title: Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study.
abstract: OBJECTIVE
  Little is known about the impact of HIV infection on biological ageing in sub-Saharan Africa. The study aimed to assess biological ageing in South African HIV-infected adults and HIV-seronegative individuals using two validated biomarkers, telomere length and CDKN2A expression (a mediator of cellular senescence).
  
  
  METHODS
  A case-control study.
  
  
  METHODS
  Two hundred and thirty-six HIV-infected adults aged at least 30 years and 250 age and sex frequency matched HIV-seronegative individuals were recruited from clinics in township communities in Cape Town. Biological ageing was evaluated by measurement of telomere length and CDKN2A expression in peripheral blood leukocytes.
  
  
  RESULTS
  The median ages of the HIV-infected and HIV-seronegative participants were 39 and 40 years, respectively. Among HIV-infected participants, 87.1% were receiving antiretroviral therapy (ART), their median CD4⁺ cell count was 468 cells/μl and 84.3% had undetectable viral load. Both biomarkers were validated against chronological age in HIV-seronegative individuals. Telomere length was significantly shorter in HIV-infected individuals than in HIV-seronegative individuals (mean relative T/S ratio ±SE:0.91 ± 0.007 vs. 1.07 ± 0.008, P < 0.0001). CD2NKA expression was higher in HIV-infected participants than in HIV-seronegative individuals (mean expression: 0.45 ± 0.02 vs. 0.36 ± 0.03, P = 0.003). Socioeconomic factors were not associated with biological ageing in HIV-infected participants. However, in participants on ART with undetectable viral load, biomarker levels indicated greater biological ageing in those with lower current CD4⁺ cell counts.
  
  
  CONCLUSIONS
  Telomere length and CDKN2A expression were both consistent with increased biological ageing in HIV-infected individuals. Prospective studies of the impact of HIV on biological ageing in sub-Saharan Africa are warranted.
authors.affiliation: aInternational Centre for Eye Health, Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK bDesmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa cDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London dInstitute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, Scotland eMRC Tropical Epidemiology Group, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Sophia
authors.initials: S
authors.lastname: Pathai
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.forename: Clare E
authors.initials: CE
authors.lastname: Gilbert
authors.forename: Dagmara
authors.initials: D
authors.lastname: McGuinness
authors.forename: Liane
authors.initials: L
authors.lastname: McGlynn
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.forename: Jennifer
authors.initials: J
authors.lastname: Port
authors.forename: Theresa
authors.initials: T
authors.lastname: Christ
authors.forename: Karen
authors.initials: K
authors.lastname: Barclay
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
mesh_terms: D000328:Adult; D000375:Aging / Q000097:blood*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007962:Leukocytes / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D013019:South Africa; D016615:Telomere / Q000378:metabolism*; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16