CONHIV14 - HIV-related Infections, Co-infections and Cancers, etc. – Part three - page 6

Central nervous system penetration-effectiveness (CPE) rank does not reliably
predict neurocognitive impairment in HIV-infected individuals
Libertone R, Lorenzini P, Balestra P, Pinnetti C, Ricottini M, Plazzi MM, Menichetti S, Zaccarelli M,
Nicastri E, Bellagamba R, Ammassari A, Antinori A
National Institute for Infectious Diseases “Lazzaro Spallanzani”, Rome, Italy.
Background
Central nervous system (CNS) Penetration-Effectiveness
(CPE) rank was proposed in 2008 as estimate of
penetration of ARV regimen into the CNS, and validated
as predictor of CSF HIV-1 replication. Results on
predictive role of CPE on neurocognitive and clinical
outcome were conflicting.
Methods
Retrospective, cross-sectional analysis of neurocognitive profile in HIV-
infected cART-treated patients.
All patients underwent neuropsychological (NP) assessment by
standardized and comprehensive battery of 14 tests on 5 different domains.
People were classified as having NCI if they scored >1 standard deviation
(SD) below the normal mean in at least 2 tests, or >2 SD below in 1 test.
Linear and logistic regression analyses were fitted using as outcome:
-NPZ8 score used as continuous outcome (neg values if performance was
below the mean)
-impaired/not impaired as binary outcome.
Variables were retained in multivariable analysis if they had a p-value <0.05.
Conclusions
In our analysis, higher CPE rank is associated to poorly performing at neuropsychological tasking. Even if selection bias could not be
excluded due to retrospective cross-sectional design, these results fitted with the direct correlation between high CPE and HIV
dementia recently recorded in a large observational database. We think that CPE use to guide ART in patients neurocognitively
impaired should be revised.
Results
P 123
Male gender, n
820
81.7%
Age, years , median
49
IQR 43-56
Years of education, median
13
IQR 8-13
Mode of HIV transmission, n heterosexual
358
35.7%
homosexual
504
50.3%
IVDU
96
9.6%
other/unknown
44
4.4%
HCV-Ab positivity, n
183
18.3%
CDC stage C, n
32
3.2%
CD4 at NPA, cell/mmc, median
586
IQR 428-764
HIV-RNA at NPA, n detectable
161
16.1%
<40
200
20.0%
not detectable
637
63.8%
BMI, n normal
627
62.5%
underweight
33
3.3%
overweight/obesity
337
33.6%
ARV regimen, n 2 NRTIs+NNRTI
505
50.4%
2 NRTIs+PI boosted
327
32.6%
2 NRTIs+II
20
2.0%
NRTI-sparing
111
11.1%
other
40
4.0%
CPE, median
7
IQR 6-7
CPE, mean
6.6 min-max 3-13
Patients’ characteristics
Scatter plot of NZP8 score and CPE N=1003 consecutive NPA test
Multivariable linear and logistic regression.
N=1003 consecutive NPA test
Beta = -0.06
R-squared = 0.006
P = 0.018
1003 consecutive NPA over 660 patients.
430 pts contributed only 1 NPA, 163 pts 2 NPA,
67 pts contributed 3 NPA or more.
MULTIVARIABLE
Beta
95% CI
p
Age (per 10 years increase)
-0.10 -0.16 -0.03 0.002
Years from HIV test
-0.02 -0.02 -0.01 0.001
HIV-RNA <40 cp/ml at NPA
0.36
0.18
0.54 <0.001
CD4 at NPA, cell/mmc
>500
Ref
350-500
-0.28 -0.43 -0.12 0.001
<350
-0.38 -0.57 -0.19 <0.001
Education (per 1 yr more)
0.05
0.03
0.07 <0.001
BMI
underwight
-0.29 -0.64
0.07 0.110
normal
Ref
overweight
0.14
0.01
0.28 0.039
obesity
0.08 -0.21
0.36 0.599
HCV co-infection
negative
Ref
positive
-0.17 -0.34
0.01 0.060
HBV co-infection
negative
Ref
positive
-0.27 -0.65
0.10 0.152
Type of current ARV regimen
2 NRTIs+NNRTI
Ref
2 NRTI+PI boosted
0.05 -0.09
0.19 0.513
2 NRTI+II
-0.33 -0.83
0.18 0.207
NRTIs sparing
-0.15 -0.42
0.13 0.291
Other
0.40
0.08
0.73 0.015
CPE score (per 1 point higher)
-0.09 -0.14 -0.03 0.002
MULTIVARIABLE
OR
95% CI
p
Age (per 10 years increase)
1.04 1.02 1.05 <0.001
Mode of HIV transmission
heterosexual contacts
1.00
homosexual contacts
1.14 0.81 1.59 0.459
IVDU
0.94 0.51 1.74 0.855
other/unknown
0.93 0.44 1.95 0.841
CDC stage C
1.72 0.77 3.84 0.186
Years from HIV test
(per 1 yr incr.)
1.04 1.02 1.07 <0.001
HIV-RNA <40 cp/ml at NPA
0.70 0.45 1.07 0.102
CD4 at NPA, cell/mmc
>500
1.00
350-500
2.20 1.42 3.42 <0.001
<350
1.57 1.07 2.30 0.021
Education (per 1 yr more)
0.83 0.80 0.87 <0.001
HCV co-infection
negative
1.00
positive
1.29 0.82 2.03 0.269
Type of current ARV regimen
2 NRTIs+NNRTI
1.00
2 NRTI+PI boosted
1.30 0.92 1.85 0.135
2 NRTI+II
1.70 0.53 5.41 0.369
NRTIs sparing
1.09 0.56 2.15 0.792
Other
0.81 0.38 1.76 0.599
CPE score (per 1 point higher)
1.23 1.07 1.41 0.003
-6
-4
-2
0
2
NPZ8 score
0
5
10
15
CPE
NPZ 8 score
E
MULTIVARIABLE
Beta 95% CI
p
Male gender vs female
-0.11 -0.34 0.12
0.350
Age (per 10 years increase)
-0.01 -0.02 0.00
0.005
Mode of HIV transmission
heterosexual contacts
Ref
homosexual contacts
-0.04 -0.24 0.16
0.725
IVDU
0.28 -0.05 0.62
0.099
other/unknown
0.20 -0.22 0.63
0.350
Years from HIV test
(per 1 yr incr.)
-0.02 -0.03 -0.01
0.002
HIV-RNA <40 cp/ml at NPA
0.30 0.09 0.51
0.006
CD4 at NPA, cell/mmc
>500
Ref
350-500
-0.36 -0.58 -0.14
0.002
<350
-0.21 -0.41 -0.02
0.034
Education (per 1 yr more)
0.06 0.04 0.08 <0.001
BMI
underwight
-0.38 -0.79 0.02
0.065
normal
Ref
overweight
0.07 -0.10 0.24
0.448
obesity
0.03 -0.37 0.44
0.870
HCV co-infection
negative
Ref
positive
-0.31 -0.56 -0.07
0.012
Type of current ARV regimen
2 NRTIs+NNRTI
Ref
2 NRTI+PI boosted
0.06 -0.12 0.24
0.535
2 NRTI+II
-0.06 -0.62 0.51
0.836
NRTIs sparing
-0.02 -0.40 0.36
0.909
Other
0.35 -0.04 0.74
0.076
CPE score (per 1 point higher) -0.05 -0.12 0.02
0.194
MULTIVARIABLE
OR
95% CI
p
Age (per 10 years increase)
1.04 1.02 1.06 <0.001
Mode of HIV transmission
heterosexual contacts
1.00
homosexual contacts
1.07 0.71 1.62 0.736
IVDU
1.09 0.55 2.18 0.804
other/unknown
0.52 0.18 1.56 0.245
CDC stage C
1.77 0.77 4.10 0.182
Years from HIV test
(per 1 yr incr.)
1.02 1.00 1.05 0.088
HIV-RNA <40 cp/ml at NPA
0.76 0.46 1.23 0.264
CD4 at NPA, cell/mmc
>500
1.00
350-500
1.96 1.18 3.25 0.010
<350
1.46 0.92 2.32 0.109
Education (per 1 yr more)
0.84 0.80 0.89 <0.001
HCV co-infection
negative
1.00
positive
1.38 0.82 2.34 0.228
Type of current ARV regimen
2 NRTIs+NNRTI
1.00
2 NRTI+PI boosted
1.09 0.71 1.65 0.700
2 NRTI+II
1.11 0.29 4.29 0.880
NRTIs sparing
0.97 0.41 2.29 0.942
Other
0.75 0.31 1.81 0.527
CPE score (per 1 point higher)
1.13 0.95 1.34 0.170
Multivariable linear and logistic regression.
N=660 first NPA test
1,2,3,4,5 7,8,9,10,11,12
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