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The relative susceptibility of people with HIV (PWH) to SARS-CoV-2 infection is debated. Numerous studies have been published with apparently contradictory findings but comparisons are difficult because they have been conducted in populations with different characteristics (e.g., age, prevalence of co-morbidities), they have used different comparison groups (e.g., HIV-negative cohorts, COVID-19 hospitalized patients, general population), and because of challenges to measure the most important confounders. Here, we review the evidence regarding risk and severity of SARS-CoV-2 infection in PWH compared with persons without HIV. Articles originate largely from high-income settings where the majority of the PWH are on ART. There was early evidence supporting higher frequency of SARS-CoV-2 testing in PWH but no evidence that, in PWH on ART, HIV infection increases susceptibility to SARS-CoV-2 infection, once confounding by socio-economic characteristic is taken into account and in spite of higher SARS-CoV-2 testing intensity. Most publications identify increased COVID-19 severity in PWH compared with people without HIV from the general population or compared with COVID-19 hospitalized patients. The only study with an ideal comparison group, the VACS, which minimizes confounding by design, has not, to date, identified differences in COVID-19 disease severity by HIV. Publications consistently identify that COVID-19 severity in PWH is not homogeneous and increases with age and baseline comorbidities. Because PWH have a higher prevalence of comorbidities than people without HIV, examining their respective contribution to poor health outcomes is not straight forward as they could mediate some or all the effect HIV may have on COVID-19 outcomes.

International audience; Background: Global HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identified worldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015.Methods: We assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched the PubMed, Embase (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) databases for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data were collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses were done for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, CRD42017067164.Findings: Our global data collection yielded an HIV-1 molecular epidemiology database of 383 519 samples from 116 countries in 1990-2015. We found that the proportion of recombinants increased over time, both globally and in most regions, reaching 22·8% (7 978 517 of 34 921 639) of global HIV-1 infections in 2010-15. Both the proportion and the number of distinct CRFs detected increased over time to 16·7% and 57 CRFs in 2010-15. The global and regional distribution of HIV-1 recombinants was diverse and evolved over time, and we found large regional variation in the numbers (0-44 CRFs), types (58 distinct CRFs), and proportions (0-80·5%) of HIV-1 recombinants. Globally, CRF02_AG was the most prevalent recombinant, accounting for 33·9% (2 701 364 of 7 978 517) of all recombinant infections in 2010-15. URFs accounted for 26·7% (2 131 450 of 7 978 517), CRF01_AE for 23·0% (1 838 433), and other CRFs for 16·4% (1 307 270) of all recombinant infections in 2010-15. Although other CRFs accounted for small proportions of infections globally (

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.

Purpose of review The COVID-19 pandemic materialized in 2020, the year the international community had expected to meet the interim targets to end AIDS by 2030. Forty years into the HIV pandemic, the COVID-19 pandemic challenges the achievements made in HIV and may even reverse some of them. Recent findings This article provides an overview of the impact of COVID-19 on people with, and at risk of, HIV infection. It addresses where the global response to HIV was expected to be by 2020, analyzes the impact of COVID-19 on HIV-related outcomes and reviews the impact of HIV on COVID-19 related outcomes. Summary The COVID-19 pandemic has had a profound impact on the response to HIV infection through disruption of prevention, testing, and access to antiretroviral treatment, as well as on the management of long-term HIV and mental health. This negative impact has been unequal throughout the world and across populations and deepens inequities in health. HIV does not increase Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility once confounders are taken into account and inconsistencies are reported regarding its direct role on clinical severity. In post-COVID-19 scenarios, new models for HIV testing and care are likely to be consolidated. Monitoring responses needs high-quality epidemiological data and collaborative research.

Supplemental Digital Content is available in the text, Introduction: HIV cohort data from high-income European countries were compared with the UNAIDS Spectrum modelling parameters for these same countries to validate mortality rates and excess mortality estimates for people living with HIV (PLHIV) on antiretroviral therapy (ART). Methods: Data from 2000 to 2015 were analysed from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for Austria, Denmark, France, Italy, the Netherlands, Spain, and Switzerland. Flexible parametric models were used to compare all-cause mortality rates in the ART-CC and Spectrum. The percentage of AIDS-related deaths and excess mortality (both are the same within Spectrum) were compared, with excess mortality defined as that in excess of the general population mortality. Results: Analyses included 94 026 PLHIV with 585 784 person-years of follow-up, from which there were 5515 deaths. All-cause annual mortality rates in Spectrum for 2000–2003 were 0.0121, reducing to 0.0078 in 2012–2015, whilst the ART-CC's corresponding annual mortality rates were 0.0151 [95% confidence interval (95% CI): 0.0130–0.0171] reducing to 0.0049 (95% CI: 0.0039–0.0060). The percentage of AIDS-related deaths in Spectrum was 74.7% in 2000–2003, dropping to 43.6% in 2012–2015. In the ART-CC, AIDS-related mortality constitutes 45.3% (95% CI: 38.4–52.9%) of mortality in 2000–2003 and 26.7% (95% CI: 19–46%) between 2012 and 2015. Excess mortality in the ART-CC was broadly similar to the Spectrum estimates, dropping from 75.3% (95% CI: 60.3–95.2%) in 2000–2003 to 30.7% (95% CI: 25.5–63.7%) in 2012–2015. Conclusion: All-cause mortality assumptions for PLHIV on ART in high-income European settings should be adjusted in Spectrum to be higher in 2000–2003 and decline more quickly to levels currently captured for recent years.

The effectiveness of antiretroviral therapy and its increasing availability globally means that millions of people living with HIV now have a much longer life expectancy. However, people living with HIV have disproportionately high incidence of major comorbidities and reduced health-related quality of life. Health systems must respond to this situation by pioneering care and service delivery models that promote wellness rather than mere survival. In this Series paper, we review evidence about the emerging challenges of the care of people with HIV beyond viral suppression and identify four priority areas for action: integrating HIV services and non-HIV services, reducing HIV-related discrimination in health-care settings, identifying indicators to monitor health systems' progress toward new goals, and catalysing new forms of civil society engagement in the more broadly focused HIV response that is now needed worldwide. Furthermore, in the context of an increasing burden of chronic diseases, we must consider the shift that is underway in the HIV field in relation to burgeoning policy and programmatic efforts to promote healthy ageing.

