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To monitor relative vaccine effectiveness (rVE) against COVID-19-related hospitalisation of the first, second and third COVID-19 booster (vs complete primary vaccination), we performed monthly Cox regression models using retrospective cohorts constructed from electronic health registries in eight European countries, October 2021-July 2023. Within 12 weeks of administration, each booster showed high rVE (≥ 70% for second and third boosters). However, as of July 2023, most of the relative benefit has waned, particularly in persons ≥ 80-years-old, while some protection remained in 65-79-year-olds.

Background: Within the ECDC-VEBIS project, we prospectively monitored vaccine effectiveness (VE) against COVID-19 hospitalisation and COVID-19-related death using electronic health registries (EHR), between October 2021 and November 2022, in community-dwelling residents aged 65-79 and ≥80 years in six European countries., Methods: EHR linkage was used to construct population cohorts in Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal. Using a common protocol, for each outcome, VE was estimated monthly over 8-week follow-up periods, allowing 1 month-lag for data consolidation. Cox proportional-hazards models were used to estimate adjusted hazard ratios (aHR) and VE = (1 - aHR) × 100%. Site-specific estimates were pooled using random-effects meta-analysis., Results: For ≥80 years, considering unvaccinated as the reference, VE against COVID-19 hospitalisation decreased from 66.9% (95% CI: 60.1; 72.6) to 36.1% (95% CI: -27.3; 67.9) for the primary vaccination and from 95.6% (95% CI: 88.0; 98.4) to 67.7% (95% CI: 45.9; 80.8) for the first booster. Similar trends were observed for 65-79 years. The second booster VE against hospitalisation ranged between 82.0% (95% CI: 75.9; 87.0) and 83.9% (95% CI: 77.7; 88.4) for the ≥80 years and between 39.3% (95% CI: -3.9; 64.5) and 80.6% (95% CI: 67.2; 88.5) for 65-79 years. The first booster VE against COVID-19-related death declined over time for both age groups, while the second booster VE against death remained above 80% for the ≥80 years., Conclusions: Successive vaccine boosters played a relevant role in maintaining protection against COVID-19 hospitalisation and death, in the context of decreasing VE over time. Multicountry data from EHR facilitate robust near-real-time VE monitoring in the EU/EEA and support public health decision-making., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. MH is data science adviser for ProPublica, Advisory Board Member of ADIA Lab, and consultant for Cytel.

Background: We estimated the association between the level of restriction in nine different fields of activity and SARS-CoV-2 transmissibility in Spain, from 15 September 2020 to 9 May 2021., Methods: A stringency index (0-1) was created for each Spanish province ( n  = 50) daily. A hierarchical multiplicative model was fitted. The median of coefficients across provinces (95% bootstrap confidence intervals) quantified the effect of increasing one standard deviation in the stringency index over the logarithmic return of the weekly percentage variation of the 7-days SARS-CoV-2 cumulative incidence, lagged 12 days., Results: Overall, increasing restrictions reduced SARS-CoV-2 transmission by 22% (RR = 0.78; one-sided 95%CI: 0, 0.82) in 1 week, with highest effects for culture and leisure 14% (0.86; 0, 0.98), social distancing 13% (0.87; 0, 0.95), indoor restaurants 10% (0.90; 0, 0.95) and indoor sports 6% (0.94; 0, 0.98). In a reduced model with seven fields, culture and leisure no longer had a significant effect while ceremonies decreased transmission by 5% (0.95; 0, 0.96). Models R 2 was around 70%., Conclusion: Increased restrictions decreased COVID-19 transmission. Limitations include remaining collinearity between fields, and somewhat artificial quantification of qualitative restrictions, so the exact attribution of the effect to specific areas must be done with caution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barbeito, Precioso, Sierra, Vegas-Azcárate, Fernández Balbuena, Vitoriano, Goméz-Ullate, Cao, Monge and the Study Group for Non-Pharmaceutical Interventions in Spain.)

