CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Poster and Themed Discussion Abstracts

418 ABCG2 RS2231142 INFLUENCES TFV CONCENTRATIONS IN PLASMA AND URINE Margherita Bracchi 1 , Megan Neary 2 , Nicole Pagani 1 , Laura Else 2 , Saye Khoo 2 , Zaheer Abbas 1 , David Hawkins 1 , Graeme Moyle 1 , Andrew Owen 2 , Marta Boffito 3 1 Chelsea and Westminster Hosp, London, UK, 2 Univ of Liverpool, Liverpool, UK, 3 Chelsea and Westminster NHS Fndn Trust, London, UK Background: Tenofovir (TFV) disoproxil fumarate (TDF) is recommended by WHO as a first-line antiretroviral therapy and its use post-patent expiry is predicted to increase. This study investigated the association between pharmacogenetic variants linked to TFV metabolism / excretion, and TFV plasma and urine concentrations in patients receiving TFV as part of different regimens. Methods: This prospective, longitudinal, PK evaluation studied a total of 56 HIV positive patients receiving TFV combined with raltegravir (RAL) (n = 18), dolutegravir (DTG) (n = 19) or elvitegravir and cobicistat (EVG/COBI) (n = 19). Whole blood, plasma and urine samples were taken for pharmacogenetic and pharmacokinetic analysis at study week 4. TFV concentration in blood plasma and urine at steady state were determined using validated LC-MS/MS. ABCC4 4131T>C (rs3742106), ABCC10 2843T>C (rs2125739), ABCC10 526G>A (rs9349256), ABCC2 1249G>A (rs2273697), ABCC2 -24C>T (rs717620), ABCC2 3563T>A (rs17222723), ABCC2 3972C>T (rs3740066) and ABCG2 421C>A (rs2231142) were genotyped using TaqMan assays. Associations between patient genotype and TFV concentrations were determined through univariate and multivariate linear regression. Results: The study group included HIV-infected adults (53 men, 3 women). Patient ethnicities were Caucasian (n = 42), Black (n = 2), Asian (n = 4), Mixed Race (n = 2) and Other (n = 3), 3 patients had unspecified ethnicity. All genotypes were in Hardy-Weinberg equilibrium. ABCG2 421C>A (rs2231142) was associated with lower TFV plasma (P = 0.030, β = -0.213) and urine (P = 0.001, β = -0.473) concentrations (log10 ng/mL). No other genetic associations were observed. Ethnicity classification of ‘Other’ was associated with lower plasma (P = 0.047, β=-0.353) and urine (P = 0.030, β = -0.476) TFV concentrations compared to the Caucasian ethnicity group but the extremely small number of these patients should be considered. Patients receiving EVG/COBI were associated with lower urine (P = 0.006, β = -0.325) TFV concentration compared to the RAL group. Conclusion: This is the first study to demonstrate that ABCG2 421C>A (rs2231142) influences TFV plasma and urine concentrations. TDF but not TFV has previously been demonstrated to interact with ABCG2 and thus further investigation is warranted to confirm and elucidate the mechanism of this association. 419 TFV-DP IN DRIED BLOOD SPOTS (DBS) FOLLOWING DIRECTLY OBSERVED THERAPY: DOT-DBS STUDY Peter Anderson 1 , Albert Y. Liu 2 , Jose Castillo-Mancilla 1 , Sharon Seifert 1 , Cricket McHugh 1 , Theresa Wagner 2 , Susan Buchbinder 2 , Lane Bushman 1 , Jennifer J. Kiser 1 , Samantha MaWhinney 1

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