title: Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial.
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01299948.
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.|Medical Mission Institute, Salvatorstrasse 7, 97067 Würzburg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Kasang
authors.affiliation: Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.|Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kalluvya
authors.affiliation: Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.
authors.forename: Charles
authors.initials: C
authors.lastname: Majinge
authors.affiliation: Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kongola
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.|Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mlewa
authors.affiliation: Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.
authors.forename: Irene
authors.initials: I
authors.lastname: Massawe
authors.affiliation: Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.
authors.forename: Rogatus
authors.initials: R
authors.lastname: Kabyemera
authors.affiliation: Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.
authors.forename: Kinanga
authors.initials: K
authors.lastname: Magambo
authors.affiliation: HIV-Intensive Care Unit, Schwabstr. 26, 70197 Stuttgart, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Ulmer
authors.affiliation: University Clinic of Würzburg, Division of Infectious Diseases, Dept. of Internal Medicine, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Gschmack
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Horn
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Eleni
authors.initials: E
authors.lastname: Koutsilieri
authors.affiliation: Division of Medical Virology, National Health Laboratory Service / University of Stellenbosch, Tygerberg 7505, South Africa.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Preiser
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hofmann
authors.affiliation: University of Würzburg, Institute of Mathematics and Informatics, Chair of Mathematics VIII (Statistics), Am Hubland, 97074 Würzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hain
authors.affiliation: Medical Mission Institute, Salvatorstrasse 7, 97067 Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Dölken
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Weissbrich
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Rethwilm
authors.affiliation: Medical Mission Institute, Salvatorstrasse 7, 97067 Würzburg, Germany.
authors.forename: August
authors.initials: A
authors.lastname: Stich
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Scheller
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D055118:Medication Adherence; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D007155:Immunologic Factors; D011239:Prednisolone
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