title: Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdom: multicentre cohort study.
abstract: OBJECTIVE
  To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options.
  
  
  METHODS
  Multicentre cohort study.
  
  
  METHODS
  Six large HIV treatment centres in southeast England.
  
  
  METHODS
  All individuals seen for care between 1 January 1996 and 31 December 2002.
  
  
  METHODS
  Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden.
  
  
  RESULTS
  Information is available on 16,593 individuals (13,378 (80.6%) male patients, 10,340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10,207 of the 16,593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of "viral load failure" with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3.
  
  
  CONCLUSIONS
  The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients.
authors.affiliation: Department of Primary Care and Population Sciences, Royal Free and UC Medical School, London NW3 2PF. c.sabin@pcps.ucl.ac.uk
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Teresa
authors.initials: T
authors.lastname: Hill
authors.forename: Fiona
authors.initials: F
authors.lastname: Lampe
authors.forename: Ryanne
authors.initials: R
authors.lastname: Matthias
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bhagani
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.forename: Mike S
authors.initials: MS
authors.lastname: Youle
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: George
authors.initials: G
authors.lastname: Scullard
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017211:Treatment Failure; D019562:Viral Load