Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease A Large Retrospective Registry

[EN] OBJECTIVES: This study explored the association of ischemic burden, as measured by vasodilator stress cardiovascular magnetic resonance (CMR), with all-cause mortality and the effect of revascularization on all-cause mortality in patients with stable ischemic heart disease (SIHD). Background: In patients with SIHD, the association of ischemic burden, derived from vasodilator stress CMR, with all-cause mortality and its role for decision-making is unclear. METHODS: The registry consisted of 6,389 consecutive patients (mean age: 65 +/- 12 years; 38% women) who underwent vasodilator stress CMR for known or suspected SIHD. The ischemic burden (at stress first-pass perfusion imaging) was computed (17-segment model). The effect of CMR-related revascularization (within the following 3 months) on all-cause mortality was retrospectively explored using the electronic regional health system registry. RESULTS: During a 5.75-year median follow-up, 717 (11%) deaths were documented. In multivariable analyses, more extensive ischemic burden (per 1-segment increase) was independently related to all-cause mortality (hazard ratio: 1.04; 95% confidence interval: 1.02 to 1.07; p 5 segments, n = 432; 10% vs. 24%; p = 0.01). CONCLUSIONS: In a large retrospective registry of unselected patients with known or suspected SIHD who underwent vasodilator stress CMR, extensive ischemic burden was related to a higher risk of long-term, all-cause mortality. Revascularization was associated with a protective effect only in the restricted subset of patients with extensive CMR-related ischemia. Further research will be needed to confirm this hypothesis-generating finding.Dr. Marcos-Garces and Mr. Gavara contributed equally to the study. This work was supported by the Instituto de Salud Carlos III and co-funded by Fondo Europeo de Desarrollo Regional (FEDER) (grant numbers PI17/01836, PIE15/00013, CIBERCV16/11/00486). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.Marcos-Garces, V.; Gavara, J.; Monmeneu, JV.; Lopez-Lereu, MP.; Bosch, MJ.; Merlos, P.; Pérez, N.... (2020). Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease A Large Retrospective Registry. JACC: Cardiovascular Imaging. 13(8):1674-1686. https://doi.org/10.1016/j.jcmg.2020.02.027S16741686138Bodi, V., Sanchis, J., Lopez-Lereu, M. P., Nunez, J., Mainar, L., Monmeneu, J. V., … Llacer, A. (2007). Prognostic Value of Dipyridamole Stress Cardiovascular Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease. Journal of the American College of Cardiology, 50(12), 1174-1179. doi:10.1016/j.jacc.2007.06.016Vincenti, G., Masci, P. G., Monney, P., Rutz, T., Hugelshofer, S., Gaxherri, M., … Schwitter, J. (2017). Stress Perfusion CMR in Patients With Known and Suspected CAD. JACC: Cardiovascular Imaging, 10(5), 526-537. doi:10.1016/j.jcmg.2017.02.006Bodi, V., Husser, O., Sanchis, J., Núñez, J., Monmeneu, J. V., López-Lereu, M. P., … Llacer, Á. (2012). Prognostic Implications of Dipyridamole Cardiac MR Imaging: A Prospective Multicenter Registry. Radiology, 262(1), 91-100. doi:10.1148/radiol.11110134Katritsis, D. G., Mark, D. B., & Gersh, B. J. (2018). Revascularization in stable coronary disease: evidence and uncertainties. Nature Reviews Cardiology, 15(7), 408-419. doi:10.1038/s41569-018-0006-zKelle, S., Chiribiri, A., Vierecke, J., Egnell, C., Hamdan, A., Jahnke, C., … Gebker, R. (2011). Long-Term Prognostic Value of Dobutamine Stress CMR. JACC: Cardiovascular Imaging, 4(2), 161-172. doi:10.1016/j.jcmg.2010.11.012Caliendo, M., & Kopeinig, S. (2008). SOME PRACTICAL GUIDANCE FOR THE IMPLEMENTATION OF PROPENSITY SCORE MATCHING. Journal of Economic Surveys, 22(1), 31-72. doi:10.1111/j.1467-6419.2007.00527.xTimmis, A., Raharja, A., Archbold, R. A., & Mathur, A. (2018). Validity of inducible ischaemia as a surrogate for adverse outcomes in stable coronary artery disease. Heart, 104(21), 1733-1738. doi:10.1136/heartjnl-2018-313230Hachamovitch, R., Hayes, S. W., Friedman, J. D., Cohen, I., & Berman, D. S. (2003). Comparison of the Short-Term Survival Benefit Associated With Revascularization Compared With Medical Therapy in Patients With No Prior Coronary Artery Disease Undergoing Stress Myocardial Perfusion Single Photon Emission Computed Tomography. Circulation, 107(23), 2900-2907. doi:10.1161/01.cir.0000072790.23090.41Hachamovitch, R., Rozanski, A., Shaw, L. J., Stone, G. W., Thomson, L. E. J., Friedman, J. D., … Berman, D. S. (2011). Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy. European Heart Journal, 32(8), 1012-1024. doi:10.1093/eurheartj/ehq5002013 ESC guidelines on the management of stable coronary artery disease. (2013). European Heart Journal, 34(38), 2949-3003. doi:10.1093/eurheartj/eht296Doenst, T., Haverich, A., Serruys, P., Bonow, R. O., Kappetein, P., Falk, V., … Sigusch, H. (2019). PCI and CABG for Treating Stable Coronary Artery Disease. Journal of the American College of Cardiology, 73(8), 964-976. doi:10.1016/j.jacc.2018.11.053A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease. (2009). New England Journal of Medicine, 360(24), 2503-2515. doi:10.1056/nejmoa0805796Boden, W. E., O’Rourke, R. A., Teo, K. K., Hartigan, P. M., Maron, D. J., Kostuk, W. J., … Weintraub, W. S. (2007). Optimal Medical Therapy with or without PCI for Stable Coronary Disease. New England Journal of Medicine, 356(15), 1503-1516. doi:10.1056/nejmoa070829Van Nunen, L. X., Zimmermann, F. M., Tonino, P. A. 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COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women