Evolución de la epidemia de la infección por el VIH pediátrico en España, a partir de los datos de la cohorte de la red española de VIH en pediatría (CoRISpe)

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina preventiva, salud pública y microbiología. Fecha de lectura: 23-01-2020Esta tesis tiene embargado el acceso al texto completo hasta el 23-07-202

Sociodemographic changes and trends in the rates of new perinatal HIV diagnoses and transmission in Spain from 1997 to 2015

Retrospective study; Spanish Paediatric HIV Network; Rates of perinatal HIVEstudio retrospectivo; Red Española de VIH Pediátrico; Tasas de VIH perinatalEstudi retrospectiu; Xarxa espanyola de VIH Pediàtrica; Taxes de VIH perinatalBackground: There are not enough nationwide studies on perinatal HIV transmission in connection with a combination of antiretroviral treatments in Spain. Our objectives were to study sociodemographic changes and trends in the rates of HIV diagnoses and perinatal transmission in Spain from 1997 to 2015. Methods: A retrospective study using data from Spanish Paediatric HIV Network (CoRISpe) and Spanish Minimum Basic Data Set (MDBS) was performed. HIV- diagnosed children between 1997 and 2015 were selected. Sociodemographic, clinical and immunovirological data of HIV-infected children and their mothers were studied in four calendar periods (P1: 1997-2000; P2: 2001-2005; P3: 2006-2010; P4: 2011-2015). Rates of perinatal HIV diagnoses and transmission from 1997 to 2015 were calculated. Results: A total of 532 HIV-infected children were included in this study. Of these children, 406 were Spanish (76.3%) and 126 immigrants (23.7%). A decrease in the number of HIV diagnoses, 203 (38.2%) children in the first (P1), 149 (28%) in the second (P2), 130 (24.4%) in the third (P3) and 50 (9.4%) in the fourth (P4) calendar periods was studied. The same decrease in the Spanish HIV-infected children (P1, 174 (46.6%), P2, 115 (30.8%), P3, 65 (17.4%) and P4, 19 (5.1%)) was monitored. However, an increase in the number of HIV diagnoses by sexual contact (P1: 0%; P2: 1.3%; P3: 4.6%; P4: 16%) was observed. The rates of new perinatal HIV diagnoses and perinatal transmission in Spanish children decreased from 0.167 to 0.005 per 100,000 inhabitants and 11.4% to 0.4% between 1997 and 2015, respectively. Conclusions: A decline of perinatal HIV diagnoses and transmission was observed. However, an increase of teen-agers HIV diagnoses with sexual infection was studied. Public awareness campaigns directed to teen-agers are advisable to prevent HIV infection by sexual contact.This work has been partially funded by Red Temática de Investigación en SIDA (RED RIS) supported by Instituto de Salud Carlos III (ISCIII) (RD12/0017/0035, RD12/0017/0037 and RD16/0025/0019), project as part of the Plan R+D+I (2008-2011; 2013-2016) and cofinanced by ISCIII Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER), RISEPICLIN-19/2015, Fondo para la Investigación Sanitaria of the Spanish Ministry of Science and Innovation (FIS PI13/00422, PI16/01863), CYTED (214RT0482) and EPIICAL Project. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. COST CA17140 Cancer Nanomedicine-Front The Bench to Bebside. We thank the Spanish HIV HGM BioBank supported by ISC III project RETIC PT13/0010/0028 and PT17/0015/0042. No funding for this work was received from National Institutes of Health (NIH), Wellcome Trust and Howard Hughes Medical Institute (HHMI

A new tool for the paediatric HIV research:general data from the Cohort of the SpanishPaediatric HIV Network (CoRISpe)

