Interim results from an ongoing Phase 2b clinical trial indicate that once-daily dolutegravir, an investigational new integrase inhibitor, may be as safe and effective as Sustiva in people with HIV who have not previously been treated.

“Dolutegravir administered once daily…showed a rapid and sustained response at all doses explored through week 48,” said Dr. Jan van Lunzen, who presented the results yesterday at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2011).

“The drug in all dose groups was well tolerated, with fewer discontinuations occurring than in the [Sustiva] comparator arm,” he added.

Based on the results, Dr. van Lunzen stated that several Phase 3 clinical trials have been initiated with the highest dolutegravir dosage tested.

Dolutegravir (S/GSK1349572) is a potential new integrase inhibitor being developed by ViiV Healthcare (a joint venture by GlaxoSmithKline and Pfizer). Currently, the only approved integrase inhibitor is Isentress (raltegravir), which is marketed by U.S. pharmaceutical company Merck.

The clinical trial was designed to test the safety and efficacy of several dolutegravir dosages relative to Sustiva (efavirenz), which, when combined with Truvada (emtricitabine/tenofovir) in the form of Atripla (efavirenz/emtricitabine/tenofovir), is the most commonly prescribed first-line regimen to treat HIV.

The study includes 205 participants, who were randomly assigned to one of four groups. The first group is being treated with 10 mg of dolutegravir once daily, the second takes 25 mg of dolutegravir once daily, the third receives 50 mg of dolutegravir once daily, and the fourth takes Sustiva. All groups take the drugs in combination with either Truvada or Epzicom (abacavir/lamivudine).

Results showed that after 48 weeks, most participants in all four groups had successfully achieved an undetectable viral load (amount of HIV in the blood): 91 percent, 88 percent, 90 percent, and 82 percent of the participants, respectively.

Sixteen week results presented at a previous conference suggested that participants taking dolutegravir achieved an undetectable viral load faster than participants taking Sustiva. The 48 week results showed that the more rapid response to dolutegravir was sustained throughout the study period.

Participants taking dolutegravir had slightly higher increases in CD4 (white blood cell) counts after 48 weeks than participants taking Sustiva (231 cells per microliter versus 174 cells per microliter), but the difference was not large enough to be considered significant.

There were fewer moderate to severe side effects reported in the dolutegravir trial groups than in the Sustiva group (8 percent of participants versus 20 percent). Participants taking dolutegravir also had smaller increases in “bad” cholesterol levels during the course of the trial than participants taking Sustiva, with little or no increase in cholesterol levels overall.

In total, two participants stopped taking dolutegravir and four stopped taking Sustiva due to side effects.

The trial will continue for an additional 48 weeks.

Two Phase 3 clinical trials for dolutegravir are currently recruiting participants. The first trial will test the safety and efficacy of dolutegravir versus Isentress in treatment experienced patients who have not previously been treated with integrase inhibitors. The second trial will test the efficacy of dolutegravir in people who have failed therapy with Isentress.

Two other Phase 3 trials are ongoing but are not currently recruiting participants.

For more information, please see the study presentation or abstract on the IAS 2011 conference website.