Abstract
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]) (r2=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) (r2=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 |
References
- 1.Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suárez I, Riera M, et al. Switching to dual therapy (ATV/RIT+3TC) vs Standard triple therapy (aATV/RIT+two nucleos(t)ides) is safe and effective in patients on virologically stable antiretroviral therapy: 48-week primary endpoint results from a randomized clinical trial (SALT study); 20th IAC; 2014. Jul 20–25, Abstract LBPE18. [Google Scholar]
- 2.Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789–99. doi: 10.1212/01.WNL.0000287431.88658.8b. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Carey CL, Woods SP, Rippeth JD, Gonzalez R, Moore DJ, Marcotte TD, et al. Initial validation of a screening battery for the detection of HIV-associated cognitive impairment. Clin Neuropsychol. 2004;18(2):234–48. doi: 10.1080/13854040490501448. [DOI] [PubMed] [Google Scholar]