Safety and Tolerability of 1 Month Daily (1HP) and 3 Months Weekly (3HP) Isoniazid and Rifapentine With Pharmacokinetics of Dolutegravir (DTG) in Pregnant People With HIV

• Status: Not yet recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: Female

Summary

Open-label, two-arm, randomized multicenter study to investigate the safety, tolerability, and pharmacokinetics (PK), and potential interactions between dolutegravir (DTG) and rifapentine (RPT) during pregnancy in people with HIV when RPT is given with isoniazid (INH) daily for 4 weeks (1HP) or weekly for 3 months (3HP) as part of tuberculosis (TB) preventive therapy (TPT). Adults (age ≥18) who are pregnant with a singleton pregnancy (confirmed by ultrasound) at a gestational age of 20-34 weeks and virally suppressed on an existing DTG-based plus two nucleoside reverse transcriptase inhibitors (NRTI) antiretroviral (ART) regimen for at least four weeks may participate.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Aurum Institute NPC
• Collaborators: Johns Hopkins University; University of Washington; Weill Medical College of Cornell University
• Treatments: Isoniazid; Rifampin; Rifapentine

Criteria

Inclusion Criteria:

1. Age > 18 years

2. Weight > 50 kg

3. Documented HIV infection

4. At least 4 weeks of ART and virally suppressed on dolutegravir plus two NRTIs

5. Undetectable HIV-1 viral load

6. Pregnancy at 20-34 weeks as confirmed by ultrasound

7. Singleton pregnancy

Exclusion Criteria:

1. Confirmed or suspected TB disease

2. Likely to move from the study area during the study period

3. Known exposure to pulmonary TB cases with known or suspected resistance to isoniazid or rifampicin in the source case

4. TB treatment within the past year

5. TB preventive therapy within the last year

6. Sensitivity or intolerance to isoniazid or rifamycins

7. On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens

8. Suspected acute hepatitis or known chronic liver disease; HBsAg positivity; severe hepatic impairment

9. Alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN)

10. Total bilirubin ≥ 2.5 times the ULN

11. Absolute neutrophil count (ANC) < 750 cells/mm3

12. Creatinine clearance < 50 ml/min

13. Self-reported alcohol use exceeding 21 units per week

14. Karnofsky status < 80

15. On prohibited medications e.g. dofetilide