br Methods br Results br Discussion In

Methods
Results
Discussion In the general population BNP has been established as a marker for selective serotonin reuptake inhibitor failure diagnosis. Moreover, there is growing evidence that elevated levels of natriuretic-peptides may improve CV risk prediction in the general population above traditional risk factors [[16], [17], [18]]. In the STOP-HF trial, BNP-based screening and cardiological work-up in patients with BNP > 50 pg/ml significantly reduced the rate of incident heart failure [19]. Our findings in an HIV-infected cohort support the previous observations in HIV-negative individuals (or in general populations), that increased BNP-levels are independently associated with CV events and mortality, even after adjusting for traditional CV risk factors and HIV specific parameters. Especially, BNP-levels of >100 pg/ml are linked to significantly increased risk. Recently, several published studies in small cohorts showed that high BNP levels are associated with an increased risk and burden of CVD in HIV-infected patients [[20], [21], [22]]. However, data on long-term follow-up evaluating the prognostic value of BNP in HIV positive patients are lacking. To our knowledge, this is the first study, to assess the association of BNP, CV events and mortality over a prospective follow-up of 10 years in an HIV-positive cohort, demonstrating BNP to have a high impact on the incidence of CV events and mortality. Moreover, until now, for primary prevention purposes there are no established thresholds for BNP. In patients with dyspnea and suspected heart failure the current guidelines of the European Society of Cardiology recommend measurement of BNP with different thresholds for acute and chronic symptoms (BNP: 35 and 100 pg/ml) [23]. Therefore, we evaluated the predictive value of these thresholds and found relevant associations with CV events. We additionally determined BNP thresholds based on our cohort of <5 pg/ml, >5 to ≤20 pg/ml and >20 to ≤35 pg/ml which were associated with a lower CV morbidity. These risk prediction thresholds may also help to identify patients at higher risk for CV events, even if there is no heart failure present.
Conclusions
Funding This study was in part supported by ViiV Healthcare, Gilead, MSD and Janssen.
Conflict of interest
Introduction Antibodies to HIV appear shortly after infection. The titer and avidity of anti-HIV antibodies generally increase over time, but may be impacted by antiretroviral treatment (ART), CD4 T cell decline, and other factors (Koenig et al., 2013, Fiebig et al., 2003). The breadth and specificity of anti-HIV antibodies also evolve during the course of infection (Geiß and Dietrich, 2015). A detailed understanding of the serologic response to HIV infection is helpful for understanding HIV immune containment and for vaccine development. Multiplexed immunoassays have been used to analyze the specificity of anti-HIV antibodies. These include a microarray assay composed of 15 recombinant HIV env protein targets and five gp41 peptide targets (Dotsey et al., 2015), and an assay based on the Luminex platform that includes six recombinant HIV protein targets (Curtis et al., 2012). Phage display technology has also been used to screen HIV peptides for binding to immobilized antibodies (Delhalle et al., 2012). In this report, we used a massively multiplexed antibody profiling system to analyze the fine specificity of the antibody response to HIV infection. This system is based on phage immunoprecipitation sequencing (PhIP-Seq) (Larman et al., 2011). Testing is performed by incubating samples with a bacteriophage library that expresses peptides encoded by oligonucleotides generated by high-throughput DNA synthesis. The abundance and specificity of antibodies in test samples are assessed by immunoprecipitating phage-antibody complexes, and then amplifying and sequencing the DNA in the captured phage particles. The “VirScan” phage library includes >96,000 peptides that span the genomes of >200 viruses that infect humans (the human “virome”) (Xu et al., 2015). We performed PhIP-Seq using the VirScan library to analyze HIV antibodies from individuals with known duration of HIV infection, ranging from <1 month to 8.7 years. This allowed us to examine dynamic changes in antibody diversity and the fine specificity of HIV antibodies from individuals with early to late stage infection, including individuals on ART and individuals with advanced HIV disease.