Although suppression of apoptosis contributes to immune-reconstitution during potent antiretroviral therapy, its relationship with the majors indicators of response to therapy, that is, changes in CD4(+) cell counts and in viral loads (VL), is still debated. We extended our previous study by collecting data on the relationships among apoptosis and immunological and virological parameters during a long-term follow-up of HIV patients with an overall positive response to potent antiretroviral therapy. We report results from 15 patients who completed two years of therapy. In a smaller group of patients, we focused our attention on investigating the specific contribution of the CD8(+) subset in the overall changes in lymphocyte apoptosis, which occur concomitantly with the response to the therapy. Our data, while again confirming that inhibition of PBMC apoptosis is a phenomenon strictly related to a positive response to potent antiretroviral therapy, suggest that CD4(+) cell rescue is not directly dependent on inhibition of CD4(+) cell apoptosis but rather on that of the CD8(+) subset.