It is common opinion that, in addition to potent antiretroviral regimens which effectively reduce plasma viremia, new strategies should be developed to ensure the reduction of cell-associated HIV DNA load together with HIV RNA plasma levels. The present study explored whether the number of provirus-infected cells can be reduced by combined antiviral and immunomodulatory regimens. Thus, 14 naive patients (with CD4 > 400/microl and plasma HIV RNA copies > 5000/ml) were randomly assigned to receive highly active antiretroviral therapy (HAART) alone or HAART plus rIL-2. Plasma viremia (measured by a commercial RT-PCR assay) and the number of provirus-infected cells (measured by an endpoint cell dilution PCR assay) were monitored at the enrollment and after 12 weeks of treatment. The results indicate that while HAART and HAART plus rIL-2 are both able to significantly reduce plasma viremia after 12 weeks of treatment, a significant reduction of the number of provirus-infected cells can be achieved only by treatment with HAART plus rIL-2.