Long-acting formulations of the non-nuke rilpivirine (Edurant and in Complera, Eviplera) and the second-generation integrase inhibitor S/GSK 1265744 (’744) are being developed. As these drugs may be used together in the future—and in the case of rilpivirine, with another integrase inhibitor, dolutegravir—it is important to assess any drug interactions that may occur.

Experiments were done with 28 healthy HIV-negative volunteers given dolutegravir 50 mg/day and/or rilpivirine 25 mg/day. The experimental integrase inhibitor ’744 at a dose of 30 mg/day was also tested in combination with rilpivirine. All drugs were taken for between five and 12 days.

Researchers found that very modest increases in dolutegravir and rilpivirine levels in the blood were seen; these increases averaged about 20%. Researchers working for GSK and Janssen (the manufacturers of the integrase inhibitors and rilpivirine, respectively) stated that this was “unlikely to be associated with safety concerns.”

Side effects were as follows:

• rilpivirine – one case of insomnia
• rilpivirine with or without dolutegravir – four cases of mild headache
• ’744 with or without rilpivirine – decreased appetite

—Sean R. Hosein

REFERENCE:

Ford S, Gould E, Chen S, et al. Lack of pharmacokinetic interaction between rilpivirine and the integrase inhibitors dolutegravir and S/GSK 1265744. In: Program and abstracts of the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, 9-12 September 2012. San Francisco, California. Abstract A-1249.