Tenofovir has shown promising evidence of improving COVID-19 clinical outcomes in observational studies, still to be confirmed in clinical trials. Disease severity might be reduced under prophylaxis with the prodrug tenofovir disoproxil fumarate (TDF), while the protection seems to decrease, or even to lack, when using the alternative prodrug tenofovir alafenamide fumarate (TAF). Aiming to understand why TDF-prophylaxis might reduce COVID-19 severity upon infection we developed a multi-scale analysis framework combining in vitro susceptibility data, molecular docking, and within-host dynamics modeling, and using remdesivir–the only antiviral approved to date against COVID-19– as a point of reference.First, our docking model predicted that intracellularly active tenofovir diphosphate binds into the SARS-CoV-2 RNA polymerase in the same site as the antiviral remdesivir triphosphate, but presents lower binding energy, likely reducing the overall inhibition of viral replication and making the antiviral efficacy more susceptible to the drug intracellular concentration. Second, using data from in vitro viral cultures with plausible TDF therapeutic concentrations, we estimated that the drug can inhibit SARS-COV-2 replication at an efficacy ranging between 54-99% conditional to the viral cycle length. Third, assuming values approximating this range of inhibition for in vivo viral replication during human SARS-COV-2 infection, we found that prophylaxis with TDF with high penetration into viral target cells is capable of delaying viral replication, mitigating direct cell damage and allowing time for the host to mount the adaptive immunity. Last, we found that the potential antiviral effect can be substantially reduced when TDF is given after infection begins. Our work provides a potential mechanistic explanation of the observed clinical effect of TDF against SARS-CoV-2 infection. The proposed inference framework can help to optimize the evaluation of antiviral therapies for COVID-19, in particular those targeting the RNA dependent RNA polymerase.

BackgroundRecruitment into randomized trials of hydroxychloroquine (HCQ) for prevention of COVID-19 has been adversely affected by a widespread conviction that HCQ is not effective for prevention. In the absence of an updated systematic review, we conducted a meta-analysis of randomized trials that study the effectiveness of HCQ to prevent COVID-19.MethodsA search of PubMed and medRxiv with expert consultation found ten completed randomized trials: seven pre-exposure prophylaxis trials and three post-exposure prophylaxis trials. We obtained or calculated the risk ratio of COVID-19 diagnosis for assignment to HCQ versus no HCQ (either placebo or usual care) for each trial, and then pooled the risk ratio estimates.ResultsThe pooled risk ratio estimate of the pre-exposure prophylaxis trials was 0.72 (95% CI: 0.58-0.91) when using either a fixed effect or a standard random effects approach, and 0.72 (95% CI: 0.52-1.00) when using a conservative modification of the Hartung-Knapp random effects approach. The corresponding estimates for the post-exposure prophylaxis trials were 0.91 (95% CI: 0.71-1.16) and 0.91 (95% CI: 0.54-1.55). All trials found a similar rate of serious adverse effects in the HCQ and no HCQ groups.DiscussionA benefit of HCQ as prophylaxis for COVID-19 cannot be ruled out based on the available evidence from randomized trials. However, the “not statistically significant” findings from early prophylaxis trials were widely interpreted as definite evidence of lack of effectiveness of HCQ. This interpretation disrupted the timely completion of the remaining trials and thus the generation of precise estimates for pandemic management before the development of vaccines.

In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.

Summary Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86–1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95–1·22) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. Funding National Institutes of Health.

Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

People living with HIV (PLHIV) are more likely than the general population to develop AIDS‐defining malignancies (ADMs) and several non‐ADMs (NADMs). Information is lacking on survival outcomes and cause‐specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996–2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause‐specific mortality rates (MR) after diagnosis of specific cancers and compared 5‐year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006–2015: ADMs 102 (95% CI 92–113) per 1,000 years versus 88 (78–100), viral NADMs 134 (106–169) versus 111 (93–133) and nonviral NADMs 264 (232–300) versus 226 (206–248). Estimated 5‐year survival for PLHIV diagnosed with liver (29% [19–39%]), lung (18% [13–23%]) and cervical (75% [63–84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67–81%]). Among ART‐treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS., What's new? People with HIV live longer than they used to, thanks to advances in antiretroviral therapy. These improvements reduced the incidence of AIDS‐defining malignancies, such as Kaposi's sarcoma, but the increased life expectancy has led to more diagnoses of cancers not traditionally associated with HIV. Here, the authors studied cause‐specific mortality among people with HIV diagnosed with cancer. For those people, within 5 years after a cancer diagnosis, cause of death was more likely to be cancer than AIDS. Survival rates after diagnosis varied by cancer type, but were similar to rates among the general population.

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.

