Increased carotid intima-media thickness associated with antibody responses to varicella-zoster virus and cytomegalovirus in HIV-infected patients.

OBJECTIVE: We investigated the relationship of the Herpesviridiae with inflammation and subclinical atherosclerosis in HIV-infected patients. METHODS: Prospective study including virologically suppressed HIV-infected patients. IgG antibodies against herpesviruses, carotid intima-media thickness (cIMT), endothelial function through flow-mediated dilatation (FMD) of the brachial artery, and blood atherosclerosis biomarkers (hsCRP, TNF-α, IL-6, MCP-1, MDA, sCD14, sCD163, VCAM-1, ICAM-1, D-dimer, and PAI-1) were measured. RESULTS: 136 patients with HIV viral load <200 copies/ml were included. 93.4% patients were infected with herpes simplex virus type-1, 55.9% with herpes simplex virus type-2, 97.1% with varicella-zoster virus, 65.4% with human herpesvirus-6, 91.2% with cytomegalovirus, and 99.3% with Epstein-Barr virus. Previous AIDS diagnosis was associated with higher cytomegalovirus IgG titers (23,000 vs 17,000 AU, P = 0.011) and higher varicella-zoster virus IgG titers (3.19 vs 2.88 AU, P = 0.047), and there was a positive correlation of the Framingham risk score with IgG levels against cytomegalovirus (Spearman's Rho 0.216, P = 0.016) and Herpes simplex virus-2 (Spearman's Rho 0.293, P = 0.001). IgG antibodies against cytomegalovirus correlated in adjusted analysis with the cIMT (P = 0.030). High seropositivity for varicella-zoster virus (OR 2.91, 95% CI 1.05-8.01, P = 0.039), and for cytomegalovirus (OR 3.79, 95% CI 1.20-11.97, P = 0.023) were predictors for the highest quartile of the cIMT in adjusted analyses. PAI-1 levels were independently associated with cytomegalovirus IgG titers (P = 0.041), IL-6 and ICAM-1 levels with varicella-zoster virus IgG (P = 0.046 and P = 0.035 respectively), and hsCRP levels with Herpes simplex virus-2 IgG (P = 0.035). CONCLUSION: In virologically suppressed HIV-infected patients, antibody responses against herpesviruses are associated with subclinical atherosclerosis, and with increased inflammation and coagulation biomarkers

Coinfection with human herpesvirus 8 is associated with persistent inflammation and immune activation in virologically suppressed HIV-infected patients.

Infection with co-pathogens is one of the postulated factors contributing to persistent inflammation and non-AIDS events in virologically-suppressed HIV-infected patients. We aimed to investigate the relationship of human herpesvirus-8 (HHV-8), a vasculotropic virus implicated in the pathogenesis of Kaposi's sarcoma, with inflammation and subclinical atherosclerosis in HIV-infected patients.Prospective study including virologically suppressed HIV-infected patients. Several blood biomarkers (highly-sensitive C-reactive protein [hsCRP], tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, malondialdehyde, plasminogen activator inhibitor [PAI-1], D-dimer, sCD14, sCD163, CD4/CD38/HLA-DR, and CD8/CD38/HLA-DR), serological tests for HHV-8 and the majority of herpesviruses, carotid intima-media thickness, and endothelial function through flow-mediated dilatation of the brachial artery were measured.A total of 136 patients were included, 34.6% of them infected with HHV-8. HHV-8-infected patients were more frequently co-infected with herpes simplex virus type 2 (HSV-2) (P<0.001), and less frequently with hepatitis C virus (HCV) (P = 0.045), and tended to be older (P = 0.086). HHV-8-infected patients had higher levels of hsCRP (median [interquartile range], 3.63 [1.32-7.54] vs. 2.08 [0.89-4.11] mg/L, P = 0.009), CD4/CD38/HLA-DR (7.67% [4.10-11.86]% vs. 3.86% [2.51-7.42]%, P = 0.035) and CD8/CD38/HLA-DR (8.02% [4.98-14.09]% vs. 5.02% [3.66-6.96]%, P = 0.018). After adjustment for the traditional cardiovascular risk factors, HCV and HSV-2 infection, the associations remained significant: adjusted difference between HHV-8 positive and negative patients (95% confidence interval) for hsCRP, 74.19% (16.65-160.13)%; for CD4/CD38/HLA-DR, 89.65% (14.34-214.87)%; and for CD8/CD38/HLA-DR, 58.41% (12.30-123.22)%. Flow-mediated dilatation and total carotid intima-media thickness were not different according to HHV-8 serostatus.In virologically suppressed HIV-infected patients, coinfection with HHV-8 is associated with increased inflammation and immune activation. This might contribute to increase the risk of non-AIDS events, including accelerated atherosclerotic disease

Comparison of Combined Nose-Throat Swabs with Nasopharyngeal Aspirates for Detection of Pandemic Influenza A/H1N1 2009 Virus by Real-Time Reverse Transcriptase PCR▿

