Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy

Abstract

Objective: To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviral therapy (cART).

Design: Prospective study of Thai AHI participants examined at 3 and 6 months after initiation of cART.

Methods: Thirty-six AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test, Color Trails 1 & 2 (CT1, CT2), and Trail Making Test A. Raw scores were standardized to 251 age- and education-matched HIV-uninfected Thais. To account for learning effects, change in NP performance was compared with that of controls at 6 months. Analyses included multivariable regression, nonparametric repeated measures analysis of variance, and Mann-Whitney U test.

Results: Baseline NP scores for the AHI group were within normal range (z-scores range: -0.26 to -0.13). NP performance improved on CT1, CT2, and Trail Making Test A in the initial 3 months (P < 0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (P = 0.018). Participants who performed >1 SD below normative means on ≥2 tests (n = 8) exhibited higher baseline cerebrospinal fluid HIV RNA (P = 0.047) and had no improvement after cART.

Conclusions: Most AHI individuals had normal NP performance, and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance, which correlated with higher cerebrospinal fluid HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals.

Figure 1. Baseline Neuropsychological (NP) Performance of AHI Participants

Z-scores on Grooved Pegboard = −0.17; Color Trails 1 = −0.20; Color Trails 2 = −0.13; and Trail Making A = −0.26. Eight participants performed >1 SD below norm means on ≥2 NP tests.

Figure 2. Baseline Correlations

Blue dot = Fiebig I/II (HIV RNA+, HIV IgM−), Orange dot = Fiebig III/IV (HIV IgM+, HIV IgG−). NP performance was negatively correlated with cerebrospinal fluid (CSF) viral load (VL) (r=−0.493, p=0.023) and days post-transmission (r=−0.389, p=0.019). NPZ-4 scores did not correlate with depression (p=0.336) or anxiety measures (p=0.861).

Figure 3. Longitudinal Neuropsychological Performance after ART Initiation

Significant improvement was seen in week 0 to week 12 in processing speed (Color Trials 1, p = 0.000; Trail Making A, p = 0.008) and executive functioning (Color Trails 2, p=0.005) in the total cohort. No change in motor performance.

Figure 4. Comparison of Neuropsychological Performance Improvement in AHI participants and HIV-Uninfected Controls

When compared to HIV-uninfected controls in NP performance at 6 months, AHI participants only had a greater improvement in one processing test (Color Trails 1, p = 0.018).