Two pharmacokinetic studies from AIDS 2018 help elucidate the disposition of tenofovir alafenamide (TAF) and cobicistat-boosted darunavir during pregnancy.
The IMPAACT P1026s study examined plasma concentrations of TAF with and without cobicistat in 43 pregnant women. For women taking 25 mg of TAF daily (as part of the single-pill combination regimen TAF/emtricitabine/rilpivirine [Odefsey]), TAF AUCs in both the 2nd and 3rd trimesters were much lower than those observed at 6-12 weeks postpartum (162 vs 184 vs 390 ng*hr/mL). For women taking TAF 10 mg with cobicistat 150 mg (in the regimen TAF/emtricitabine/elvitegravir/cobicistat [Genvoya]), AUCs were comparable across the 2nd and 3rd trimesters versus postpartum (197 vs 209 vs 213 ng*hr/mL).
IMPAACT P1026s also looked at the pharmacokinetic profile of darunavir boosted with cobicistat in 29 pregnant women. Both the AUC and trough concentrations of darunavir were significantly lower in the 2nd and 3rd trimesters compared with postpartum (AUC: 47.22 vs 43.62 vs 96.03 µg*hr/mL, and C24: 0.44 vs 0.49 vs 1.45 µg/mL). Trough values for many women fell below EC50 levels for wild-type HIV virus, and were substantially lower than trough values achieved in studies of once-daily darunavir/ritonavir or twice-daily darunavir/ritonavir in pregnant women. Data on cobicistat levels were not presented in this study, but are being examined by the study team.
Clinical Bottom Line
This results of this study showed that TAF levels in the 2nd and 3rd trimesters were sharply lower than they were after pregnancy. However, TAF levels remained close to those found in nonpregnant women if TAF was used in a regimen containing cobicistat. Additional studies, including evaluations of maternal viral load and infant outcomes, are needed before TAF should be used during pregnancy. TAF currently is not recommended by the U.S. DHHS guidelines for use in pregnant women, due to lack of data.
The study results also suggest that, because of the low darunavir AUC and trough levels observed with darunavir/cobicistat during the 2nd and 3rd trimesters, pregnant women who require a darunavir-containing regimen should use ritonavir as the pharmacokinetic booster. At this time, darunavir/cobicistat-based regimens should be avoided in pregnant women unless used in consultation with a perinatal HIV expert.
Momper JD, Best B, Wang J, et al. Tenofovir alafenamide pharmacokinetics with and without cobicistat in pregnancy. In: Program and abstracts of the 22nd International AIDS Conference; July 23-27, 2018; Amsterdam. Abstract THAB0302.
Momper JD, Best B, Wang J, et al. Pharmacokinetics of darunavir boosted with cobicistat during pregnancy and post-partum. In: Program and abstracts of the 22nd International AIDS Conference; July 23-27, 2018; Amsterdam. Abstract WEPEB118.