TLR agonists enhance responsiveness of inflammatory innate immune cells in HLA-B*57-positive HIV patients.

HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E. coli LPS-B5 and CpG-ODN-2216, we observed greater induction of IL-6/IL-1beta double-positive CD14+CD16++ monocytes as well as IFN-gamma-positive cytotoxic CD56highCD16neg NK cells in HLA-B*57- versus HLA-B*44-positive HIV patients, while TNF-alpha induction remained unchanged. Differences were not seen in the other monocyte and NK cell subsets or in HLA-matched healthy controls. Our findings show that, in virally suppressed HIV infection, HLA-B*57 is associated with enhanced responsiveness of inflammatory innate immune cells to TLR ligands, possibly contributing to increased vulnerability in sepsis. KEY MESSAGES: • HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. • HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. • In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. • NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. • HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands.

Survival of HIV/HCV co-infected patients before introduction of HCV direct acting antivirals (DAA).

HIV/HCV infection is supposed to substantially reduce survival as compared to HIV mono-infection. Here, we compared longtime-survival and causes of death in a cohort of HIV- and HIV/HCV-co-infected patients on combined antiretroviral therapy (cART), before introduction of HCV direct acting antivirals (DAA). 322 Caucasian patients with HIV (n = 176) and HIV/HCV-infection (n = 146) were enrolled into this study. All patients were recruited between 2003 and 2004 and followed until 01.01.2014. We compared overall survival between the two groups by the Kaplan-Meyer method and identified independent factors associated with long-time survival by conditional Cox regression analysis. In total 46 (14.3%) patients died during the observation period (HIV infection: n = 23 (13.1%), HIV/HCV infection: n = 23 (15.8%) but overall-survival did not differ significantly between HIV/HCV-infected and HIV mono-infected patients (p = 0.619). Survival was substantially better in patients with complete suppression of HIV replication below the level of detection than in those with residual viremia (p = 0.001). Age (p = 0.008), γ-glutamyltranspeptidase (p < 0.0001) and bilirubin (p = 0.008) were significant predictors of survival irrespective from HCV co-infection. Complete repression of HIV replication on cART is the key factor determining survival both in HIV- and HIV/HCV-co-infected patients, while HCV co-infection and therapy without DAAs seem to affect survival to a lesser extent. Thus, patients with HIV/HCV co-infection require particularly intensive cART.