PLoS ONE (Jan 2016)

Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial.

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

DOI
https://doi.org/10.1371/journal.pone.0146678
Journal volume & issue
Vol. 11, no. 1
p. e0146678

Abstract

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HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients.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.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.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.ClinicalTrials.gov NCT01299948.