Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

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

Authors: 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, on behalf of the COAT and ORCAS Trial Teams

Published in: BMC Neurology | Issue 1/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Meyer AC, Kendi CK, Penner JA, Odhiambo N, Otieno B, Omondi E, et al. The impact of routine cryptococcal antigen screening on survival among HIV-infected individuals with advanced immunosuppression in Kenya. Trop. Med. Int. Heal. 2013;18:495–503.CrossRef
2.
French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 2002;16:1031–8.CrossRefPubMed
3.
Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23:525–30.CrossRefPubMed
4.
5.
6.
Liechty CA, Solberg P, Were W, Ekwaru JP, Ransom RL, Weidle PJ, et al. Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Heal. 2007;12:929–35.CrossRef
7.
Ganiem AR, Indrati AR, Wisaksana R, Meijerink H, Van Der Ven A, Alisjahbana B, et al. Asymptomatic cryptococcal antigenemia is associated with mortality among HIV-positive patients in Indonesia. J Int AIDS Soc. 2014;17:1–7.
8.
Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, et al. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis. 2010;51:448–55.CrossRefPubMedPubMedCentral
9.
Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS. Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis. 2009;48:856–62.CrossRefPubMedPubMedCentral
10.
11.
12.
13.
14.
Carlson RD, Rolfes MA, Birkenkamp KE, Nakasujja N, Rajasingham R, Meya DB, et al. Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study. Metab Brain Dis. 2014;29:269–79.CrossRefPubMedPubMedCentral
15.
Levine AJ, Hinkin CH, Ando K, Santangelo G, Martinez M, Valdes-Sueiras M, et al. An exploratory study of long-term neurocognitive outcomes following recovery from opportunistic brain infections in HIV+ adults. J Clin Exp Neuropsychol NIH Public Access. 2008;30:836–43. [cited 2017 Apr 16]. Available from: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18608693.CrossRef
16.
17.
Sacktor N, Nakajujja N, Okonkwo O, Skolasky RL, Robertson K, Musisi S, et al. Longitudinal neuropsychological test performance among HIV seropositive individuals in Uganda. J Neuro-Oncol. 2013;19:48–56.
18.
Wechsler D. Wechsler adult intelligence scale - revised (WAIS-R). San Antonio, TX: Psychological Corporation; 1981.
19.
D’Elia LF, Satz P, Uchiyama CL, White T. Color Trails test. Professional manual. Psychological Assessment Resources: Odessa, FL; 1996.
20.
Maj M, D’Elia L, Satz P, Janssen R, Zaudig M, Uchiyama C, et al. Evaluation of two new neuropsychological tests designed to minimize cultural bias in the assessment of HIV-1 seropositive persons: a WHO study. Arch Clin Neuropsychol. 1993;8:123–35.CrossRefPubMed
21.
Spreen O, Strauss E. A compendium of neuropsychological tests: administration, norms, and commentary. 2nd ed. New York: Oxford University Press; 1998.
22.
Reitan RM. Manual for administration of neuropsychological test batteries for adults and children. Bloomington, IN: Indiana University Press; 1969.
23.
24.
Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, et al. The International HIV dementia scale: a new rapid screening test for HIV dementia. AIDS. 2005;19:1367–74.PubMed
25.
Robertson KR, Nakasujja N, Wong M, Musisi S, Katabira E, Parsons TD, et al. Pattern of neuropsychological performance among HIV positive patients in Uganda. BMC Neurol. 2007;7:8.CrossRefPubMedPubMedCentral
26.
Price RW, Yiannoutsos CT, Clifford DB, Zaborski L, Tselis A, Sidtis JJ, et al. Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS clinical trial group and neurological AIDS research consortium study team. AIDS. 1999;13:1677–85.CrossRefPubMed
27.
Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: Macleod CM, editor. Eval. Chemother. Agents. New York: Columbia University Press; 1949. p. 191–205.
28.
Radloff LS. The CES-D scale: a self-reported depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–401.CrossRef
29.
Beekman ATF, Deeg DJH, van Limbeek J, Braam AW, de Vries MZ, van Tilburg W. Criterion validity of the Center for Epidemiologic Studies Depression scale (CES-D): results from a community-based sample of older subject in the Netherlands. Psychol Med. 1997;27:231–5. Available from: http://​dare.​ubvu.​vu.​nl/​handle/​1871/​23024.
30.
31.
Feldmesser M, Harris C, Reichberg S, Khan S, Casadevall A. Serum cryptococcal antigen in patients with AIDS. Clin Infect Dis. 1996;23:827–30.CrossRefPubMed
32.
Robertson KR, Robertson WT, Ford S, Watson D, Fiscus S, Harp AG, et al. Highly active antiretroviral therapy improves neurocognitive functioning. J Acquir Immune Defic Syndr. 2004;36:562–6.CrossRefPubMed
33.
Sacktor N, Nakasujja N, Skolasky R, Robertson K, Wong M, Musisi S, et al. Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa. Neurology. 2006;67:311–4.CrossRefPubMed
34.
Grund B, Wright EJ, Brew BJ, Price RW, Roediger MP, Bain MP, et al. Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect. J Neuro-Oncol. 2013;19:383–92.
35.
Butler EK, Boulware DR, Bohjanen PR, Meya DB. Long term 5-year survival of persons with Cryptococcal meningitis or asymptomatic subclinical Antigenemia in Uganda. PLoS One. 2012;7:5–9.
36.
37.
Mfinanga S, Chanda D, Kivuyo SL, Guinness L, Bottomley C, Simms V, et al. Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial. Lancet (London, England). 2015;385:2173–2182. [cited 2015 Aug 13]. Available from: http://​www.​sciencedirect.​com/​science/​article/​pii/​S014067361560164​7.
Metadata
Title
Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: a comparison of three prospective cohorts
Authors
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
on behalf of the COAT and ORCAS Trial Teams
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0878-2

Other articles of this Issue 1/2017

BMC Neurology 1/2017 Go to the issue

Erratum

Erratum to: clinical predictors of seizure recurrence after the first post-ischemic stroke seizure

Case report

Listeria monocytogenes infection associated with alemtuzumab – - a case for better preventive strategies

Research article

Reasons for discontinuation of subcutaneous interferon β-1a three times a week among patients with multiple sclerosis: a real-world cohort study

Research article

Short-term motor learning through non-immersive virtual reality task in individuals with down syndrome

Research article

Meta-analysis on the prevalence of REM sleep behavior disorder symptoms in Parkinson’s disease

Research article

Post-operative re-bleeding in patients with hypertensive ICH is closely associated with the CT blend sign