Objective: We aimed to estimate the proportion of postmigration HIV acquisition among HIV-positive migrants in Europe. Design: To reach HIV-positive migrants, we designed a cross-sectional study performed in HIV clinics. Methods: The study was conducted from July 2013 to July 2015 in 57 clinics (nine European countries), targeting individuals over 18 years diagnosed in the preceding 5 years and born abroad. Electronic questionnaires supplemented with clinical data were completed in any of 15 languages. Postmigration HIV acquisition was estimated through Bayesian approaches combining extensive information on migration and patients' characteristics. CD4+ cell counts and HIV-RNA trajectories from seroconversion were estimated by bivariate linear mixed models fitted to natural history data. Postmigration acquisition risk factors were investigated with weighted logistic regression. Results: Of 2009 participants, 46% were MSM and a third originated from sub-Saharan Africa and Latin America & Caribbean, respectively. Median time in host countries was 8 years. Postmigration HIV acquisition was 63% (95% confidence interval: 57-67%); 72% among MSM, 58 and 51% in heterosexual men and women, respectively. Postmigration HIV acquisition was 71% for Latin America and Caribbean migrants and 45% for people from sub-Saharan Africa. Factors associated with postmigration HIV acquisition among heterosexual women and MSM were age at migration, length of stay in host country and HIV diagnosis year and among heterosexual men, length of stay in host country and HIV diagnosis year. Conclusion: A substantial proportion of HIV-positive migrants living in Europe acquired HIV postmigration. This has important implications for European public health policies. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Purpose of review The purpose is to describe and understand the sociodemographic determinants of survival in people living with HIV within high-income countries in the context of the current recommendation of universal antiretroviral therapy for all HIV-infected persons, irrespective of their CD4 cell count. Recent findings Survival rates in people living with HIV have experienced remarkable increases in the last decade because of more efficacious and well tolerated treatments. Still, these improvements are unevenly distributed between regions across the world as well as within regions. HIV outcomes are heavily influenced by what are known as the 'social determinants' of health which have traditionally encompassed the gender, race/ethnicity, and socioeconomic axes. The evidence that these social determinants are now more important than before (more and earlier interventions are now available), has become stronger in the last 2 years. Summary Because antiretroviral therapy is now recommended for all HIV-infected persons, sociodemographic factors limiting access to testing, treatment, and retention in care will undoubtedly jeopardize the UNAIDS aspirational objective to end AIDS by 2030. Innovative interventions targeting individuals with social vulnerability are urgently needed to ensure that social inequalities do not continue to be linked with higher mortality.

AIMS To compare patients who acquired HIV infection through use of injected drugs (HIV-IDU) with patients who acquired HIV by sexual transmission (HIV-ST) in terms of late presentation (LP), delay in anti-retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS. DESIGN Prospective multi-centre cohort study of HIV-infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS). SETTING Thirty-one centres from the Spanish public health-care system. PARTICIPANTS A total of 9355 patients were included (1064 HIV-IDU and 8291 HIV-ST) during 2004-13. MEASUREMENTS We compared LP (defined as presentation for care with a CD4 cell count

This study performed a content analysis of the language of the Spanish judgements addressing the sexual transmission of HIV in order to determine its possible interrelationship with HIV-related stigma. All judgements and writs dictated by Spanish penal and civil jurisdictions between 1981 and December 2016 were obtained through a systematic search of the Spanish legal databases. The inclusion criterion was that the possible transmission of HIV was judged as an individual infraction, regardless of whether other infractions were involved. Twenty judgements were selected and analysed through direct content analysis assisted by the software MAXQDA 12. The majority of the cases (85%) were brought before the penal jurisdiction. Most of the judgements applied the crimes of bodily harm or grievous bodily harm (75%). Aspects closely related to the determinants of HIV-related stigma, such as the perception of HIV as a severe and easily transmitted infection, and attributions of responsibility and blame to people with HIV, were found in the judgements' reasoning. They were associated with outdated scientific and technical knowledge. Furthermore, some arguments found are repeated literally and successively in several judgments from different years, ignoring medical advances. Most plaintiffs were unaware of their sexual partner's HIV status. The scarce results found regarding the concealment of HIV status suggested that fear of stigma could be the reason thereof. The results suggested that training legal professionals in the epidemiological, clinical, and social aspects of HIV could influence stigma reduction, leading to a more objective consideration of the characteristics of this infection.

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.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.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.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: To analyse knowledge, attitudes and sexual practices on HIV/AIDS, and estimate HIV prevalence among residents of Sucre (Bolivia). Methodology: Population-based survey of residents aged 15-49 randomly selected during 2008/2009. Blood samples were collected on Whatman-filter paper and tested with enzyme-linked immunosorbent assay. Knowledge on HIV/AIDS, sexual risk practices and discriminatory attitudes against people living with HIV/AIDS (PLWHA) were modelled with multiple logistic regression. Results: Of 1499 subjects, 59% were women. All subjects were HIV-negative. Inadequate knowledge of HIV/AIDS transmission and prevention was observed in 67% and risk factors varied by gender (interaction p-value

INTRODUCTION: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. METHODS: We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. RESULTS: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). CONCLUSIONS: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival. We would like to thank the following cohorts for participating in this study; the AIDS Therapy Evaluation Project Netherlands (ATHENA); ANRS CO4 French Hospital Database on HIV (FHDH); ANRS CO3 Aquitaine Cohort, France; Departments of Internal Medicine at University of Cologne and Bonn, Germany; K€oln/Bonn Cohort, Germany; Italian Cohort of Antiretroviral-Na€ıve Patients (ICONA); CORIS, Spain; Proyecto para la Informatizaci on del Seguimiento Cl ınico-epidemiol ogico de la Infecci on por HIV y SIDA (PISCIS), Spain; Royal Free Hospital Cohort, London UK; Swiss HIV Cohort Study (SHCS); The Multicenter Study Group on EuroSIDA; Southern Alberta Clinic, Canada; HIV Atlanta Veterans affairs Cohort Study (HAVACS), USA; UAB 1917 Clinic Cohort, Birmingham, Alabama, USA; Veterans Ageing Cohort Study (VACS8),USA; Vanderbilt- Meharry and Tennessee Center for AIDS Research, Nashville, Tennessee, USA; University of Washington Harborview Medical Center, USA; € Osterreichische HIV-Kohortenstudie (OEHIVKOS), Austria; Danish HIV Cohort Study, Denmark; VACH, (Spain); and HAART Observational Medical Evaluation and Research (HOMER), British Columbia, Canada. We would also like to thank the ART-CC Steering group. Sí

