CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Methods: Patients were participants of a completed observational study evaluating predictors of IRIS in HIV-infected patients with CD4 count ≤ 100cells/ m L starting ART. CD4 count and HIV-RNA were tested at week (wk) 0, 2, 4, 8, 12, 24, 36 and 48. T cell responses to mycobacterial antigens were assessed on batched cryopreserved samples using flow cytometry, after stimulation with tuberculin-PPD or heat-killed Mycobacterium avium complex (MAC). Results: Patient (Pt) 1: 31 yo man with culture-positive MAC unmasking IRIS manifesting as cervical lymphadenopathy that failed to resolve despite anti-MAC therapy, drainage and prednisone over 4 months. Lymphadenopathy reduced after infliximab 5mg/kg every 2 wks, 3 doses. Pt 2: 41 yo man with culture positive disseminated TB (pulmonary and knee arthritis) and paradoxical TB-IRIS. He improved after high dose systemic and intra-articular corticosteroids but subsequently developed chylothorax due to obstruction of thoracic duct by enlarged lymph nodes. He improved after a single dose of infliximab 4mg/kg. Pt 3: 42 yo man with culture positive disseminated TB and paradoxical TB-IRIS manifesting as fevers and lymphadenopathy not responding to prednisone or drainage. Lymphadenopathy resolved gradually after infliximab 5mg/Kg every 2 wks, 3 doses. Prednisone was successfully tapered off in all patients after infliximab. All patients had sterile mycobacterial cultures prior to infliximab and did not experience a clinical relapse. After infliximab administration, CD4 T cell cytokine responses to mycobacterial antigens were preserved (Fig). At week 48, HIV-RNA was <50 copies/mL and CD4 count improved for all patients (Fig). Conclusions: Infliximab use was associated with clinical improvement in steroid-unresponsive mycobacterial IRIS without obvious adverse impact on immune recovery and virologic control in 3 patients. TNF blockade for severe mycobacterial IRIS merits further assessment in clinical trials.

Poster Abstracts

CD4 T cell IFN-y and TNF responses after stimulation with mycobacterial antigens are preserved post infliximab use.

814 CD8 T Cells in Lesions of PML-IRIS Express CCR5: Rationale for the Use of Maraviroc Guillaume Martin-Blondel 2 ; Jan Bauer 1 ; Emmanuelle Uro-Coste 2 ; Hervé Dumas 2 ; Hans Lassmann 1 ; David Brassat 2 ; Pierre Delobel; Roland Liblau 3 ; Bruno Marchou 2 1 University of Vienna, Vienna, Austria; 2 Toulouse University Hospital, Toulouse, France; 3 Inserm, Toulouse, France

Background: Therapeutic strategies modulating the deleterious immune response underlying immune reconstitution inflammatory syndrome (IRIS) are warranted. It has been suggested that CCR5 antagonists might be beneficial in the management of IRIS associated with progressive multifocal leukoencephalopathy (PML). Here, we analyzed the expression of CCR5 on immune cells infiltrating PML-IRIS lesions in 5 HIV-infected patients. Methods: We performed a retrospective cross-sectional study of all HIV-infected patients diagnosed with PML-IRIS in the Toulouse University Hospital, France, between January 2000 and January 2010. Brain biopsies were collected from 5 patients and their histopathological features were compared to those of 4 HIV-infected patients with classical PML. All biopsies were performed before any steroid therapy. Results: In all cases, histological analysis revealed demyelinating lesions and the presence of JC virus-infected cells, confirming PML. In PML-IRIS patients, the inflammatory infiltrates were dominated by CD3 + T cells, which were nearly exclusively composed of CD8 + T cells. Double stainings of CCR5 with CD3, CD8, CD20 (B-cells) and Iba-1 (Macrophages) showed that most of the perivascular and parenchymal infiltrating CD8 + T cells strongly expressed CCR5 on their surface. Macrophages also express CCR5, but to a lesser extent. Classical PML lesions were devoid of inflammatory infiltrates.

495

CROI 2015