Background: Single-dose vaccination was widely recommended in the pre-Omicron era for persons with previous SARS-CoV-2 infection. The effectiveness of a second vaccine dose in this group in the Omicron era is unknown., Methods: We linked nationwide population registries in Spain to identify community-dwelling individuals aged 18-64, with a positive SARS-CoV-2 test before single-dose mRNA vaccination (mRNA-1273 or BNT162b2). Every day between 3 January and 6 February 2022 we matched 1:1 individuals receiving a second mRNA vaccine dose and controls on sex, age, province, first dose type and time, month of primary infection, and number of previous tests. We then estimated Kaplan-Meier risks of confirmed SARS-CoV-2 reinfection. We performed a similar analysis in a Delta-dominant period, between 19 July and 30 November 2021., Results: In the Omicron period, estimated effectiveness (95% CI) of a second dose was 62.2% (58.2-66.4%) 7-34 days after administration, similar across groups defined by age, sex, type of first vaccine, and time since the first dose. Estimated effectiveness was 65.4% (61.1-69.9%) for mRNA-1273 and 52.0% (41.8-63.1%) for BNT162b2. Estimated effectiveness was 78.5% (67.4-89.9%), 66.1% (54.9-77.5%), and 60.2% (55.5-64.8%) when primary infection had occurred in the Delta, Alpha, and pre-Alpha periods, respectively. In the Delta period, the estimated effectiveness of a second dose was 8.8% (-55.3% to 81.1%)., Conclusions: Our results suggest that, over 1 month after administration, a second dose of mRNA vaccine increases protection against SARS-CoV-2 reinfection with the Omicron variant among individuals with single-dose vaccination and previously infected with another variant., Competing Interests: Potential conflicts of interest. M. A. H. reports consulting fees from ProPublica for work as a Data Science Advisor and from Cytel for work as a Methodological consultant. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures., Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC., Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%., Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves., (Copyright © 2021 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease., Methods: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted Odds Ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls., Results: We included 5,345 Alpha and 11,974 Delta infections in June-July and, 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years., Conclusion: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups., (© 2022 Published by Elsevier España, S.L.U. on behalf of Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.)

In this paper we compared brand-specific COVID-19 vaccine effectiveness (VE) during August 2021 in persons born 1962-1971 and vaccinated during June. For SARS-CoV-2 symptomatic infection, protection was lower for Janssen (56%; CI95%: 53-59) or AstraZeneca [Vaxzevria] (68%; CI95%: 65-70), compared to Pfizer-BioNTech [Comirnaty] (78%; CI95%: 77-78), AstraZeneca/Pfizer (86%; CI95%: 80-90) or Moderna [Spikevax] (89%; CI95%: 88-90). VE against hospitalization was ranged 86% for Janssen to 97%-98% for other vaccines.

Background: The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster., Methods: In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR., Findings: Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2-52·4). Estimated effectiveness was 52·5% (51·3-53·7) for an mRNA-1273 booster and 46·2% (43·5-48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5-61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford-AstraZeneca), 55·3% (52·3-58·2) with mRNA-1273 (Moderna), 49·7% (48·3-51·1) with BNT162b2 (Pfizer-BioNTech), and 48·0% (42·5-53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0-47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0-53·3) if administered more than 180 days after primary scheduled completion., Interpretation: Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster., Funding: None., Competing Interests: Declaration of interests We declare no competing interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65-79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.

We conducted a registries-based cohort study of long-term care facility residents >65 years of age offered vaccination against severe acute respiratory syndrome coronavirus 2 before March 10, 2021, in Spain. Risk for infection in vaccinated and nonvaccinated persons was compared with risk in the same persons in a period before the vaccination campaign, adjusted by daily-varying incidence and reproduction number. We selected 299,209 persons; 99.0% had >1 dose, 92.6% had 2 doses, and 99.8% of vaccines were Pfizer/BioNTech (BNT162b2). For vaccinated persons with no previous infection, vaccine effectiveness was 81.8% (95% CI 81.0%-82.7%), and 11.6 (95% CI 11.3-11.9) cases were prevented per 10,000 vaccinated/day. In those with previous infection, effectiveness was 56.8% (95% CI 47.1%-67.7%). In nonvaccinated residents with no previous infection, risk decreased by up to 81.4% (95% CI 73.3%-90.3%). Our results confirm vaccine effectiveness in this population and suggest indirect protection in nonvaccinated persons.

