Effects of prednisolone on disease progression in antiretroviral-untreated HIV infection : a 2-year randomized, double-blind placebo-controlled clinical trial

Kasang, Christa ; Kalluvya, Samuel ; Majinge, Charles ; Kongola, Gilbert ; Mlewa, Mathias ; Massawe, Irene ; Kabyemera, Rogatus ; Magambo, Kinanga ; Ulmer, Albrecht ; Klinker, Hartwig ; Gschmack, Eva ; Horn, Anne ; Koutsilieri, Eleni ; Preiser, Wolfgang ; Hofmann, Daniela ; Hain, Johannes ; Müller, Andreas ; Dölken, Lars ; Weissbrich, Benedikt ; Rethwilm, Axel ; Stich, August ; Scheller, Carsten (2016)

CITATION: Kasang, C., et al. 2016. Effects of prednisolone on disease progression in antiretroviral-untreated HIV infection : a 2-year randomized, double-blind placebo-controlled clinical trial. PLoS ONE, 11(1):e0146678, doi:10.1371/journal.pone.0146678.

The original publication is available at http://journals.plos.org/plosone

Article

Background: HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. Methods: Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/μl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/μl. Results: No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/μl compared to -37.42 ± 10.77 cells/μl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. Conclusions: This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection.

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