TAF exposures during pregnancy and postpartum appear adequate but more data are needed
Polly Clayden, HIV i-Base
Plasma tenofovir alafenamide (TAF) exposures during pregnancy were within the typical range of those in non-pregnant adults but higher than expected postpartum when dosed at 25 mg – according to data from IMPAACT P1026s presented at AIDS 2018.
TAF is a prodrug of tenofovir, manufactured by Gilead, the originator company, as part of a fixed dose combination either with or without the pharmacokinetic (PK) booster cobicistat (COBI). TAF is given at a dose of 25 mg unboosted and 10 mg when boosted with 150 mg COBI.
IMPAACT P1026s is an ongoing, non-randomised, open-label, multi-centre, phase 4 study conducted to characterise antiretroviral PK in HIV positive pregnant women. Those eligible to enroll in the TAF arms were receiving the drug as part of routine clinical care at an IMPAACT site. Mark Mirochnick presented findings from this evaluation of TAF administered with or without COBI on behalf of the study group.
The investigators obtained intensive steady state PK profiles of TAF following once-daily dosing of either rilpivirine/emtricitabine/TAF (R/F/TAF) 25/200/25 mg or elvitegravir/COBI/emtricitabine/TAF (E/C/F/TAF) 150/150/200/10 mg during the second and third trimesters and 6–12 weeks postpartum. Maternal plasma and cord blood samples were collected at delivery
Target TAF exposure was assessed relative to the 10th percentile value in non-pregnant adults.
There were 31 participants enrolled in the TAF 25 mg and 27 in the TAF/COBI 10/150 mg arms. All women were from the US. Their median age at delivery was approximately 32 years. Postpartum sampling was performed at a median of approximately 9 weeks.
Plasma TAF exposures during pregnancy and postpartum were in the range of those observed in non-pregnant adults.
TAF exposure with 25 mg was lower during pregnancy compared with postpartum but Professor Mirochnick explained that this difference was driven by higher than expected AUC postpartum. See Table 1.
Table 1: GMR second and third trimesters/postpartum
|GMR (90% CI)
|GMR (90% CI)
|TAF 25 mg||n=14||n=25|
|AUC0-t (ng*hr/mL)||0.57 (0.34 to 0.98)||0.66 (0.54 to 0.82)|
|TAF/COBI 10/150 mg||n=14||n=22|
|AUC0-t (ng*hr/mL)||0.79 (0.50 to 1.27)||0.86 (0.66 to 1.12)|
The proportion of participants exceeding the TAF target AUC ranged from 84–96% without differences during pregnancy and postpartum.
One grade 2 maternal adverse event (probable hepatic steatosis) was considered to be possibly related to study drug.
Congenital anomalies considered possibly related to study drugs included left congenital pseudoarthrosis clavicle in one infant and renal cyst in another.
At the time of analysis 46 infants were HIV negative, 8 indeterminate and 4 pending.
Analyses of all maternal delivery samples, cord blood samples and infant washout samples are not yet complete but TAF was below the limit of quantification (3.95 ng/mL) in all 15 cord blood samples tested to date.
This group are planning to look at intracellular levels of TAF in pregnancy and postpartum.
These are the first publicly presented data on TAF in pregnancy.
TAF 25 mg is considered to be a potential component of optimised ART for low- and middle-income countries. But lack of data in populations who are treated in these settings, including pregnant women, has meant that it has not been recommended in WHO guidelines or included in the Essential Medicines List.
Before TAF can be recommended for use in pregnancy additional safety and outcome data from larger numbers of women and their infants (including preconception exposure) as well as intracellular PK data are needed.
Momper JD et al. Tenofovir alafenamide pharmacokinetics with and without cobicistat in pregnancy.AIDS 2018. Amsterdam. 23–27 July 2018. Oral abstract THAB0302.