus infection (4 percent), joint pain (4 percent), nausea (4 percent), and urinary tract infection (3 percent).

Although diarrhea was equally common in both treatment groups in the first month of treatment, diarrhea was reported more often after the first month by patients receiving elvitegravir.

One percent of patients assigned to elvitegravir experienced serious side effects, compared to two percent of patients assigned to Isentress. Two patients (0.5 percent) and eight patients (2 percent) died in each group, respectively, during the study period.

The trial will continue for an additional 48 weeks. In addition, studies are ongoing of elvitegravir as a component of the investigational single-tablet combination “Quad” (cobicistat/elvitegravir/emtricitabine/tenofovir) regimen in previously untreated HIV-positive adults.

Gilead stated in July that it plans to apply for approval of elvitegravir in the U.S. and Europe in 2012.

For more information, please see the study in The Lancet Infectious Diseases (abstract).