Skip to main content

Advertisement

SpringerLink
Log in

Prevalence of non-confounded HIV-associated neurocognitive impairment in the context of plasma HIV RNA suppression

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

HIV-associated neurocognitive disorder is known to occur in the context of successful combination antiretroviral therapy (cART; plasma HIV RNA <50 copies/ml). Here, we newly provide an analysis of its prevalence and nature in the absence of medical or psychiatric confounds that may otherwise inflate the prevalence rate. We enrolled a cohort of 116 advanced HIV + individuals on cART (51% virally suppressed (VS)). They were screened for active Hepatitis C, current substance use disorder and were assessed with standard neuropsychological (NP) testing. Our results showed that out of the entire sample, NP impairment occurred in 18.1% (21/116) in VS individuals which was not statistically different from the 24.1% (28/116) that were found to be NP-impaired and not VS. In comparison with NP-normal-VS persons, NP impairment in VS individuals was associated with shorter duration of current cART and lower pre-morbid ability. Higher cART CNS penetration effectiveness tended to be associated with lesser cognitive severity in NP-impaired VS individuals. Current CD4 cell count, depression symptoms and past CNS HIV-related diseases did not specifically account for persistent NP impairment in VS individuals. In conclusion, despite suppression of systemic viral load, non-confounded HIV-related NP-impairment prevalence reached 18.1%. Of the potential explanations for this persistent deficit, a “burnt-out” form of the disease and immune reconstitution inflammatory syndrome were the less likely explanations, while a shorter current cART duration and lower pre-morbid intellectual capacity were significant. Nonetheless, predictive modelling with these last two factors misclassified 27% and had low sensitivity (43%) emphasising that other yet-to-be-defined factors were operative.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Basso MR, Bornstein RA (2000) Estimated pre-morbid intelligence mediates neurobehavioral change in individuals infected with HIV across 12 months. J Clin Exp Neuropsychol 22:208–218

    Article  PubMed  CAS  Google Scholar 

  • Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, Sabin C, Phillips A, Porter K (2008) Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Ann Neurol 63:213–221

    Article  PubMed  Google Scholar 

  • Brew BJ (2004) Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. AIDS 18:S75–S78

    Article  PubMed  CAS  Google Scholar 

  • Brew BJ, Crowe SM, Landay A, Cysique LA, Guillemin G (2008) Neurodegeneration and Ageing in the HAART Era. J Neuroimmune Pharmacol 6:6

    Google Scholar 

  • Byrd D, Morgello S, Franklin D, Heaton RK, Grant I (2009) Substance use and HIV infection: neurocognitive effect, the CHARTER Cohort. In: 16th Conference on Retroviruses and Opportunistic Infections. http://www.retroconference.org/2009/Abstracts/34478.htm: Montreal, Canada, pp 478

  • Carey CL, Woods SP, Gonzalez R, Conover E, Marcotte TD, Grant I, Heaton RK (2004) Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol 26:307–319

    Article  PubMed  Google Scholar 

  • Carter SL, Rourke SB, Murji S, Shore D, Rourke BP (2003) Cognitive complaints, depression, medical symptoms, and their association with neuropsychological functioning in HIV infection: a structural equation model analysis. Neuropsychology 17:410–419

    Article  PubMed  Google Scholar 

  • Churchill MJ, Wesselingh SL, Cowley D, Pardo CA, McArthur JC, Brew BJ, Gorry PR (2009) Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol 66:253–258

    Article  PubMed  Google Scholar 

  • Cinque P, Brew BJ, Gisslen M, Hagberg L, Price RW (2007) Cerebrospinal fluid markers in central nervous system HIV infection and AIDS dementia complex. Handb Clin Neurol 85:261–300

    Article  PubMed  Google Scholar 

  • Cole MA, Margolick JB, Cox C, Li X, Selnes OA, Martin EM, Becker JT, Aronow HA, Cohen B, Sacktor N, Miller EN (2007) Longitudinally preserved psychomotor performance in long-term asymptomatic HIV-infected individuals. Neurology 69:2213–2220

    Article  PubMed  CAS  Google Scholar 

  • Cunningham P, Smith D, Satchell C, Cooper DA, Brew B (2000) Evidence for independant development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid. AIDS 14:1949–1954

    Article  PubMed  CAS  Google Scholar 

  • Cysique L, Maruff P, Brew B (2004a) Antiretroviral therapy in HIV infection: are neurologically active drugs important? Arch Neurol 61:1699–1704

    Article  Google Scholar 

  • Cysique L, Maruff P, Brew B (2004b) Prevalence and pattern of neuropsychological impairment in HIV/AIDS-infection across pre and post- highly active antiretroviral therapy eras: a combined study of 2 cohorts. J Neurovirol 10:350–357

    Article  Google Scholar 

  • Cysique L, Vaida F, Letendre S, Gibson S, Woods S, Cherner M, McCutchan JA, Heaton RK, Ellis RJ (2009) Dynamics of cognitive change in impaired HIV + individuals initiating antiretroviral therapy. Neurology 27:27

