CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

431 Pharmacokinetics of Crushed Elvitegravir Combination Tablet GivenWith Drip Feed Angela Colbers 1 ; Mieke de Hoon 1 ; Reinout van Crevel 1 ; Martine Kruijssen 1 ; Marjolijn Duisenberg-van Essenberg 2 ; Evertine Abbink 1 ; David M. Burger 1 1 Radboud Univ Med Cntr, Nijmegen, Netherlands; 2 Elisabeth-TweeSteden Ziekenhuis, Tilburg, Netherlands Background: If HIV-patients are unconscious or cannot swallow tablets for other reasons, antiretroviral medication is often crushed and solved prior to administration. Currently, there is no information about crushing the fixed-dose combination of elvitegravir/cobicistat/emtricitabine/tenofovir (E/C/E/T). Crushing can influence pharmacokinetics (PK) leading to altered drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Therefore crushing of E/C/E/T is not recommended. A possible PK interaction between elvitegravir (EVG) and drip feed is expected, based on the interaction between EVG and antacids. No interaction occurs between other pH-increasing drugs (omeprazole) and EVG, therefore the interaction is most likely caused by complexation between EVG and cations. Methods: An open-label, 3-period, randomized, cross-over, trial in 24 healthy volunteers was conducted. Subjects randomly received a single dose of STB with a 7-day washout period. Reference treatment A: E/C/E/T whole tablet with breakfast (350 kcal), intervention treatments B: crushed and suspended E/C/E/T with breakfast and C: crushed and suspended E/C/E/T with drip feed (350kcal). To show bioequivalence between reference A versus B and C a 32-h PK profile was measured for EVG, COBI (cobicistat), FTC (emtricitabine) and TDF (tenofovir). Geometric mean ratios (GMR) with 90% confidence interval (CI) for AUC and Cmax were calculated. Safety and tolerability were evaluated. Results: 24 healthy volunteers (23 Caucasian and 1 mixed-race,12 female), 37(20-54) years and BMI of 24(19-29) (median (range)) were included in the trial. The GMR (90% CI) of Cmax and AUC of EVG were 117% (106-129) and 109% (99-120) for B vs A, 104% (94-115) and 104% (94-114) for C vs A. GMR of Cmax and AUC for COBI were 83% (76-91) and 89% (82-97) for B vs A and 101% (92-110) and 102% (94-111) for C vs A. For FTC the GMR of AUC and Cmax were 89% (83-97) and 99% (95-104) for B vs A and 96% (89-104) and 101% (97-106) for C vs A. For TDF the GMR of AUC and Cmax were 81% (71-92) and 100% (92-113) for B vs A and 94% (83-107) 105% (97-108) for C vs A. No SAEs were reported during the trial. Conclusions: AUCs fell within the bioequivalence ranges for all compounds. For Cmax the 90% CI were just outside the bioequivalence range, but this was considered not clinically relevant. E/C/E/T can be crushed and suspended and given with drip feed. 432 Minimal Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients José Moltó 1 ; Fredzzia Graterol 2 ; Cristina Miranda 1 ; Ioana Bancu 2 ; Saye Khoo 3 ; Alieu Amara 3 ; Anna Bonjoch 1 ; Bonaventura Clotet 1 1 Lluita Contra la SIDA Fndn, Germans Trias i Pujol Univ Hosp, Barcelona, Spain; 2 Hosp Universitari Germans Trias i Pujol, Badalona, Spain; 3 Univ of Liverpool, Liverpool, UK Background: Dolutegravir can be safely administered to HIV-infected patients with advanced kidney disease (GRF <30 ml/min). However, little is known about dolutegravir removal by hemodialysis in patients with end-stage renal disease (ESRD). Our objective, therefore, was to evaluate the effect of hemodialysis on dolutegravir clearance in five anuric ESRD HIV-infected patients undergoing routine hemodialysis.

Poster Abstracts

Methods: Exploratory clinical trial including 5 HIV-infected patients on stable antiretroviral treatment with ESRD undergoing routine hemodialysis. After enrolment (day 1), dolutegravir (Tivicay, Viiv) 50 mg once daily was added to antiretroviral treatment for five days. Blood samples were collected at the beginning and at the end of the dialysis session on day 5. Additionally, paired blood samples going into (predialyzer) and out (postdialyzer) of the dialyzer membrane, as well as a dialysate sample were collected during the dialysis session. Dolutegravir concentrations in plasma and in dialysate were determined by LC-MS/MS.

Results: Five patients were included in the study. Two patients underwent conventional hemodialysis sessions while the three remaining underwent online hemodiafiltration (HDF-OL). Blood flows were held constant at 300 ml/min for patients on conventional hemodialysis, and at 400 ml/min for patients on HDF-OL. Dialysate flow was held constant at 500 ml/min for all participants. Dolutegravir concentrations in plasma and in dialysate are depicted in the table. Mean dolutegravir concentrations in plasma at the end of the dialysis session remained 30 fold above the protein binding-adjusted 90% inhibitory concentration. Conclusions: Our results showminimal removal of dolutegravir by hemodialysis. Dolutegravir dosage adjustments seem, therefore, to be unnecessary in HIV-infected patients with ESRD undergoing hemodialysis.

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CROI 2016