TY - JOUR A1 - Horn, Anne A1 - Scheller, Carsten A1 - du Plessis, Stefan A1 - Arendt, Gabriele A1 - Nolting, Thorsten A1 - Joska, John A1 - Sopper, Sieghart A1 - Maschke, Matthias A1 - Obermann, Mark A1 - Husstedt, Ingo W. A1 - Hain, Johannes A1 - Maponga, Tongai A1 - Riederer, Peter A1 - Koutsilieri, Eleni T1 - Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals JF - Journal of Neural Transmission N2 - Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-naïve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 % CI 1.72–8.96; p = 0.001, Fishers exact test). 42.6 % HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 % uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 %, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease. KW - HIV KW - HAND KW - dopamine KW - DAT KW - polymorphism KW - CSF Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132385 VL - 120 ER - 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 -