CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

by LCMS or a low-cost qualitative assay excluded the presence of PI mutations in pol with a high degree of certainty. Drug level testing at PI failure is a highly accurate screening strategy to identify patients who would benefit from costly drug resistance testing. 462 PLASMA EFV AND TFV VS DRIED BLOOD SPOT TFV-DP TO PREDICT VIRAL SUPPRESSION IN WOMEN Tamsin K. Phillips 1 , Phumla Sinxadi 1 , Elaine J. Abrams 2 , Allison Zerbe 2 , Nai- Chung Hu 1 , Yolanda Gomba 1 , Kirsty Brittain 1 , Jennifer Norman 1 , Lubbe Wiesner 1 , Landon Myer 1 , Gary Maartens 1 1 University of Cape Town, Cape Town, South Africa, 2 ICAP at Columbia University, New York, NY, USA Background: Tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) strongly predicts viral suppression (VS) in people on antiretroviral (ARV) treatment but the assay is expensive and time-consuming. There are no data on the relative performance of DBS TFV-DP and plasma ARV concentrations to predict VS. Methods: A cross-sectional analysis was done among HIV-positive, non- pregnant, black South African women who started tenofovir disoproxil fumarate, emtricitabine, and efavirenz (EFV) in a prior pregnancy and had not switched regimens. Blood was drawn to analyse EFV and tenofovir (TFV) concentrations in plasma and TFV-DP in DBS. A three-item scale measured 30-day self-reported adherence. Logistic regression (reported as adjusted odds ratios [aOR] with 95% confidence intervals [CI]) and area under the curve (AUC) from receiver operating characteristic (ROC) analyses were used to estimate the relationship between ARV concentration and VS (<50 copies/mL). Results: We enrolled 137 women (mean 33 years old; median 4 years on ART). The proportions of plasma EFV, TFV and DBS TFV-DP concentration below the limit of quantification differed by VS (p<0.001): 76%, 78% and 74% in 49 unsuppressed women, versus 2%, 11% and 2% in 88 suppressed women. In women with VS, median plasma EFV, TFV and DBS TFV-DP concentrations were 1.9µg/mL (IQR 1.4-2.7), 44.3ng/mL (IQR 26.6-61.5) and 961.5 fmol/punch (IQR 695.5-1364.5), respectively. All ARVs were predictive of VS in ROC analyses: DBS TFV-DP (0.926 [0.876-0.976]) had a higher AUC than plasma TFV (0.864 [0.797- 0.932]; p=0.006) while plasma EFV (0.903 [0.839-0.967]) was not significantly different from DBS TFV-DP (p=0.138) or plasma TFV (p=0.140). All ARV assays performed better than self-report (Figure). Using existing thresholds for TFV-DP in DBS from healthy volunteers, the association with VS strengthened with increasing concentration (reference <350 fmol/punch: 350-699 fmol/punch aOR 37 [8-178]; 700-1249 fmol/punch aOR 47 [13-175]; ≥1250 fmol/punch aOR 175 [20-1539]); this dose-response relationship was not evident for plasma EFV or TFV. “White coat adherence” (defined as DBS TFV-DP <350 fmol/punch with any detectable plasma TFV) was only detected in 4 women. Conclusion: Plasma EFV, TFV and DBS TFV-DP were all strong predictors of VS in this cohort. While TFV-DP concentrations provide additional insight into adherence behaviour, plasma EFV and TFV concentrations performed almost as well and may warrant consideration as adherence tests in low-resource settings.

463 TENOFOVIR DIPHOSPHATE IN DRIED BLOOD SPOTS FOLLOWING ESCALATING TAF/FTC DOSING

Jenna Yager 1 , Jose R. Castillo-Mancilla 1 , Mustafa E. Ibrahim 1 , Kristina M. Brooks 1 , Cricket McHugh 1 , Samantha MaWhinney 1 , Mary Morrow 1 , Scott McCallister 2 , Lane R. Bushman 1 , Jennifer J. Kiser 1 , Peter L. Anderson 1 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Gilead Sciences, Inc, Foster City, CA, USA Background: The DISCOVER study will compare daily tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) versus tenofovir alafenamide (TAF)/ FTC (25mg/200mg) as HIV pre-exposure prophylaxis (PrEP). DISCOVER uses tenofovir-diphosphate (TFV-DP) in red blood cells measured with dried blood spots (DBS) as an objective adherence measure as it exhibits a 17 day half-life and has a large dynamic range of accumulation that is proportional to adherence. Adherence benchmarks were previously established following TDF/ FTC dosing, but not TAF/FTC dosing. This independent study assessed expected benchmarks for TFV-DP in DBS with TAF/FTC dosing. Methods: HIV-uninfected adults at low risk for HIV infection were randomized to one of 6 sequences consisting of two directly observed TAF/FTC dosing regimens (33%, 67% or 100% of daily dosing). Each regimen was given for 12 weeks, separated by a 12-week washout. Doses were observed in person or by video streaming. Blood was collected pre-dose and 4 hours post-dose on day 1, then weekly throughout the study including washout. DBS (5x25 µL) were collected on protein saver cards. TFV-DP was quantified from various punch sizes to target adherence benchmarks close to those previously observed for TDF/FTC dosing. Available samples fromweeks 10, 11, & 12 (first TAF/FTC regimen) were analyzed. Results: Twenty-six participants began study treatment; one was excluded from the analysis for protocol violations. Nine of 25 were randomized to receive 33% of daily dosing, 8 to 67%, and 8 to 100%. Eleven of 25 were male, 16 white, 5 African-American, and 4 Hispanic. Mean (SD) BMI was 25.4 (5.1) kg/m2. TFV-DP values varied by < 10% across weeks 10-12, suggesting steady-state by week 10. When using a 3mm punch, TFV-DP was ~1/8th the median values previously established for TDF/FTC (based on a 3mm punch). These previously established medians were 518, 946, and 1542 fmol/punch for 33%, 67%, and 100% of daily TDF/FTC dosing; coefficients of variation (CVs) were 25-30%. Using 2x7mm punches resulted in TFV-DP median (IQR) values at week 12 of 663 (613-741), 1351 (991-1586), and 1928 (1526-2559) fmol/punches for 33%, 67%, and 100% daily dosing (Figure). Week 12 CVs ranged from 28-33%. Conclusion: Following TAF/FTC dosing, two 7mm punches resulted in TFV-DP benchmarks and CVs comparable to those previously established for TDF/ FTC. TFV-DP concentrations appeared to increase in direct proportion to dose, supporting the use of TFV-DP in DBS as an objective adherence measure for TAF/ FTC regimens.

Poster Abstracts

CROI 2019 170