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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS



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Dementia, HIV-Associated (HAD)

John N. Ratchford, M.D., Jeffrey Rumbaugh, M.D., Ph.D., and Anita Venkataramana, M.B.B.S.

  • No specific incidence/prevalence data from Zambia.
  • Epidemiology of HAD has been difficult to assess in Africa - neuropsychological testing time consuming and not easily validated in African populations (outside of research setting).
  • 2 studies have found relatively high rates of HAD in Uganda (~1/3), but another study found low rates in Ethiopia.
  • Some authors have postulated differences in neurological effects by HIV subtype (clade), but definitive data lacking.
  • Brain imaging and CSF HIV VL not typically done in Zambia but still important to rule out CNS OI with LP.
  • Definitive Dx of HAD in Zambia difficult without formal neuropsychological testing, but clinical Dx possible as described below.
  • Primary treatment of HAD in Zambia is HAART; one small study from Uganda (Sacktor N, Nakasujja N, Skolasky R, et al.) found improvements in cognitive function on HAART. 


Zambia Information Author: David Riedel, M.D.


  • HIV is found in brain in macrophages, microglia, and multinucleated giant cells. 
  • Neurons injured indirectly when infected cells release noxious substances. 


  • HAD is subacute decline in cognitive function due to HIV. 
  • Also known as HIV encephalopathy or AIDS-dementia complex.
  • Milder cognitive impairment is called HIV-associated cognitive/motor complex. The term HIV-associated neurocognitive dysfunction (HAND) is now frequently used and refers to neurocognitive dysfunction of any degree of severity, since severe forms (HAD) are now relatively rare and mild forms much more frequent.
  • Dementia is AIDS-defining illness in 3%. 
  • Incidence declining, but ultimately affects ~25% of AIDS patients.
  • Early Sx: apathy, impaired memory, difficulty with reading and calculation, decreased libido, depressive symptoms, waning interest in work & hobbies causing social withdrawal, occasionally mania or psychosis. 
  • Later Sx: psychomotor slowing, poor memory, slowed movement. At end-stage patients can be mute, bedbound, and incontinent. 
  • Considered a "subcortical dementia" due to absence of signs like aphasia and apraxia seen in "cortical dementias" like Alzheimer disease.
  • Motor symptoms like gait dysfunction, poor balance, and tremor may be present.
  • Often accompanied by HIV-related myelopathy or neuropathy.
  • Severity rated from 0 to 4: 0-normal, 0.5-subclinical, 1-mild, 2-moderate, 3-severe, 4-end stage.
  • When untreated, mean survival ~6 months.


  • DDx includes PML, CNS toxoplasmosis, primary CNS lymphoma, CMV encephalitis, neurosyphilis, vitamin B12 or thiamine deficiency, delirium, depression, medication/drug effect, or other causes of dementia. 
  • Differs from delirium in that there is no alteration of consciousness or attention.
  • Exam may show frontal release signs, hyperreflexia, and increased tone.
  • Consider OI if focal signs or fever present. 
  • Workup includes brain MRI, neuropsychological testing, serologic testing as needed to rule out vitamin deficiency, syphilis.
  • MRI usually shows atrophy and ill-defined white matter hyperintensities on T2-weighted scans.
  • CSF analysis not essential, but may be needed to rule out OI.
  • CSF findings nonspecific: may be acellular or show a lymphocytic pleocytosis; protein elevated in 65%.



  • ART is mainstay of treatment.
  • Drugs with greater CNS penetration, including AZT, d4T, 3TC, ABC, NVP, IDV, and LPV/r, are more effective at decreasing CSF viral load, but unclear whether this results in greater clinical benefit. 
  • IRIS can occasionally be seen following initiation of ART-usually due to PML.
  • No other adjunctive treatments have proven benefit.
Non-ART therapies

  •  Treatment of co-morbid depression, mania, or psychosis may be necessary.
  •  HAD patients are sensitive to psychoactive medications.

Drug Comments

ART ART is only effective treatment for HAD. Use CNS-penetrating agents if possible without sacrificing virologic suppression.


Common Practice

  • Monitor response to ART.
  •  If neurologic deterioration, perform brain MRI to rule out IRIS or OI.
  • Neuropsychological testing can be repeated to evaluate longitudinal change. 



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