HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: Differences in rates, nature, and predictors

Robert K. Heaton, Donald R. Franklin, Ronald J. Ellis, J. Allen McCutchan, Scott L. Letendre, Shannon LeBlanc, Stephanie H. Corkran, Nichole A. Duarte, David B. Clifford, Steven P. Woods, Ann C. Collier, Christina M. Marra, Susan Morgello, Monica Rivera Mindt, Michael J. Taylor, Thomas D. Marcotte, J. Hampton Atkinson, Tanya Wolfson, Benjamin B. Gelman, Justin C. McArthurDavid M. Simpson, Ian Abramson, Anthony Gamst, Christine Fennema-Notestine, Terry L. Jernigan, Joseph Wong, Igor Grant

Research output: Contribution to journalArticle

878 Scopus citations

Abstract

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV-) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV - participants from the pre-CART era (1988-1995; N=857) and CART era (2000-2007; N=937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the. CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.

Original languageEnglish (US)
Pages (from-to)3-16
Number of pages14
JournalJournal of neurovirology
Volume17
Issue number1
DOIs
StatePublished - Feb 2011

Keywords

  • Combination antiretroviral therapy
  • HIV
  • HIV dementia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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    Heaton, R. K., Franklin, D. R., Ellis, R. J., McCutchan, J. A., Letendre, S. L., LeBlanc, S., Corkran, S. H., Duarte, N. A., Clifford, D. B., Woods, S. P., Collier, A. C., Marra, C. M., Morgello, S., Rivera Mindt, M., Taylor, M. J., Marcotte, T. D., Atkinson, J. H., Wolfson, T., Gelman, B. B., ... Grant, I. (2011). HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: Differences in rates, nature, and predictors. Journal of neurovirology, 17(1), 3-16. https://doi.org/10.1007/s13365-010-0006-1