CONHIV14 - HIV-related Infections, Co-infections and Cancers, etc. – Part three - page 7

Ignacio Perez-Valero | Pº Castellana 261 | Madrid 28034, Spain | +34917277099 |
Poster #
P124
CNS safety at 48-week of switching to ATV/r plus 3TC or two nucleos(t)ides in
HIV-suppressed patients on stable ART: The SALT neurocognitive substudy.
Pérez Valero I*
1
, Pasquau J
2
, Rubio R
3
, Ribero A
4
, Santos J
5
, Sanz J
6
, Mariño A
7
, Crespo M
8
, Hernandez J
9,
Iribarren JA
10
, Gutierrez F
11
, Terron A
12
, Esteban H
13
, Pérez-Molina JA
14
.
1.Hospital Universitario La Paz, Madrid, Spain; 2. Hospital Virgen de las Nieves, Internal Medicine, Granada, Spain: 3. Hospital Universitario 12 de Octubre, Madrid, Spain; 4. Hospital Reina Sofia, Internal Medicine, Cordoba, Spain.
5.
Hospital Virgen de la Victoria, Internal Medicine, Malaga, Spain; 6. Hospital de Alcala de Henares, Internal Medicine, Alcala de Henares, Spain; 7. Hospital Arquitecto Marcide, Internal Medicine, Ferrol, Spain; 8. Hospital Vall d'Hebron,
Internal Medicine, Barcelona, Spain; 9. Hospital San Cecilio, Internal Medicine, Granada, Spain; 10. Hospital de Donostia, Internal Medicine, San Sebastian, Spain; 11. Hospital de Elche, Internal Medicine, Elche, Spain; 12. Hospital de
Jerez, Internal Medicine, Jerez, Spain; 13. Fundación SEIMC-GESIDA, Madrid, Spain; 14. Hospital Ramón y Cajal, Infectious Diseases, Madrid, Spain
Due to their low CNS penetrance, there are concerns about the
capacity of non-conventional PI-based ART (monotherapy and
dual therapies) to preserve neurocognitive (NC) performance.
There is no evidence regarding the capacity of ATV/r plus 3TC to
preserve neurocognitive function in HIV-suppressed patients
switching therapy from conventional triple therapy to ATV/r plus
3TC dual therapy.
BACKGROUND
STUDY DESIGN
1.
Working memory:
Trail Making Test – Part A.
2.
Executive Functioning:
Trail Making Test – Part B.
3.
Speed of Information Processing:
WAIS-III Digit Symbol
task
4.
Visual & Motor Skills:
Grooved Pegboard Test (dominant
and non-dominant hand).
NEUROCOGNITIVE EVALUATION
Patients enrolled in the SALT study who agreed to participate
in the NC sub-study were neurocognitively assessed at
baseline and weeks 48 & 96.
Neurocognitive evaluation (NPZ-5) was performed following
recommended AAN 2007 – Frascati diagnostic criteria.
Change in NC was estimated and compared using Global
Deficit Score (GDS) variation from baseline to week 48. The
prevalence and the incidence of neurocognitive impairment
group were also reported.
The estimation of dual therapy effect on GDS change,
compared to triple therapy, was performed by ANCOVA were a
linear regression was fitted over GDS at follow-up adjusting by
baseline GDS. We also adjusted by baseline confounders.
As a sensitivity analysis, we fitted a linear regression directly
over the values of GDS change (CHANGE). The ANCOVA
method has the advantage of providing the most accurate
estimator avoiding the bias known as regression to the mean.
Potential confounders: Age, gender, ethnicity, risk group for
HIV transmission, years on ART, years since HIV detection,
years of HIV indetectability , CD4 count (current and nadir),
years of education, AIDS, presence of medical, neurological or
psychiatric comorbidities, co-infection with hepatitis C,
previous use of boosted atazanavir and total cholesterol/HDL
ratio.
Variables with a significant p value <0.2 in bivariate analysis
were retained in the model.
METHODS
Global Deficit Score:
This quantitative neurocognitive score was calculated
from T-scores obtained in each of the 5 neurocognitive
task assessed (1).
Neurocognitive impairment:
Defined as a neurocognitive performance of
≤ -1 SD in ≥ 2 of the 5 neurocognitive task
assessed (2).
(1) Carey C et al. J Clin Neuropsychol 2004; 18:234-249.
