Low levels of plasma viremia (below 50 copies/ml of HIV-1 RNA) can be detected in the majority of HIV+ subjects successfully treated with HAART. Aim of our study was to evaluate the impact of different antiretroviral regimens on this residual viremia and on proviral HIV-1 DNA in HAART-treated subjects with plasma HIV RNA <400 cp/ml and no history of virological failure. To this purpose, a cross-sectional analysis of 319 HIV-positive patients on HAART with plasma HIV RNA <400 cp/ml was performed. Subjects had been on HAART for a median of 3.6 years: the current regimen included two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI) in 104 (32.6%) cases, of which 73 treated with a boosted PI; two NRTIs plus a non-NRTI (NNRTI) were prescribed in 166 (52.2%) cases, and NRTIs-only in 49 cases (15.4%). Patients treated with PI had the lowest nadir CD4 cell count (237+191 cells/microl) compared to patients treated with NNRTI (384+192 cells/microl) or NRTIs-only (387+222 cells/microl). Cell-associated HIV-1 DNA was measured in 231 subjects. Residual viremia was measured in 238 subjects with plasma HIV-1 RNA levels < 50 copies/ml. Multivariate analysis showed that the use of NNRTI was independently associated to low levels of residual viremia and high levels of HIV-1DNA, whereas the use of PI was independently associated to low levels of HIV-1 DNA. The better virological performance of NNRTI in terms of low residual viremia is consistent with specific literature data, whereas the greater impact of PI on the viral reservoirs is noteworthy and needs further investigations.