Treating patients co-infected with HIV and tuberculosis (TB) can be tricky – as rifampin, a key sterilizing drug in TB regimens – can reduce concentrations of antiretrovirals administered at the same time, as well as other drug-drug complications. Early efforts to combat this phenomenon have unearthed a potential treatment candidate – an increased dose of dolutegravir (DTG), an investigational HIV integrase inhibitor currently in Phase III trials.
Dr. Kelly Dooley of Johns Hopkins University presented her team’s findings from a safety and tolerability study looking at DTG given twice daily with rifampin to an audience at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) Thursday in Seattle. In a study presented Wednesday at CROI – 88 percent of HIV-infected patients given DTG 50 mg once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) maintained a viral load of less than fifty copies per milliliter at 96 weeks.
Dooley’s study involved 12 HIV-uninfected, healthy individuals who received different treatment options at different time intervals:
- Period one – DTG 50 mg once daily seven days
- Period two – DTG 50 mg twice daily for seven days
- Period three – DTG 50 mg twice daily plus standard dosing of rifampin for two weeks
Eleven of the 12 participants completed all sampling periods, and none dropped out as a result of adverse events. The team found that DTG 50 mg twice daily plus rifampin was well tolerated, and resulted in DTG concentrations similar if not higher to DTG 50 mg once daily alone.
Although the study had some limitations – such as a very small sample size of all HIV-uninfected participants – it might represent a nice new treatment option for patients who require concomitant treatment of HIV and TB, Dooley said, and called for evaluation of co-administration of the treatment in co-infected patients. Dooley noted that it is unclear when DTG will be available for public use, but a licensing application will likely be submitted by late 2012.