(2) Antinori A et al. Neurology 2007; 69:1789–1799
NEUROCOGNITIVE BATTERY
CHANGES IN NEUROCOGNITIVE
PERFORMANCE BY GDS
BASELINE CHARACTERISTICS
ATV/r + 3TC
N = 76
ATV/r + 2 NRTI
N = 82
p
Male. N (%)
54 (71.1)
63 (76.8)
0.47
Age. Mean (SD)
43.1 (10.3)
41.6 (8.6)
0.32
Immigrants. N (%)
19 (25)
18 (22)
0.09
Years of education. Mean (SD)
13 (4.7)
13.6 (5.0)
0.48
AIDS N (%)
24 (31.6)
22 (26.8)
0.60
Years since HIV detection. Mean (SD)
7.5 (6.2)
7.3 (6.4)
0.57
Years with HIV-RNA <50 cop/mL. Mean (SD)
3.1 (2.9)
3 (2.7)
0.92
CD4 (cells/mm3). Median (IQR)
Nadir
211(70-325)
193 (130-300)
0.90
At baseline
575 (388-772)
624 (417-825)
0.12
Years of ART. Mean (SD)
3.8 (3)
3.6 (2.3)
0.94
Hepatitis C antibody positive. N (%)
16 (21.1)
16 (19.5)
0.85
Aterogenic index (TC/HDL). Median (IQR)
3.9 (3.3-4.8)
3.9 (3.3-4.7)
0.76
Presence of neurological comorbidities. N (%)
3 (3.9)
8 (9.8)
0.21
Presence of psychiatric comorbidities. N (%)
36 (47.4)
42 (51.2)
0.64
Presence of cardiovascular comorbidities. N (%)
45 (59.2)
41 (50)
0.27
Receiving ATV/r before entering the study. N (%)
25 (32.9)
43 (27.2)
0.15
Prevalence of neurocognitive impairment, N (%)
51 (68)
51 (63)
0.61
Similar GDS evolution was observed in patients receiving dual
therapy (ATV/r + 3TC) or triple therapy (ATV/r + 2NRTI).
STUDY FLOW CHART
Baseline characteristic of patients that agreed and refused
participation in the neurocognitive sub-study were similar except for
patients who refused had longer time since HIV diagnosis, ART
initiation and HIV undetectability.
NEUROCOGNITIVE IMPAIRMENT
Neurocognitive impairment distribution at week 48 by groups
CONCLUSIONS
Neurocognitive stability was observed after 48
weeks in the majority of patients whether dual
therapy (ATV/r + 3TC) or triple therapy (ATV/r
+ 2NRTI) was used.
Incidence rates of neurocognitive impairment
and neurocognitive recovery were also similar
between dual and triple therapy groups.
CRUDE AND ADJUSTED EFFECT OF DUAL
THERAPY (ATV/R + 3TC) OVER GDS
DISTRIBUTION BY NEUROCOGNITIVE TASKS
ATV/r + 3TC
N = 76
ATV/r + 2 NRTI
N = 82
p
GDS Mean (95% CI)
Baseline
1.1 (0.9 to 1.3)
1.1 (0.8 to 1.3)
0.69
Follow-up
0.9 (0.7 to 1.2)
1.0 (0.8 to 1.3)
0.71
Crude mean change in GDS (95%CI)
-0.26 (-0.4 to 0.00)
-0.08 (-0.40 to 0.40)
0.14
Crude† effect of Monotherapy over change in
GDS (95% Confidence Interval)
-0.16 (-0.38 to 0.06)
1
0.15
Adjusted†† effect of Monotherapy over
change in GDS (95% Confidence Interval)
0.11 (-0.33 to 0.10
1
0.29
†Regression over global deficit score (GDS) at follow-­‐up visit, adjusted only by baseline GDS.
††AddiBonally adjusted by confounders
:
ethnicity, receiving ATV/r prior inclusion and CD4 cell count.
ATV/r + 3TC
ATV/r + 2 NRTI
Global Deficit Score
The SALT neurocognitive sub-study was designed to compare NC change in
aviremic patients randomized to switch to ATV/r + 3TC (dual therapy) or ATV/r +
2NRTI (triple therapy) after 48 and 96 weeks of follow up.
p = 0.137
Dual therapy was not associated with worse neurocognitive change
Incidence of Neurocognitive impairment at 48 week
EFFICACY & SAFETY
ATV/r + 3TC
N = 76
ATV/r + 2 NRTI
N = 82
p
HIV RNA <50 Cop/mL, n (%)
59 (77.6)
68 (82.9)
0.40
HIV RNA >50 Cop/mL, n (%)
4 (5.3)
4 (4.9)
0.91
Discontinuation due to Adverse Events, n (%)
2 (2.6)
4 (4.9)
0.46
ICF withdrawal, n (%)
5 (6.6)
5 (6.1)
0.90
Lost of follow up, n (%)
2 (2.6)
1 (1.2)
0.52
Others, n (%)
4 (5.3)
0 (0)
0.11
Per protocol TLOVR efficacy analysis results for patients enrolled in the SALT
neurocognitive sub-study at week 48.
ATV/r + 3TC
N = 76
ATV/r + 2 NRTI
N = 82
p
Grade III-IV adverse events, n (%)
44 (58.7)
50 (61)
0.77
III-IV Adverse events at week 48 by treatment groups.
p = 0.49
1,2,3,4,5,6 8,9,10,11,12
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