    Google Scholar 

  • Cysique LA, Deutsch R, Atkinson JH, Young C, Marcotte TD, Dawson L, Grant I, Heaton RK (2007) Incident major depression does not affect neuropsychological functioning in HIV-infected men. J Int Neuropsychol Soc 13:1–11

    Article  PubMed  Google Scholar 

  • Cysique LA, Maruff P, Brew BJ (2006) Variable benefit in neuropsychological function in HIV-infected HAART-treated patients. Neurology 66:1447–1450

    Article  PubMed  Google Scholar 

  • Cysique LA, Maruff P, Bain MP, Wright E, Brew BJ (2011) HIV and Age Do Not Substantially Interact in HIV-Associated Neurocognitive Impairment. J Neuropsychiatry Clin Neurosci 23:83–89

    PubMed  Google Scholar 

  • Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, Hellmann NS, Petropoulos CJ, McCune JM, Hellerstein MK, Grant RM (2001) Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med 344:472–480

    Article  PubMed  CAS  Google Scholar 

  • Dore GJ, McDonald A, Li Y, Kaldo JM, Brew BJ (2003) Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 17:1539–1545

    Article  PubMed  Google Scholar 

  • Ellis RJ, Gamst AC, Capparelli E, Spector SA, Hsia K, Wolfson BS, Abramson I, Grant I, McCutchan JA (2000) Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 54:927–936

    PubMed  CAS  Google Scholar 

  • Goggin KJ, Zisook S, Heaton RK, Atkinson HJ, Marshall S, McCuthchan JA, Chandler JL, Grant I, group atH (1997) Neuropsychological performance of HIV-1 infected men with major depression. J Int Neuropsychol Soc 3:457–464

    PubMed  CAS  Google Scholar 

  • Gulick R, Staszewski S (2002) New drugs for HIV therapy. AIDS 16:S135–S144

    Article  PubMed  CAS  Google Scholar 

  • Heaton RK, Franklin1 D, Clifford D, Woods S, Rivera Mindt M, Vigil O, Taylor M, Marcotte T, Atkinson H, Grant I (2009) HIV-associated neurocognitive impairment remains prevalent in the era of combination ART: The CHARTER study. In: 16th Conference on retroviruses and opportunistic infections. http://www.retroconference.org/2009/Abstracts/35664.htm: Montreal, Canada, pp 154

  • Heaton RK, Miller SW, Taylor MJ, Grant I (2004) Revised comprehensive norms for an expanded halstead-reitan battery: demographically adjusted neuropsychological norms for African American and Caucasian adults scoring program. Psychological Assessment Resources, Odessa

    Google Scholar 

  • Hilsabeck RC, Castellon SA, Hinkin CH (2005) Neuropsychological aspects of coinfection with HIV and hepatitis C virus. Clin Infect Dis 41(Suppl 1):S38–S44

    Article  PubMed  Google Scholar 

  • Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ (2008) Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65:65–70

    Article  PubMed  Google Scholar 

  • Letendre S, McClernon D, Ellis R, Muñoz-Moreno J, Way L, Franklin D, Heaton R, Grant I, CHARTER Group (2009) Persistent HIV in the Central Nervous System during Treatment is Associated with Worse ART Penetration and Cognitive Impairment. In: 16th Conference on Retroviruses and Opportunistic Infections. Montreal, Canada, pp 484b

  • Letendre S, McCutchan J, Childers M, Woods S, Lazzaretto D, Heaton R, Grant I, Ellis R, Group. H (2004) Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol 56:416–423

    Article  PubMed  Google Scholar 

  • Lovibond SH, Lovibond PF (1995) Manual for the Depression Anxiety Stress Scales, 2nd edn. Psychology Foundation, Sydney

    Google Scholar 

  • McCutchan JA, Wu JW, Robertson K, Koletar SL, Ellis RJ, Cohn S, Taylor M, Woods S, Heaton R, Currier J, Williams PL (2007) HIV suppression by HAART preserves cognitive function in advanced, immune-reconstituted AIDS patients. AIDS 21:1109–1117

    Article  PubMed  Google Scholar 

  • Nelson H, Willison J (1982) National Adult Reading Test (NART). Test manual, 2nd edn. NFER-NELSON, Windsor

    Google Scholar 

  • Norman MA, Evans JD, Miller SW, Heaton RK (2000) Demographically corrected norms for the California Verbal Learning Test. J Clin Exp Neuropsychol 22:80–94

    Google Scholar 

  • Perneger TV (1998) What's wrong with Bonferroni adjustments. BMJ 316:1236–1238

    PubMed  CAS  Google Scholar 

  • Riedel DJ, Pardo CA, McArthur J, Nath A (2006) Therapy insight: CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome. Nat Clin Pract Neurol 2:557–565

