Page 1 EFFECTS ON RENAL FUNCTION OF A SWITCH FROM TENOFOVIR (TDF) TO ABACAVIR (ABC)- BASED HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART), WITH OR WITHOUT.

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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 #: WEAB0202Organ Dysfunction in HIV: It's ComplicatedWednesday, 3 July 2013 14:30-16:00Session Room 2

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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 HSRo 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.

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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):773-7802. A Mocroft et al. AIDS 2010, 24 :1667-783. L Ryom et al .JID Feb 2013

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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 .

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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) <200 copies/mL for >3 months

prior to the switch, and HLA-B*5701 negative.o 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.

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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.

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Baseline CharacteristicsVariable Category n (%) (n=225) Median (Q1-Q3)#

Gender Female 45 (20%) —

Male 180 (80%) —

Treatment naïve No 149 (66.2%) —

Yes 76 (33.8%) —

ATV * 3rd drug at time of switch No 99 (44%) —

Yes 126 (56%) —

ADI ** prior to switch No 185 (82.2%) —

Yes 40 (17.8%) —

Age at switch — 225 47 (42-55)

CD4 cells prior to switch, cells/mm3 — 220 440 (310-620)

pVL <200c/ml, prior to switch — 225 (100%) _

*Atazanavir **ADI: AIDS defining illnes# Q1-Q3: 25th – 75th percentiles

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Results Laboratory Parameters

Parameter Baseline At 3 months At 6 months At 12 months

Creatinine, umol/L 100 (84-119) 90 (77-99) * 89 (77-99)* 87 (77-98)*

eGFR, mL/min 69 (58-82) 78 (69-94) * 81 (71-92)* 81 (69-92)*

Phosphorus, mmol/L 0.80 (0.69-0.94) 0.96 (0.86-1.11)* 0.97 (0.84-1.08)* 0.96 (0.83-1.08)*

UACR, mg/mmol 3.4 (1.0-12.3) 1.3 (0.7-6.6)* 1.2 (0.6-5.1)* 1.3 (0.5-4.7)**

CD4, cells/mm3 440 (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<0.01Values: Median (25th – 75th percentiles);

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Results Laboratory Parameters Stratify By 3rd ARV

Parameter ATV as 3rd Drug (n=126) Other 3rd ARV** Drug (n=99)

Baseline At 3 months At 6 months At 12 months Baseline At 3 months At 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 (25th – 75th percentiles)

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Changes In Median Creatinine Stratified By 3rd Drug In The Regimen

Baseline 3 Months 6 Months 12 Months75

80

85

90

95

100

105

Other ARV's as 3rd DrugATV as 3rd Drug

n=66 n=93 n=40 n=61 n=61 n=76 n=53 n=73

*

Um

ol/L

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Changes In Median eGFRStratified By 3rd Drug In The Regimen

Baseline 3 Months 6 Months 12 Months0

10

20

30

40

50

60

70

80

90 Other ARV's as 3rd DrugATV as 3rd Drug

n=62 n=89 n=35 n=57 n=59 n=78 n=51 n=72

mL/

min

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Changes In Median Serum PhosphorusStratified By 3rd Drug In The Regimen

Baseline 3 Months 6 Months 12 Months0

0.2

0.4

0.6

0.8

1

1.2Other ARV's as 3rd DrugATV as 3rd Drug

n=52 n=85 n=29 n=48 n=41 n=66 n=28 n=56

*

mm

ol/L

* p<0.01

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Changes In Lipids After TDF to ABC Switch In All Patients

3 m 6 m 12 m-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

-0.01-0.1 -0.06

Triglycerides

3 m 6 m 12 m-0.1

0.0

0.1

0.2

0.3

0.4

0.5

0.21 0.20 0.20

HDLP<0.001

3 m 6 m 12 m-0.8-0.6-0.4-0.2

00.20.40.60.8

-0.16 -0.18-0.05

LDL

3 m 6 m 12 m-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

0.08 0.060.21

Total Cholesterol

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SummaryIn 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.

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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.

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Thank you