The purpose of this research study is see if taking medications to prevent tuberculosis (TB) affect the drug levels in blood of a commonly used HIV medication called dolutegravir (DTG) and if an extra dose of DTG is needed during this TB preventive treatment. The other medicines, rifapentine (RPT) and isoniazid (INH), are drugs used to prevent active TB in people who have been exposed to TB. This study will also help us make sure that people tolerate the medicines and that they are safe when given together. In many countries, DTG is the recommended first-line treatment for HIV. DTG, RPT, and INH are proven beneficial treatments for people living with HIV and latent TB, but it is unclear whether these treatments work differently when taken together. Understanding how DTG interacts with the short-term treatment for latent TB (1HP) is very important for delivering both treatments effectively.
Purpose of the Study: To see if taking a medicine to treat TB called RPT, affects the levels of DTG (an HIV medicine) in the blood or not.
Requirements to Enter Study: This study is for people living with HIV between the ages of 18-65 and who either tested positive for the bacteria that causes tuberculosis (TB) or live in a country where TB infection occurs frequently. Participants must be taking dolutegravir as part of a three drug regimen to treat HIV and must have a viral load < 50 copies/ml. In addition to these criteria, blood samples will be drawn for lab tests to check general health. Participants will also need to weigh at least 40 kilograms and have either a chest x-ray or CT scan of their lungs to check for active TB disease.
Treatment: Participants will continue ART medications that include DTG and 2 nucleoside reverse transcriptase inhibitors for the entire study period.
TB medication to prevent active TB disease will begin at entry into the study and include the RPT and a second medication used to treat TB called isoniazid (INH) along with daily vitamin B6, to decrease the risk of side effects from INH.
The study will have two (2) groups. Group 2 will only open after the results from Group 1 are reviewed.
Below are the medicines that you will take during the study depending on which Group you are in:
Group 1
- DTG 50 mg orally twice daily – about 12 hours apart
- 1st dose will be taken in the morning; this will not be supplied by the study
- 2nd dose will be taken in the evening; this will be supplied by the study for 4 weeks
- 1HP: INH 300 mg + RPT 600 mg orally once daily (in the morning) for 4 weeks (supplied by the study)
Group 2 (upon opening)
- DTG 50 mg orally once daily (in the morning) (not supplied by the study)
- 1HP: INH 300 mg + RPT 600 mg orally once daily (in the morning) for 4 weeks (supplied by the study)
You will continue taking your existing ART drugs while on the study – your ART must include 2 NRTIs (excluding TAF) during the study. Your ART will not be provided by the study.
You will also receive pyridoxine (vitamin B6) 25 or 50 mg with each dose of INH based on the current local, national, or international dosing guidelines.
Because the blood draws on study visits will be dependent on the time you take the drugs, you will need to take your HIV drugs and drugs provided by the study (except second dose of DTG if you are in Arm 1) in the morning during the duration of the study. If you generally take your HIV drugs in the evening, you will need to switch to taking them in the morning for this study, including at least 3 days before the Day 0 visit. On the study visit days, you will hold on taking the drugs until you arrive at the clinic.
Duration of Study: Most people will be on this study for six weeks (4 weeks on study treatment and two weeks of follow-up). You may be on study up to 11 weeks if you have to have additional follow-up visits to check your viral load. There are 7 or 8 scheduled visits during this time.