There are approximately from 1,100 to 1,200 HIV-infected children in a follow-up in Spain. In 2008 an open, multicentral, retrospective and prospective Cohort of the Spanish Paediatric HIV Network (CoRISpe) was founded. The CoRISpe is divided into the node 1 and node 2 representing geographically almost the whole territory of Spain. Since 2008 seventy-five hospitals have been participating in the CoRISpe. All the retrospective data of the HIV-infected children have been kept in the CoRISpe since 1995 and prospective data since 2008. In this article we are going to present the notion of CoRISpe, its role, the structure, how the CoRISpe works and the process how a child is transferred from Paediatric to Adults Units. The main objective of the CoRISpe is to contribute to furthering scientific knowledge on paediatric HIV infection by providing demographic, sociopsychological, clinical and laboratory data from HIV-infected paediatric patients. Its aim is to enable high-quality research studies on HIV-infected children

New diagnoses of human immunodeficiency virus infection in the Spanish pediatric HIV Cohort (CoRISpe) from 2004 to 2013

Vertical human immunodeficiency virus (HIV) infection has decreased in industrialized countries in recent decades, but there are no studies on the mechanisms of HIV transmission among infected children in Spain. Our aim was to study the characteristics and trends of diagnoses of vertically HIV-infected children in Spain from 2004 to 2013. Vertically HIV-infected children were selected if they were diagnosed from 2004 to 2013, were aged 0 to 18 years old, and were included in the Cohort of the Spanish Pediatric HIV Network (CoRISpe). Demographic, clinical, immunological, and virological data at diagnosis were obtained. The rate of diagnoses of vertically HIV-infected children was calculated as the number of cases per 100,000 inhabitants. Obstetric data of mothers of Spanish children and prophylaxis at childbirth and postpartum were obtained. A total of 218 HIV-infected children were included in the study. Of this sample, 182 children (83.5%) were perinatally HIV infected, and 125 out of those 182 children (68.7%) were born in Spain. The vertically HIV-infected Spanish children were diagnosed earlier and were in better clinical and immunological condition at diagnosis than were foreign children. The rate of vertically HIV-infected children declined from 0.09 in 2004 to 0.03 in 2013 due to the decrease in the rate of children born in Spain (0.08 in 2004 vs 0.01 in 2013). A total of 60 out of 107 mothers (56.1%) of Spanish children were diagnosed at or after childbirth. However, this number declined between 2004 and 2013. The rate of new HIV diagnoses of vertically HIV-infected children decreased significantly between 2004 and 2013 from 0.09 to 0.03 per 100,000 inhabitant

New diagnoses of human immunodeficiency virus infection in the Spanish pediatric HIV Cohort (CoRISpe) from 2004 to 2013

Vertical human immunodeficiency virus (HIV) infection has decreased in industrialized countries in recent decades, but there are no studies on the mechanisms of HIV transmission among infected children in Spain. Our aim was to study the characteristics and trends of diagnoses of vertically HIV-infected children in Spain from 2004 to 2013. Vertically HIV-infected children were selected if they were diagnosed from 2004 to 2013, were aged 0 to 18 years old, and were included in the Cohort of the Spanish Pediatric HIV Network (CoRISpe). Demographic, clinical, immunological, and virological data at diagnosis were obtained. The rate of diagnoses of vertically HIV-infected children was calculated as the number of cases per 100,000 inhabitants. Obstetric data of mothers of Spanish children and prophylaxis at childbirth and postpartum were obtained. A total of 218 HIV-infected children were included in the study. Of this sample, 182 children (83.5%) were perinatally HIV infected, and 125 out of those 182 children (68.7%) were born in Spain. The vertically HIV-infected Spanish children were diagnosed earlier and were in better clinical and immunological condition at diagnosis than were foreign children. The rate of vertically HIV-infected children declined from 0.09 in 2004 to 0.03 in 2013 due to the decrease in the rate of children born in Spain (0.08 in 2004 vs 0.01 in 2013). A total of 60 out of 107 mothers (56.1%) of Spanish children were diagnosed at or after childbirth. However, this number declined between 2004 and 2013. The rate of new HIV diagnoses of vertically HIV-infected children decreased significantly between 2004 and 2013 from 0.09 to 0.03 per 100,000 inhabitants

