HAND SIGNS AND SYMPTOMS IN THE ART-ERA

The comprehensive chapter ‘Clinical Aspects of HIV-Related Neurocognitive Disorders’ provides the Frascati definitions of HIV-associated neurocognitive disorders (HAND) (asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia (HAD), an international scale established in 2005 and published in 2007 to create comparable diagnostic standards for HIV-associated brain disease. This had become necessary because the clinical presentation of these diseases had changed in the cART (combined antiretroviral therapy) era. Whilst in the pre-cART period, HAD had been a severe disease ending up in tetraplegia, mutism and incontinence and led obligatoriously to death, nowadays, affected patients show improvement in cognitive functions under antiretroviral treatment and only some reveal a ‘burnt out disease’ as the authors point out. Moreover, physicians are confronted with patients’ complaints on mild cognitive deficits preventing them from leading a normal life. The CHARTER (CNS HIV Antiretroviral Therapy Effects Research) study from the United States reported a prevalence of HIV-associated brain disease as high as 52%; with 33% ANI accounts for the majority of these deficits. Other cohorts [1] show similar results. Moreover, the predictors for HAND are comparable. Surprisingly, in the US cohort, 44% of the patients under treatment had detectable plasma viral loads, which is definitely a higher percentage than in other cohorts so that neither viral resistance nor lack of adherence only can explain the cognitive deficits because they are comparable between cohorts despite differences in treatment efficiency. The Australian cohort of Brew reveals a HAND level of only 20% in effectively treated patients (plasma viral load below the level of detection) [2]. The authors underline that the rates of cognitive decline in HIV-positive patients might be positively influenced by early HIV diagnosis and start of antiretroviral therapy. There are to date no published data with respect to progression rates between ANI, MND and HAD except from abstracts.

Brew and Davies conclude that the prevalence of HAND is to date not clear. They point out that there might be differences between cohorts because of confounding factors. However, the most important statement is that mild deficits still exist, which is not accepted by all research groups across the world [3].

HAND is described by Brew and Davies as a subcortical process with prominent motor disturbances that have been found to be a very early sign of HIV-associated brain disease in the pre-cART era [4] and nowadays indicate HAND progression [1]. Under modern treatment, deficits develop over longer periods of time and there is only an accelerated course in individuals with broad resistance profiles.

The classical symptoms for HIV-associated brain disease are motor, cognitive and emotional deficits. Brew and Davies describe four major changes in the cART era: symptom fluctuation over months also in the absence of confounding factors and without any treatment changes, active or inactive disease, milder presentation of HAND in the cART era and hints for a different phenotype of HAND. The authors claim that early symptoms are more often impaired concentration and slowing of information processing than motor deficits. According to the Hawaii cohort, this is not true for elder HIV-positive patients where extrapyramidal symptoms are predominant [5]. With respect to different phenotypes, especially more cortical deficits, the relationship to Alzheimer’s disease is an important aspect in the light of worldwide ageing HIV cohorts.

MODERN DIAGNOSTIC AND THERAPEUTIC MANAGEMENT OF HAND

The diagnostic and therapeutic management of HIV-positive patients with HAND has improved over the last years. The authors suggest determining first whether the disease is active or inactive through history and family interviews. An important topic is the evaluation of depressive symptoms, which can be HAND-associated or be mimicking it. Opportunistic infections have to be excluded by imaging procedures and cerebrospinal fluid (CSF) analysis. Drug and pharmacological history is another important topic.

The next step in assessing active disease is to determine whether it is progressive, regressive or stable; it might be difficult to differentiate stable from inactive disease, for which the authors suggest examining viral and immunological activity in the CSF; there is none in inactive disease. cART should be adapted in progressive and stable HAND.

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