The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness., (Copyright © 2020 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures., Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC., Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%., Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves., (Copyright © 2021 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Residents in long-term care facilities (LTCF) experienced a large morbidity and mortality during the COVID-19 pandemic in Spain and were prioritised for early COVID-19 vaccination. We used the screening method and population-based data sources to obtain estimates of mRNA COVID-19 vaccine effectiveness for elderly LTCF residents. The estimates were 71% (95% CI: 56-82%), 88% (95% CI: 75-95%), and 97% (95% CI: 92-99%), against SARS-CoV-2 infections (symptomatic and asymptomatic), and COVID-19 hospitalisations and deaths, respectively.

Ambulance dispatches for respiratory syndromes reflect incidence of influenza-like illness in primary care. Associations are highest in children (15%-34% of respiratory calls attributable to influenza), out-of-office hours (9%), and highest urgency-level calls (9%-11%). Ambulance dispatches might be an additional source of data for severe influenza surveillance.

Background: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown., Methods: A prospective cohort of human immunodeficiency virus (HIV)-infected participants with suppressed virological replication was recruited to compare whole-blood telomere length (measured by quantitative multiplex polymerase chain reaction analysis) in participants with current exposure to tenofovir disoproxil fumarate (TDF) to that in participants never exposed to TDF., Results: A total of 172 participants were included: 67 were in the TDF group, and 105 were in the non-TDF group (75 were receiving 2 nucleosides [of whom 69 were receiving abacavir], 25 were receiving a nucleos[t]ide reverse transcriptase inhibitor [N{t}RTI]-sparing regimen, and 5 were receiving lamivudine as the only nucleoside). After 2 years, the mean blood telomere length increased significantly in the whole cohort. The TDF group had significantly smaller gains in telomere length than the non-TDF group. In the analysis restricted to participants receiving N(t)RTIs, TDF exposure was not associated with an independent negative effect. In the non-TDF group, participants treated with 2 nucleosides also had significantly smaller gains in telomere length than those receiving N(t)RTI-sparing regimens or lamivudine as the only nucleoside., Discussion: In HIV-infected adults with prolonged virological suppression, treatment with TDF or abacavir was associated with smaller gains in blood telomere length after 2 years of follow-up.

