Multivariate normative comparison, a novel method for more reliably detecting cognitive impairment in HIV infection

AIDS. 2015 Mar 13;29(5):547-57. doi: 10.1097/QAD.0000000000000573.


Objective: The objective of this study is to assess whether multivariate normative comparison (MNC) improves detection of HIV-1-associated neurocognitive disorder (HAND) as compared with Frascati and Gisslén criteria.

Methods: One-hundred and three HIV-1-infected men with suppressed viremia on combination antiretroviral therapy (cART) for at least 12 months and 74 HIV-uninfected male controls (comparable regarding age, ethnicity, sexual orientation, premorbid intelligence and educational level), aged at least 45 years, underwent neuropsychological assessment covering six cognitive domains (fluency, attention, information processing speed, executive function, memory, and motor function). Frascati and Gisslén criteria were applied to detect HAND. Next, MNC was performed to compare the cognitive scores of each HIV-positive individual against the cognitive scores of the control group.

Results: HIV-infected men showed significantly worse performance on the cognitive domains of attention, information processing speed and executive function compared with HIV-uninfected controls. HAND by Frascati criteria was highly prevalent in HIV-infected [48%; 95% confidence interval (95% CI) 38-58] but nearly equally so in HIV-uninfected men (36%; 95% CI 26-48), confirming the low specificity of this method. Applying Gisslén criteria, HAND-prevalence was reduced to 5% (95% CI 1-9) in HIV-infected men and to 1% (95% CI 1-3) among HIV-uninfected controls, indicating better specificity but reduced sensitivity. MNC identified cognitive impairment in 17% (95% CI 10-24) of HIV-infected men and in 5% (95% CI 0-10) of the control group (P = 0.02, one-tailed), showing an optimal balance between sensitivity and specificity.

Conclusion: Prevalence of cognitive impairment in HIV-1-infected men with suppressed viremia on cART estimated by MNC was much higher than that estimated by Gisslén criteria, while the false positive rate was greatly reduced compared with the Frascati criteria.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / diagnosis*
  • AIDS Dementia Complex / epidemiology
  • Anti-Retroviral Agents / therapeutic use
  • Cohort Studies
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests*
  • Prevalence
  • Prospective Studies


  • Anti-Retroviral Agents