Background Here, we aimed to evaluate regional differences in all-cause, AIDS- and non-AIDS-related mortality in HIV-positive men and women started on combination antiretroviral therapy (cART) in Europe, Canada and the US. Methods The ART Cohort Collaboration (ART-CC) combines 19 cohorts of individuals started on cART in Europe and North America (NA). We analysed patients infected via injecting drug use (IDU) or heterosexual sex using Cox proportional hazards models. Results A total of 32,443 European (45.9% women), 1,162 (32.5% women) Canadian and 2,721 (15.5% women) US patients were included. In Europe and NA, women were younger, more likely to have acquired HIV heterosexually, be AIDS-free and have higher CD4+ T-cell counts and lower HIV-1 RNA at baseline. European women had lower rates of all-cause (adjusted hazard ratio: 0.76; 95% CI 0.68, 0.84) and non-AIDS mortality (0.67; 0.57, 0.78) than men, but AIDS-mortality rates were similar (0.90; 0.75, 1.09). Women had lower mortality due to non-AIDS infections (0.6 versus 1.3 per 1,000 person-years), liver diseases (0.4 versus 1.7), non-AIDS malignancies (0.6 versus 2.0) and cardiovascular diseases (0.6 versus 1.0). Between-sex differences in all-cause mortality were larger in heterosexuals (0.70; 0.61, 0.80) than in IDU (0.88; 0.73, 1.05; interaction P-value =0.043). No sex differences in all-cause mortality were found in Canada (hazard ratio women 1.13; 0.82, 1.56) or US (hazard ratio women 1.12; 0.79, 1.58). Conclusions The increasing importance of non-AIDS mortality is leading to emergent sex differences among HIV-positive patients in Europe, as in the general population. Despite the better clinical characteristics at cART initiation, women in NA had similar mortality to men.

Background High numbers of human immunodeficiency virus type 1 (HIV-1) infections among people who inject drugs (PWID) have been diagnosed in Athens, Greece, since 2011. We aimed to trace the geographic origin of HIV-1 infection for migrants who inject drugs and to investigate whether transmissions occur more frequently among migrants than among Greek nationals. Methods Multiple cross-sectional studies were pooled to assemble all persons diagnosed with HIV-1 in Greece between 1 January 2011 and 31 October 2014. Phylogenetic analyses used maximum likelihood estimation. The hypothesis of ethnic compartmentalization was tested by reconstructing ancestral states of characters at the tips using the criterion of parsimony over a set of bootstrap trees. Results Of 2274 persons, 38.4% were PWID. Phylogenetic analyses showed the existence of 4 major PWID-specific local transmission networks (LTNs): CRF14_BG (437 [58.6%]), CRF35_AD (139 [18.6%]), subtype B (116 [15.6%]), and subtype A (54 [7.2%]). Of 184 non-Greek PWID, 78.3% had been infected within the PWID-LTNs. For 173 (94.3%), the origin of their infection was assumed to be in Greece (postmigration). For PWID infected within LTNs, transmissions for subtype A and CRF14_BG occurred more frequently among migrants than would be expected by chance (phyloethnic study). Conclusions Our analysis showed that the majority of infections among migrants occurred postmigration. The existence of significant transmission networking among migrants highlights that this population is a priority for HIV prevention. As molecular analysis can estimate the probable country of HIV infection, it can help to inform the design of public health strategies.

The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).

Knowledge of human papillomavirus (HPV) type distribution in populations at risk for anal cancer is needed. Here, we describe the anal HPV genotype distribution in a large Spanish cohort (Cohort of the Spanish HIV Research Network HPV [CoRIS-HPV]) of HIV-positive men who have sex with men (MSM) according to geographical origin, age, and cytological status. A cross-sectional analysis of baseline data from 1,439 HIV-infected MSM (2007 to 2012) was performed. Anal HPV genotyping was performed using the Linear Array HPV genotyping test. Descriptive analyses of subject characteristics, prevalences, and 95% confidence intervals (CI) were performed. The global prevalences of HPV, high-risk HPV (HR-HPV), and low-risk HPV (LR-HPV) types were 95.8%, 83.0%, and 72.7%, respectively. Among the HR-HPV types, HPV16 was the most common, followed by HPV59, -39, -51, -18, and -52. The prevalence of multiple HR-HPV infections was 58.5%. There were no differences in the crude analyses between Spanish and Latin-American MSM for most HPV types, and a peak in prevalence for most HPV types was seen in patients in their late thirties. Globally and by specific HPV groups, men with abnormal anal cytologies had a higher prevalence of infection than those with normal cytologies. This study has the largest number of HIV-positive MSM with HPV genotype data analyzed according to cytological status as far as we know. The information gained from this study can help with the design of anal cancer prevention strategies in HIV-positive patients.

Objectives The aim of the study was to assess the adequacy of initial antiretroviral therapy (ART), in terms of its timing and the choice of regimens, according to the Spanish national treatment guidelines [Spanish AIDS Study Group−National Plan for AIDS (GeSIDA-PNS) Guidelines] for treatment-naive HIV-infected patients. Methods A prospective cohort study of HIV-positive ART-naive subjects attending 27 centres in Spain from 2004 to 2010 was carried out. Regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Delayed start of treatment was defined as starting treatment later than 12 months after the patient had fulfilled the treatment criteria. Multivariate logistic and Cox regression analyses were performed. Results A total of 6225 ART-naive patients were included in the study. Of 4516 patients who started treatment, 91.5% started with a recommended or alternative treatment. The use of a nonrecommended treatment was associated with a CD4 count > 500 cells/μL [odds ratio (OR) 2.03; 95% confidence interval (CI) 1.14–3.59], hepatitis B (OR 2.23; 95% CI 1.50–3.33), treatment in a hospital with 5 log HIV-1 RNA copies/ml. The use of a nonrecommended regimen was significantly associated with mortality [hazard ratio (HR) 1.61; 95% CI 1.03–2.52; P = 0.035] and lack of virological response. Conclusions Compliance with the recommendations of Spanish national guidelines was high with respect to the timing and choice of initial ART. The use of nonrecommended regimens was associated with a lack of virological response and higher mortality.

