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Background:  Before HAART introduction, HIV-associated neurocognitive impairment was recognized as an independent risk factor for death. Our aim was to determine whether neurocognitive impairment represents a negative prognostic factor for mortality also in patients treated with HAART.

Methods:  Since 1996, we have been conducting a prospective study on mortality among patients at risk for neurocognitive impairment referred for neuropsychological evaluation (a battery of 17 standardized neuropsychological tests). At baseline, patients were classified as having or not having a neurocognitive impairment according to their neuropsychological performance relative to normative data, after the exclusion of confounding factors (i.e. opportunistic infections or tumors of the CNS, current drug abuse, major neurological or psychiatric disorders). All patients were treated with HAART. Differences in survival according to neurocognitive diagnosis were assessed by means of the Kaplan-Meier method and by the Cox proportional hazard model. Hazard ratios (HR) and their 95% confidence intervals (CI) were adjusted for confounding factors: age, sex, HIV transmission modality, baseline variables (disease stage, CD4⁺cell count, and viral load), and virological response to HAART (either durable virological suppression or virological failure).

Results:  At baseline, among the 432 enrolled patients, 238 (55.1%) were designated neurocognitively impaired and 194 (44.9%) neurocognitively unimpaired. Of the 238 neurocognitively impaired cases. 16 (6.7%) met the criteria for AIDS dementia complex. The median follow-up period was 32.4 months (interquartile range: 18.6 to 63.9). Overall,  47 deaths were recorded, 38 among impaired and 9 among unimpaired patients. The median probability survival was not reached in neither of the 2 patient groups: after 84 months of follow-up, the estimated survival proportions were 68.5% in the impaired group and 84.9% in the unimpaired group (p <0.001). Such a negative survival prognostic effect persisted when the multivariate analysis was carried on. After adjustment for confounding factors, neurocognitively impaired patients showed a 2.5-fold increased risk of death, as compared to unimpaired patients (HR=2.5; 95% CI: 1.1 to 5.7).

Conclusions:  Among HIV-positive patients receiving HAART, patients with HIV-associated neurocognitive impairment had an independent and statistically significant higher risk of death then subjects without neurological impairment. Our study highlights the clinical relevance of HIV-related CNS involvement even in the HAART era.

Keywords: Neurocognitive impairment; AIDS dementia complex; Survival