TY  - JOUR
A1  - Kasang, Christa
A1  - Kalluvya, Samuel
A1  - Majinge, Charles
A1  - Kongola, Gilbert
A1  - Mlewa, Mathias
A1  - Massawe, Irene
A1  - Kabyemera, Rogatus
A1  - Magambo, Kinanga
A1  - Ulmer, Albrecht
A1  - Klinker, Hartwig
A1  - Gschmack, Eva
A1  - Horn, Anne
A1  - Koutsilieri, Eleni
A1  - Preiser, Wolfgang
A1  - Hofmann, Daniela
A1  - Hain, Johannes
A1  - Müller, Andreas
A1  - Dölken, Lars
A1  - Weissbrich, Benedikt
A1  - Rethwilm, Axel
A1  - Stich, August
A1  - Scheller, Carsten
T1  - Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial
JF  - PLoS One
N2  - 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.
KW  - HIV
KW  - immune activation
KW  - viral load
KW  - drug adherence
KW  - viral replication
KW  - AIDS
KW  - HIV infections
KW  - highly-active antiretroviral therapy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146479
VL  - 11
IS  - 1
ER  -