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.

INTRODUCTION: 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.

Table 1

Baseline characteristics

	ATV/r + 3TC N = 76 (48.1%)	ATV/r + 2 NRTI N = 82 (51.9%)	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 (%)	19 (25%)	18 (22%)	0.09
Years of education. Mean (SD)	13.0 (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 c/mL. Mean (SD)	3.1 (2.9)	3.0 (2.7)	0.92
Nadir CD4 (cells/mm3). Median (IQR)	211 (70–325)	193 (130–300)	0.90
Baseline CD4 (cells/mm3). Median (IQR)	575 (388–772)	624 (417–825)	0.12
Years of ART. Mean (SD)	3.8 (3.0)	3.6 (2.3)	0.94
Hepatitis C Antibody +. N (%)	16 (21.1)	16 (19.5)	0.85
Aterogenic index (Total CHO/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