Transcript File

Drug resistance profile at failure
of integrase inhibitors containing
regimens
Antiretroviral Resistance Cohort Analysis
www.hivarca.net
April 20, 2016
Drug resistance profile at failure
of integrase inhibitors containing regimens
• The driver criterium for the selection of the patients
was the availability of a genotypic drug resistance
test on integrase region after the start of an
antiretroviral regimen containing a INI, according
to the viral load; the tests have been performed
on RNA from plasma/serum samples, excluding
whole blood, PBMC and liquor matrix in order to
depict the drug resistance profile to INIs at
virological failure.
• Since 2008 a total of 294 genotypic drug
resistance tests on integrase region at potential
virological failure from patients administered with
an INI-based antiretroviral regimen has been
selected for the analysis.
Test INI 2008 - 2016
50
45
40
35
30
25
20
15
10
5
0
2008
2009
2010
2011
2012
2013
2014
2015
2016
INI genotypic resistance test since 2008
Feature
Value
Age, median (IQR)
47 (41-52)
Male gender, %
198 (67.3)
Ethnicity, Caucasian
202 (68.7)
Log viral load, median (IQR) at baseline
3.8 (3.1-4.8)
CD4 cell counts, median (IQR) at baseline
246 (95-406)
%CD4 cell counts, median (IQR) at baseline
15.0 (7.6-23.0)
Nadir CD4 cell counts, median (IQR)
.…
Zenith viral load, median (IQR)
….
Log viral load, median (IQR) at failure
3.4 (2.7-4.4)
CD4 cell counts, median (IQR) at failure
296 (176-477)
%CD4 cell counts, median (IQR) at failure
17.0 (9.0-24.0)
Years since HIV diagnosis, median (IQR)
….
Total weeks of treatment, median (IQR)
103 (61-139)
Past treatment lines, median (IQR)
Subtype B, %
RAL/EVG/DTG
10 (5-14)
206 (70)
269/1/24
Test Stratification performed at different VL
Total: 184 (known viral load)
33.7%
59
41
28
18
VL<200
200≤VL<500
22
16
500≤VL<1000
1000 ≤VL<10000
10000<VL<100000
≥100000
Reasons for INI-based regimen discontinuation
Reason for INI interruption
Not reported
N
%
143
48.6
Virological failure
97
32.9
Adherence issues
12
4.1
Immunological failure
4
1.4
Intensification
3
1.0
Other
5
1.7
Supervised interruption
3
1.0
Toxicity
7
2.4
Simplification
9
3.1
11
3.7
Obsolete therapy
INI major drug resistance mutations according to VL rank
(all INI interruption reasons n=184)
Major: 155 or 148 or 143
Other: other than 155, 148 or 143
16
None
13
16
11
11
6
VL < 200
7
8
4
6
200 ≤ VL < 500
30
8
3
18
2
6
500 ≤ VL < 1000
major
1000 ≤ VL < 10000 10000 ≤ VL < 100000
other
7
12
>100000
none
p=0.01
INI major drug resistance mutations according to VL rank
(only virological/immunological failure n=79)
Major: 155 or 148 or 143
6
Other: other than 155, 148 or 143
4
None
3
1
1
1
18
0
4
2
VL < 200
3
2
2
200 ≤ VL < 500
4
0
5
14
9
500 ≤ VL < 1000
major
1000 ≤ VL < 10000 10000 ≤ VL < 100000
other
>100000
none
p=0.02
Preliminary results
•The GRT at LLV is performed as a routine test,
according to the current Guidelines (33.7% for INI
tests)
•The prevalence of drug-resistance mutations is
higher if VL>1000 cp/mL than if VL<1000 cp/mL
(both for all patients and for patients presenting
virological/immunological failures)
•The rate of viral rebound in presence of at least 1
INI major drug resistance mutations (via 155
and/or 148 and/or 143 pathway) is 42.4% and
63.3%
for
all
patients
and
for
only
virological/immunological failures, respectively.
In progress analysis
•Impact of viral subtype and gender
•Evaluation of background regimen
•Presence of 155 vs 148 vs 143 according to VL
rank
•Co-presence of 155 and/or 148 and/or 143
mutations according to VL rank
•Impact of other INI mutation (other than 155,
148 and 143) on susceptibility to INI
•Impact of other INI mutation on virological
rebound without INI major mutations
•Most of the patients have been treated with
RAL: evaluation of susceptibility to Elvitegravir
and Dolutegravir