CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Adjusted Odds Ratio (OR) for change from baseline to week 4 post-ART initiation levels of biomarkers associated with TB IRIS and early mortality among advanced HIV/TB patients in Botswana

Change from baseline to week 4 post-ART levels of biomarkers that were associated with TB IRIS or death at p<0.25 in unadjusted analyses were stratified into quartiles and assessed for association with either outcome in logistic regression models. # Adjusting for BMI or NVP use did not change ORs for listed biomarker and TB IRIS. *Model included pre-ART CD4 count, female sex, and presence of baseline OI. PPD=purified protein derivative used to measure TB-specific cellular immune responses in ELISPOT assay. **Independent association between biomarker and outcome. Conclusions: Divergent inflammatory biomarker profile and cellular immune response characterized early mortality, while linked innate and adaptive immune responses were seen among TB IRIS following ART initiation. Interventions that decrease inflammation without inhibiting adaptive immune function hold promise in treatment of advanced HIV/ TB. 811 WITHDRAWN 812 Exuberant Pathogen-Specific Th1 CD4+ T-Cell Responses in MAC-IRIS in HIV Infection Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory immune response that can be observed after initiation of antiretroviral therapy (ART) in HIV-infected patients with severe lymphopenia and underlying opportunistic infections. The pathogenesis of IRIS is unclear but T-cells are thought to be an important contributor. Pathogen-specific T-cell responses significantly increase after ART but it is unclear how they compare to T-cell responses in HIV uninfected persons with similar infections. Methods: In a completed observational cohort of HIV+, ART-naïve patients with CD4 count <100 cells/ m L initiating ART, we identified those with Mycobacterium avium Complex (MAC) IRIS infections. Patients were followed for up to 96 weeks after ART initiation. Similarly, HIV- patients with MAC infections were identified from a natural history study of mycobacterial disease. Cryopreserved peripheral blood mononuclear cells were stimulated with heat-killed sonicated MAC and cytokine responses by T-cells were measured using flow cytometry. MAC-specific (sp)-CD4-T-cell % among different time points in MAC+HIV+ patients were compared using the Wilcoxon matched-pairs signed rank test and compared to MAC+HIV- patients using the Mann-Whitney test. Results: Samples were available from 12 HIV+ patients with unmasking or paradoxical MAC-IRIS at pre-ART, IRIS, and/or a late time point (36-96 wks post-ART initiation) and from 14 HIV-MAC+ patients. HIV+ patients had a median age of 38 yrs, median baseline CD4 was 8 cells/ m L, median HIV-RNA was 340,276 copies/mL and developed IRIS at a median of 41 days after ART initiation. HIV- patients had a median age of 66.5 yrs and had pulmonary MAC diagnosed according to ATS criteria. There was no significant difference in the % CD4 T-cells producing TNF (P=0.32) or IFN- γ (P=0.07) in response to MAC between HIV- and HIV+ patients pre-ART (Fig). After ART initiation, the proportion of responding CD4 T-cells in HIV+ patients was significantly higher than HIV- patients (TNF: P<0.01; IFN- γ : P<0.001) during IRIS and remained higher even after the resolution of IRIS (TNF: P<0.01; IFN- γ : P<0.001). Kimberly F. Faldetta 1 ; Denise C. Hsu 1 ;Virginia Sheikh 1 ; Gregg Roby 2 ; Kenneth Olivier 1 ; Irini Sereti 1 1 National Institutes of Health (NIH), Rockville, MD, US; 2 National Institutes of Health (NIH), Bethesda, MD, US

Poster Abstracts

CD4 T-cell responses after stimulation with heat-killed sonicated MAC. Conclusions: CD4 T-cell responses during MAC-IRIS in HIV infected patients are significantly higher compared to HIV- people with MAC infections. These data suggest a prominent role of CD4 T-cells in MAC-IRIS immunopathology. 813 A Paradoxical Treatment of Mycobacterial Immune Reconstitution Inflammatory Syndrome Denise C. Hsu; Kimberly F. Faldetta; Luxin Pei ; DelmyraTurpin;Virginia Sheikh; Irini Sereti National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, US Background: Tumor necrosis factor (TNF) blockade in the treatment of autoimmune diseases has been linked to reactivation of tuberculosis (TB). Immune reconstitution inflammatory syndrome (IRIS) can complicate anti-retroviral therapy (ART) initiation in HIV patients with mycobacterial disease and can cause significant morbidity and even mortality. Corticosteroid use is the mainstay of therapy. We report the use of infliximab (anti-TNF antibody) in 3 patients with steroid-unresponsive mycobacterial-IRIS.

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CROI 2015