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 sub-study.
BACKGROUND
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 performance (NP).


METHODS
We evaluated the NP change of aviremic participants of the SALT clinical trial (1) switching therapy to dual therapy (DT: ATV/r+3TC) or triple therapy (TT: ATV/r+2NRTI) who agreed to perform an NP assessment (NPZ-5) at baseline and W48. Neurocognitive impairment and NP were assessed using AAN-2007 criteria (2) and global deficit scores (GDS) (3). Neurocognitive change (GDS change: W48 - baseline) and the effect of DT on NP evolution crude and adjusted by significant confounders were determined using ANCOVA.


RESULTS
A total of 158 patients were included (Table 1). They had shorter times because HIV diagnosis, ART initiation and HIV-suppression and their virologic outcome at W48 by snapshot was higher (79.1% vs 72.7%; p=0.04) compared to the 128 patients not included in the sub-study. By AAN-2007 criteria, 51 patients in each ART group (68% vs 63%) were neurocognitively impaired at baseline (p=0.61). Forty-seven patients were not reassessed at W48: 30 lost of follow-up (16 DT-14 TT) and 17 had non-evaluable data (6 DT-11 TT). Patients retested were more likely to be men (78.9% vs 61.4%) and had neurological cofounders (9.6% vs 0%) than patients non-retested. At W48, 3 out of 16 (5.7%) patients on DT and 6 out of 21 (10.5%) on TT who were non-impaired at baseline became impaired (p=0.49) while 10 out of 37 (18.9%) on DT and 7 out of 36 (12.3%) on TT who were neurocognitively impaired at baseline became non-impaired (p=0.44). Mean GDS changes (95% CI) were: Overall -0.2 (-0.3 to -0.04): DT -0.26 (-0.4 to -0.07) and TT -0.08 (-0.2 to 0.07). NP was similar between DT and TT (0.15). This absence of differences was also observed in all cognitive tests. Effect of DT: -0.16 [-0.38 to 0.06]) (r(2)=0.16) on NP evolution was similar to TT (reference), even after adjusting (DT: -0.11 [-0.33 to 0.1], TT: reference) by significant confounders (geographical origin, previous ATV use and CD4 cell count) (r(2)=0.25).


CONCLUSIONS
NP stability was observed after 48 weeks of follow up in the majority of patients whether DT or TT was used to maintain HIV-suppression. Incidence rates of NP impairment or NP impairment recovery were also similar between DT and TT.
Internal Medicine, H.U. La Paz, Madrid, Spain.
Ignacio Pérez
IP
Valero
Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain.
Juan
J
Pasquau
Internal Medicine, H.U. Doce de Octubre, Madrid, Spain.
Rafael
R
Rubio
Internal Medicine, Hospital Reina Sofia, Cordoba, Spain.
Antonio
A
Ribero
Internal Medicine, Hospital Virgen de la Victoria, Malaga, Spain.
Jose
J
Santos
Internal Medicine, Hospital de Alcala de Henares, Alcala de Henares, Spain.
Jesus
J
Sanz
Internal Medicine, Hospital Arquitecto Marcide, Ferrol, Spain.
Ana
A
Mariño
Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
Manel
M
Crespo
Internal Medicine, Hospital San Cecilio, Granada, Spain.
Jose
J
Hernandez
Internal Medicine, Hospital de Donostia, San Sebastian, Spain.
Jose Antonio
JA
Iribarren
Internal Medicine, Hospital de Elche, Elche, Spain.
Felix
F
Gutierrez
Internal Medicine, Hospital de Jerez, Jerez, Spain.
Alberto
A
Terron
Fundación SEIMC-GESIDA, Madrid, Spain.
Herminia
H
Esteban
Infectious Diseases, Hospital Ramón y Cajal, Madrid, Spain.
Jose Antonio
JA
Pérez-Molina