The aim of our study was to determine the baseline prevalence of anal squamous intraepithelial lesions (SIL) and associated risk factors in HIV-infected men who have sex with men (MSM) in a Spanish ongoing multicenter cohort. CoRIS-HPV started in 2007, nested in the Spanish AIDS Research Network Cohort (CoRIS). Anal liquid cytology testing was performed. High-risk human papillomavirus (HR-HPV) infection was determined, and positive samples were genotyped. We analyzed all subjects up to April 2011. Multivariate logistic regression analyses were performed. A total of 551 subjects with baseline anal liquid cytologies were analyzed; 37.0% negative for intraepithelial lesion, 9.0% atypical squamous cells of uncertain significance (ASCUS), 41.0% low-grade SIL, 4.0% high-grade SIL and 9.0% inadequate. Prevalence of anal SIL (excluding ASCUS) in valid samples (n = 450) was 54.7% (95% confidence interval [CI] = 49.9–59.3). Globally HR-HPV prevalence was 81.7% (95% CI = 78.0–85.2). Multiple infections (≥2 HR-HPV genotypes) were documented in 77.7% (95% CI = 73.1–82.0). The only risk factor associated with anal SIL was the number of HR-HPV types; MSM with five or more HR-HPV genotypes had an odds ratio (OR) of anal SIL seven times greater (OR = 7.4; 95% CI = 2.8–19.6) than those with one HR-HPV genotype. No associations were found for age, educational level, smoking, geographical origin, CD4 T-cell count, antiretroviral treatment or number of sexual partners. The prevalence of anal SIL in young HIV-positive MSM is high, and the main risk factor is multiple infections with HR-HPV types.

Background: Clinical guidelines recommend immediate initiation of combined antiretroviral therapy for all HV-positive individuals. However, those guidelines are based on trials of relatively young participants. Methods: We included HIV-positive antiretroviral therapy-naive, AIDS-free individuals aged 50-70 years after 2004 in the HIV-CAUSAL Collaboration. We used the parametric g-formula to estimate the 5-year risk of all-cause and non-AIDS mortality under (1) immediate initiation at baseline and initiation at CD4 count, (2)

BACKGROUND: There is a heavy and disproportionate burden of human immunodeficiency virus (HIV) infection among migrant communities living in Europe. Despite this, the published evidence related to HIV testing, prevention, and treatment needs for migrants is sparse. OBJECTIVE: The aim of this study was to identify the factors associated with access to primary care and HIV testing among migrant groups living in Europe. METHODS: A Web-based survey (available in 14 languages) was open to all people aged 18 years and older, living outside their country of birth in the World Health Organization (WHO) European area. Community organizations in 9 countries promoted the survey to migrant groups, focusing on those at a higher risk of HIV (sub-Saharan Africans, Latin Americans, gay or bisexual men, and people who inject drugs). Multivariable analysis examined factors associated with access to primary care and previous history of an HIV test. RESULTS: In total, 559 women, 395 heterosexual men, and 674 gay or bisexual men were included in the analysis, and 68.1% (359/527) of women, 59.5% (220/371) of heterosexual men, and 89.6% (596/664) of gay or bisexual men had tested for HIV. Low perceived risk was the reason given for not testing by 62.3% (43/69) of gay or bisexual men and 83.3% (140/168) of women and heterosexual men who reported never having tested for HIV. Access to primary care was >60% in all groups. Access to primary care was strongly positively associated with living in Northern Europe compared with Southern Europe (women: adjusted odds ratio, aOR 34.56 [95% CI 11.58-101]; heterosexual men: aOR 6.93 [95% CI 2.49-19.35], and gay or bisexual men: aOR 2.53 [95% CI 1.23-5.19]), whereas those with temporary residency permits were less likely to have access to primary care (women: aOR 0.41 [95% CI 0.21-0.80] and heterosexual men: aOR 0.24 [95% CI 0.10-0.54] only). Women who had experience of forced sex (aOR 3.53 [95% CI 1.39-9.00]) or postmigration antenatal care (aOR 3.07 [95% CI 1.55-6.07]) were more likely to have tested for HIV as were heterosexual men who had access to primary care (aOR 3.13 [95% CI 1.58-6.13]) or reported "Good" health status (aOR 2.94 [95% CI 1.41-5.88]). CONCLUSIONS: Access to primary care is limited by structural determinants such as immigration and health care policy, which varies across Europe. For those migrants who can access primary care and other health services, missed opportunities for HIV testing remain a barrier to earlier testing and diagnosis for migrants in Europe. Clinicians should be aware of these potential structural barriers to HIV testing as well as low perception of HIV risk in migrant groups. This project received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under EuroCoord grant agreement number 260694. IF was funded by a Doctoral Research Fellowship from the National Institute for Health Research (NIHR). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research (NIHR), or the Department of Health. Additional funding was received from Gilead Sciences Europe Ltd; NIHR Clinical Research Network, the United Kingdom; Foundation for AIDS Research and Prevention in Spain (FISPSE) Project 361036/10; Consortium of Biomedical Research in Epidemiology and Public Health, Spain; Spanish HIV Research Network for Excellence (RD06/006 and RD12/0017/0018); Research and Development Fund, Public Health Service of Amsterdam; and the Swiss HIV Cohort Study (project #727), supported by the Swiss National Science Foundation (grant #148522) and by the Swiss HIV Cohort Study research foundation. No funder had any role in the study, writing of the manuscript, or decision to submit for publication. Sí

