Cognitive Impairment

Algorithm for Diagnosis and Management of Cognitive Impairment in PLWH without Obvious Confounding Conditions


CSF = cerebrospinal fluid
GDR = genotypic drug resistance test
HAD = HIV-associated dementia
LOQ = Limit of quantification
MND = mild neurocognitive disorders
MRI = brain magnetic resonance imaging
NP = neuropsychological
OIs = opportunistic infections
RCT = randomised controlled trial


  • Diagnosis and Management of Cognitive Impairment in PLWH without Obvious Confounding Conditions


i Obvious confounding conditions: 

  1. Severe psychiatric conditions
  2. Use of anticholinergic drugs with high burden score for cognitive impairment (e.g. amitriptyline, chlorpromazine)
  3. Abuse of psychotropic drugs
  4. Alcohol abuse
  5. Sequelae from previous CNS-OIs, pre-treatment cognitive disease or other neurological diseases
  6. Current CNS-OIs or other neurological diseases

ii  The following questions may be used to guide initial assessments (other screening assessments are acceptable)

  1. Do you experience frequent memory loss (e.g. do you forget the occurrence of special events even the more recent ones, appointments, etc.)? 
  2. Do you feel that you are slower when reasoning, planning activities, or solving problems? 
  3. Do you have major difficulties paying attention (e.g. to a conversation, book or film)?

Answering “yes” to one or more of these questions may suggest the presence of cognitive disorders, although not necessarily linked to HIV.

iii See Depression: Screening and Diagnosis and Anxiety Disorders: Screening and Diagnosis

iv NP examination should include tests exploring the following cognitive domains: fluency, executive functions, speed of information processing, attention/working memory, verbal and visual learning, verbal and visual memory, motor skills plus assessment of daily functioning

v Cognitive impairment is defined by impairment in cognitive function on the above neuro-psychological test where performance is compared to age and education-matched appropriate controls and is considered clinically significant

vi Neurological examination, brain MRI and CSF examination are required to exclude other pathologies (consultation with neurologist specialist may be required) and to further characterise possible HIV-associated cognitve impairment by including assessment of CSF HIV-RNA level and, where appropriate, evidence for genotypic drug resistance (GDR) in a paired CSF and plasma sample

vii CSF escape definition Either CSF HIV-RNA above LOQ and plasma HIV-RNA below LOQ; or HIV-RNA above LOQ in both CSF and plasma, with CSF HIV-RNA greater than plasma HIV-RNA. In CSF escape:

  • Avoid dual ART therapies
  • Include dual nucleoside backbones in ART regimens where possible
  • Avoid ATV (boosted or unboosted) due to association with CSF escape in retrospective cohorts
  • Avoid RAL 1200 mg qd due to lack of evidence in CSF escape
  • Consider DTG 50 mg bid in cases with documented or suspected INSTI resistance

viii Including situations that do not fulfill the CSF escape definition, but can benefit from ART optimisation

ix Avoid EFV because of its possible effects on cognitive function and potentially confounding CNS effects due to neuropsychiatric effects