ORCID Profile
0000-0002-0076-0224
Current Organisation
National Institutes of Health
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Publisher: Oxford University Press (OUP)
Date: 06-2011
Publisher: Case Western Reserve University
Date: 02-08-2017
Abstract: Background: In HIV infection, lymphoid tissue is disrupted by fibrosis. Angiotensin converting enzyme inhibitors have anti-fibrotic properties. We completed a pilot study to assess whether the addition of lisinopril to antiretroviral therapy (ART) reverses fibrosis of gut tissue, and whether this leads to reduction of HIV RNA and DNA levels.Methods: Thirty HIV-infected in iduals on ART were randomized to lisinopril at 20mg daily or matching placebo for 24 weeks. All participants underwent rectal biopsies prior to starting the study drug and at 22 weeks, and there were regular blood draws. The primary end point was the change in HIV RNA and DNA levels in rectal tissue. Secondary outcomes included the change in 1) HIV levels in blood 2) Gag-specific T-cell responses 3) levels of T-cell activation and 4) collagen deposition.Results: The addition of lisinopril did not have a significant effect on the levels of HIV RNA or DNA in gut tissue or blood, Gag-specific responses, or levels of T-cell activation. Lisinopril also did not have a significant impact on lymphoid fibrosis in the rectum, as assessed by quantitative histology or heavy water labeling.Conclusions: Treatment with lisinopril for 24 weeks in HIV-infected adults did not have an effect on lymphoid fibrosis, immune activation, or gut tissue viral reservoirs. Further study is needed to see if other anti-fibrotic agents may be useful in reversing lymphoid fibrosis and reducing HIV levels.Clinical Trials Registration: NCT01535235
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2010
Publisher: Oxford University Press (OUP)
Date: 26-03-2013
DOI: 10.1093/CID/CIT196
Publisher: Springer Science and Business Media LLC
Date: 21-06-2014
DOI: 10.1007/S11904-014-0213-0
Abstract: An immune reconstitution disorder occurs in up to 40 % of severely immunodeficient HIV patients who commence antiretroviral therapy (ART), with an immune reconstitution inflammatory syndrome (IRIS) being encountered most commonly. Differences in the immunopathogenesis of an IRIS associated with different types of pathogen have become apparent but common features have also been defined. These include severe immunodeficiency prior to commencing ART associated with a high pathogen load and 'compensatory' immune responses, particularly innate immune responses, which inadequately control the pathogen and increase the risk of immunopathology as the immune system recovers on ART. Prevention of an IRIS may be achieved by optimising therapy for opportunistic infections before ART is commenced, delaying ART or using immunomodulatory therapy to prevent or suppress the immune response that causes the immunopathology. However, further clinical studies are required to examine these options in a systematic manner for the various types of IRIS.
Publisher: Oxford University Press (OUP)
Date: 18-01-2013
Publisher: American Society of Clinical Oncology (ASCO)
Date: 12-2016
Abstract: Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma–associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Twenty-two patients were treated 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 17 (77%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73% 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60% 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100% 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy ( P = .03). Significant increases in CD4 + and CD8 + cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma–associated herpesvirus viral load at week 4 ( P = .05). Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support, at least in part, an immunologic mechanism of activity.
Publisher: Oxford University Press (OUP)
Date: 12-12-2015
DOI: 10.1093/CID/CIV996
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-02-2015
Publisher: Oxford University Press (OUP)
Date: 15-03-2011
No related grants have been discovered for Irini Sereti.