Jyoti S. Mathad
Pregnancy does not increase the rate of rifapentine clearance, indicating that there is no need for a dose adjustment of the 3-month tuberculosis prevention regimen of weekly isoniazid and rifapentine during pregnancy, according to findings from CROI.
“A woman is more likely to develop tuberculosis (TB) in the first 90 days after she has a baby than at any other time in her life, especially if she has HIV,” Jyoti S. Mathad, MD, MS, assistant professor of medicine, obstetrics and gynecology, at Weill Cornell Medical College, told Healio. “WHO currently recommends that all people with HIV, including pregnant women, take medications to prevent TB, but a recent trial raised concerns about the most common regimen used during pregnancy: 6 months of daily isoniazid. That's a problem, because the more cutting-edge treatments, such as 3 months of weekly isoniazid and rifapentine (3HP), which has improved safety and adherence in nonpregnant people, has not been tested at all in pregnant women.”
She added: “This data gap is particularly disappointing, because a 3-month regimen would be ideal for pregnant women — it could be completed during the antepartum period, when women come for regular medical care anyway.”
Mathad and colleagues designed the IMPAACT 2001 trial, a phase I/II study, to evaluate the pharmacokinetics and safety of 3HP among pregnant women with or without HIV who had latent TB infection or a household contact with active pulmonary TB.
According to the study, 50 pregnant women were split equally between two cohorts. Cohort 1 had dosing and pharmacokinetics sampling in the second and third trimesters. In cohort 2, these measures were taken in the third trimester and the postpartum period. Pharmacokinetics samples were taken at the time of the first (pre-dose, 0.5h, 1h, 2h, 4h, 5h, 8h, 12h, 24h, 48h and 72h post-dose) and 12th doses (pre-dose, 1h, 4h, 24h and 48h post-dose).
“The purpose of this study was to generate the data needed to help extend the use of 3HP to pregnant women,” Mathad said. “This study was designed to help us identify the right dose for pregnant women with and without HIV and provide some initial safety data to guide future studies and implementation.”
There were 20 pregnant women with HIV in the study, all of whom were taking efavirenz-based ART. The median CD4 count was 510 cells/mm3. All participants finished the 3HP regimen with no drug-related serious adverse events and no cases of active TB in women or their infants. Additionally, among women without HIV, oral clearance of rifapentine was 36% lower during pregnancy (1.24 L/h) than in the postpartum period (1.68 L/h). Among women with HIV, oral clearance of rifapentine was the same during pregnancy and the postpartum period (1.60 vs.1.61 L/ hr), which was 34% higher (P < .001) compared with pregnant women without HIV.
“The rifapentine regimen used in nonpregnant people results in equivalent drug exposure levels in pregnant women, including those with HIV,” Mathad concluded. “This suggests that the treatment will be equally effective in pregnant patients. The safety data from our trial [are] encouraging, but we will need larger studies to establish the safety of this regimen definitively.” – by Caitlyn Stulpin
Mathad JS, et al. Abstract 144LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.
Disclosure: Mathad reports no relevant financial disclosures.