High drug resistance prevalence among vertically HIV-Infected patients transferred from pediatric care to adult units in Spain

BACKGROUND: Antiretroviral treatment (ART) has contributed to increased life expectancy of HIV-1 infected children. In developed countries, an increasing number of children reaching adulthood are transferred to adult units. The objectives were to describe the demographic and clinical features, ART history, antiviral drug resistance and drug susceptibility in HIV-1 perinatally infected adolescents transferred to adult care units in Spain from the Madrid Cohort of HIV-1 infected children. METHODS: Clinical, virological and immunological features of HIV-1 vertically infected patients in the Madrid Cohort of HIV-infected children were analyzed at the time of transfer. Pol sequences from each patient were recovered before transfer. Resistance mutations according to the InternationaI AIDS Society 2011 list were identified and interpreted using the Stanford algorithm. Results were compared to the non-transferred HIV-1 infected pediatric cohort from Madrid. RESULTS: One hundred twelve infected patients were transferred to adult units between 1997 and 2011. They were mainly perinatally infected (93.7%), with a mean nadir CD4+-T-cells count of 10% and presented moderate or severe clinical symptoms (75%). By the time of transfer, the mean age was 18.9 years, the mean CD4+T-cells count was 627.5 cells/ml, 64.2% presented more than 350 CD4+T-cells/ml and 47.3% had ≤200 RNA-copies/ml. Most (97.3%) were ART experienced receiving Highly Active ART (HAART) (84.8%). Resistance prevalence among pretreated was 50.9%, 76.9% and 36.5% for Protease Inhibitors (PI), Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Non-NRTI (NNRTI), respectively. Resistance mutations were significantly higher among transferred patients compared to non-transferred for the PI+NRTI combination (19% vs. 8.4%). Triple resistance was similar to non-transferred pediatric patients (17.3% vs. 17.6%). CONCLUSION: Despite a good immunological and virological control before transfer, we found high levels of resistance to PI, NRTI and triple drug resistance in HIV-1 infected adolescents transferred to adult units

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

CoRISpe (Cohorte Nacional de VIH pediátrica de la RED RIS).[Background] Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution.[Methods] Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit.[Results] 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5–6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1).Peer reviewe

A new tool for the paediatric HIV research: general data from the Cohort of the Spanish Paediatric HIV Network (CoRISpe)

Abstract There are approximately from 1,100 to 1,200 HIV-infected children in a follow-up in Spain. In 2008 an open, multicentral, retrospective and prospective Cohort of the Spanish Paediatric HIV Network (CoRISpe) was founded. The CoRISpe is divided into the node 1 and node 2 representing geographically almost the whole territory of Spain. Since 2008 seventy-five hospitals have been participating in the CoRISpe. All the retrospective data of the HIV-infected children have been kept in the CoRISpe since 1995 and prospective data since 2008. In this article we are going to present the notion of CoRISpe, its role, the structure, how the CoRISpe works and the process how a child is transferred from Paediatric to Adults Units. The main objective of the CoRISpe is to contribute to furthering scientific knowledge on paediatric HIV infection by providing demographic, sociopsychological, clinical and laboratory data from HIV-infected paediatric patients. Its aim is to enable high-quality research studies on HIV-infected children.</p

Secukinumab does not impair the immunogenic response to the influenza vaccine in patients

