title: HIV associated neurocognitive disorders (HAND) in Malawian adults and effect on adherence to combination anti-retroviral therapy: a cross sectional study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Brain Infection Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom; Malawi-Liverpool-Wellcome Clinical Research Programme, Queen Elizabeth Central Hospital, College of Medicine, Blantyre, Malawi.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Kelly
authors.affiliation: Department of Medicine, College of Medicine, Blantyre, Malawi; Dignitas International, Zomba, Malawi.
authors.forename: Joep J
authors.initials: JJ
authors.lastname: van Oosterhout
authors.affiliation: Department of Medicine, College of Medicine, Blantyre, Malawi.
authors.forename: Chisomo
authors.initials: C
authors.lastname: Ngwalo
authors.affiliation: Department of Mental Health, College of Medicine, Blantyre, Malawi.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Stewart
authors.affiliation: Brain Infection Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Benjamin
authors.affiliation: Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Robertson
authors.affiliation: HIV Pharmacology Group, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.affiliation: Department of Medicine, College of Medicine, Blantyre, Malawi.
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Allain
authors.affiliation: Brain Infection Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom; Walton Centre NHS Foundation Trust, Liverpool, United Kingdom; Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Solomon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008295:Malawi; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009483:Neuropsychological Tests; D015995:Prevalence; D012307:Risk Factors; D055815:Young Adult