Novel integrase inhibitor dolutegravir shows promise for HIV-1 treatment

Aug 3 2012

By Sarah Guy, MedWire Reporter

The once-daily integrase inhibitor dolutegravir (DTG) has shown promise in a phase III noninferiority study comparing it with twice-daily raltegravir (RAL) for treatment of HIV-1, indicate study results presented at the 19th International AIDS Conference in Washington DC, USA.

DTG had a rapid and durable antiviral response in HIV-1-infected antiretroviral-naive adult patients, and was tolerated well, with rates of treatment discontinuation because of adverse events comparable to RAL.

"DTG plus NRTIs [nucleoside reverse transcriptase inhibitors] could be an option for first-line HIV treatment," say researcher François Raffi (University of Nantes, France) and colleagues.

The team randomly assigned 827 adults, aged a mean of 36 years, with HIV-1 RNA of at least 1000 c/mL and no evidence of viral resistance to receive either DTG 50 mg per day (n=413) or RAL 400 mg twice-daily for 48 weeks, in addition to backbone NRTIs. The study's primary outcome was the proportion of patients with HIV-1 RNA less than 5 c/mL at the end of the almost year-long follow up.

In all, 88% of DTG- and 85% of RAL-treated patients achieved the primary endpoint, with this difference meeting the requisite 10% noninferiority criteria, report the researchers. Among patients with HIV-1 RNA above 100,000 at study entry, the respective proportion of patients reaching the primary outcome were 82% and 75%.

Indeed, the rate of patients in both groups who achieved an HIV-1 RNA level less than 50 c/mL was comparable, at 90% in the DTG group and 88% in the RAL group, as was the rate of patients who discontinued treatment due to adverse events, at 2% in each group.

The most common adverse events reported by the cohort were nausea (14% DTG, 13% RAL), headache (12% each group), nasopharyngitis (11% DTG, 12% RAL), and diarrhea (11% each group).

Virologic failure was observed in 5% and 8% of the DTG- and RAL-treated patients, respectively, and there was no genotypic integrase or NRTI resistance in the DTG group versus one and four participants in the RAL group, respectively.

"Data through 48 weeks continue to support dolutegravir 50 mg once daily for antiretroviral-naive subjects and provide evidence for durable efficacy and tolerability for dolutegravir in combination therapy," said Raffi when presenting the findings.

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