Background: We aimed to estimate population-level exposure to Campylobacter and associated risk factors, using three approaches for serological data analysis., Methods: Nationwide, population-based serosurvey in the Netherlands (Feb 2006-Jun 2007). Anti-Campylobacter IgG, IgM and IgA were measured using ELISA, and analysed via: a) seroincidence estimation, using reference values of antibody peak levels and decay rates over-time after Campylobacter exposure; b) two normal distributions of true positives/negatives fitted to the IgG distribution to derive seroprevalence and individual probability of being positive/negative; and c) IgG levels. Risk factors were analysed using multiple linear regressions., Results: From 1559 respondents, seroincidence was estimated at 1.61 infections/person-year (95%CI:1.58-1.64) and seroprevalence at 68.1% (65.4-70.9). The three approaches identified similar risk factors, although seroincidence had higher power and results were interpretable as risk: seroincidence was higher in females [exp(b) = 1.07(1.04-1.11)], older ages [vs. 15-34 years; for < 5, 5-14, 35-54 and 55-70 years: 0.60(0.58-0.63), 0.74(0.71-0.78), 1.08(1.03-1.13) and 1.08(1.01-1.16), respectively], non-Dutch background [Moroccan/Turkish: 1.25(1.14-1.37); Caribbean: 1.14(1.03-1.25)], low socioeconomic status [1.05(1.01-1.10)], traveling outside Europe [1.05(1.01-1.09)], and eating undercooked meat [1.04(1.01-1.08)]., Conclusion: Campylobacter exposure is much higher than clinical infection rates, but risk factors are similar to those previously described.Seroincidence is a powerful measure to study Campylobacter epidemiology, and is preferred over other methods., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: In 2016, an increase in invasive Haemophilus influenzae serotype b (Hib) disease was reported in the Netherlands in children younger than 5 years, which coincided with the introduction of the hexavalent diphtheria, tetanus, and acellular pertussis-hepatitis B virus-inactivated polio virus/Hib vaccine (DTPa-HBV-IPV/Hib) from 2011 onwards. We aimed to estimate the effectiveness of the hexavalent vaccine to assess whether this increase could be explained by decreasing effectiveness., Methods: We did a case-control study in the Netherlands. We selected patients with a Hib infection (cases) by use of the surveillance records of the Netherlands Reference Laboratory for Bacterial Meningitis (Amsterdam). Cases with a Hib infection that began from Jan 1, 2003, to Dec 31, 2016, and who were younger than age 5 years were included. Ten controls from the national vaccination register (Praeventis) were selected for each case, matched by date of birth. Vaccination status was ascertained by use of Praeventis, which details the vaccination records of children living in the Netherlands. The last recorded vaccine dose was used to classify the child as having received the hexavalent DTPa-HBV-IPV/Hib vaccine or a pentavalent vaccine (which excludes the hepatitis B virus component) or another vaccine. We estimated the effectiveness of these vaccines by use of conditional logistic regression., Findings: We included 159 (94%) of 170 cases reported and 1590 matched controls, who had a median age of 1·5 years (IQR 0·8-2·9). The remaining 11 cases could not be cross-matched with vaccination records from Praeventis. 91 (57%) of 159 cases had been vaccinated, compared with 1408 (89%) of 1590 controls. The overall vaccine effectiveness was 92·8% (95% CI 88·7-95·4), with no differences between the year of disease onset (p=0·9670). There were no differences conferred by type of vaccine given: vaccine effectiveness of the pentavalent and other vaccines was 91·8% (95% CI 86·1-95·1) versus 94·0% (89·0-96·8) for the hexavalent vaccine (OR 0·72, 95% CI 0·36-1·45; p=0·3591). Vaccine effectiveness was highest in children aged 1-2 years at disease onset (97·1-99·0%) and was lowest in children aged 3-4 years at disease onset (60·7-82·3%; p=0·0008)., Interpretation: Our results support the current vaccination programme, since Hib vaccine effectiveness has not decreased over time or by the introduction of the hexavalent DTPa-HBV-IPV/Hib vaccine. Vaccine effectiveness was high but waned with age. Alternative explanations for the increase in Hib disease therefore need to be assessed., Funding: Dutch Ministry of Health, Welfare and Sports., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Migrants are overrepresented in the European HIV epidemic. We aimed to understand the barriers and facilitators to HIV testing and current treatment and healthcare needs of migrants living with HIV in Europe., Methods: A cross-sectional study was conducted in 57 HIV clinics in nine countries (Belgium, Germany, Greece, Italy, The Netherlands, Portugal, Spain, Switzerland and United Kingdom), July 2013 to July 2015. HIV-positive patients were eligible for inclusion if they were as follows: 18 years or older; foreign-born residents and diagnosed within five years of recruitment. Questionnaires were completed electronically in one of 15 languages and linked to clinical records. Primary outcomes were access to primary care and previous negative HIV test. Data were analysed using random effects logistic regression. Outcomes of interest are presented for women, heterosexual men and gay/bisexual men., Results: A total of 2093 respondents (658 women, 446 heterosexual men and 989 gay/bisexual men) were included. The prevalence of a previous negative HIV test was 46.7%, 43.4% and 82.0% for women, heterosexual and gay/bisexual men respectively. In multivariable analysis previous testing was positively associated with: receipt of post-migration antenatal care among women, permanent residency among heterosexual men and identifying as gay rather than bisexual among gay/bisexual men. Access to primary care was found to be high (>83%) in all groups and was strongly associated with country of residence. Late diagnosis was common for women and heterosexual men (60.8% and 67.1%, respectively) despite utilization of health services prior to diagnosis. Across all groups almost three-quarters of people on antiretrovirals had an HIV viral load <50 copies/mL., Conclusions: Migrants access healthcare in Europe and while many migrants had previously tested for HIV, that they went on to test positive at a later date suggests that opportunities for HIV prevention are being missed. Expansion of testing beyond sexual health and antenatal settings is still required and testing opportunities should be linked with combination prevention measures such as access to PrEP and treatment as prevention., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Objective: We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl., Design: Cohort study based on routinely collected data from the HIV-CAUSAL collaboration., Methods: For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics., Results: In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2)., Conclusion: Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.

