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

Autor: Kasang C; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.; Medical Mission Institute, Salvatorstrasse 7, 97067 Würzburg, Germany., Kalluvya S; Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.; Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania., Majinge C; Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania., Kongola G; Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania., Mlewa M; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.; Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania., Massawe I; Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania., Kabyemera R; Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania., Magambo K; Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania., Ulmer A; HIV-Intensive Care Unit, Schwabstr. 26, 70197 Stuttgart, Germany., Klinker H; University Clinic of Würzburg, Division of Infectious Diseases, Dept. of Internal Medicine, Josef-Schneider-Str. 2, 97080 Würzburg, Germany., Gschmack E; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany., Horn A; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany., Koutsilieri E; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany., Preiser W; Division of Medical Virology, National Health Laboratory Service / University of Stellenbosch, Tygerberg 7505, South Africa., Hofmann D; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany., Hain J; University of Würzburg, Institute of Mathematics and Informatics, Chair of Mathematics VIII (Statistics), Am Hubland, 97074 Würzburg, Germany., Müller A; Medical Mission Institute, Salvatorstrasse 7, 97067 Würzburg, Germany., Dölken L; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany., Weissbrich B; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany., Rethwilm A; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany., Stich A; Medical Mission Institute, Salvatorstrasse 7, 97067 Würzburg, Germany., Scheller C; University of Würzburg, Institute of Virology and Immunobiology, Versbacher Strasse 7, 97078 Würzburg, Germany.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 Jan 26; Vol. 11 (1), pp. e0146678. Date of Electronic Publication: 2016 Jan 26 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0146678
Abstrakt: 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.
Trial Registration: ClinicalTrials.gov NCT01299948.
Databáze: MEDLINE