A pharmacokinetic study which was designed to examine drug-drug interactions between dolutegravir and isoniazid-rifapentine was stopped early due to serious, unexpected toxicities in some of the healthy volunteers.

Rifapentine is a rifamycin, as is rifampicin. Two of the four volunteers developed a flu-like syndrome and elevated transaminases. Some cytokines, especially interferon were also markedly raised. Flu-like syndrome has previously been described with intermittent use of rifampicin, but infrequently.

The concern is that dolutegravir may be contributing to the toxicities in some way. Whilst there are more questions than answers at this stage, further research will be important for South Africa as a fixed-dose combination including dolutegravir should become available during the course of 2018.

See the abstract here.