Objective: To evaluate the in vivo relevance of the inhibitory effect of tenofovir on telomerase activity observed in vitro., Design: Cross-sectional study of HIV-infected patients with suppressed virological replication (HIV RNA <50 copies/mL for more than 1 year)., Methods: Telomere length in whole blood was measured by quantitative real-time polymerase chain reaction. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders., Results: 200 patients included, 72% men, median age 49 (IQR 45-54.5), 103 with exposure to a TDF containing antiretroviral treatment (ART) regimen (69.9% for more than 5 years) and 97 never exposed to a TDF containing ART regimen. In the multivariate analysis, significant predictors of shorter telomere length were older age (P = 0.008), parental age at birth (P = 0.038), white race (P = 0.048), and longer time of known HIV infection (10-20 and ≥20 years compared with <10 years, P = 0.003 and P = 0.056, respectively). There was no association between TDF exposure and telomere length after adjusting for possible confounding factors (age, parental age at birth, race, and time of HIV infection). Total time receiving ART and duration of treatment with nucleoside reverse transcriptase inhibitors were associated with shorter telomere length, but these associations were explained by time of known HIV infection., Conclusions: Our data do not suggest that telomerase activity inhibition caused by TDF in vitro leads to telomere shortening in peripheral blood of HIV-infected patients.

In vitro, tenofovir and abacavir induced a significant dose-dependent inhibition of telomerase activity at therapeutic concentrations in peripheral blood mononuclear cells of healthy subjects. Median inhibition of telomerase activity by tenofovir at 0.5 and 1 μM was 29% [Interquartile range (IQR) 29%-34%, P = 0.042] and 28% (IQR 28%-41%, P = 0.042), respectively. Abacavir inhibition was 12% (IQR 9%-13%, P = 0.043) at 3 μM and 14% (IQR 10%-29%, P = 0.043) at 10 μM. Tenofovir and abacavir did not change human telomerase reverse transcriptase (hTERT) levels or mRNA levels of other telomerase complex genes. Exposure to emtricitabine or darunavir did not affect telomerase activity, hTERT protein levels, or mRNA levels of telomerase/shelterin genes.

Immigrant populations, especially those from endemic countries, living in the European Union (EU) suffer a disproportionate burden of HIV, delayed diagnosis and poorer access to antiretroviral treatment. While International Organisations are developing recommendations aimed at increasing the uptake of HIV testing, the feasibility and real outcomes of these measures remain unexplored. The aim of this review was, firstly to identify the recommendations of the main International Organisations (IO) on HIV testing in immigrants. Secondly, to describe the challenges for implementing and expanding HIV testing and counselling interventions targeting immigrants by interviewing key informants. The importance of HIV testing in immigrants is discussed, along with the appropriateness of universal HIV testing approaches vs most at risk targeted approaches. Also addressed is, pre- and post-HIV test counselling characteristics and community initiatives suitable to reach this population and, finally the legal issues regarding access to treatment for illegal immigrants., (Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Public health surveillance is the systematic and continuous collection, analysis, dissemination and interpretation of health-related data for planning, implementation and evaluation of public health initiatives. Apart from the health system, social determinants of health include the circumstances in which people are born, grow up, live, work and age, and they go a long way to explaining health inequalities. A surveillance system of the social determinants of health requires a comprehensive and social overview of health. This paper analyses the importance of monitoring social determinants of health and health inequalities, and describes some relevant aspects concerning the implementation of surveillance during the data collection, compilation and analysis phases, as well as dissemination of information and evaluation of the surveillance system. It is important to have indicators from sources designed for this purpose, such as continuous records or periodic surveys, explicitly describing its limitations and strengths. The results should be published periodically in a communicative format that both enhances the public's ability to understand the problems that affect them, whilst at the same time empowering the population, with the ultimate goal of guiding health-related initiatives at different levels of intervention., (Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Migrants represent around one third of patients newly diagnosed with HIV in Spain and they constitute a population with higher vulnerability to its negative consequences due to the socio-cultural, economical, working, administrative and legal contexts. Migrants are diagnosed later, which worsens their individual prognosis and facilitates the maintenance of the HIV epidemic. In spite of the different barriers they experience to access healthcare in general, and HIV-related services in particular, access to antiretroviral treatment has been similar to that of the autochthonous population. However, benefits of treatment have been not, with women in general and men from Sub-Saharan Africa exhibiting the worse response to treatment. We need to proactively promote earlier diagnosis of HIV infection, the adoption of preventive measures to avoid new infections, and to deliver accessible, adapted and high-quality health-care., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Our objective was to describe the methodological limitations and recommendations identified by authors of original articles on immigration and health in Spain. A literature review was conducted of original articles published in Spanish or English between 1998 and 2012 combining keywords on immigration and health. A total of 311 articles were included; of these, 176 (56.6%) mentioned limitations, and 15 (4.8%) made recommendations. The most frequently mentioned limitations included the following: reduced sample sizes; internal validity and sample representativeness issues, with under- or overrepresentation of specific groups; problems of validity of the collected information and missing data mostly related to measurement tools; and absence of key variables for adjustment or stratification. Based on these results, a series of recommendations are proposed to minimise common limitations and advance the quality of scientific production on immigration and health in our setting., (Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.)

