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Pharmacokinetics of Tenofovir Alafenamide When Co-administered With Other HIV Antiretrovirals.

Pharmacokinetics of Tenofovir Alafenamide When Co-administered With Other HIV Antiretrovirals.
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Begley R, Das M, Zhong L, Ling J, Kearney BP, Custodio JM,


Begley R, Das M, Zhong L, Ling J, Kearney BP, Custodio JM, (click to view)

Begley R, Das M, Zhong L, Ling J, Kearney BP, Custodio JM,

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Journal of acquired immune deficiency syndromes (1999) 2018 04 10() doi 10.1097/QAI.0000000000001699

Abstract
BACKGROUND
Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete regimen (elvitegravir/cobicistat/emtricitabine (F)/tenofovir alafenamide (TAF), rilpivirine/F/TAF, bictegravir/F/TAF), or for use with other ARVs (F/TAF), for treatment of HIV. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Disposition of TAF may be altered by co-medications that can inhibit or induce P-gp or BCRP transporters. The effects of ARVs on the pharmacokinetics (PK) of TAF were evaluated in 3 studies.

METHODS
Healthy participants received TAF administered alone or with rilpivirine (RPV) in study 1; with dolutegravir (DTG), ritonavir boosted atazanavir (ATV+RTV), lopinavir (LPV/RTV), or darunavir (DRV+RTV) in study 2; and with the pharmacokinetic enhancer cobicistat (COBI), or efavirenz (EFV) in study 3.

RESULTS
Across the three studies, 98 participants received treatment with TAF and a coadministered agent (n=10-34/cohort). All study treatments were well tolerated. TAF and TFV exposures were unaffected following co-administration with RPV and DTG. Co-administration with Pgp/BCRP inhibitors such as COBI or PI based regimens (ATV+RTV, LPV/r or DRV+RTV) resulted in a range of 6% to 183% increases in TAF and 105% to 316% increases in TFV exposure, while co-administration with a Pgp inducer, EFV, resulted in a 15% to 24% decrease in TAF and TFV exposure.

CONCLUSIONS
Evaluation of the drug interaction between TAF and other commonly prescribed boosted and unboosted ARVs provides characterization of the susceptibility of TAF and/or TFV PK to inhibitors or inducers of Pgp/BCRP transporters.

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