    Article  PubMed  Google Scholar 

  • Roberston K, Roberston TW, Ford S, Watson D, Fiscus S, Harp AG, Hall D (2004) Highly Active Antiretroviral Therapy improves neurocognitive functioning. J Acquir Immune Defic Syndr 36:562–566

    Article  Google Scholar 

  • Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21:1915–1921

    Article  PubMed  Google Scholar 

  • Rumbaugh JA, Nath A (2006) Developments in HIV neuropathogenesis. Curr Pharm Des 12:1023–1044

    Article  PubMed  CAS  Google Scholar 

  • Sacktor N, McDermott M, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo P, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8:136–142

    Article  PubMed  Google Scholar 

  • Schweinsburg BC, Taylor MJ, Alhassoon OM, Gonzalez R, Brown GG, Ellis RJ, Letendre S, Videen JS, McCutchan JA, Patterson TL, Grant I (2005) Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol 11:356–364

    Article  PubMed  CAS  Google Scholar 

  • Sevigny JJ, Albert SM, McDermott MP, McArthur JC, Sacktor N, Conant K, Schifitto G, Selnes OA, Stern Y, McClernon DR, Palumbo D, Kieburtz K, Riggs G, Cohen B, Epstein LG, Marder K (2004) Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia. Neurology 63:2084–2090

    PubMed  CAS  Google Scholar 

  • Stern RA, Silva SG, Chaisson N, Evans DL (1996) Influence of cognitive reserve on neuropsychological functioning in asymptomatic human immunodeficiency virus-1 infection. Arch Neurol 53:148–153

    PubMed  CAS  Google Scholar 

  • Stern Y (2002) What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc 8:448–460

    Article  PubMed  Google Scholar 

  • Stern Y, McDermott M, Albert S, Palumbo P, Selnes OA, McArthur JC, Sacktor N, Schifitto G, Kieburtz K, Epstein L, Marder K, Disorders ftDcotToH-DaRC (2001) Factors associated with incident human immonodefiency virus-dementia. Arch Neurol 58:473–479

    Article  PubMed  CAS  Google Scholar 

  • Strauss E, Sherman EMS, Spreen O (2006) A compendium of neuropsychological tests: administration, norms, and commentary. Oxford University Press, Oxford

    Google Scholar 

  • Trillo-Pazos G, Kandanearatchi A, Eyeson J, King D, Vyakarnam A, Everall IP (2004) Infection of stationary human brain aggregates with HIV-1 SF162 and IIIB results in transient neuronal damage and neurotoxicity. Neuropathol Appl Neurobiol 30:136–147

    Article  PubMed  CAS  Google Scholar 

  • Uchiyama CL, D’Elia LF, Dellinger AM, Selnes OA, et al. (1994) Longitudinal comparison of alternate versions of the symbol digit modalities test: issues of form comparability and moderating demographic variables. Clin Neuropsychol 8:209–218

    Google Scholar 

  • Valcour V, Paul R (2006) HIV infection and dementia in older adults. Clin Infect Dis 42:1449–1454

    Article  PubMed  Google Scholar 

  • Valcour V, Shikuma C, Watters M, Poff P, Selnes O, Holck P, Grove J, Sacktor N (2004) Higher frequency of dementia in older HIV-1 individuals. The Hawaii aging with HIV-1 cohort. Neurology 63:822–827

    PubMed  CAS  Google Scholar 

  • Wright EJ, Grund B, Robertson K, Brew BJ, Roediger M, Bain MP, Drummond F, Vjecha MJ, Hoy J, Miller C, Penalva de Oliveira AC, Pumpradit W, Shlay JC, El-Sadr W, Price RW (2010) Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons. Neurology 75:864–873

    Article  PubMed  CAS  Google Scholar 

  • Yeni P, Hammer S, Carpenter C, Cooper D, Fischl M, Gatell J, Gazzard B, Hirsch M, Jacobsen D, Katzenstein D, Montaner J, Richman D, Saag M, Schechter M, Schooley R, Thompson M, Vella S, Volberding P (2002) Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel. JAMA 288:222–235

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Brain Sciences University of New South Wales post-doctoral fellowship.

Author information

Authors and Affiliations

  1. Brain Sciences, University of New South Wales, Sydney, Australia

    Lucette A. Cysique & Bruce J. Brew

  2. Department of Neurology, St. Vincent’s Hospital, Xavier Building, Level 4, 390 Victoria Street, Darlinghurst, Sydney, 2010, NSW, Australia

    Lucette A. Cysique & Bruce J. Brew

Authors
  1. Lucette A. Cysique
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruce J. Brew
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lucette A. Cysique.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cysique, L.A., Brew, B.J. Prevalence of non-confounded HIV-associated neurocognitive impairment in the context of plasma HIV RNA suppression. J. Neurovirol. 17, 176–183 (2011). https://doi.org/10.1007/s13365-011-0021-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-011-0021-x

Keywords

Search

Navigation