DELAY IN DIAGNOSIS AMONG AIDS-PRESENTER IN TWO HOSPITALS IN THE NORTH EAST OF ITALY

Introduction. Most common causes of death in HIV patients in high income countries are related to late presentation (LP), defined as presenting for care with a CD4 count <350 cell/µL or with an AIDS-defining event. Data by ECDC illustrate that during years 2008-2012 in Italy, 5382 AIDS cases occurred with 2307 AIDS-related death. LP is associated to reduced life expectancy, higher risk of HIV transmission and economic implications. In this preliminary study we aimed to calculate the delay in HIV diagnosis in patients with symptoms of AIDS-disease and to characterize AIDS-events more frequently related to delay. Methods We retrospectively analyzed data of patients with new HIV diagnosis and less than 350 T-CD4 cells/µL in period 2008-13 in Rovigo and Ferrara hospitals; furthermore, we calculated the days between the first contact with any health care provider because of onset of AIDS-disease symptoms and diagnosis of HIV/AIDS. We also evaluated risk factors for delay in diagnosis. Results. An overall of 233 new diagnoses was recorded by the two centers and 47.6% were LP. Of these, 33.3% were AIDS-presenter and 7.2% died. Median age of LP was 43 ys (IQR 35-52); 72.1% males; 18.9% non-nationals. Risk factors related with HIV transmission were HET 55% (n.45), MSM 18.9% (n.12), IDU 5.4% (n.3), unknown, 20.7% (n. 18). Among 37 AIDS-presenters (M 76%, F 24%; HET 60%, MSM 16.5%, unknown, 23.5%), we recorded the following AIDS events: 10 wasting syndromes, 9 PCP, 7 esophageal candidiasis, 6 Kaposi’s Sarcoma (KS), 5 CMV disease, 3 neurotoxoplasmosis (NT), 3 Non Hodgkin Lymphomas, 3 Progressive Multifocal Leukoencephalopathy, 2 TB, 1 AIDS dementia complex (ADC), 1 Atypical mycobacteriosis, 1 Candida pneumonia, 1 Cryptococcosis*. Of these patients, 24,5% had more than 1 AIDS event at diagnosis. We found a median delay of 48,5 days (IQR 16-154), which was maximum in patients with (180 days) and KS (150 d) and minimum in those with NT, (10 d) and TB (9 d). Mortality among AIDS presenters was 23%. There were no significant differences in delay of diagnosis between national and non-national, male and female and risk factors. Conclusions In our centers, LP demographic features agree with national data. Despite the presence AIDS events, HIV test was performed with a median delay of more than 45 d; some conditions such as ADC or KS were associated with a lateness of 6-5 months respectively. By contrast, TB seemed to be linked with a quicker HIV-test performance, probably due to physicians’ awareness of the epidemiological relevance of coinfection TB-HIV. Typical AIDS events, as KS and esophageal candidiasis, were associated with a relevant delay. “Late testing” even in presence of an AIDS event shows how nowadays HIV is a less perceived issue. Our study points out the need of improving physicians’ consciousness about AIDS to detect it and starting HAART together with other specific therapy as soon as possible

SIGNIFICANCE OF PROGNOSTIC VALUE OF ANEMIA IN PREDICTING OPPORTUNISTIC INFECTIONS IN HIV-INFECTED LATE PRESENTER PATIENTS STARTING ANTIRETROVIRAL THERAPY

Introduction Anemia represents a well-known complication of HIV infection, especially in end-stage disease. Several factors could have an impact on Hemoglobin (HB) level in this disease, such as opportunistic infections, neoplasia and drugs. Many studies have demonstrated how developing of anemia is related with an higher incidence of AIDS, non-AIDS defining events or deaths, even if most of them concern to pre-HAART era; to our knowledge, few data examine the relationship between HB level at baseline and the risk of new AIDS events and new admissions to hospital among late presenters (LP) in the HAART-era. Methods We analyzed retrospectively patients’ data with new diagnosis of HIV and less than 350 T-CD4 cells/µL in period 2008-2013 in 2 HIV centers of North Italy; Santa Maria della Misericordia of Rovigo and Sant’Anna - University of Ferrara hospitals. Patients were sorted by HB level at baseline and divided in two groups: Group A and Group B, with and without anemia, respectively. Anemia was defined according the World Health Organization definition (Hb <13.0 g/dL in males, <12.0 g/dL in females). Chi-square Fisher’s exact test was emplojed to analyze differences among the two groups for new AIDS-events, new hospital admissions and virological failure. T-student test was used to evaluate differences among cell-T CD4+ in two groups. Results Of the 233 new diagnoses reported in 2008-2013 by the two centers, 47.6% were LP patients. Of these, 56 (71.8%) were males (22 Group A; 34 Group B) and 22 (28.2%) were females (12 Group A; 10 Group B). The median age of LP was 43 years (IQR 35-52) in Group A and 43 (IQR 36-52) in Group B. Risk factors related with HIV transmission were HET in 45 patients (20 Group A, 25 Group B), MSM in 12 (6 Group A, 6 Group B), IDU in 3 (2 Group A, 1 Group B), Other/Unknown 18 (6 Group A, 12 Group B). Of the 233 new diagnoses, 111 (47.6%) were LP; of these, (7.2%) died. Due to lack of data, 25 patients were excluded. 34 LP patients (43.6%) had anemia at diagnosis, compared to 44 (56.4%) patients without anemia. Total median values of T-CD4+-cells observed at the moment of diagnosis of HIV was 116/µL (IQR 59-217); in Group A, 74/µL (IQR 50-147) compared to 180/µL (IQR 76-245) (p0,05). Virological failure occurred in 11 patients (32.3%) in Group A, 9 (20.5%) in Group B (p>0,05). After beginning of HAART, 9 patients developed at least one new AIDS event (total number of new AIDS-events was 13) in Group A, 1 (1 new AIDS events) in Group B (p 0,05) Conclusion Despite beginning of HAART, patients who present late at diagnosis continue to have high risk of developing new AIDS-events or to be re-admitted at hospital. Both patient groups at moment of diagnosis had a median of T-CD4 cells count <200/µL, thus being at risk of developing AIDS. HB value before starting HAART seems to have an important prognostic role to pinpoint, among LP, who has an higher risk of new AIDS events. For this reason LP with anemia should be monitored with a closer follow-up to identify as soon as possible worsening of health-condition

Immune System Deficiencies Do Not Alter SARS-CoV-2 Evolutionary Rate but Favour the Emergence of Mutations by Extending Viral Persistence

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral therapies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants which strongly challenged containment measures and some therapeutic treatments. To assess whether impaired immunity could lead to the increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimise the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients experienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low-frequency mutations. This study suggests that a compromised immune system alone does not affect SARS-CoV-2 within-host genomic variability

Nogo-A reduces ceramide de novo biosynthesis to protect from heart failure

Growing evidence correlate the accrual of the sphingolipid ceramide in plasma and cardiac tissue with heart failure (HF). Regulation of sphingolipid metabolism in the heart and the pathological impact of its derangement remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of endoplasmic reticulum, abundant in the vascular wall, down-regulates the sphingolipid de novo biosynthesis, via serine palmitoyltransferase (SPT), first and rate liming enzyme, to impact vascular functions and blood pressure. Nogo-A, a splice isoform of Nogo, is transiently expressed in cardiomyocyte (CM) following pressure overload. Cardiac Nogo is upregulated in dilated and ischemic cardiomyopathies in animals and humans. However, its biological function in the heart remains unknown