14647
2016
eng
e0146678
1
11
article
1
2017-03-31
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Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial
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.
PLoS One
10.1371/journal.pone.0146678
urn:nbn:de:bvb:20-opus-146479
PLoS ONE 11(1): e0146678. doi:10.1371/journal.pone.0146678
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
eng
uncontrolled
HIV
eng
uncontrolled
immune activation
eng
uncontrolled
viral load
eng
uncontrolled
drug adherence
eng
uncontrolled
viral replication
eng
uncontrolled
AIDS
eng
uncontrolled
HIV infections
eng
uncontrolled
highly-active antiretroviral therapy
Medizin und Gesundheit
open_access
Institut für Mathematik
Institut für Virologie und Immunbiologie
Medizinische Klinik und Poliklinik II
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14647/054_Scheller_journal.pone.0146678.pdf
5965
2011
eng
article
1
2012-06-30
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HIV drug resistance (HIVDR) in antiretroviral therapy-naive patients in Tanzania not eligible for WHO threshold HIVDR survey is dramatically high
Background: The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients ,25 years is representative for HIVDR in the rest of the therapy-naive population. Methods and Findings: HIVDR was determined in 88 sequentially enrolled ART-naive patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged, 25 years and 68 patients were aged 25–63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072–0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients .25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095–0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma. Conclusions: ART-naive patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naive population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naive HIV-infected population.
urn:nbn:de:bvb:20-opus-69024
6902
PLoS One (2011) 6:8, doi:10.1371/journal.pone.0023091
Christa Kasang
Samuel Kalluvya
Charles Majinge
August Stich
Jochen Bodem
Gilbert Kongola
Graeme B. Jacobs
Mathias Mllewa
Miriam Mildner
Irina Hensel
Anne Horn
Wolfgang Preiser
Gert van Zyl
Hartwig Klinker
Eleni Koutsilieri
Axel Rethwilm
Carsten Scheller
Benedikt Weissbrich
deu
swd
Tansania
deu
swd
HIV
Medizin und Gesundheit
open_access
Institut für Virologie und Immunbiologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5965/scheller_journal.pone.0023091.pdf
13798
2011
eng
e23091
8
6
article
1
2016-08-29
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HIV Drug Resistance (HIVDR) in Antiretroviral Therapy-Naïve Patients in Tanzania Not Eligible for WHO Threshold HIVDR Survey Is Dramatically High
Background
The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population.
Methods and Findings
HIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25–63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072–0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095–0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma.
Conclusions
ART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population.
PLoS One
10.1371/journal.pone.0023091
urn:nbn:de:bvb:20-opus-137988
PLoS ONE 6(8): e23091. doi:10.1371/journal.pone.0023091
Christa Kasang
Samuel Kalluvya
Charles Majinge
August Stich
Jochen Bodem
Gilbert Kongola
Graeme B. Jacobs
Mathias Mlewa
Miriam Mildner
Irina Hensel
Anne Horn
Wolfgang Preiser
Gert van Zyl
Hartwig Klinker
Eleni Koutsilieri
Axel Rethwilm
Carsten Scheller
Benedikt Weissbrich
eng
uncontrolled
Tanzania
eng
uncontrolled
antimicrobial resistance
eng
uncontrolled
antiretroviral therapy
eng
uncontrolled
HIV
eng
uncontrolled
sequence databases
eng
uncontrolled
mutation databases
eng
uncontrolled
antiretrovirals
eng
uncontrolled
HIV diagnosis and management
Medizin und Gesundheit
open_access
Institut für Virologie und Immunbiologie
Missionsärztliche Klinik
Medizinische Klinik und Poliklinik I
Förderzeitraum 2011
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13798/Kasang_journal.pone.0023091.pdf
6712
2012
eng
article
1
2013-07-16
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HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients
Background: HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression. Methods: In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA. Results: CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 105 ng/ml [0.2-42.4 × 105] vs. 1.1 × 105 [0.5-12.2 × 105]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone. Conclusions: Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.
urn:nbn:de:bvb:20-opus-75100
7510
BMC Infectious Diseases (2012) 12: 14, doi:10.1186/1471-2334-12-14
Christa Kasang
Albrecht Ulmer
Norbert Donhauser
Barabara Schmidt
August Stich
Hartwig Klinker
Samuel Kalluvya
Eleni Koutsilieri
Axel Rethwilm
Carsten Scheller
deu
swd
HIV
deu
swd
Prednisolon
Medizin und Gesundheit
open_access
Institut für Virologie und Immunbiologie
Förderzeitraum 2012
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6712/Scheller_1471_2334_12_14.pdf