title: HIV subtype D is associated with dementia, compared with subtype A, in immunosuppressed individuals at risk of cognitive impairment in Kampala, Uganda.
abstract: BACKGROUND
  In the United States, clade B is the predominant human immunodeficiency virus (HIV) subtype, whereas in sub-Saharan Africa, clades A, C, and D are the predominant subtypes. HIV subtype may have an impact on HIV disease progression. The effect of HIV subtype on the risk of dementia has, to our knowledge, not been examined. The objective of this study was to examine the relationship between HIV subtype and the severity of HIV-associated cognitive impairment among individuals initiating antiretroviral therapy in Uganda.
  
  
  METHODS
  Sixty antiretroviral-naive HIV-infected individuals with advanced immunosuppression who were at risk of HIV-associated cognitive impairment underwent neurological, neuropsychological, and functional assessments, and gag and gp41 regions were subtyped. Subtype assignments were generated by sequence analysis using a portion of the gag and gp41 regions.
  
  
  RESULTS
  Thirty-three HIV-infected individuals were infected with subtype A, 2 with subtype C, 9 with subtype D, and 16 with A/D recombinants. Eight (89%) of 9 HIV-infected individuals with subtype D had dementia, compared with 7 (24%) of 33 HIV-infected individuals with subtype A (P = .004).
  
  
  CONCLUSIONS
  These results suggest that, in untreated HIV-infected individuals with advanced immunosuppression who are at risk of developing HIV-associated cognitive impairment, HIV dementia may be more common among patients infected with subtype D virus than among those infected with subtype A virus. These findings provide the first evidence, to our knowledge, to demonstrate that HIV subtypes may have a pathogenetic factor with respect to their capacity to cause cognitive impairment. Additional studies are needed to confirm this observation and to define the mechanism by which subtype D leads to an increased risk of neuropathogenesis.
authors.affiliation: Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sacktor@jhmi.edu
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.forename: Noeline
authors.initials: N
authors.lastname: Nakasujja
authors.forename: Richard L
authors.initials: RL
authors.lastname: Skolasky
authors.forename: Mona
authors.initials: M
authors.lastname: Rezapour
authors.forename: Kevin
authors.initials: K
authors.lastname: Robertson
authors.forename: Seggane
authors.initials: S
authors.lastname: Musisi
authors.forename: Elly
authors.initials: E
authors.lastname: Katabira
authors.forename: Allan
authors.initials: A
authors.lastname: Ronald
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
mesh_terms: D015526:AIDS Dementia Complex / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D015700:HIV Envelope Protein gp41 / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000032:analysis; D014454:Uganda; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D015700:HIV Envelope Protein gp41; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; C514787:gp41 protein, Human immunodeficiency virus 1