Investigating the safety of tuberculosis treatment in pregnant individuals with HIV

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

This study is testing a new treatment for tuberculosis in pregnant people with HIV to see if it is safe and how well it works alongside their current HIV medications.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 252 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: The Aurum Institute NPC (Academic / other)
• Locations: 3 sites (Tembisa, Gauteng and 2 other locations)
• Trial ID: NCT05122026 on ClinicalTrials.gov

What this trial studies

This open-label, two-arm, randomized multicenter study aims to evaluate the safety, tolerability, and pharmacokinetics of dolutegravir combined with isoniazid and rifapentine in pregnant individuals living with HIV. Participants will be randomized into two groups: one receiving daily isoniazid and rifapentine for one month, and the other receiving rifapentine weekly for three months, alongside their existing antiretroviral therapy. The study will monitor HIV viral load and conduct safety assessments throughout the treatment period. Additionally, pharmacokinetic data will be collected to understand the interaction between the medications during pregnancy.

Who should consider this trial

Good fit: Ideal candidates include pregnant individuals aged 18 and older, with a confirmed singleton pregnancy and who are virally suppressed on a dolutegravir-based antiretroviral regimen.

Not a fit: Patients with confirmed or suspected tuberculosis disease or those who have had recent tuberculosis treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve tuberculosis preventive treatment options for pregnant individuals with HIV, enhancing maternal and fetal health outcomes.

How similar studies have performed: Other studies have shown promising results with similar approaches in managing tuberculosis in HIV-positive populations, indicating potential for success in this study.

Eligibility 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

Where this trial is running

Tembisa, Gauteng and 2 other locations

• The Aurum Institute: Tembisa Clinical Research Centre — Tembisa, Gauteng, South Africa (Recruiting)
• Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital — Klerksdorp, North-West, South Africa (Recruiting)
• FAMily Centre for Research with Ubuntu (FAMCRU) — Cape Town, South Africa (Recruiting)

Study contacts

• Principal investigator: Dr Vaneshree Govender — Aurum Institute
• Study coordinator: Jayajothi Moodley

Conditions HIV Seropositivity; Pregnancy; Tuberculosis Infection; Dolutegravir; 3HP; Rifapentine; pharmacokinetic; TB preventive treatment