Objective To evaluate whether immunological response to influenza vaccination is impaired in patients who are receiving secukinumab. Patients and methods Subjects suffering from psoriatic arthritis or ankylosing spondylitis who were receiving treatment with secukinumab and healthy volunteers were included. All participants received seasonal inactivated trivalent influenza vaccine recommended by the WHO in the 2017–2018 northern hemisphere influenza season, which contained an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus and a B/Brisbane/60/2008-like virus. Haemagglutination inhibition was used to evaluate basal antibody (Ab) titres against the three influenza vaccine virus strains just before vaccination and at least 4 weeks after the vaccine administration. Response to vaccine was considered as >4-fold increases in Ab titre. Results Thirty subjects, 17 patients and 13 healthy controls, with a follow-up duration of 33±8 days, were analysed. There were no demographic differences between groups. Patients and controls achieved a median of 4.6-fold and 4.0-fold increases, respectively, for anti H1N1 and almost 4.0 (3.7) for patients and 5.3 for controls for anti-B Ab. Both groups presented a poor response against H3N2, with <1.5-fold increase. Seroconversion rates were similar in both groups. Secukinumab did not influence the response to the influenza vaccine (relative risk: 1.09 (95% CI 0.58 to 2.07) for H1N1, RR: 1.53 (95% CI 0.15 to 15.0) for H3N2 and RR: 0.72 (95% CI 0.32 to 1.83) for B strain). Conclusion In our study, secukinumab has no effect on the immunogenic response to the influenza vaccine.Comité Ético del Hospital Universitario La Paz (ID: PI-3076)No data JCR 20191.715 SJR (2019) Q1, 49/225 Immunology, 38/202 Immunology and Allergy, 9/64 RheumatologyNo data IDR 2019UE

Sociodemographic changes and trends in the rates of new perinatal HIV diagnoses and transmission in Spain from 1997 to 2015

[Background] There are not enough nationwide studies on perinatal HIV transmission in connection with a combination of antiretroviral treatments in Spain. Our objectives were to study sociodemographic changes and trends in the rates of HIV diagnoses and perinatal transmission in Spain from 1997 to 2015.[Methods] A retrospective study using data from Spanish Paediatric HIV Network (CoRISpe) and Spanish Minimum Basic Data Set (MDBS) was performed. HIV- diagnosed children between 1997 and 2015 were selected. Sociodemographic, clinical and immunovirological data of HIV-infected children and their mothers were studied in four calendar periods (P1: 1997–2000; P2: 2001–2005; P3: 2006–2010; P4: 2011–2015). Rates of perinatal HIV diagnoses and transmission from 1997 to 2015 were calculated.[Results] A total of 532 HIV-infected children were included in this study. Of these children, 406 were Spanish (76.3%) and 126 immigrants (23.7%). A decrease in the number of HIV diagnoses, 203 (38.2%) children in the first (P1), 149 (28%) in the second (P2), 130 (24.4%) in the third (P3) and 50 (9.4%) in the fourth (P4) calendar periods was studied. The same decrease in the Spanish HIV-infected children (P1, 174 (46.6%), P2, 115 (30.8%), P3, 65 (17.4%) and P4, 19 (5.1%)) was monitored. However, an increase in the number of HIV diagnoses by sexual contact (P1: 0%; P2: 1.3%; P3: 4.6%; P4: 16%) was observed. The rates of new perinatal HIV diagnoses and perinatal transmission in Spanish children decreased from 0.167 to 0.005 per 100,000 inhabitants and 11.4% to 0.4% between 1997 and 2015, respectively.[Conclusions] A decline of perinatal HIV diagnoses and transmission was observed. However, an increase of teen-agers HIV diagnoses with sexual infection was studied. Public awareness campaigns directed to teen-agers are advisable to prevent HIV infection by sexual contact.This work has been partially funded by Red Temática de Investigación en SIDA (RED RIS) supported by Instituto de Salud Carlos III (ISCIII) (RD12/0017/0035, RD12/0017/0037 and RD16/0025/0019), project as part of the Plan R+D+I (2008–2011; 2013–2016) and cofinanced by ISCIII- Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER), RIS-EPICLIN-19/2015, Fondo para la Investigación Sanitaria of the Spanish Ministry of Science and Innovation (FIS PI13/00422, PI16/01863), CYTED (214RT0482) and EPIICAL Project. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. COST CA17140 Cancer Nanomedicine-Front The Bench to Bebside. We thank the Spanish HIV HGM BioBank supported by ISC III project RETIC PT13/0010/0028 and PT17/0015/0042. No funding for this work was received from National Institutes of Health (NIH), Wellcome Trust and Howard Hughes Medical Institute (HHMI).Peer reviewe