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 journalArticle

Abstract

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
Volume17
Issue number1
DOIs
StatePublished - Jun 12 2017

Fingerprint

HIV
Antigens
Cryptococcal Meningitis
Fluconazole
Karnofsky Performance Status
Central Nervous System Infections
CD4 Lymphocyte Count
Meningitis
Morbidity
Mortality

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Montgomery, M. P., Nakasujja, N., Morawski, B. M., Rajasingham, R., Rhein, J., Nalintya, E., ... and on behalf of the COAT and ORCAS Trial Teams (2017). Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: A comparison of three prospective cohorts. BMC Neurology, 17(1), [110]. DOI: 10.1186/s12883-017-0878-2

Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia : A comparison of three prospective cohorts. / Montgomery, Martha P.; Nakasujja, Noeline; Morawski, Bozena M.; Rajasingham, Radha; Rhein, Joshua; Nalintya, Elizabeth; Williams, Darlisha A.; Huppler Hullsiek, Kathy; Kiragga, Agnes; Rolfes, Melissa A.; Donahue Carlson, Renee; Bahr, Nathan C.; Birkenkamp, Kate E.; Manabe, Yukari C.; Bohjanen, Paul R.; Kaplan, Jonathan E.; Kambugu, Andrew; Meya, David B.; Boulware, David R.; and on behalf of the COAT and ORCAS Trial Teams.

In: BMC Neurology, Vol. 17, No. 1, 110, 12.06.2017.

Research output: Contribution to journalArticle

Montgomery, MP, Nakasujja, N, Morawski, BM, Rajasingham, R, Rhein, J, Nalintya, E, Williams, DA, Huppler Hullsiek, K, Kiragga, A, Rolfes, MA, Donahue Carlson, R, Bahr, NC, Birkenkamp, KE, Manabe, YC, Bohjanen, PR, Kaplan, JE, Kambugu, A, Meya, DB, Boulware, DR & and on behalf of the COAT and ORCAS Trial Teams 2017, 'Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: A comparison of three prospective cohorts' BMC Neurology, vol 17, no. 1, 110. DOI: 10.1186/s12883-017-0878-2
Montgomery MP, Nakasujja N, Morawski BM, Rajasingham R, Rhein J, Nalintya E et al. Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: A comparison of three prospective cohorts. BMC Neurology. 2017 Jun 12;17(1). 110. Available from, DOI: 10.1186/s12883-017-0878-2

Montgomery, Martha P.; Nakasujja, Noeline; Morawski, Bozena M.; Rajasingham, Radha; Rhein, Joshua; Nalintya, Elizabeth; Williams, Darlisha A.; Huppler Hullsiek, Kathy; Kiragga, Agnes; Rolfes, Melissa A.; Donahue Carlson, Renee; Bahr, Nathan C.; Birkenkamp, Kate E.; Manabe, Yukari C.; Bohjanen, Paul R.; Kaplan, Jonathan E.; Kambugu, Andrew; Meya, David B.; Boulware, David R.; and on behalf of the COAT and ORCAS Trial Teams / Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia : A comparison of three prospective cohorts.

In: BMC Neurology, Vol. 17, No. 1, 110, 12.06.2017.

Research output: Contribution to journalArticle

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abstract = "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.",
keywords = "AIDS dementia complex, Cryptococcal meningitis, Cryptococcus, HIV, Neurocognitive disorders, Neuropsychological tests",
author = "Montgomery, {Martha P.} and Noeline Nakasujja and Morawski, {Bozena M.} and Radha Rajasingham and Joshua Rhein and Elizabeth Nalintya and Williams, {Darlisha A.} and {Huppler Hullsiek}, Kathy and Agnes Kiragga and Rolfes, {Melissa A.} and {Donahue Carlson}, Renee and Bahr, {Nathan C.} and Birkenkamp, {Kate E.} and Manabe, {Yukari C.} and Bohjanen, {Paul R.} and Kaplan, {Jonathan E.} and Andrew Kambugu and Meya, {David B.} and Boulware, {David R.} and {and on behalf of the COAT and ORCAS Trial Teams}",
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T1 - Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia

T2 - BMC Neurology

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.

AU - and on behalf of the COAT and ORCAS Trial Teams

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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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