Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: A comparison of three prospective cohorts

Martha P. Montgomery, Noeline Nakasujja, Bozena M. Morawski, Radha Rajasingham, Joshua Rhein, Elizabeth Nalintya, Darlisha A. Williams, Kathy Huppler Hullsiek, Agnes Kiragga, Melissa A. Rolfes, Renee Donahue Carlson, Nathan C. Bahr, Kate E. Birkenkamp, Yukari C. Manabe, Paul R. Bohjanen, Jonathan E. Kaplan, Andrew Kambugu, David B. Meya, David R. Boulware, and on behalf of the COAT and ORCAS Trial Teams

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia. Methods: Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants. Results: Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001). Conclusion: Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.

Original languageEnglish (US)
Article number110
JournalBMC neurology
Issue number1
StatePublished - Jun 12 2017

Bibliographical note

Funding Information:
This research was made possible through support from the Centers for Disease Control and Prevention (U01GH000517), Fogarty International Center and National Institute of Neurologic Diseases and Stroke (R21NS065713, R01NS086312, R25TW009345), and National Institute of Allergy and Infectious Diseases (U01AI089244, T32AI055433, K24AI096925). These funding bodies had no role in the study design, in the collection, analysis, or interpretation of data, or in the writing of the manuscript.

Publisher Copyright:
© 2017 The Author(s).


  • AIDS dementia complex
  • Cryptococcal meningitis
  • Cryptococcus
  • HIV
  • Neurocognitive disorders
  • Neuropsychological tests


Dive into the research topics of 'Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: A comparison of three prospective cohorts'. Together they form a unique fingerprint.

Cite this