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Abstract: Background: Recent data have shown that plasma levels of lipopolysaccharide (LPS) are a quantitative indicator of microbial translocation in HIV infected individuals. Objectives: To assess the impact of residual viral replication on plasma LPS in HAART-treated HIV+ subjects with <50copies/ml HIV-1 RNA and to evaluate LPS changes during repeated HAART interruptions not exceeding 2-month duration. Study design: LPS was measured in 44 HIV+ subjects at T0 (during HAART) and at day 15 of the first and fourth HAART interruption. Ten uninfected, healthy donors were studied as well. Residual plasma HIV-1 RNA was measured at T0 by an ultra-ultrasensitive method with limit of detection of 2.5copies HIV-1 RNA/ml. Subjects with less than 2.5copies/ml (fully suppressed – FS) were compared to those with 2.5–50copies/ml (partially suppressed – PS). Results: At T0, plasma LPS levels were comparable in FS and uninfected subjects, whereas in PS they were higher than in uninfected subjects (p =0.049). After 4 HAART interruptions, they did not change significantly. However, LPS values were lower in FS than in PS (p =0.020). An inverse correlation was found between CD4 and LPS levels (p =0.044) in PS group only. Conclusions: A reduced degree of microbial translocation was seen in subjects with a more complete suppression of viral replication. Repeated HAART interruptions had no significant impact on plasma LPS levels. [Copyright &y& Elsevier]