CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

91 NEAR-PERFECT ACCURACY OF A REAL-TIME URINE TENOFOVIR TEST COMPARED TO LAB-BASED ELISA Matthew A. Spinelli 1 , Warren Rodrigues 2 , Guohong Wang 2 , Michael Vincent 2 , David Glidden 1 , Randy Stalter 3 , Patricia A.Defechereux 1 , Madeline Deutsch 1 , Robert M. Grant 1 , Kenneth Ngure 4 , Nelly R. Mugo 3 , Jared Baeten 3 , Monica Gandhi 1 , for the Partners PrEP and IBrEATHe 1 University of California San Francisco, San Francisco, CA, USA, 2 Abbott Labs, Abbott Park, IL, USA, 3 University of Washington, Seattle, WA, USA, 4 Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya Background: Therapeutic drug monitoring measures adherence to tenofovir (TFV)-based PrEP more accurately than self-report but has not been available at the point-of-care (POC) until now. We developed an ELISA using a highly-selective antibody to TFV in urine and previously validated it against spectrometry-based methods with high accuracy. We have now developed a lateral flow immunoassay (LFA) using this antibody, which permits testing at the POC. A cut-off for the LFA of 1,500 ng/ml was previously selected from a directly observed therapy study to accurately classify recent dosing. The objective of this analysis was to compare a novel POC test for PrEP to laboratory- based ELISA in diverse patient populations. Methods: Urine samples were analyzed using the ELISA and POC LFA test from two cohorts of PrEP users taking tenofovir disoproxil fumarate/emtricitabine: the Partners PrEP Study, which recruited heterosexual men and women, and the IBrEATHe Study, which recruited transwomen using estrogen and transmen using testosterone hormone therapy. We calculated the sensitivity and specificity of the POC test compared to laboratory-based ELISA at a cut-off of 1,500 ng/ml. Results: Overall, 684 urine samples were tested from 324 participants in the two cohorts. In Partners PrEP, 454 samples from 278 participants (41% cisgender women) were tested; the median age was 33 years (interquartile range [QR] of 28-39). In IBrEATHe, 231 samples from 46 individuals (50% transwomen) were tested; the median age was 31 (IQR 25-40). Overall, of the 505 samples with tenofovir (TFV) levels greater than or equal to the cut-off using lab-based ELISA, 505 of the POC test results were also positive, yielding 100% sensitivity. Of the 179 samples with TFV levels below the cut-off, 178 were negative with the POC test, yielding 99.4% specificity. The accuracy of the POC LFA was 99.8% compared to ELISA. Conclusion: In 324 women and men (both cisgender and transgender) taking PrEP, the sensitivity, specificity, and accuracy of a novel POC test for urine TFV all exceeded 99%when compared to a lab-based ELISA method. Given the association of low urine TFV levels with HIV seroconversion events, the simplicity of using the LFA, and its expected low cost, this POC test is a promising tool to support adherence to PrEP that could be widely scalable to real-world clinical settings. Adherence support using this POC test should be evaluated in a randomized controlled trial.

1 Yale University, New Haven, CT, USA, 2 Hospital Universitario de Bellvitge, Barcelona, Spain, 3 Hoag Medical Group, Newport Beach, CA, USA , 4 Hennepin Healthcare Research Institute, Minneapolis, MN, USA, 5 University of California Davis, Davis, CA, USA, 6 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 7 University College London, London, UK, 8 Gilead Sciences, Inc, Foster City, CA, USA, 9 Maple Leaf Medical Clinic, Toronto, ON, Canada, 10 Hvidovre Hospital, Hvidovre, Denmark, 11 University Hospital Klinikum rechts der Isar, Munich, Germany Background: In DISCOVER, a multinational, double-blind, randomized controlled trial, F/TAF compared to F/TDF demonstrated noninferior efficacy for HIV prevention and improved bone mineral density (BMD) and renal safety biomarkers at week (W) 48. We now report W96 safety outcomes. Methods: We evaluated renal and lipid parameters and weight changes in participants on F/TAF vs F/TDF through W96. BMD was evaluated in a substudy and also examined in younger participants (age <25 yrs) who are still accruing bone mass. We also examined glomerular function, proteinuria, and biomarkers of proximal tubular injury (PTI; β2M/Cr, RBP/Cr) in participants ≥50 yrs of age and those with moderate renal impairment (eGFR 60‒<90 mL/min). Results: Among 5387 participants evaluated, unlike those on F/TDF (n=2693), F/TAF users had significantly increased BMD, with the magnitude of between- group differences increasing between W48 to W96 (Table 1). Participants <25 yrs had greater declines in BMD on F/TDF with a greater magnitude of difference between groups than those ≥25 yrs. Overall, F/TAF users had increases in eGFR and declines in UPCR and PTI biomarkers. Older participants on F/TDF had a greater magnitude of decline in eGFR and a greater increase in UPCR and PTI markers compared to younger F/TDF users. Similarly, those with eGFR 60‒<90 mL/min had greater statistically significant changes in PTI markers, if on TDF, compared with those with eGFR ≥90 mL/min. Those on F/TAF had stable lipids through W96, whereas those on F/TDF had decreases in lipids at W48 and W96. Those on F/TDF had a smaller weight increase than those on F/TAF through W96 (Table 1). Conclusion: These DISCOVER data allow for the largest single-variable comparison of the two tenofovir prodrugs without underlying HIV infection and in the absence of third antiretroviral agents. Overall, those on F/TAF had increased BMD compared to declines in those on F/TDF, with more pronounced differences in younger participants. Older participants on F/TDF and those with impaired renal function had more adverse impact on renal biomarkers. Lipid and weight changes were consistent with the known lipid-lowering and weight suppressive effects of TDF, respectively. F/TAF is a safe, longer-term option for PrEP, with certain subgroups experiencing a greater magnitude of benefit in BMD and renal biomarkers.

Oral Abstracts

92 LONGER-TERM SAFETY OF F/TAF AND F/TDF FOR HIV PREP: DISCOVER TRIAL WEEK-96 RESULTS Onyema Ogbuagu 1 , Daniel Podzamczer 2 , Laura C. Salazar 3 , Keith Henry 4 , David M.Asmuth 5 , David Wohl 6 , Richard Gilson 7 , Yongwu Shao 8 , Ramin Ebrahimi 8 , Christoph Carter 8 , Moupali Das 8 , Scott McCallister 8 , Jason M. Brunetta 9 , Gitte Kronborg 10 , Christoph D. Spinner 11

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CROI 2020