CROI 2015 Program and Abstracts

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Oral Abstracts

and chronic renal impairment (CRI) as confirmed (>3 months apart) eGFR <70 ml/min/1.73m 2 . Poisson regression was used to estimate the incidence of CKD associated with cumulative exposure to or time since stopping tenofovir (TDF),ritonavir-boosted atazanavir (ATV/r), lopinavir (LPV/r), other ritonavir-boosted protease inhibitors (BPI) or abacavir (ABC). Results: 23560 persons were included with median baseline eGFR 110ml/min/1.73m 2 (IQR 100–125), age 39 years (IQR 33–45) and CD4 440/mm 3 (IQR 293–629). During a median follow-up of 6.3 years (IQR 4.4–8.0), 210 persons developed CKD (0.9%; incidence 1.48/1000 PYFU; 95% CI 1.28–1.68). The crude incidence of CKD increased as exposure to TDF, LPV/r and ATV/r increased, but not as clearly for BPI and ABC (Figure). After adjustment, there was a significant increase in CKD associated with increasing exposure to TDF, ATV/r and LPV/r (all p<0.0001) but not other BPI (p=0.44) or ABC (p=0.12; Figure). Results were consistent for CRI and when limited to those currently on ARVs. There was a decrease in the incidence of CKD as time since stopping TDF increased, with no clear picture for the other ARVs. Those who had stopped TDF for >2 years had a significantly raised incidence of CKD (adjusted incidence rate ratio 2.47; 95% CI 1.36–4.48) compared to those never exposed to TDF.

Conclusions: The association between TDF, ATV/r, LPV/r and CKD in persons with an initially normal eGFR was not limited to an increased incidence immediately after starting the ARV, but clearly persisted with increasing exposure to TDF, LPV/r and ATV/r. After 6 years exposure, the relative risk of CKD was increased by 97%, 320% and 140% for TDF, ATV/r and LPV/r respectively. A clear decrease in the incidence of CKD after stopping ARVs was only observed for TDF; but the incidence remained significantly higher 2 years after stopping compared to those who had never started TDF. 143LB Renal and Bone Safety of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate Paul E. Sax 7 ; Michael S. Saag 2 ; MichaelT.Yin 3 ; Frank A. Post 4 ; Shinichi Oka 8 ; Ellen Koenig 5 ; BenoitTrottier 9 ; Jaime Andrade-Villanueva 6 ; Huyen Cao 1 ; MarshallW. Fordyce 1 1 Gilead Sciences Inc, Foster City, CA, US; 2 University of Alabama at Birmingham, Birmingham, AL, US; 3 College of Physicians and Surgeons, Columbia University, New York, NY, US; 4 King’s College Hospital, London, United Kingdom; 5 Dominican Institute for Virologic Studies, Santo Domingo, Dominican Republic; 6 Unidad de VIH del Hospital Civil de Guadalajara, Guadalajara, Mexico; 7 Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, US; 8 National Center for Global Health and Medicine, Japan, Tokyo, Japan; 9 Clinique Medicale l’Actuel, Montreal, Canada Background: Off-target renal and bone side effects may occur with tenofovir disoproxil fumarate (TDF) use. Compared with TDF, tenofovir alafenamide (TAF) results in significantly reduced plasma tenofovir (TFV) and may have less renal and bone toxicity. Methods: Treatment naïve HIV-1 + adults were randomized 1:1 to a single tablet regimen of E/C/F/TAF or E/C/F/TDF once daily in two double blind studies. Assessments included measures of renal function and bone mineral density (BMD). Four pre-specified secondary safety endpoints were tested: serum creatinine, treatment-emergent proteinuria, spine and hip BMD. Week 48 off-target side effects data are described. Results: Combined, the two studies randomized and treated 1,733 subjects. Plasma TFV was >90% lower (mean [%CV] AUC tau 297 (20) vs. 3,410 (25) nghr/mL) in the E/C/F/TAF arm, compared to the E/C/F/TDF arm. Serum creatinine (mean [SD] change: +0.08 [0.124] vs +0.11 [0.217] mg/dL, p<0.001), quantified proteinuria (UPCR, median [Q1, Q3] % change; -3 [-35, +43] vs +20 [-23, +76], p<0.001), albuminuria (UACR, median [Q1, Q3] % change; -5 [-33, +36] vs +7 [-27, +62], p=0.001), retinol binding protein (RBP:Cr, median [Q1, Q3] % change; +9 [-23, +49] vs +51 [+3, +133]), beta-2-microglobulin ( β -2-Mg:Cr, median [Q1, Q3] % change; -32 [-57, +4] vs +24 [-34, +168]), and fractional excretion of phosphate (median [Q1, Q3] % change; +0.9 [-2.0, +4.5] vs +1.7 [-1.6, +5.3]), all favored E/C/F/TAF. There were no cases of proximal tubulopathy in either arm. Mean (SD) % decrease in BMD was significantly less in the E/C/F/TAF arm for both lumbar spine (-1.30 [3.08] vs -2.86 [3.25], p <0.001) and total hip (-0.66 [3.26] vs -2.95 [3.41], p <0.001). Increases from baseline in bone turnover biomarkers (C-telopeptide and P1NP) and parathyroid hormone were significantly smaller in the E/C/F/TAF group compared with the E/C/F/TDF arm (p < 0.001 for all). Increases in fasting lipid parameters (total cholesterol, HDL, direct LDL, and triglycerides) were greater in the E/C/F/TAF arm (p < 0.001 for all). Conclusions: Through 48 weeks, subjects receiving E/C/F/TAF had significantly better outcomes related to renal and bone health than those treated with E/C/F/TDF; lipid outcomes favored E/C/F/TDF. Collectively these data demonstrate important safety benefits of TAF relative to TDF, especially given the aging of the HIV population and the need for long-term treatment. 144 Special Presentation: Update on National Heart, Lung, and Blood Institute High-Impact AIDS Research Monica Shah National Heart, Lung, and Blood Institute, Bethesda, MD, US

Oral Abstracts

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CROI 2015