When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study

Objectives: To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts. Design: The mean increase in CD4 cell count and rate of virological failure after commencing HAARTwere measured in antiretroviral-naive patients(1421) in a large, nonrandomized multicentre, observational study in Italy (ICONA). Clinical endpoints were a Iso evaluated in a subset of patients who started HAARTwith 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. (C) 2001 Lippincott Williams & Wilkins.