The neurologic phenotype of South African patients with HIV-associated neurocognitive impairment.

Abstract

The neurologic manifestations of HIV include a spectrum of HIV-associated neurocognitive disorders, as well as a cluster of neurologic symptoms and signs. The neurologic manifestations have been modified but not eradicated by antiretroviral therapy (ART). We describe the neurologic phenotype in South African patients with predominant HIV-1 subtype C infection on ART and its association with neurocognitive impairment and efavirenz and 8-hydroxy-efavirenz concentrations. We conducted a cross-sectional analysis of the neurologic examination findings of HIV+ patients with neurocognitive impairment and used multiple linear regression to explore associations with neurocognitive impairment, efavirenz, and 8-hydroxy-efavirenz pharmacokinetics (plasma and CSF). We included 80 participants established on ART (median 40 months) of which 72 (90%) were female. The median age was 35 (interquartile range [IQR], 32-42) and the median Global Deficit Score was 0.94 (IQR 0.63-1.36). We found associations between neurocognitive impairment and neurologic signs: gait (slow walking speed [p = 0.03; R2 = 0.06], gait ataxia [p < 0.01; R2 = 0.21], and abnormal gait appearance [p < 0.01; R2 = 0.18]); coordination (upper limb bradykinesia [p < 0.01; R2 = 0.10] and lower limb bradykinesia [p = 0.01; R2 = 0.10]); reflexes (jaw jerk [p = 0.04; R2 = 0.05] and palmomental response [p = 0.03; R2 = 0.06]); ocular signs (impaired smooth pursuit [p = 0.01; R2 = 0.09] and impaired saccades [p < 0.01; R2 = 0.15]); and motor signs (spasticity [p ≤ 0.01; R2 = 0.15] and muscle weakness [p = 0.01; R2 = 0.08]). No significant associations were found between plasma and CSF efavirenz or 8-hydroxy efavirenz concentrations and any neurologic sign. We found that individual neurologic signs were associated with neurocognitive impairment in South African HIV+ patients with predominant HIV-1 subtype C infection on ART and could be used in clinical practice to assess severity. PACTR201310000635418.