Local epidemics gone viral: Evolution and diffusion of the Italian HIV-1 recombinant form CRF60_BC

The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18-37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy

Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

Reference values for exhaled nitric oxide (reveno) study

BACKGROUND: Despite the widespread use of fractional exhaled nitric oxide (FE(NO)) as a biomarker of airways inflammation, there are no published papers describing normal FE(NO )values in a large group of healthy adults. OBJECTIVE: The aim of this study was to establish adult FE(NO )reference values according to the international guidelines. METHODS: FE(NO )was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently. RESULTS: The main result of the study was the significant difference in FE(NO )values between men and women, thus indicating that gender-based reference FE(NO )values are necessary. The FE(NO )levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women. CONCLUSION: We propose reference FE(NO )values for healthy adult men and women that could be used for clinical and research purposes

Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection

Background: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO). Methods: In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia. Results: The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate. Conclusion: In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.Original Publication: Jonna Idh, Anna Westman, Daniel Elias, Feleke Moges, Assefa Getachew, Aschalew Gelaw, Tommy Sundqvist, Tony Forslund, Addis Alemu, Belete Ayele, Ermias Diro, Endalkachew Melese, Yared Wondmikun, Sven Britton, Olle Stendahl and Thomas Schoen, Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection, 2008, BMC INFECTIOUS DISEASES, (8), 146. http://dx.doi.org/10.1186/1471-2334-8-146 Publisher: BioMed Central http://www.biomedcentral.com

Late presentation and loss to follow-up of immigrants newly diagnosed with HIV in the HAART era

To compare clinical characteristics and therapeutic management of newly HIV-diagnosed immigrants to natives. Patients with a first HIV diagnosis from 1996 to 2010 were included. Of 716 new diagnoses, 85 (12 %) were immigrants. Migrants were younger, more frequently females and sexually infected, less likely to voluntarily request testing, and less HCV-coinfected. Late presenters (CD4 <350 or AIDS) were 76 % among migrants versus 56 % in natives (p = 0.006) with an increasing trend over time. HAART was initiated in 76.5 % of natives and 72.4 % of immigrants; the number/type of adverse events and treatment discontinuation were similar. Immigrants received more NNRTIs-based regimens. A similar proportion of patients reached virological suppression at month 1-3-6 after HAART initiation, but 43 % of immigrants versus 27 % of natives resulted lost to follow-up (p < 0.001). Diagnosis of HIV was often delayed among migrants, who also presented a higher rate of lost to follow-up