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Key Considerations for People Living with HIV



HIV is neurovirulent and a substantial proportion of HIV-infected people not receiving highly active antiretroviral therapy (HAART) demonstrate clinically relevant central nervous system (CNS) symptoms.1

  • HIV-associated neurocognitive disorders (HAND) remain common despite the use of HAART.2
  • The prevalence of HAND remains high in patients with long-standing suppression of viremia,3 though it typically has milder symptoms in the era of HAART and may often be undiagnosed1
  • HAND can affect activities of daily living and present challenges with employment.4 It may also be associated with decreased medication adherence5 and reduced life expectancy6

Classification of HAND

HAND encompasses a spectrum of neurocognitive effects that may be associated with HIV infection. These can be classified into the following categories, and in each case there should be no evidence of another (non-HIV) pre-existing cause:7

  • asymptomatic neurocognitive impairment (ANI)
    • acquired impairment in cognitive function that involves at least two ability domains and does not interfere with everyday functioning
    • does not meet criteria for delirium or dementia


  • mild neurocognitive disorder (MND)
    • acquired impairment in cognitive functioning that involves at least two ability domains and results in at least mild interference in daily functioning
    •  does not meet criteria for delirium or dementia


  • HIV-associated dementia (HAD)
    • marked acquired impairment in cognitive functioning that involves at least two ability domains (typically multiple domains), especially in learning of new information, slowed information processing, and defective attention/concentration, and produces marked interference with day-to-day functioning

While HAART has reduced the incidence of HAD in developed countries, the prevalence of ANI and MND appear to be rising as patient survival increases.8  

  • In addition, there is evidence to suggest that HAD is not an inevitable consequence of MND; a fluctuating course may occur, with some patients showing improvement in neurocognitive signs/symptoms over time1
Drug class 4 3 2 1
NRTIs zidovudine (ZDV) abacavir (ABC)
emtricitabine  (FTC)
didanosine (ddl)
lamivudine (3TC)
stavudine  (d4T)
tenofovir (TDF)
zalcitabine (ddl)
NNRTIs nevirapine (NVP) delavirdine (DLV)
efavirenz (EFV)
etravirine  (ETR)  
PIs indinavir/r  (IDV/r) darunavir/r (DRV)
fosamprenavir/r  (FPV)
indinavir (IDV)
lopinavir/r  (LPV/r)
atazanavir (ATV)
atazanavir/r (ATV/r)
fosamprenavir (FPV)
nelfinavir (NFV)
ritonavir (RTV)
saquinavir (SQV)
saquinavir/r (SQV/r)
tipranavir/r (TPV/r)
Entry/fusion inhibitors   maraviroc (MRV)   enfuvirtide (ENF)
Integrase inhibitors   raltegravir (RAL)    

Figure 1. Prevalence of HAND  

Created from: McArthur J, Steiner J, et al. Ann Neurol. 2010;67:699–714; Antinori A, Arendt G, et al. Neurology. 2007; 69: 1789–1799


1. Valcour V, Sithinamsuwan P, Letendre S, et al. Pathogenesis of HIV in the central nervous system. Curr HIV/AIDS Rep. 2011; 8:54–61.  
2. Heaton RK, Franklin DR, Ellis RJ, et al.HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011; 17:3–16.
3. Simioni S, Cavassini M, Annoni JM, et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010; 24:1243–1250.
4. Heaton RK, Velin RA, McCutchan JA, et al. Neuropsychological impairment in human immunodeficiency virus-infection: implications for employment. HNRC Group. HIV Neurobehavioral Research Center. Psychosom Med. 1994; 56:8–17.
5. Woods SP, Moran LM, Carey CL, et al.Prospective memory in HIV infection: is "remembering to remember" a unique predictor of self-reported medication management? Arch Clin Neuropsychol. 2008; 23:257–270.
6. Sevigny JJ, Albert SM, McDermott MP, et al.An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection. Arch Neurol. 2007; 64:97–102.
7. Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007; 69:1789–1799.
Singh D. Neurocognitive Impairment In PLWHA: Clinical Features And Assessment. Southern African Journal of HIV Medicine. 2009; 10(3):30–34.