Background & Aims: Hepatitis C virus (HCV) incidence among HIV-positive men who have sex with men (MSM) has increased since 2000, although there are regional differences. We aimed to 1) estimate trends in HCV incidence among HIV-positive MSM, 2) assess the association between incidence and geographical region, age and HIV-related measurements and, 3) assess temporal changes from HIV seroconversion to HCV infection. Methods: Data was used from MSM with well-estimated dates of HIV seroconversion from the CASCADE Collaboration (19902014). Smoothly varying trends in HCV incidence over time were allowed, using restricted cubic splines. The association of calendar year, age, CD4 count (lagged), HIV RNA (lagged), geographical region and HIV infection stage (recent vs. chronic) with HCV incidence were assessed using Poisson regression. Results: Of 5,941 MSM, 337 acquired HCV during follow-up. HCV incidence significantly increased from 0.7/1,000 person-years in 1990 to 18/1,000 person-years in 2014. Recent calendar years, younger age, recent HIV infection and higher HIV RNA levels were significantly associated with HCV incidence, while CD4 count was not. Trends differed by geographical region; while incidence appeared to have stabilized in Western Europe and remained stable in Southern Europe, it continued to increase in Northern Europe in recent years. Time from HIV to HCV infection significantly decreased over time (p

Objective: We aimed to characterize non-AIDS events (NAEs) occurring in newly diagnosed HIV-infected patients in a contemporary cohort. Methods: The Cohort of the AIDS Research Network (CoRIS) is a prospective, multicenter cohort of HIV-infected adults antiretroviral naive at entry, established in 2004. We evaluated the incidence of and the mortality due to NAEs and AIDS events through October 2010. Poisson regression was used to investigate factors associated with a higher incidence of NAEs. Results: Overall, 5185 patients (13.306 person-years of follow-up), median age (interquartile range) 36 (29–43) years, participated in the study. A total of 86.5% patients had been diagnosed in 2004 or later. The incidence rate of NAEs was 28.93 per 1000 person-years [95% confidence interval (CI) 26.15–32.07], and of AIDS-defining events 25.23 per 1000 person-years (95% CI 22.60–28.16). The most common NAEs were psychiatric, hepatic, malignant, renal, and cardiovascular related. After adjustment, age, higher HIV-viral load, and lower CD4 cell count at cohort entry were associated with the occurrence of NAEs, whereas likelihood significantly decreased with sexual transmission and higher educational level. Additionally, antiretroviral therapy was inversely associated with the development of some NAEs, specifically of psychiatric [incidence rate ratio (95% CI) 0.54 (0.30–0.96)] and renal-related [incidence rate ratio (95% CI) 0.31 (0.13–0.72)] events. One hundred and seventy-three (3.33%) patients died during the study period. NAEs contributed to 28.9% of all deaths, with an incidence rate (95% CI) of 3.75 (2.84–4.94) per 1000 person-years. Conclusion: In patients newly diagnosed with HIV infection, NAEs are a significant cause of morbidity and mortality. Our results suggest a protective effect of antiretroviral therapy in the occurrence of NAEs, in particular of psychiatric and renal-related events. 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27:181–189

Background: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual’s time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy). Methods: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting. Results: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death. Conclusions: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.

BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV-related discrimination. We propose adding a 'fourth 90' to the testing and treatment target: ensure that 90 % of people with viral load suppression have good health-related quality of life. The new target would expand the continuum-of-services paradigm beyond the existing endpoint of viral suppression. Good health-related quality of life for PLHIV entails attention to two domains: comorbidities and self-perceived quality of life. CONCLUSIONS: Health systems everywhere need to become more integrated and more people-centered to successfully meet the needs of virally suppressed PLHIV. By doing so, these systems can better meet the needs of all of their constituents - regardless of HIV status - in an era when many populations worldwide are living much longer with multiple comorbidities.

Few population-based studies have assessed awareness of hepatitis C virus (HCV) seropositivity and chronic infection. We report awareness of HCV seropositivity and chronic infection and correlates of awareness in a multi-city (Bronx, Miami, Chicago, and San Diego) community-dwelling population sample of United States (US) Hispanics/Latinos recruited during 2008-2011. Included were 260 HCV-seropositive participants, among whom 190 had chronic HCV. Among those with chronic HCV, 46 % had been told by a doctor that they had liver disease and 32 % had been told that they had HCV-related liver disease. Among those with chronic HCV who also lacked health insurance (37 % of those with chronic HCV), only 8 % had been told that they had HCV-related liver disease. As compared with the uninsured, those with insurance were over five times more likely to be aware of having HCV-related liver disease (44 %). Sex, age, education, city of residence, and birthplace were not associated with HCV awareness. Less than half of Hispanics/Latinos were aware of their HCV chronic infection. Lack of health insurance may be an important barrier to HCV awareness in this population.

BACKGROUND The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged

Background: Migrants form a substantial proportion of the population affected by the human immunodeficiency virus (HIV) epidemic in Europe, yet HIV prevention for this population is hindered by poor understanding of access to care and of postmigration transmission dynamics. Objective: We present the design and methods of the advancing Migrant Access to health Services in Europe (aMASE) study, the first European cross-cultural study focused on multiple migrant populations. It aims to identify the structural, cultural, and financial barriers to HIV prevention, diagnosis, and treatment and to determine the likely country of HIV acquisition in HIV-positive migrant populations. Methods: We delivered 2 cross-sectional electronic surveys across 10 countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Switzerland, and United Kingdom). A clinic survey aimed to recruit up to 2000 HIV-positive patients from 57 HIV clinics in 9 countries. A unique study number linked anonymized questionnaire data to clinical records data (viral loads, CD4 cell counts, viral clades, etc). This questionnaire was developed by expert panel consensus and cognitively tested, and a pilot study was carried out in 2 countries. A Web-based community survey (n=1000) reached those living with HIV but not currently accessing HIV clinics, as well as HIV-negative migrants. It was developed in close collaboration with a community advisory group (CAG) made up of representatives from community organizations in 9 of the participating countries. The CAG played a key role in data collection by promoting the survey to higher-risk migrant groups (sub-Saharan Africans, Latin Americans, men who have sex with men, and people who inject drugs). The questionnaires have considerable content overlap, allowing for comparison. Questions cover ethnicity, migration, immigration status, HIV testing and treatment, health-seeking behavior, sexual risk, and drug use. The electronic questionnaires, which were available in 15 languages, allowed for complex routing, preventing respondents from answering irrelevant questions. Results: In total, we recruited 2249 participants from 57 HIV clinics as part of the clinic survey and retrieved 1637 complete responses as part of the community survey. Conclusions: The findings will provide much-needed information for improving HIV prevention interventions and access to services for migrant communities. [JMIR Res Protoc 2016;5(2):e74]

