Bictegravir versus Sofosbuvir/Velpatasvir/Voxilaprevir
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Study Design
The DDI studies were multiple-dose, randomized, and cross-over in design. Subjects received HIV ARV regimens including bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) 50/200/25 mg, FTC/rilpivirine (RPV)/TAF 200/25/25 mg, elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF 150/150/ 200/10 mg, or darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg + FTC/tenofovir disoproxil fumarate (TDF) 200/300 mg and HCV DAAs SOF/VEL/VOX (400/100/100 mg) + VOX (100 mg), alone or in combination. The additional 100 mg of VOX was administered to the healthy subjects to approximate systemic VOX exposures observed in the HCV-infected population. Steady-state plasma concentrations of SOF, its predominant circulating nucleoside metabolite GS-331007, VEL, VOX, and ARVs were analyzed and PK parameters were calculated. Geometric least-squares means ratios and 90% confidence intervals (combination vs alone) for PK parameters (AUC, Cmax, and Ctau [as applicable]) were estimated and compared against lack of PK alteration boundaries of 70% to 143% for all analytes. Safety assessments were conducted throughout the study.
Study Results
116 of 120 enrolled subjects (n=30/cohort) completed the studies; overall, 4 subjects discontinued due to withdrawal of consent. The majority of adverse events (AEs) were Grade 1 or 2 and there were no discontinuations due to AEs and no serious AEs. Overall exposure (AUC) of BIC, FTC, RPV, DRV, and EVG was unaltered by coadministration with SOF/VEL/VOX. COBI and RTV AUC were 50% and 45% higher, respectively, when administered with SOF/VEL/VOX. TAF and TFV AUC were 52% to 58% higher and 67% to 79% higher, respectively, when the unboosted regimens were administered with SOF/ VEL/VOX. TAF and TFV AUC from EVG/COBI/ FTC/TAF were unaltered when coadministered with SOF/VEL/VOX. TFV AUC from DRV+RTV+ FTC/TDF was 39% higher when administered with SOF/VEL/VOX. Overall exposure (AUC) of SOF and VEL were unaltered following administration of SOF/ VEL/VOX with the ARV regimens. GS-331007 was 43% higher when EVG/COBI/FTC/TAF was administered with SOF/VEL/VOX. VOX AUC was unaffected by administration with unboosted regimens, but higher VOX AUC (143% to 171%) were observed with boosted ARV regimens.
Study Conclusions
Study treatments were well tolerated. There were no clinically relevant changes in the PK of ARVs, SOF, GS-331007, or VEL with coadministration. Unboosted regimens did not impact VOX PK; higher VOX exposures were observed with boosted ARV regimens.
References
Garrison K, Mogalian E, Zhang H, Ma G, West S, Martin H. Evaluation of drug-drug interactions between sofosbuvir/velpatasvir/voxilaprevir and boosted or unboosted hiv antiretroviral regimens. International Workshop On Clinical Pharmacology Of Antiviral Therapy. Chicago, IL, USA. 18; June 2017.
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