Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

This is a drug interaction study in HIV negative, TB-monoinfected participants coming to the end of continuation phase of TB therapy, to study the pharmacokinetic changes to dolutegravir when administered with standard, medium and high dose rifampicin.

Inclusion Criteria:

• Ability to give informed consent prior to participation
• Willing and able to comply with all study requirements
• Receiving standard doses of RIF and INH
• HIV antibody negative
• Male or non-pregnant, non-breastfeeding female
• Study participation will not extend length of ATT by more than 4 weeks

Exclusion Criteria:

• < 18 years
• Body weight < 50 kg
• eGFR < 60 mL/min
• Abnormal LFTs including ALT > 2.5 ULN
• HIV antibody positive
• Non-standard TB regimen (containing RHZE)
• Women of childbearing age unless using effective contraception
• Family history of sudden cardiac death
• Prior history of cardiac disease that precludes the use of low dose digoxin
• Medical or psychiatric condition that might affect participation in the study based on investigator judgement
• Regular consumption of grapefruit or grapefruit juice
• ECG abnormalities that preclude the use of low dose digoxin (intermittent complete heart block, second degree AV block, supraventricular arrhythmia associated with conducting pathways, ventricular tachycardia or fibrillation)