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 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 × 106 cells/l in patients starting HAART with a CD4 cell count < 200, 201–350 and > 350 × 106 cells/l, respectively. Patients starting HAART with a CD4 cell count < 200 × 106 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 × 106 cells/l. There was no difference in risk between the 201–350 and the > 350 × 106 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 × 106 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 × 106 cells/l. The increase in CD4 cells restored by HAART is meaningful in that they are associated with reduced risk of disease/death.
From the aRoyal Free Centre for HIV Medicine & Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Campus, London, UK, the bInstitute of Infectious and Tropical Diseases, University of Milan, the cClinic of Infectious and Tropical Diseases, University of Brescia, dIRCCS L. Spallanzani, Rome, the eDepartment of Infectious Diseases, Cattolica University, Rome, the fCentro Operativo AIDS, Istituto Superiore di Sanita, Rome, the gDepartment of Infectious Diseases, Piacenza Hospital, Piacenza, the hDepartment of Infectious Diseases, Sacco Hospital, Milan, the iDepartment of Infectious Diseases, Lecce Hospital, Lecce, the jDepartment of Infectious Diseases, Galliera Hospital, Genoa, the kDepartment of Infectious Diseases, Casa del Sole, Palermo, the lDepartment of Infectious Diseases, University of Ancona, and the mDepartment of Infectious Diseases, St Anna Hospital, Como, Italy. *See the Appendix for study members.
Requests for reprints to Mr A. Cozzi Lepri, Royal Free Centre for HIV Medicine & Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill St, London NW3 2PF, UK.
Received: 8 December 2000;
revised: 26 February 2001; accepted: 8 March 2001.
Sponsorship: This study was supported by an unrestricted educational grant provided by GSK Italy and by Ministero della Sanità- Progetti di Ricerca Finalizzata ICS 120.5/RF98.86.