Background: Migrants are considered a key group at risk for HIV infection. This study describes the epidemiology of HIV and the distribution of late HIV presentation among migrants within the European Union/European Economic Area during 2007-2012., Methods: HIV cases reported to European Surveillance System (TESSy) were analyzed. Migrants were defined as people whose geographical origin was different than the reporting country. Multiple logistic regression was used to model late HIV presentation., Results: Overall, 156,817 HIV cases were reported, of which 60,446 (38%) were migrants. Of these, 53% were from Sub-Saharan Africa, 12% from Latin America, 9% from Western Europe, 7% from Central Europe, 5% from South and Southeast Asia, 4% from East Europe, 4% from Caribbean, and 3% from North Africa and Middle East. Male and female migrants from Sub-Saharan Africa and Latin America had higher odds of late HIV presentation than native men and women. Migrants accounted for 40% of all HIV notifications in 2007 versus 35% in 2012. HIV cases in women from Sub-Saharan Africa decreased from 3725 in 2007 to 2354 in 2012. The number of HIV cases from Latin America peaked in 2010 to decrease thereafter. HIV diagnoses in migrant men who have sex with men increased from 1927 in 2007 to 2459 in 2012., Conclusions: Migrants represent two-fifths of the HIV cases reported and had higher late HIV presentation. HIV epidemic in migrant populations in European Union/European Economic Area member states is changing, probably reflecting the global changes in the HIV pandemic, the impact of large-scale ART implementation, and migration fluctuations secondary to the economic crisis in Europe.

Background: Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL., Methods: We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders., Findings: Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9)., Interpretation: The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART., Funding: National Institutes of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience., Methods: We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes., Results: A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone., Conclusions: Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown., Methods: We prospectively included aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates., Results: Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95% confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P = .91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45 [6.3%]; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes., Conclusions: The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: The objective of this work is to study the impact of HAART at a population level and to identify socio-demographic factors that may affect it, which is essential for deciding interventions., Methods: An open, prospective cohort of HIV seroconverters recruited in the Centro Sanitario Sandoval (1986-2009), and followed up in collaboration with referral hospitals in the Comunidad Autónoma de Madrid. Cumulative incidence of AIDS and death was calculated by the multiple decrements method, and predictive Fine & Gray models were developed to identify associated factors. A calendar period (<1997; ≥ 1997) was introduced as a proxy of HAART availability., Results: A total of 479 HIV seroconverters were identified. Hazard Ratio (HR) for progression to AIDS was 0.215 (95% CI: 0.11-0.519; P<.01) for the period ≥ 1997. Risk increased with age at the time of seroconversion (for each year older HR=1.071; 95% CI: 1.038-1.105; P<.01), but only prior to 1997. In the following period, only a high educational level showed to be a protective factor (HR=0.982; 95% CI: 0.936-1.031; P=.06). HR for progression to death was 0.134 (95% CI: 0.052-0.346; P<.01) for the period after 1997, 0.383 (95% CI: 0.168-0.875; P=.02) in people with high educational level and 1.048 (95% CI: 1.014-1.084; P<.01) for each year increase in age at seroconversion, both latter effects being homogeneous throughout the two periods., Conclusion: HAART has had a great impact on the risk of progression to AIDS and death, but this benefit appears to be influenced by age at HIV infection and educational level of the patient, which highlights the importance of a global approach to case management and of the implementation of policies that address social inequities in health., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)