Data assessing the diagnostic accuracies of use of different respiratory samples for the detection of the novel influenza A/H1N1 2009 virus by molecular methods are lacking. The objective of this study was to compare the sensitivity of combined nose and throat swabs (CNTS) with that of nasopharyngeal aspirates (NPA). This was a prospective study of adults and children with suspected influenza. Real-time reverse transcriptase PCR testing was used for the virological diagnosis. Of the 2,473 patients included, 264 with paired CNTS and NPA were randomly selected. Novel influenza A/H1N1 virus was identified in at least one sample for 115 (43.6%) patients, the majority of them young adults. In 109 patients (94.8%) the virus was identified in the CNTS, and in 98 (85.2%) it was identified in the NPA (P = 0.02). In 93 patients (80.1%), the virus was identified in both specimens. Spearman's rho correlation coefficient between the two methods was 0.82 (P < 0.001). There were no significant differences in accuracy between the specimens when patients were stratified according to demographic or clinical characteristics except in the case of women, in whom the sensitivity of CNTS was higher (P = 0.01). The combination of CNTS and NPA had a significantly higher sensitivity in identifying the virus than did each method alone (P = 0.02 for the comparison of the combination of both sampling methods with CNTS, and P < 0.001 for the comparison with NPA). We conclude that in patients with the novel influenza A/H1N1 virus, the diagnostic yield of CNTS is higher than that of NPA. The combination of both sampling methods increases the likelihood of diagnosing the virus

Procalcitonin for selecting the antibiotic regimen in outpatients with low-risk community-acquired pneumonia using a rapid point-of-care testing: A single-arm clinical trial

<div><p>Objective</p><p>We aimed to assess the role of procalcitonin (PCT) to guide the initial selection of the antibiotic regimen for low-risk community-acquired pneumonia (CAP).</p><p>Methods</p><p>A single-arm clinical trial was conducted including outpatients with CAP and Pneumonia Severity Index risk classes I-II. Antimicrobial selection was based on the results of PCT measured with a rapid point-of-care testing. According to serum PCT levels, patients were assigned to two treatment strategies: oral azithromycin if PCT was <0.5 ng/ml, or levofloxacin if levels were ≥0.5 ng/ml. Primary outcome was clinical cure rate. Short-term and long-term outcomes were assessed. Results were compared with those of a historical standard-of-care control-group treated in our centre.</p><p>Results</p><p>Of 253 subjects included, 216 (85.4%) were assigned to azithromycin. Pneumococcal infection was diagnosed in 26 (12%) and 21 (56.8%) patients allocated to azithromycin and levofloxacin groups, respectively. No patients in the azithromycin group developed bacteraemia. Atypical organisms were more common in patients given azithromycin (18.5% vs 8.1%, respectively). The majority (93%) of patients with atypical pneumonia had low PCT levels. Clinical cure rates were 95.8% in the azithromycin group, 94.6% in the levofloxacin group, and 94.4% in the historical control group. No 30-day mortality or recurrences were observed, and the 3-year rates of recurrence and mortality were very low in both groups. Adverse events occurrence was also infrequent.</p><p>Conclusion</p><p>A PCT-guided strategy with a rapid point-of-care testing safely allowed selecting empirical narrow-spectrum antibiotics in outpatients with CAP.</p><p>Trial registration</p><p>The study is registered with ClinicalTrials.gov, number <a href="https://clinicaltrials.gov/ct2/show/NCT02600806" target="_blank">NCT02600806</a></p></div

Correlation between the levels of biomarkers and IgG antibodies against several herpesviruses.

<p>cIMT, carotid intima-media thickness; FMD, flow-mediated dilatation; hsCRP, highly-sensitive C-reactive protein; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, intercellular cell adhesion molecule-1; IL-6, interleukin-6; MDA, malondialdehyde; TNF-α, tumour necrosis factor-alpha; PAI-1, plasminogen activator inhibitor-1; MCP-1, monocyte chemoattractant protein-1; HSV-1, herpes simplex virus type 1; VZV, varicella zoster virus; HHV-6, human herpesvirus 6; EBV, Epstein-Barr virus; CMV, cytomegalovirus.</p

Relationship of IgG antibody levels against HSV-2, CMV and VZV with cIMT quartiles.

<p>cIMT categories correspond to total cIMT quartiles, calculated as the media of the sum of all cIMT measurements and divided as follows: 1^st quartile (category 1): 0.49–0.65 mm; 2^nd quartile (category 2): ≥0.65–0.78 mm; 3^rd quartile (category 3): ≥0.78–0.98 mm; 4^th quartile (category 4): ≥0.98–1.80 mm.</p

Baseline characteristics of the patients.

<p>Continuous variables are expressed in median (interquartile range), unless indicated. Categorical variables are expressed in no. (%).</p><p>cIMT, carotid intima-media thickness; FMD, flow-mediated dilatation; hsCRP, highly-sensitive C-reactive protein; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, intercellular cell adhesion molecule-1; IL-6, interleukin-6; MDA, malondialdehyde; TNF-α, tumour necrosis factor-alpha; PAI-1, plasminogen activator inhibitor-1; MCP-1, monocyte chemoattractant protein-1; HSV-1, herpes simplex virus type-1; VZV, varicella zoster virus; HHV-6, human herpesvirus 6; EBV, Epstein-Barr virus; CMV, cytomegalovirus; IQR, interquartile range; AU, absorbance units.</p