title: Impact of HIV-1 viral subtype on disease progression and response to antiretroviral therapy.
abstract: BACKGROUND
  Our intention was to compare the rate of immunological progression prior to antiretroviral therapy (ART) and the virological response to ART in patients infected with subtype B and four non-B HIV-1 subtypes (A, C, D and the circulating recombinant form, CRF02-AG) in an ethnically diverse population of HIV-1-infected patients in south London.
  
  
  METHODS
  A random sample of 861 HIV-1-infected patients attending HIV clinics at King's and St Thomas' hospitals' were subtyped using an in-house enzyme-linked immunoassay and env sequencing. Subtypes were compared on the rate of CD4 cell decline using a multi-level random effects model. Virological response to ART was compared using the time to virological suppression (< 400 copies/ml) and rate of virological rebound (> 400 copies/ml) following initial suppression.
  
  
  RESULTS
  Complete subtype and epidemiological data were available for 679 patients, of whom 357 (52.6%) were white and 230 (33.9%) were black African. Subtype B (n = 394) accounted for the majority of infections, followed by subtypes C (n = 125), A (n = 84), D (n = 51) and CRF02-AG (n = 25). There were no significant differences in rate of CD4 cell decline, initial response to highly active antiretroviral therapy and subsequent rate of virological rebound for subtypes B, A, C and CRF02-AG. However, a statistically significant four-fold faster rate of CD4 decline (after adjustment for gender, ethnicity and baseline CD4 count) was observed for subtype D. In addition, subtype D infections showed a higher rate of virological rebound at six months (70%) compared with subtypes B (45%, p = 0.02), A (35%, p = 0.004) and C (34%, p = 0.01)
  
  
  CONCLUSIONS
  This is the first study from an industrialized country to show a faster CD4 cell decline and higher rate of subsequent virological failure with subtype D infection. Further studies are needed to identify the molecular mechanisms responsible for the greater virulence of subtype D.
authors.affiliation: Department of HIV/GU Medicine, King's College London School of Medicine at Guy's, St Thomas' hospitals, Weston Education Centre, UK. philippa.easterbrook@hotmail.com
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Easterbrook
authors.forename: Mel
authors.initials: M
authors.lastname: Smith
authors.forename: Jane
authors.initials: J
authors.lastname: Mullen
authors.forename: Siobhan
authors.initials: S
authors.lastname: O'Shea
authors.forename: Ian
authors.initials: I
authors.lastname: Chrystie
authors.forename: Annemiek
authors.initials: A
authors.lastname: de Ruiter
authors.forename: Iain D
authors.initials: ID
authors.lastname: Tatt
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: Mark
authors.initials: M
authors.lastname: Zuckerman
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents