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<p>Abstract</p> <p>Background</p> <p>HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.</p> <p>Methods</p> <p>In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA.</p> <p>Results</p> <p>CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], <it>p </it>= 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; <it>p </it>= 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; <it>p </it>= 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; <it>p </it>= 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; <it>p </it>= 0.0782). Viral load in both groups was similar (0.8 × 10⁵ng/ml [0.2-42.4 × 10⁵] vs. 1.1 × 10⁵[0.5-12.2 × 10⁵]; <it>p </it>= 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.</p> <p>Conclusions</p> <p>Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.</p>