Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe

This work received support from the Dirección General de Farmacia, Ministerio de Sanidad, Servicios Sociales e Igualdad, Government of Spain, grant EC11-272; European Network of Excellence EUROPRISE (Rational Design of HIV Vaccines and Microbicides), grant LSHP-CT-2006-037611; European Research Infrastructures for Poverty Related Diseases (EURIPRED). Seventh Framework Programme: FP7-Capacities-infrastructures-2012-1, grant agreement 312661; Instituto de Salud Carlos III, Subdirección General de Evaluación, and Fondo Europeo de Desarrollo Regional (FEDER), Plan Nacional I + D + I, through project RD12/0017/0026; Consellería de Sanidade, Government of Galicia, Spain (MVI 1291/08); and the Osakidetza-Servicio Vasco de Salud, Basque Country, Spain (MVI-1255-08). Marcos Pérez-Losada was supported by a DC D-CFAR Research Award from the District of Columbia Developmental Center for AIDS Research (P30AI087714) and by an University Facilitating Fund award from George Washington University. Aurora Fernández-García is supported by CIBER in Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain.We recently reported the rapid expansion of an HIV-1 subtype F cluster among men who have sex with men (MSM) in the region of Galicia, Northwest Spain. Here we update this outbreak, analyze near full-length genomes, determine phylogenetic relationships, and estimate its origin. For this study, we used sequences of HIV-1 protease-reverse transcriptase and env V3 region, and for 17 samples, near full-length genome sequences were obtained. Phylogenetic analyses were performed via maximum likelihood. Locations and times of most recent common ancestors were estimated using Bayesian inference. Among samples analyzed by us, 100 HIV-1 F1 subsubtype infections of monophyletic origin were diagnosed in Spain, including 88 in Galicia and 12 in four other regions. Most viruses (n = 90) grouped in a subcluster (Galician subcluster), while 7 from Valladolid (Central Spain) grouped in another subcluster. At least 94 individuals were sexually-infected males and at least 71 were MSM. Seventeen near full-length genomes were uniformly of F1 subsubtype. Through similarity searches and phylogenetic analyses, we identified 18 viruses from four other Western European countries [Switzerland (n = 8), Belgium (n = 5), France (n = 3), and United Kingdom (n = 2)] and one from Brazil, from samples collected in 2005?2011, which branched within the subtype F cluster, outside of both Spanish subclusters, most of them corresponding to recently infected individuals. The most probable geographic origin and age of the Galician subcluster was Ferrol, Northwest Galicia, around 2007, while the Western European cluster probably emerged in Switzerland around 2002. In conclusion, a recently expanded HIV-1 subtype F cluster, the largest non-subtype B cluster reported in Western Europe, continues to spread among MSM in Spain; this cluster is part of a larger cluster with a wide geographic circulation in diverse Western European countries.Publisher PDFPeer reviewe

Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain

In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries

Manejo del dolor en la fibrodisplasia osificante progresiva

The fibrodysplasia ossificans progressiva is a disease of low prevalence, 1 case per 2 million inhabitants, hereditary, severely disabling, characterized by a process of ossification in skeletal muscles, fascia, tendons and ligaments, without effective treatment, evolving by thrusts which are accompanied by severe pain, resulting in a posteriori, after several thrusts, to installing permanent baseline pain. We analyze the most salient features of the disease, common history, its presentation, its evolution, the accompanying pain and its treatment. This is done to combat the pain, since there is no treatment at present, for the underlying disease, and will vary according to the time course of the same, beginning itself with paracetamol and NSAIDs in early stages, giving rise then to the use of opioids. In regard to pain crises, buds secondary heterotopic ossification, currently there is consensus regarding the use of high potency anti-inflammatory corticosteroids. With pain as a relevant in this disease, we found no publication that specifically addresses; therefore we consider this presentation timely. We report the case of a person of 27 years, female gender, fibrodysplasia ossificans progressiva carrier controlled for years in our unit, for its severe painful crises and baseline pain also installed in recent years. We report the presentation of the disease, its evolution, its current status, as well as treatments that have been made, well as the handling of her latest, recent and more severe pain thrust, based on high-dose dexamethasone, and the use of pregabalin as an adjuvant. It concludes with recommendations for treating painful crises, based on the use of corticosteroids, and baseline pain management always present in these patients, based on the use of opioids.La fibrodisplasia osificante progresiva es una enfermedad de escasa prevalencia, 1 caso cada 2 millones de habitantes, hereditaria, severamente incapacitante, caracterizada por un proceso de osificación en músculos esqueléticos, fascias, tendones y ligamentos, sin tratamiento eficaz y que evoluciona por empujes, que se acompañan de dolor intenso, dando lugar a posteriori, después de varios empujes, a la instalación de dolor basal permanente. Analizamos las características más salientes de la enfermedad, su historia habitual, su forma de presentación, su evolución, el dolor acompañante y su tratamiento. Este se realiza para combatir el dolor, ya que no existe tratamiento en el momento actual, para la enfermedad de fondo, y será variable de acuerdo al momento evolutivo de la misma, comenzándose con paracetamol y AINE en etapas iniciales, para dar lugar luego al uso de opioides. En lo que se refiere a las crisis de dolor, secundarias a brotes de osificación heterotópicos, existe consenso actualmente en cuanto a la utilización de corticoides de alta potencia antiinflamatoria. Siendo el dolor un hecho relevante en esta patología, no hemos encontrado ninguna publicación que lo aborde específicamente, por lo cual entendemos oportuna esta comunicación. Presentamos el caso de persona de 27 años, sexo femenino, portadora de fibrodisplasia osificante progresiva, controlada desde hace años en nuestra Unidad por sus crisis dolorosas severas, así como también por dolor basal instalado en los últimos años. Se relata la presentación de la enfermedad, su evolución, su estado actual, los tratamientos que se han realizado, así como el manejo de su última, reciente y más severa crisis de dolor, en base a dexametasona en altas dosis, y al uso de pregabalina como coadyuvante. Se concluye con recomendaciones para tratar los empujes dolorosos, basadas en el uso de corticoides, así como el manejo del dolor basal siempre presente en estos pacientes, fundamentado en el uso de opioides

Characteristics and outcomes of chronic pain patients referred to hospital pain clinics: a prospective observational study

BACKGROUND: Understanding the patient referral patterns and medical profiles of patients attending hospital pain clinics, and the therapies offered to them, can provide a useful starting point for evaluating their effectiveness and identifying areas for improvement. METHODS: A prospective observational study was carried out. Sociodemographic and clinical data were gathered at twelve centres. The diagnoses and pain treatments provided by the referring doctors were compared with the ones provided by pain clinicians. Pain severity and patients' quality of life were measured prospectively. Descriptive statistics were compared. RESULTS: Two-hundred sixty-nine patients referred to 12 outpatient hospital pain clinics in Catalonia were followed for 3 months. Most were referred by orthopaedists (50.0%) or primary care physicians (20.2%). The mean age and time since pain onset were 59.4 and 4.1 years, respectively. Pain clinicians changed the diagnostic labels of 48.5% of the patients. Nearly all patients (89.2%) were receiving pain medications prior to referral. Treatment was modified in 94.8%. Pain clinicians used more interventional and/or alternative therapies (65.1% of patients), opioids (46.8%) and co-adjuvants (38.2%). Three months after referral, the 24-h worst and current pain severity had decreased by 30.9% and 27.8% on average, respectively. The mean (effect size) improvements in a quality of life (the EuroQol 5 Dimensions index) and pain (visual analogue scale) scores were, respectively, 0.16 (0.73) and 6.7 (0.31). CONCLUSIONS: Pain clinicians refined the diagnoses and treatments of patients referred to hospital pain clinics and improved outcomes. Relatively few patients are referred from primary care considering the prevalence of chronic pain in this setting.This research received funds from Laboratorios del Doctor Esteve, S.A

Characteristics and outcomes of chronic pain patients referred to hospital pain clinics: a prospective observational study

