CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

literature and known PK characteristics of TAF and TDF. TFV-DP concentrations in the ileum and rectumwere lower with TAF compared with TDF; this may be due to better bioavailability of TAF vs. TDF and thus a lower fraction of unabsorbed drug in the gastrointestinal lumen. The higher LN concentrations of TFV-DP achieved with TAF demonstrate that drug penetration into this compartment can be modified in HIV-infected persons. This finding allows pharmacodynamic evaluations to investigate whether enhanced LN concentrations elicit a different virologic response.

Oral Abstracts

105 USING EHR DATA TO IDENTIFY POTENTIAL PrEP CANDIDATES IN A LARGE HEALTH CARE SYSTEM Julia L. Marcus 1 , Leo Hurley 2 , Stacey Alexeeff 2 , Douglas Krakower 3 , Michael J. Silverberg 2 , Jonathan E. Volk 4 1 Harvard Medical School, Boston, MA, USA, 2 Kaiser Permanente Division of Research, Oakland, CA, USA, 3 Beth Israel Deaconess Medical Center, Boston, MA, USA, 4 Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA Background: HIV preexposure prophylaxis (PrEP) prevents HIV acquisition but uptake has been limited. Electronic health record (EHR) data may help identify patients who are at high risk of HIV acquisition and could benefit from PrEP. Methods: We developed and validated a prediction model to identify potential PrEP candidates in a cohort of members of Kaiser Permanente Northern California not diagnosed with HIV and having ≥2 years of enrollment and ≥1 outpatient visit during 2007-2017. Using EHR data on 68 demographic, clinical, and behavioral variables potentially predictive of HIV risk, we applied logistic regression and machine learning methods to predict incident HIV cases in a derivation dataset of patients entering the cohort in 2007-2014. We assessed performance of candidate models by cross-validated area under the curve (AUC, range 0-1). We evaluated how the best-performing model might perform prospectively by validating it among members entering the cohort in 2015- 2017, and compared this full model with simpler models using only traditional risk factor variables (i.e., men who have sex with men [MSM] and sexually transmitted infections [STIs]). Results: Of 3,751,740 eligible patients in 2007-2017, there were 1422 incident HIV cases. The best-performing model for predicting incident HIV was least absolute shrinkage and selection operator (Lasso), with an AUC of 0.90 in 2007- 2014. The final model included 41 predictors, such as Black race, home ZIP code, urine positivity for methadone, and use of medications for erectile dysfunction. The full model performed well when validated prospectively using 2015-2017 data (AUC 0.89). Model performance remained high when excluding the MSM variable (AUC 0.87) or STI variables (AUC 0.90), but was reduced when including only MSM (AUC 0.74), STIs (AUC 0.61), or both (AUC 0.78; Figure). Patients in the top 1% of HIV risk scores included 45/68 (66%) male HIV cases but 0/13 (0%) female HIV cases among those entering the cohort in 2015-2017. Using the top 1% of risk scores to define potential PrEP candidates in 2015-2017, we identified 6076 candidates, of whom 5577 (92%) were not currently on PrEP. Conclusion: Prediction models using EHR data can identify patients who are at high risk of HIV acquisition but not using PrEP, and should be tested as a strategy to improve PrEP use. Models using rich clinical data outperformmodels using only traditional risk factors. Additional EHR variables or other data are needed to identify females who may benefit from PrEP.

104LB THE PHASE 3 DISCOVER STUDY: DAILY F/TAF OR F/TDF FOR HIV PREEXPOSURE PROPHYLAXIS

Charles B. Hare 1 , Josep Coll 2 , Peter Ruane 3 , Jean-Michel Molina 4 , Kenneth H. Mayer 5 , Heiko Jessen 6 , Robert M. Grant 1 , Joss J. De Wet 7 , Melanie Thompson 8 , Edwin DeJesus 9 , Ramin Ebrahimi 10 , Robertino Mera Giler 10 , Moupali Das 10 , Diana Brainard 10 , Scott McCallister 10 1 University of California San Francisco, San Francisco, CA, USA, 2 Hospital Germans Trias i Pujol, Barcelona, Spain, 3 Peter J Ruane, MD Inc, Los Angeles, CA, USA, 4 University Paris Diderot, Paris, France, 5 Harvard Medical School, Boston, MA, USA, 6 Praxis Jessen² + Kollegen, Berlin, Germany, 7 Spectrum Health, Grand Rapids, MI, USA, 8 AIDS Research Consortium of Atlanta, Atlanta, GA, USA, 9 Orlando Immunology Center, Orlando, FL, USA, 10 Gilead Sciences, Inc, Foster City, CA, USA Background: Emtricitabine/tenofovir disoproxil fumarate (F/TDF) prevents HIV infection when used as daily pre-exposure prophylaxis (PrEP). Compared to TDF, tenofovir alafenamide (TAF) has higher intracellular tenofovir (TFV)-DP levels, lower plasma TFV levels, and improved renal and bone safety when used for HIV treatment. This study describes the efficacy and safety of F/TAF vs F/TDF for PrEP in cis-men who have sex with men (MSM) and transgender women (TGW) who are at high risk of HIV acquisition. Methods: This randomized (1:1), double-blind, active-controlled study was conducted in North America and Europe at sites with high HIV prevalence in MSM. Entry required ≥2 episodes of condomless anal sex (CAS) in past 12W or rectal gonorrhea/chlamydia or syphilis in past 24W. Participants received daily blinded F/TAF (200/25 mg) or F/TDF (200/300 mg), with matching placebo; pill counts and blood levels were used to measure adherence. Primary endpoint was the HIV infection rate per 100 person years (PY) when 50% completed 96W. Renal safety, 3 anatomic site sexually transmitted infection (STI) testing and risk behavior were assessed every 12W. Using CDC reported HIV surveillance data we calculated the background “HIV incidence rate” in at risk individuals not on PrEP from 105 US metropolitan statistical areas (MSAs) for comparison. Results: 5387 adults were treated at 94 sites in 11 countries, with 3226 (60%) in the US. Mean age was 36, range 18-76 years, 9% Black, 1% TGW, 23% had prior PrEP use and 41% had >3 receptive CAS partners in the 90 days before study entry. 90% of participants completed ≥48W on study, with median follow up of 84W. For this analysis, 85% remained on study drug: 6% discontinued by participant choice and 6%were lost to follow up. On-study sexual HIV risk persisted with an STI rate of 99.5/100PY. Across both arms, there were 21 HIV diagnoses-an infection rate of 0.26/100 PY-a figure significantly lower than the expected HIV infection rate for those at risk but not on PrEP in the US (Table). Both drugs were tolerated well with 1.5% AE-related discontinuations, with GI most common. Conclusion: In a multinational population of cis-MSM and TGW at risk of sexual HIV infection, the HIV incidence rate on either F/TAF or F/TDF was very low and significantly less than the background rate in those at risk but not on PrEP in the US. In almost 2 years of follow up, both F/TAF and F/TDF, given daily, were tolerated and had low discontinuation rates.

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CROI 2019