TY - JOUR
T1 - Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia
T2 - A comparison of three prospective cohorts
AU - and on behalf of the COAT and ORCAS Trial Teams
AU - Montgomery, Martha P.
AU - Nakasujja, Noeline
AU - Morawski, Bozena M.
AU - Rajasingham, Radha
AU - Rhein, Joshua
AU - Nalintya, Elizabeth
AU - Williams, Darlisha A.
AU - Huppler Hullsiek, Kathy
AU - Kiragga, Agnes
AU - Rolfes, Melissa A.
AU - Donahue Carlson, Renee
AU - Bahr, Nathan C.
AU - Birkenkamp, Kate E.
AU - Manabe, Yukari C.
AU - Bohjanen, Paul R.
AU - Kaplan, Jonathan E.
AU - Kambugu, Andrew
AU - Meya, David B.
AU - Boulware, David R.
N1 - 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).
PY - 2017/6/12
Y1 - 2017/6/12
N2 - 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.
AB - 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.
KW - AIDS dementia complex
KW - Cryptococcal meningitis
KW - Cryptococcus
KW - HIV
KW - Neurocognitive disorders
KW - Neuropsychological tests
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U2 - 10.1186/s12883-017-0878-2
DO - 10.1186/s12883-017-0878-2
M3 - Article
C2 - 28606065
AN - SCOPUS:85020452637
SN - 1471-2377
VL - 17
JO - BMC neurology
JF - BMC neurology
IS - 1
M1 - 110
ER -