We evaluated the costs and effectiveness of starting highly active antiretroviral therapy (HAART) at different points during the course of HIV infection, defined on the basis of CD4 T-lymphocytes counts. The study considered 3,250 HAART-naive patients of the Italian Cohort Naive Antiretrovirals (ICONA), enrolled and followed between 1997 and 2002. In correspondence to the thresholds of 500, 350, and 200 CD4 cells/mm(3), we selected immediate and deferred groups accounting for lead-time bias. The effects of immediate vs. deferred treatment on AIDS-free survival and direct health costs were estimated stratifying on the propensity score of immediate HAART initiation. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness acceptability curve were also obtained. Although immediate HAART initiation did not affect incidence AIDS and death at high CD4 levels, starting HAART with 200-349 CD4 cells/mm(3) rather than deferring it below 200 CD4 cells/mm(3), proved to be cost-effective.