CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

acquisition among injectable contraceptive users in some observational studies. For studies of HIV prevention among women, Yc DNA detection is a feasible biomarker to obtain and complements self-reported sexual behavior data. 866 Higher Cumulative TFV/FTC Levels in PrEP AssociatedWith Decline in Renal Function Monica Gandhi 1 ; DavidV. Glidden 1 ; AlbertY. Liu 2 ; Howard Horng 1 ; K. R. Amico 3 ; Kathleen Mulligan 1 ; Sybil Hosek 4 ; Mauro Schechter 5 ; Kenneth H. Mayer 6 ; Robert Grant 1 ; for the iPrEx StudyTeam 1 Univ of California San Francisco, San Francisco, CA, USA; 2 San Francisco Dept of PH, San Francisco, CA, USA; 3 Univ of Michigan Sch of PH, Ann Arbor, MI, USA; 4 John H. Stroger Jr Hosp of Cook County, Chicago, IL, USA; 5 Projeto Praça Onze, Universidade Fed do Rio de Janeiro, Rio de Janeiro, Brazil; 6 The Fenway Inst, Fenway Hlth, Boston, MA, USA Background: PrEP is proven to reduce the risk of HIV acquisition. Drug levels (as markers of adherence) have been critical to interpreting disparate outcomes in PrEP trials, but can also be assessed (as markers of exposure) in relationship to adverse effects. Concentrations of tenofovir (TFV) and emtricitabine (FTC) in hair represent cumulative exposure and may be associated with toxicities in HIV-uninfected persons. We report for the first time, in a large PrEP demonstration study, the relationship between TFV/FTC levels in hair and renal function over time.

Methods: The iPrEx Open Label Extension (OLE) study enrolled HIV-negative MSM and transwomen and all were on PrEP. Hair samples were collected every 12 weeks and levels of TFV/ FTC measured via liquid chromatography/tandemmass spectrometry. Serum creatinine (Cr) was measured every 12 weeks and glomerular renal function (eGFR) estimated by Cockcroft-Gault (CG) or the MDRD equation. The association between change in eGFR over time (adjusted for baseline eGFR) and TFV/FTC levels (categorized into quartiles) was analyzed by generalized estimating equations. Results: Hair data and creatinine measures were available for 1144 person-visits in 202 participants followed for a median of 16.8 months. Median age 29 years (19-70); 91%MSM; 22%White, 11% Black, 6% Asian, 60% Latino/mixed. Baseline mean Cr level was 0.89mg/ dL with a median baseline eGFR of 112mL/min (99-128). The eGFR for all participants on TFV/ FTC decreased over 18 months, but there was a monotonic relationship between % decrease in eGFR with increasing quartile of hair level for TFV (p 0.008) and FTC (p 0.006) ( Figure ). For instance, mean % change in eGFR from baseline was -2.6ml/min (SE 0.8) in person-visits with TFV levels in the 1st quartile, but -5.6 (SE 0.7) when hair levels were in the 4 th quartile. The odds of eGFR falling below 70 ml/min (6.1% of sample) increased with increasing quartile of TFV/FTC concentration (OR 4.4 (1.1-17.4) for 4 th TFV hair quartile, p trend 0.045; OR 4.0 (0.9- 17.2) for 4 th FTC quartile, p trend 0.027). Conclusions: We show for the first time that greater long-term exposure to TFV or FTC in patients on PrEP is associated with declining renal function over time. Hair levels of TFV/FTC were associated with decreases in eGFR and a higher likelihood of eGFR falling to <70mL/min in a monotonic fashion in iPrEX OLE. Establishing thresholds of TFV/FTC exposure that protect from HIV, but minimize the risk of toxicity, is essential to the real-world roll-out of PrEP.

867 Changes in Renal Function AssociatedWith TDF/FTC PrEP Use in the US Demo Project Albert Y. Liu 1 ; EricVittinghoff 2 ; Peter L. Anderson 3 ; Stephanie Cohen 1 ; Susanne Doblecki-Lewis 4 ; Oliver Bacon 1 ;Wairimu Chege 5 ; Susan P. Buchbinder 1 ; Michael Kolber 4 ; Richard Elion 6 ; for the Demo ProjectTeam 1 San Francisco Dept of PH, San Francisco, CA, USA; 2 Univ of California San Francisco, San Francisco, CA, USA; 3 Univ of Colorado, Denver, CO, USA; 4 Univ of Miami, Miami, FL, USA; 5 DAIDS, NIAID, NIH, Bethesda, MD, USA; 6 George Washington Univ Sch of Med, Washington, DC, USA

Poster Abstracts

Background: Several trials have demonstrated the safety and efficacy of TDF/FTC pre-exposure prophylaxis (PrEP). Renal toxicity was uncommon in randomized trials of healthy individuals, but has not been assessed in clinical settings. We evaluated changes in renal function among participants enrolled in the open-label US PrEP Demonstration Project. Methods: The Demo Project enrolled HIV-negative MSM and transwomen (TGW) in STI clinics and a community health center. Eligible participants [creatinine clearance (CrCl) ≥60 ml/min] were offered 48 weeks of TDF/FTC PrEP. Creatinine (Cr) was measured every 12 weeks and CrCl estimated by the Cockcroft Gault equation. Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were measured in a subset of subjects. The associations of time-dependent factors with visit-to-visit changes in CrCl were assessed using linear mixed models.

Results: From October 2012 to January 2014, 557 MSM and TGW enrolled. Median age was 35 (range 18-65); 48%were White, 35% Latino, 7% Black, 5% Asian, and 6% other; 98%were MSM. Baseline median Cr was 0.92 (0.59-1.55), with a median CrCl of 124 ml/min (71-309). DBS were tested at 1,067 person-visits among 294 participants, with TFV-DP levels consistent with ≥4 doses/week in 82% of person-visits. Median CrCl declined 6 ml/min (5%) from baseline to week 12 and remained stable through week 48 (p=0.96), with no differences by race/ethnicity, weight, or NSAID use. However, 30% had >10% decline in CrCl at week 12. TFV-DP levels ≥2 vs. <2 doses/week were associated with a greater decline in CrCl at week 12 (-7.6 ml/min vs. +3.6 ml/ min, p=0.001) (figure). In a multivariable model, age<25 (7.7 ml/min greater decline), use of hypertension or diabetes medications (6.1 ml/min greater decline), and TFV-DP levels ≥2 doses/week (12.8 ml/min greater decline) were independently associated with greater CrCl loss. The age effect was not explained by alcohol or recreational drug use. No subjects had CrCl <60 ml/min during follow-up. TDF/FTC was held in 3 subjects due to elevated creatinine, however these were not confirmed on repeat testing, and PrEP was restarted in all cases with no further interruptions. Conclusions: MSM initiating PrEP in the Demo Project had an overall modest, non-progressive decline in renal function, with a threshold effect for TFV-DP levels >2 doses/week. Younger PrEP users and those taking medications for hypertension or diabetes had greater decreases in CrCl and may warrant additional monitoring during PrEP use.

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CROI 2016