M Harris, S Guillemi , K Chan, B Yip , M Hull, V Dias Lima, R Hogg, J Montaner

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. 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: • ABC has been associated with HSR • In some studies ABC has been associated with increased CV risk • TDF has shown slightly higher antiviral potency in some RCTs, at higher plasma viral loads.

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

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

5. Methods • In this retrospective analysis we included: • HIV+ men and women at least 19 years of age. • Receiving a stable TDF-based regimen with either FTC or 3TC plus a third drug for at least 3 months. • Plasma viral load (pVL) <200 copies/mL for >3 months prior to the switch, and HLA-B*5701 negative. • Retained the same 3rd drug upon switching. • All data were accessed via the Drug Treatment (DTP) database at the BC Centre for Excellence in HIV/AIDS.

6. Data Analysis • Multiple measurements were available for each parameter before the switch (baseline). • CD4 cell count and pVL, results were those taken immediately before the switch. • 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. Baseline Characteristics • *Atazanavir **ADI: AIDS defining illnes • # Q1-Q3: 25th – 75th percentiles

8. ResultsLaboratory Parameters *p< 0.001, ** p<0.01 Values: Median (25th – 75th percentiles);

9. Results Laboratory Parameters Stratify By 3rd ARV Values: Median (25th – 75th percentiles) ** NNRTI’s n= 55 Pi’s n= 40 RAL n= 4 * p<0.01 For comparison between groups

10. Changes In Median CreatinineStratified By 3rd Drug In The Regimen Umol/L

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

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

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

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. 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. Thank you