Tenofovir alafenamide vs ARVs
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Study Design
This was an open-label, fixed sequence, crossover study to evaluate the effect of dolutegravir (DTG) 50mg on the pharmacokinetics (PK) of tenofovir alafenamide (TAF) 10mg plus emtricitabine (FTC) 200mg (n=9). Treatments were administered in the morning with food as follows:Day 1: FTC + TAF 200/10mg QD; Days 2-14: DTG 50mg QD; Day 15: FTC + TAF 200/10mg + DTG 50mg QD.Plasma samples for PK analysis were collected over 24 hours on days 1, 14 and 15.
Study Results
Using 90% confidence intervals and geometric mean ratios, when LPV/r was co-administered with FTC and TAF the AUCinf and Cmax for TAF was 1.45 (1.14-1.84) and 2.19 (1.72-2.79), respectively, compared to administration of FTC + TAF alone.The exposure of tenofovir (TFV; active form of TAF) was also analyzed with and without LPV/r; AUCinf and Cmax of TFV was 4.16 (3.50-4.96) and 3.75 (3.19-4.39), respectively, compared to administration of FTC + TAF alone.AUC, Ctau and Cmax of LPV was 1.00 (0.92-1.09), 0.98 (0.85-1.12) and 1.00 (0.95-1.06), respectively.TAF and TFV exposure increased upon co-administration with LPV/r, and LPV was unaffected by co-administration with TAF + FTC.These results informed the authors' decision to pursue dosing of a fixed dose combination of FTC + TAF 200/10mg in combination with boosted protease inhibitors.Close monitoring for tenofovir-associated adverse effects is advised due to the very wide confidence intervals reported.
Study Conclusions
With unboosted antiretrovirals, TAF is dosed at 25 mg daily. Because of the pharmacokinetic data above, the manufacturers pursued dosing of TAF at 10 mg, due to inhibition of metabolism by CYP3A.
References
Lawson EB, H Martin, S McCallister, et al. Drug interactions between tenofovir alafenamide and hiv antiretroviral agents. 54th Interscience Conference On Antimicrobial Agents And Chemotherapy. . ; 2014.
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