HIV Associated Neurocognitive Disorders (HAND) in Malawian Adults and Effect on Adherence to Combination Anti-Retroviral Therapy: A Cross Sectional Study

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Abstract

Background

Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART.

Methods

HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery.

Results

One hundred and six HIV positive patients, with median (range) age 39 (18–71) years, 73% female and median (range) CD4 count 323.5 (68–1039) cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]). A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI); however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD) nor asymptomatic (ANI) forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696) and aOR 0.577 (CI. 0.09, 3.605; p = 0.556) respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition.

Discussion/Conclusion

Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and determination of the clinical relevance of ANI.

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Most cited references 31

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The International HIV Dementia Scale: a new rapid screening test for HIV dementia.

Ned C. Sacktor, Matthew Wong, Noeline Nakasujja … (2005)

HIV dementia is an important neurological complication of advanced HIV infection. The use of a cross-cultural screening test to detect HIV dementia within the international community is critical for diagnosing this condition. The objective of this study was to evaluate the sensitivity and specificity of a new screening test for HIV dementia, the International HIV Dementia Scale (IHDS) in cohorts from the US and Uganda. Two cross-sectional cohort studies designed to evaluate for the presence of HIV dementia. Sixty-six HIV-positive individuals in the US and 81 HIV-positive individuals in Uganda received the IHDS and full standardized neurological and neuropsychological assessments. The sensitivity and specificity of varying cut-off scores of the IHDS were evaluated in the two cohorts. In the US cohort, the mean IHDS score for HIV-positive individuals without dementia and with dementia were 10.6 and 9.3 respectively (P < 0.001). Using the cut-off of < or = 10, the sensitivity and specificity for HIV dementia with the IHDS were 80% and 57% respectively in the US cohort, and 80% and 55% respectively in the Uganda cohort. The IHDS may be a useful screening test to identify individuals at risk for HIV dementia in both the industrialized world and the developing world. Full neuropsychological testing should then be performed to confirm a diagnosis of HIV dementia.

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The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence?

Magnus Gisslén, Richard Price, Staffan Nilsson (2011)

Background A substantial prevalence of mild neurocognitive disorders has been reported in HIV, also in patients treated with combination antiretroviral therapy (cART). This includes a new disorder that has been termed asymptomatic neurocognitive impairment (ANI). Discussion ANI is identified by performance on formal neuropsychological testing that is at least 1 SD below the mean of normative scores in at least two cognitive domains out of at least five examined in patients without associated symptoms or evident functional impairment in daily living. While two tests are recommended to assess each domain, only one is required to fulfill this diagnostic criterion. Unfortunately, this definition necessitates that about 20% of the cognitively normal HIV-infected population is classified as suffering ANI. This liberal definition raises important ethical concerns and has as well diagnostic and therapeutic implications. Since neither its biological substrate, prognostic significance nor therapeutic implications are clearly established, we recommend that this diagnosis be modified or applied cautiously. Summary The diagnoses of less severe forms of neurocognitive disorders in HIV relies on the outcomes of neuropsychological testing, and a high proportion of HIV-infected patients with effective cART may be classified as neurocognitively abnormal using the current criteria. The definition of ANI is not stringent, and results in approximately 20% of the population being classified as abnormal. To us this seems an unacceptable false-positive rate.

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Depression symptoms and cognitive function among individuals with advanced HIV infection initiating HAART in Uganda

Noeline Nakasujja, Richard Skolasky, Seggane Musisi … (2010)

Background Among patients with HIV infection, depression is the most frequently observed psychiatric disorder. The presence of depressive symptoms and cognitive dysfunction among HIV patients has not been well studied in Sub-Saharan Africa. Initiation of highly active antiretroviral therapy (HAART) may have an effect on the prevalence and the change over time of depression symptoms and cognitive impairment among HIV-positive individuals. Methods We recruited 102 HIV-positive individuals at risk of cognitive impairment who were initiating HAART and 25 HIV-negative individuals matched for age and education. Depression was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D). Neurocognitive assessment included the International HIV Dementia Scale (IHDS), an 8 test neuropsychological battery and the Memorial Sloan Kettering scale. Assessments were carried out at 0, 3 and 6 months. Results The HIV-positive group had more respondents with CES-D score > 16 than the HIV-negative group at all 3 clinic visits (54%Vs 28%; 36% Vs 13%; and 30% Vs 24% respectively; all p < 0.050 OR 2.86, 95% CI: 1.03, 7.95, p = 0.044). The HIV positive group had higher likelihood for cognitive impairment (OR 8.88, 95% CI 2.64, 29.89, p < 0.001). A significant decrease in the mean scores on the CES-D (p = 0.002) and IHDS (p = 0.001) occurred more in the HIV-positive group when compared to the HIV-negative group. There was no association between clinical Memorial Sloan Kettering score and depression symptoms (p = 0.310) at baseline. Conclusion Depression symptomatology is distinct and common among cognitively impaired HIV patients. Therefore individuals in HIV care should be screened and treated for depression.

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Author and article information

Contributors

Alan Winston: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 10 June 2014

Volume: 9

Issue: 6

Electronic Location Identifier: e98962

Affiliations

[1 ]Brain Infection Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom

[2 ]Malawi-Liverpool-Wellcome Clinical Research Programme, Queen Elizabeth Central Hospital, College of Medicine, Blantyre, Malawi

[3 ]Department of Medicine, College of Medicine, Blantyre, Malawi

[4 ]Department of Mental Health, College of Medicine, Blantyre, Malawi

[5 ]Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, United States of America

[6 ]HIV Pharmacology Group, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom

[7 ]Dignitas International, Zomba, Malawi

[8 ]Walton Centre NHS Foundation Trust, Liverpool, United Kingdom

[9 ]Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom

Imperial College London, United Kingdom

Author notes

* E-mail: tsolomon@ 123456liverpool.ac.uk

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: CMK JJvO LB KRR SK TJA TS. Performed the experiments: CK CN. Analyzed the data: CK KRR SK. Contributed reagents/materials/analysis tools: KRR SK. Wrote the paper: CMK JJvO CN RCS LB KRR SK TJA TS.

Article

Publisher ID: PONE-D-14-07674

DOI: 10.1371/journal.pone.0098962

PMC ID: 4051684

PubMed ID: 24915530

SO-VID: 531de22e-c48f-4602-8326-47f7d8569c2c

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 20 February 2014

Date accepted : 8 May 2014

Page count

Pages: 11

Funding

CMK is a Wellcome Trust Training Fellow supported by the Liverpool Glasgow Wellcome Centre for Global Health Research.Grant number 099934/Z/12/A, http://www.wellcome.ac.uk/Funding. TS is an MRC Senior Clinical Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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HIV Associated Neurocognitive Disorders (HAND) in Malawian Adults and Effect on Adherence to Combination Anti-Retroviral Therapy: A Cross Sectional Study

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Abstract

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PLOS Climate

Most cited references 31

The International HIV Dementia Scale: a new rapid screening test for HIV dementia.

The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence?

Depression symptoms and cognitive function among individuals with advanced HIV infection initiating HAART in Uganda

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