Objective  To measure the evolution of proviral HIV‐1 DNA levels in patients receiving highly active antiretroviral therapy (HAART) compared to those treated with HAART plus interleukin‐2 (IL‐2) and hydroxyurea.

Design  Prospective randomised trial.

Methods  Twenty‐two HIV‐1 infected patients were randomly assigned to a five‐drug antiretroviral regimen for 72 weeks, with or without IL‐2, followed by a three‐drug regimen up to week 120 with additional hydroxyurea in patients having received IL‐2. HIV‐1 DNA levels in peripheral blood mononuclear cells (PBMC) were measured regularly using the Amplicor Monitor kit from Roche Diagnostics (Meylan, France). Potentially infectious HIV‐1 was cultured in enhanced conditions from circulating CD4 T cells at week 120.

Results  During the study period of 120 weeks, HIV‐1 DNA levels in PBMC decreased by −1.1 log in patients treated with HAART only compared with −1.8 log in patients with additional IL‐2 and hydroxyurea. A two‐phase decay rate was observed, with an inflexion point at 12 weeks. The second decay was slow, with mean half‐lives of 130.1 ± 21.3 weeks and 95.1 ± 26.3 weeks for patients on HAART and those receiving additional IL‐2 and hydroxyurea, respectively. At week 120, one out of 11 patients with HAART alone compared to six out of 11 in the group with IL‐2 and hydroxyurea had undetectable proviral DNA levels and three of them had unsuccessful recovery of replication‐competent HIV‐1 from blood CD4 T cells.

Conclusion  Therapeutic strategies combining HAART and immune interventions have higher potency to decrease the number of infected cells than HAART alone.