As HIV-infected patients are living longer thanks to highly active antiretroviral therapy (HAART), our objective as clinicians is to offer them a life expectancy and a quality of life comparable to individuals not infected by HIV. Unfortunately, several complications are emerging as a consequence of premature aging, an effect of persistent or non-reversible immune-activation and concomitant risk factors (such as smoking or use of recreational drugs) or co-infections (such as chronic hepatitis C) [
1]. HIV-associated neurocognitive disorders (HAND) could be one of the most important complications, the accepted prevalence of HAND today is approximately 50% despite the overall efficacy of HAART [
2]. Indeed, several patients are being diagnosed with a broad spectrum of neurocognitive impairments ranging from subtle alterations that are only evident through specific tests (that is, asymptomatic neurocognitive impairment (ANI)) to mild neurocognitive disorders (MND) that start having deleterious effects on patients' daily activities [
3]. Moreover, despite the fact that HIV-associated dementia (HAD) is currently controlled [
4], there is a concern that neurocognitive disorders will worsen even on HAART, leading to a resurgence of this problem in the future. This concern is based on patients on HAART who have neurological deficits despite persistent undetectable HIV RNA in plasma [
5], but with detectable HIV RNA in the cerebrospinal fluid (CSF) [
6], neuroinflammation in the CSF [
7], or ß-amyloid deposition in the brain [
8].
The American Academy of Neurology (AAN) updated the nosology of HAND in 2007, introducing ANI as a new pathological entity [
9]. The panel itself recommended using this classification only for research. Indeed, this entity had been evaluated in only two studies concerning a small number of ANI-suffering patients before consensual but not unanimous approval [
10,
11]. Notwithstanding this consideration, it has already been adopted into clinical practice. For instance, the Italian guidelines for HIV disease management suggest starting HAART in all patients with HAND, a recommendation that is stronger for those with MND but also applies to those with ANI [
12].
In the accompanying paper published in
BMC Infectious Diseases, Gisslèn
et al. [
13] emphasize that a high proportion of HIV infected patients (about 20%) may be classified as neurocognitively abnormal (though asymptomatic) using the AAN criteria. According to this classification, ANI is characterized by neuropsychological testing outcomes that are at least one standard deviation below the mean of normative scores in at least two cognitive areas among at least five domains. The authors highlighted that, according to this criterion, even in a general population with a normal distribution of the neuropsychological testing outcomes, almost 16% of the individuals will be defined as abnormal. The bottom line is that the definition of ANI may lead to an unacceptable false-positive rate and that therefore the actual problem is overestimated.