BACKGROUND: Understanding the patient referral patterns and medical profiles of patients attending hospital pain clinics, and the therapies offered to them, can provide a useful starting point for evaluating their effectiveness and identifying areas for improvement. METHODS: A prospective observational study was carried out. Sociodemographic and clinical data were gathered at twelve centres. The diagnoses and pain treatments provided by the referring doctors were compared with the ones provided by pain clinicians. Pain severity and patients' quality of life were measured prospectively. Descriptive statistics were compared. RESULTS: Two-hundred sixty-nine patients referred to 12 outpatient hospital pain clinics in Catalonia were followed for 3 months. Most were referred by orthopaedists (50.0%) or primary care physicians (20.2%). The mean age and time since pain onset were 59.4 and 4.1 years, respectively. Pain clinicians changed the diagnostic labels of 48.5% of the patients. Nearly all patients (89.2%) were receiving pain medications prior to referral. Treatment was modified in 94.8%. Pain clinicians used more interventional and/or alternative therapies (65.1% of patients), opioids (46.8%) and co-adjuvants (38.2%). Three months after referral, the 24-h worst and current pain severity had decreased by 30.9% and 27.8% on average, respectively. The mean (effect size) improvements in a quality of life (the EuroQol 5 Dimensions index) and pain (visual analogue scale) scores were, respectively, 0.16 (0.73) and 6.7 (0.31). CONCLUSIONS: Pain clinicians refined the diagnoses and treatments of patients referred to hospital pain clinics and improved outcomes. Relatively few patients are referred from primary care considering the prevalence of chronic pain in this setting.This research received funds from Laboratorios del Doctor Esteve, S.A

Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe

We recently reported the rapid expansion of an HIV-1 subtype F cluster among men who have sex with men (MSM) in the region of Galicia, Northwest Spain. Here we update this outbreak, analyze near full-length genomes, determine phylogenetic relationships, and estimate its origin. For this study, we used sequences of HIV-1 protease-reverse transcriptase and env V3 region, and for 17 samples, near full-length genome sequences were obtained. Phylogenetic analyses were performed via maximum likelihood. Locations and times of most recent common ancestors were estimated using Bayesian inference. Among samples analyzed by us, 100 HIV-1 F1 subsubtype infections of monophyletic origin were diagnosed in Spain, including 88 in Galicia and 12 in four other regions. Most viruses (n = 90) grouped in a subcluster (Galician subcluster), while 7 from Valladolid (Central Spain) grouped in another subcluster. At least 94 individuals were sexually-infected males and at least 71 were MSM. Seventeen near full-length genomes were uniformly of F1 subsubtype. Through similarity searches and phylogenetic analyses, we identified 18 viruses from four other Western European countries [Switzerland (n = 8), Belgium (n = 5), France (n = 3), and United Kingdom (n = 2)] and one from Brazil, from samples collected in 2005?2011, which branched within the subtype F cluster, outside of both Spanish subclusters, most of them corresponding to recently infected individuals. The most probable geographic origin and age of the Galician subcluster was Ferrol, Northwest Galicia, around 2007, while the Western European cluster probably emerged in Switzerland around 2002. In conclusion, a recently expanded HIV-1 subtype F cluster, the largest non-subtype B cluster reported in Western Europe, continues to spread among MSM in Spain; this cluster is part of a larger cluster with a wide geographic circulation in diverse Western European countries.</p

Maximum clade credibility tree of PR-RT sequences of the subtype F Western European cluster and Galician subcluster.

<p>Nodes supported by PP = 1 and PP = 0.95–0.99 are marked with filled and unfilled circles, respectively. Colors of terminal and internal branches represent sampling locations and most probable locations of the corresponding nodes, respectively, according to the legend on the right. For the nodes corresponding to the Galician subcluster and the Western European cluster, the posterior probabilities for the most probable locations and the tMRCAs are indicated above the subtending branches (95% HPD intervals are in parentheses).</p

Distribution of viruses of the subtype F cluster sequenced by us according to city of sample collection.

<p>Distribution of viruses of the subtype F cluster sequenced by us according to city of sample collection.</p

Bayesian skyline plot of the population growth of the subtype F cluster.

<p>The black line represents the median estimate of the effective number of infections through time (logarithmic scale) and the shaded area represents the 95% HPD credibility interval. The horizontal axis represents calendar years.</p