Published: 20 February 2024
A researcher at St George’s, University of London is leading a new clinical trial to better understand crucial drug-to-drug interactions to support shorter tuberculosis (TB) treatment for people living with HIV.
The phase two study will investigate the effect that the anti-TB medication rifapentine has on levels of the HIV medication dolutegravir in the blood of participants who have HIV-associated TB. The team will also determine whether this drug combination can be safely and effectively used together.
Dr Sean Wasserman is working with ACTG, a global clinical trials network focused on HIV and other infectious diseases. A previous ACTG study demonstrated that a four-month, four-drug TB regimen that included high-dose rifapentine was as effective as the standard six-month regimen, cutting the treatment time by one third. However, levels of dolutegravir (a recommended first-line HIV treatment) are reduced when given in combination with rifamycin drugs such as rifapentine, and so there is an urgent need to define the magnitude of interaction of these drugs.
Exploring link between anti-TB and HIV drugs
It is estimated that one third of people living with HIV worldwide are at risk for developing TB. It is therefore crucial to understand the relationship between these anti-TB and HIV medications to provide people with the best possible treatment.
The clinical trial will take place at four sites in Thailand and South Africa, with the aim to enrol 30 participants aged 18 years and older who are living with HIV, newly diagnosed with drug-sensitive TB, and are not taking antiretroviral therapy (ART) at the time of their TB diagnosis.
All participants will receive a daily high-dose rifapentine (1200 mg), moxifloxacin (400 mg), isoniazid (300 mg), and pyrazinamide (adjusted to their body weight) for eight weeks. This will be followed by daily rifapentine, moxifloxacin, and isoniazid for nine weeks. Everyone on the study will also receive dolutegravir-based ART twice a day starting after six weeks of TB therapy - dolutegravir (50 mg) with a fixed-dose combination of tenofovir disoproxil fumarate (300 mg) and lamivudine (300 mg) each morning, and dolutegravir in the evening until two weeks after completing TB treatment.
Support roll-out of shortened treatment
“While the shortened regimen is not yet part of routine care, it has been endorsed by health authorities as an equally effective and safe alternative to the standard six-month treatment. We are hopeful that the results will support the international roll-out of the shortened regimen, making it more accessible for those individuals at highest risk of TB.”
- Dr Sean Wasserman, study lead at the Institute for Infection and Immunity at St George’s, University of London -
The study is a collaboration with Johns Hopkins University. It is sponsored by the National Institute of Allergy and Infectious Diseases, and coordinated by ACTG.
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