title: When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study.
abstract: OBJECTIVE
  To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts.
  
  
  METHODS
  The mean increase in CD4 cell count and rate of virological failure after commencing HAART were measured in antiretroviral-naive patients (1421) in a large, non-randomized multicentre, observational study in Italy (ICONA). Clinical endpoints were also evaluated in a subset of patients who started HAART with a very low CD4 cell count.
  
  
  RESULTS
  After 96 weeks of therapy, the mean rise in CD4 cell count was 280, 281 and 186 x 10(6) cells/l in patients starting HAART with a CD4 cell count < 200, 201--350 and > 350 x 10(6) cells/l, respectively. Patients starting HAART with a CD4 cell count < 200 x 10(6) cells/l tended to have a higher risk of subsequent virological failure [relative hazard (RH), 1.15; 95% confidence interval (CI), 0.93--1.42] compared with patients starting with > 350 x 10(6) cells/l. There was no difference in risk between the 201--350 and the > 350 x 10(6) cells/l groups (RH, 1.0; 95% CI, 0.79--1.29). The incidence of new AIDS-defining diseases/death in patients who started HAART with a CD4 count < 50 was 0.03/person-year (95% CI, 0.10--0.33) during the time in which the patient's CD4 cell count had been raised to > 200 x 10(6) cells/l.
  
  
  CONCLUSIONS
  There was no clear immunological or virological advantage in starting HAART at a CD4 cell count > 350 rather than at 200--350 x 10(6) cells/l. The increase in CD4 cells restored by HAART is meaningful in that they are associated with reduced risk of disease/death.
authors.affiliation: Royal Free Centre for HIV Medicine & Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Campus, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Cozzi Lepri
authors.forename: A N
authors.initials: AN
authors.lastname: Phillips
authors.forename: A
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.forename: F
authors.initials: F
authors.lastname: Castelli
authors.forename: A
authors.initials: A
authors.lastname: Antinori
authors.forename: A
authors.initials: A
authors.lastname: de Luca
authors.forename: P
authors.initials: P
authors.lastname: Pezzotti
authors.forename: F
authors.initials: F
authors.lastname: Alberici
authors.forename: A
authors.initials: A
authors.lastname: Cargnel
authors.forename: P
authors.initials: P
authors.lastname: Grima
authors.forename: R
authors.initials: R
authors.lastname: Piscopo
authors.forename: T
authors.initials: T
authors.lastname: Prestileo
authors.forename: G
authors.initials: G
authors.lastname: Scalise
authors.forename: M
authors.initials: M
authors.lastname: Vigevani
authors.forename: M
authors.initials: M
authors.lastname: Moroni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis; D013997:Time Factors