Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Efficacy of Deferasirox (Exjade®) in Modulation of Iron Overload in Patients with β-Thalassemia Intermedia

Because of insufficient erythropoiesis, peripheral hemolysis and increased gastrointestinal iron absorption, iron overload is still a matter of debate in β-thalassemia intermedia (β-TI) patients, which can be overcome using iron chelators. However, data on use of iron chelators in β-TI patients is highly restricted. The aim of this study was to evaluate the efficacy of oral administration of deferasirox (Exjade® or DFX) by assessment of serum ferritin levels in β-TI patients. In this quasi-experimental study, 50 β-TI patients with serum ferritin levels >1000 ng/mL were selected and received oral DFX for 12 consecutive months. Iron overload was measured by checking serum ferritin levels every 2 months and the results were compared with the baseline level. The mean serum ferritin was decreased during 1 year of chelation therapy without any toxic effect. Although the difference between baseline ferritin and ferritin levels at the end of second month was not remarkable (p = 0.88), a significant reduction in serum ferritin was observed after 4 (p = 0.01), 6 (p = 0.001), 8 (p < 0.001), 10 (p < 0.001) and 12 months (p < 0.001) of chelation therapy compared to its baseline levels. There was no correlation between baseline ferritin levels and age (p = 0.574). In addition, no statistically significant difference was observed about change in serum ferritin levels after 6 and also 12 months of therapy between patients who had undergone splenectomy and those who did not (p = 0.796 and 0.859, respectively). Iron chelation therapy with DFX is safe and effective in reducing serum ferritin levels in β-TI patients who suffer from side effects of iron overload. © 2015 Informa Healthcare USA, Inc. All rights reserved