OBJECTIVE: We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients. METHODS: We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement. RESULTS: 54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23-4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log10 increase, 2.05 [0.91-4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log10 increase, 1.39 (1.01-1.91), P = 0.043; and OR (95% CI) per 1 log10 increase, 1.46 (1.07-1.99), P = 0.014, respectively, when adjustment included F2-IsoPs and MDA. CONCLUSION: Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation. This work has been (partially) funded by the RD12/0017/0023 project as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), FIS (PI08/893), FIS (PI13/02256), FISABIO UGP-14-197, and Contrato de Intensificación de la Actividad Investigadora INT 14/00207. The HIV Biobank, integrated in the RIS, is also supported by the ISCIII (RD06/0006/0035) and FIPSE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

Background Few data exist on tuberculosis (TB) incidence according to time from HIV seroconversion in high-income countries and whether rates following initiation of a combination of antiretroviral treatments (cARTs) differ from those soon after seroconversion. Methods Data on individuals with well estimated dates of HIV seroconversion were used to analyse post-seroconversion TB rates, ending at the earliest of 1 January 1997, death or last clinic visit. TB rates were also estimated following cART initiation, ending at the earliest of death or last clinic visit. Poisson models were used to examine the effect of current and past level of immunosuppression on TB risk after cART initiation. Results Of 19 815 individuals at risk during 1982–1996, TB incidence increased from 5.89/1000 person-years (PY) (95% CI 3.77 to 8.76) in the first year after seroconversion to 10.56 (4.83 to 20.04, p=0.01) at 10 years. Among 11 178 TB-free individuals initiating cART, the TB rate in the first year after cART initiation was 4.23/1000 PY (3.07 to 5.71) and dropped thereafter, remaining constant from year 2 onwards averaging at 1.64/1000 PY (1.29 to 2.05). Current CD4 count was inversely associated with TB rates, while nadir CD4 count was not associated with TB rates after adjustment for current CD4 count, HIV-RNA at cART initiation. Conclusions TB risk increases with duration of HIV infection in the absence of cART. Following cART initiation, TB incidence rates were lower than levels immediately following seroconversion. Implementation of current recommendations to prevent TB in early HIV infection could be beneficial.

Resumen Introduccion El objetivo de este trabajo es estudiar el impacto poblacional del TARGA e identificar los factores sociodemograficos que lo modifican, lo que resulta fundamental para orientar las intervenciones. Metodos Cohorte abierta y prospectiva de seroconvertores al VIH reclutados en el Centro Sanitario Sandoval (1986-2009) y seguidos en colaboracion con hospitales de referencia de la Comunidad de Madrid. Se calculo la incidencia acumulada de sida y muerte mediante decrementos multiples y se identificaron factores asociados mediante modelos predictivos de Fine & Gray. El periodo calendario ( Resultados Se identificaron 479 seroconvertores. El Hazard Ratio (HR) de progresion a sida fue de 0,215 (IC: 0,11-0,519; p Conclusion La introduccion del TARGA ha tenido gran impacto en el riesgo de progresion a sida y a muerte, pero este se ve influido por la edad de infeccion y por el nivel educativo, lo que senala la importancia de un abordaje global del paciente, y de implementar politicas que disminuyan las desigualdades sociales en salud.

BACKGROUND We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART). METHODS Data from HIV seroconverter cohorts in Europe, Australia and Canada (CASCADE) was used; GO was classified as: western countries (WE), North Africa and Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), and Asia (ASIA). Differences by GO were assessed using Cox models. Administrative censoring date was 30 June 2008. RESULTS Of 16 941 seroconverters, 15 548 were from WE, 158 NAME, 762 SSA, 349 LA, and 124 ASIA. We found no differences by GO in risks of AIDS (P = .99) and death (P = .12), although seroconverters from NAME (adjusted hazard ratio [aHR]: 0.57; 95% CI: 0.33-.94) and SSA (aHR: 0.74; 95% CI: 0.50-1.10) appeared to have lower mortality than WE. Chances of initiating cART differed by GO (P

Background. Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD4+ cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm(3) in the United States and from 200 to 350 cells/mm(3) in mid- and low-income countries. Robust data of time from HIV seroconversion to CD4+ cell counts of 200, 350, and 500 cells/mm(3) are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD4+ cell count initiation threshold. Methods. Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV seroconversion, we fitted mixed models on the square root of CD4+ cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age >16 years), we predicted time between seroconversion and CD4+ cell count

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

This paper provides an overview of the main statistical methods used in the analysis of data from cohort studies and presents a detailed description of the way these methods are applied in HIV/AIDS research. First, we describe methods for analyzing events in person-time data. Second, we present survival methods for the analysis of time-to-event data. In this context, we illustrate the application of these methods to describe the AIDS incubation period and survival from HIV seroconversion, to determine the factors and biological markers associated with disease progression, and to evaluate effectiveness of therapy. The review ends by illustrating the statistical methods used for the analysis of markers measured repeatedly over time.

In this paper, we provide a definition of cohort studies and reviews the main types of cohort studies used in the context of HIV infection. We discuss how the main sources of selection biases in cohort studies are those derived from the lack of observation of the event that determines the origin and/or of the event of interest due to losses to follow-up or development of a competing event, and how this bias must be appropriately taken into account following specific epidemiological methods. Although cohort studies play an essential role in the study of HIV infection, they are logistically complex and require considerable resources. Therefore, strategic planning on the quality and quantity of the information collected must always be accompanied by a resource allocation plan.

