Transcript Lorerat Quam Elle Veliqua: Resium verose triuse fen

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
Page 1
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
o
o
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.
Page 2
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
Page 3
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 .
Page 4
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.
rd
o Retained the same 3 drug upon switching.
• All data were accessed via the Drug Treatment (DTP)
database at the BC Centre for Excellence in HIV/AIDS.
Page 5
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. nonatazanavir recipients.
Page 6
Baseline Characteristics
Median (Q1-Q3)#
Variable
Category
n (%) (n=225)
Gender
Female
45 (20%)
—
Male
180 (80%)
—
No
149 (66.2%)
—
Yes
76 (33.8%)
—
No
99 (44%)
—
Yes
126 (56%)
—
No
185 (82.2%)
—
Yes
40 (17.8%)
—
Treatment naïve
ATV * 3rd drug at time of switch
ADI ** prior to switch
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
Page 7
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<0.01
Values: Median (25th – 75th percentiles);
Page 8
Results
Laboratory Parameters Stratify By 3rd ARV
ATV as 3rd Drug (n=126)
Parameter
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)
Values: Median (25th – 75th percentiles)
* p<0.01 For comparison between groups
** NNRTI’s n= 55
Pi’s n= 40
RAL n= 4
Page 9
105
100
Other ARV's as 3rd Drug
*
Umol/L
Changes In Median Creatinine
Stratified By 3rd Drug In The Regimen
ATV as 3rd Drug
95
90
85
80
75
n=66
n=93
Baseline
n=40
n=61
3 Months
n=61 n=76
6 Months
n=53
n=73
12 Months
Page 10
mL/min
Changes In Median eGFR
Stratified By 3rd Drug In The Regimen
90
Other ARV's as 3rd Drug
80
ATV as 3rd Drug
70
60
50
40
30
20
10
0
n=62 n=89
Baseline
n=35 n=57
3 Months
n=59 n=78
6 Months
n=51
n=72
12 Months
Page 11
mmol/L
Changes In Median Serum Phosphorus
Stratified By 3rd Drug In The Regimen
1.2
1
0.8
Other ARV's as 3rd Drug
ATV as 3rd Drug
*
0.6
0.4
0.2
0
* p<0.01
n=52 n=85
n=29 n=48
n=41 n=66
n=28 n=56
Baseline
3 Months
6 Months
12 Months
Page 12
Changes In Lipids After TDF to ABC Switch In All Patients
0.8
Total Cholesterol
0.8
0.6
0.6
0.4
0.4
0.21
0.2
0.08
0
0.06
0.2
0
-0.2
-0.2
-0.4
-0.4
-0.6
-0.6
-0.8
-0.8
3m
6m
0.8
P<0.001
0.4
-0.16
3m
12 m
HDL
0.5
LDL
-0.05
-0.18
6m
12 m
Triglycerides
0.6
0.4
0.3
0.2
0.21
0.2
0.20
0.20
0
-0.01
-0.1
-0.2
0.1
-0.06
-0.4
0.0
-0.6
-0.1
-0.8
3m
6m
12 m
3m
6m
12 m
Page 13
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.
Page 14
Conclusion
• Our results demonstrate that switching from TDF to ABCbased 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.
Page 15
Thank you
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