BACKGROUND: Few data have been reported on the dynamics of HIV-1 DNA during intermittent highly active antiretroviral therapy (HAART). In this study, we measured cell-associated HIV-1 DNA and provirus-infected cells during the Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) clinical trial. METHODS: HIV-1 DNA was measured by real-time polymerase chain reaction (PCR) in the peripheral blood mononuclear cells (PBMCs) of 37 subjects enrolled in the ISS-PART, a randomized clinical trial comparing 24 months of intermittent (arm B) versus continuous (arm A) HAART in chronic HIV infection. In 14 subjects, the number of provirus-infected cells was also measured at baseline and at month 24. RESULTS: At baseline, the number of HIV-1 DNA copies/10(6) PBMCs was similar in arm B (mean +/- SD: 121 +/- 172, median = 35) and arm A (mean +/- SD: 107 +/- 153, median = 10) (P = not significant [n.s.]). No significant variations occurred over time; at 24 months, the HIV-1 DNA level was 77 +/- 28 (median = 30) copies/10(6) PBMCs in arm B and 166 +/- 321 copies/10(6) PBMCs (median = 10) in arm A (P = n.s.). At baseline, the provirus-infected cell counts were 85 +/- 98 (median = 50) cells/10(6) PBMCs in arm B and 92 +/- 113 (median = 50) cells/10(6) PBMCs in arm A (P = n.s.), with no variations at 24 months. CONCLUSIONS: These findings suggest that the intermittent schedule of the ISS-PART has no major impact on viral reservoirs, at least in a midterm follow-up.