Resumen Fundamento y objetivo Describir las caracteristicas de pacientes adultos con infeccion por el virus de la inmunodeficiencia humana (VIH) segun su edad al momento de la inclusion en la Cohorte de la Red de Investigacion en Sida (CoRIS). Pacientes y metodos Analisis de una cohorte abierta, prospectiva, multicentrica de adultos con infeccion por el VIH sin tratamiento antirretroviral previo, atendidos por primera vez entre enero de 2004 y noviembre de 2008, en 28 hospitales espanoles (CoRIS). Se analizaron sus caracteristicas en la primera visita y la distribucion de las enfermedades definitorias de sida (EDS) a lo largo de la vida, segun la edad al momento de la inclusion. El retraso diagnostico se definio como pacientes con diagnostico de sida o cifra de CD4+ inferior a 200 cel/μl durante el ano posterior al diagnostico de la infeccion por el VIH. Resultados Participaron 4.418 personas; el 30,4% con 30 anos o menos, el 60,6% de entre 31 y 50 anos y el 8,9% de mayores de 50 anos. El 31,6% de los pacientes eran inmigrantes (el 44,1% entre los jovenes), el 79,6% correspondia a transmision sexual y el 15,2% tenia diagnostico de sida en la primera visita (el 28,1% entre los mayores de 50 anos). El 34,6% de los pacientes tenia retraso diagnostico (el 53,3% en los mayores de 50 anos). La distribucion de las EDS vario con la edad: las tuberculosis son mas frecuentes en jovenes y la neumonia por Pneumocystis jiroveci , la leucoencefalopatia multifocal progresiva, la encefalopatia por VIH, la neumonia recurrente y el linfoma cerebral primario son mas frecuentes en los mayores. Conclusiones Las caracteristicas inmunologicas y las EDS varian con la edad. El porcentaje de personas con retraso diagnostico es inaceptablemente alto, lo que indica que deben disenarse intervenciones dirigidas a efectuar un diagnostico mas precoz.

INTRODUCTION Since the advent of HAART, liver-related mortality has become the leading cause of non-AIDS deaths in HIV-infected patients in western countries, complications of end-stage liver disease due to chronic hepatitis B, chronic hepatitis C or both being mainly responsible. METHOD The incidence and predictors of mortality were examined in HIV-infected patients with compensated liver cirrhosis. The accuracy of three different methods (elastometry, Child-Pugh and Model for End-Stage Liver Disease scores) to predict mortality was further examined. Cirrhosis was defined for hepatic elastometry values above 14.5 kPa. RESULTS A total of 194 (11.4%) out of 1706 HIV-positive individuals were cirrhotic and were prospectively followed since October 2004 until December 2008. Overall, 89% of cirrhotic individuals had chronic hepatitis C, 10.3% chronic hepatitis B, 4.6% hepatitis delta and 4.1% liver disease of other causes or unknown cause. The overall mortality rate was 5.8 deaths per 100 patient-years. Multivariate analyses showed that age of at least 50 years (hazard ratio 4.76, 95% confidence interval 1.66-13.59, P = 0.004), CD4 cell counts below 200 cells/microl (hazard ratio 3.01, 95% confidence interval 1.26-7.23, P = 0.03) and detectable plasma HIV-RNA (hazard ratio 3.97, 95% CI, 1.53-10.27, P = 0.005) were associated with mortality. A baseline Model for End-stage Liver Disease score of at least 11 (P = 0.03) and hepatic elastometry values above 28.75 kPa (P = 0.001) were independent predictors of mortality. CONCLUSION The death rate in HIV-infected patients with compensated liver cirrhosis in the HAART era is 5.8% yearly, higher than mortality previously reported for either HIV-uninfected individuals with cirrhosis or noncirrhotic HIV-positive patients. Factors associated with mortality were older age, low CD4 cell counts and detectable plasma HIV-RNA. Both Model for End-Stage Liver Disease and especially hepatic elastometry accurately predicted mortality in this population.

The prevalence of injection drug use decreased from 67.3% in 1997 to 14.5% in 2006 among Spanish patients infected with human immunodeficiency virus (HIV). A parallel decrease in the prevalence of coinfection with hepatitis C virus was observed, from 73.8% in 1997 to 19.8% in 2006. This steady decrease in the prevalence of coinfection among Spanish patients was caused by a change in transmission routes of HIV infection.

OBJECTIVES: To compare immunological, virological and clinical outcomes in persons initiating combination antiretroviral therapy (cART of different durations within 6 months of seroconversion (early treated) with those who deferred therapy (deferred group). DESIGN: CD4 cell and HIV-RNA measurements for 'early treated' individuals following treatment cessation were compared with the corresponding ART-free period for the 'deferred' group using piecewise linear mixed models. Individuals identified during primary HIV infection were included if they seroconverted from 1st January 1996 and were at least 15 years of age at seroconversion. Those with at least 2 CD4 less than 350 cells/microl or AIDS within the first 6 months following seroconversion were excluded. RESULTS: Of 348 'early treated' patients, 147 stopped cART following treatment for at least 6 (n = 38), more than 6-12 (n = 40) or more than 12 months (n = 69). CD4 cell loss was steeper for the first 6 months following cART cessation, but subsequent loss rate was similar to the 'deferred' group (n = 675, P = 0.26). Although those treated for more than 12 months appeared to maintain higher CD4 cell counts following cART cessation, those treated for 12 months or less had CD4 cell counts 6 months after cessation comparable to those in the 'deferred' group. There was no difference in HIV-RNA set points between the 'early' and 'deferred' groups (P = 0.57). AIDS rates were similar but death rates, mainly due to non-AIDS causes, were higher in the 'deferred' group (P = 0.05). CONCLUSION: Transient cART, initiated within 6 months of seroconversion, seems to have no effect on viral load set point and limited beneficial effect on CD4 cell levels in individuals treated for more than 12 months. Its long-term effects remain inconclusive and need further investigation

Contains fulltext : 70499.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naive patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between January 2000 and December 2005. SETTING: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. STUDY PARTICIPANTS: A total of 13 546 antiretroviral-naive HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). RESULTS: Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). CONCLUSION: Among antiretroviral-naive patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.