Hiv, Tuberculosis
Conditions
Brief summary
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.
Interventions
DRUGDolutegravir
Dosed at 50 mg bd on 3 separate occasions with low, medium and high doses of rifampicin. Dosed at 50 mg od without rifampicin.
Sponsors
Infectious Disease Institute, Kampala, Uganda
Desmond Tutu HIV Centre
Helen Reynolds
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in pharmacokinetic parameter Cmin of dolutegravir | Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment | Change in dolutegravir Cmin when dosed with standard, medium, high dose rifampicin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in pharmacokinetic parameter AUC of dolutegravir | Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment | Change in dolutegravir AUC when dosed with standard, medium, high dose rifampicin |
| Change in pharmacokinetic parameter Cmax of dolutegravir | Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment | Change in dolutegravir Cmax when dosed with standard, medium, high dose rifampicin |
| Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017) | From first dose of dolutegravir until study completion approximately 2 years | Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017) |
Countries
South Africa, Uganda
Outcome results
None listed