1. Page 1 EFFECTS ON RENAL FUNCTION OF A SWITCH FROM TENOFOVIR (TDF) TO ABACAVIR (ABC)- BASED HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART), WITH OR WITHOUT ATAZANAVIR M Harris, S Guillemi, K Chan, B Yip, M Hull, V Dias Lima, R Hogg, J Montaner Abstract #: WEAB0202 Organ Dysfunction in HIV: It's Complicated Wednesday, 3 July 2013 14:30-16:00 Session Room 2

2. Page 2 Background The introduction of fixed NRTI combinations (TDF+FTC and ABC+3TC) have substantially simplified dosing schedules. TDF+FTC is generally recommended as the preferred first line NRTI backbone. ABC+3TC is recommended as alternative NRTI backbone, largely because: o ABC has been associated with HSR o In some studies ABC has been associated with increased CV risk o TDF has shown slightly higher antiviral potency in some RCTs, at higher plasma viral loads.

3. Page 3 Background However, o TDF has been associated with renal dysfunction and this may improve when TDF is replaced by ABC.. 1 o Also atazanavir (ATV) has been described as a contributor to renal dysfunction. 2,3 1.Andrew M.Am J Kidney Dis. 2011;57(5):773-780 2.A Mocroft et al. AIDS 2010, 24 :1667-78 3.L Ryom et al.JID Feb 2013

4. Page 4 Objectives To retrospectively evaluate changes in renal and lipids parameters among adults that were switched by their treating physician from TDF+3TC/FTC to ABC+3TC-based HAART To assess if ATV had an effect on renal function in this group of patients.

5. Page 5 Methods In this retrospective analysis we included: o HIV+ men and women at least 19 years of age. o Receiving a stable TDF-based regimen with either FTC or 3TC plus a third drug for at least 3 months. o Plasma viral load (pVL) 3 months prior to the switch, and HLA-B*5701 negative. o Retained the same 3 rd drug upon switching. All data were accessed via the Drug Treatment (DTP) database at the BC Centre for Excellence in HIV/AIDS.

6. Page 6 Data Analysis Multiple measurements were available for each parameter before the switch (baseline). o CD4 cell count and pVL, results were those taken immediately before the switch. o Creatinine, eGFR (MDRD equation), phosphorus, urine albumin to creatinine ratio (UACR) and lipids, results were the worst value in the 12 months before the switch. Follow up results were the closest to 3, 6 and 12 months after the switch. Wilcoxon Signed Rank Test was used to compare values before vs. after the TDF to ABC switch. Wilcoxon Rank Sum Test was used to compare atazanavir vs. non- atazanavir recipients.

7. Page 7 Baseline Characteristics VariableCategoryn (%) (n=225) Median (Q1-Q3)# GenderFemale45 (20%)— Male180 (80%)— Treatment naïveNo149 (66.2%)— Yes76 (33.8%)— ATV * 3 rd drug at time of switchNo99 (44%)— Yes126 (56%)— ADI ** prior to switchNo185 (82.2%)— Yes40 (17.8%)— Age at switch—22547 (42-55) CD4 cells prior to switch, cells/mm3—220440 (310-620) pVL <200c/ml, prior to switch—225 (100%)_ *Atazanavir **ADI: AIDS defining illnes # Q1-Q3: 25 th – 75 th percentiles

8. Page 8 Results Laboratory Parameters ParameterBaselineAt 3 monthsAt 6 monthsAt 12 months Creatinine, umol/L100 (84-119)90 (77-99) *89 (77-99)*87 (77-98)* eGFR, mL/min69 (58-82)78 (69-94) *81 (71-92)*81 (69-92)* Phosphorus, mmol/L0.80 (0.69-0.94)0.96 (0.86-1.11)*0.97 (0.84-1.08)*0.96 (0.83-1.08)* UACR, mg/mmol3.4 (1.0-12.3)1.3 (0.7-6.6)*1.2 (0.6-5.1)*1.3 (0.5-4.7)** CD4, cells/mm3440 (310-620)460 (330-670)**520 (380-700)*505 (370-690)* pVL <200 c/ml 100 %99.4%97.8%98.4% *p< 0.001, ** p<0.01 Values: Median (25 th – 75 th percentiles);

9. Page 9 Results Laboratory Parameters Stratify By 3 rd ARV ParameterATV as 3 rd Drug (n=126)Other 3 rd ARV** Drug (n=99) BaselineAt 3 monthsAt 6 months At 12 months BaselineAt 3 monthsAt 6 months At 12 months Creatinine, umol/L 95 (83-117) 90 (76-96) 87 (75-98) 86 (73-98) 103 (90-120) 91 (81- 102) 89 (80-100) 87 (80-98) eGFR, mL/min 71 (60-82) 78 (73-96) 82 (71-95) 82 (69-97) 68 (57-79) 76 (64-89) 81 (69-89) 81 (71-89) Phosphorus, mmol/L 0.82* (0.74- 0.95) 0.98 (0.88- 1.17) 1.01 (0.88- 1.09) 1.01 (0.89- 1.08) 0.74* (0.61- 0.94) 0.92 (0.82- 1.01) 0.88 (0.79- 1.01) 0.94 (0.77- 1.07) UACR, mg/mmol 3.2 (1.0-10.6) 1.2* (0.7-2.9) 1.1 (0.6-3.7) 1.1 (0.5-2.6) 3.7 (1.1-12.8) 6.6* (1.4-15.3) 1.6 (0.7-6.6) 1.7 (1.0-6.5) CD4, cells/mm3 430 (310-610) 450 (330-620) 520 (390-700) 510 (380-670) 470 (310-650) 480 (330-700) 525 (380-685) 500 (350-740) * p<0.01 For comparison between groups ** NNRTI’s n= 55 Pi’s n= 40 RAL n= 4 Values: Median (25 th – 75 th percentiles)

10. Page 10 Changes In Median Creatinine Stratified By 3 rd Drug In The Regimen Umol/L

11. Page 11 Changes In Median eGFR Stratified By 3 rd Drug In The Regimen n=62 n=89 n=35 n=57 n=59 n=78 n=51 n=72 mL/min

12. Page 12 Changes In Median Serum Phosphorus Stratified By 3 rd Drug In The Regimen mmol/L * p<0.01

13. Page 13 Changes In Lipids After TDF to ABC Switch In All Patients

14. Page 14 Summary  In 225 patients that switched from TDF to ABC-based HAART there was a significant improvement in renal function (Creatinine, eGFR, phosphatemia and UACR), without significant changes in plasma HIV RNA.  The CD4 cell count increased and lipid profile remained stable after the switch to ABC.  Similar trends were observed whether or not the third drug in the regimen was atazanavir.  We recognize this study has some limitations, including its retrospective nature, small sample size and lack of access to complete clinical data.

15. Page 15 Conclusion Our results demonstrate that switching from TDF to ABC- based HAART is effective, safe and also improves renal function parameters among patients who are responding to TDF-based HAART regardless of whether they are also on atazanavir.

16. Page 16 Thank you