Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n=41) vs. planned treatment interruption (PTI, n=47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale ( 6517 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Results: Characteristics were similar between arms with a median age of 12.6 years, CD4 + of 830 cells/\u3bcl and HIV RNA of 1.7 log 10 copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P=0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. Conclusion: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial

Epidemiological characteristics and access to end-stage liver disease care for HIV-positive patients with HCV and/or HBV coinfections in Central/Eastern European and neighboring countries – data from the ECEE network

OBJECTIVES: There is currently an urgent need to harmonize hepatitis standards of care for HIV-positive patients across Europe. The HIV epidemic in Central and Eastern Europe has often been driven by injecting drug use, therefore a higher rate of co-infection with HCV and HBV is expected in this region. We have investigated the epidemiological prevalence and treatment availability for end-stage liver disease in HIV/HCV/HBV coinfections in countries represented in the ECEE Network Group. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care regarding HIV infection in the region. Information about HIV/HCV/HBV co-infections and the availability for end-stage liver disease treatment for HIV-positive patients were collected through on-line surveys. The respondents were ECEE members from 16 countries of the region. The information on co-infection prevalence was sourced from WHO, national HIV programmes, articles published in international journals, single clinic reports, and personal information in ten of the participating countries (62.5%). RESULTS: The HIV/HCV co-infection rate was from 3% to 99%. The range of reported of HIV/HBV coinfection percentages was 2.3% to 40%. HIV/HCV/HBV co-infection ranged from 0% to 9%. Regarding treatment for end-stage liver disease, liver transplantation was an available option for HIV-positive patients in only three countries (19%). CONCLUSION: Our findings revealed only a limited number of treatment options for the end-stage liver disease in HIV-positive patients for the vast majority of Central and Eastern European countries. There are gaps in epidemiological surveillance in this region. It appears there are many differences in the number of co-infected patients among Central and Eastern European and neighboring countries, but there is no unification of information sources

Enhanced HIV-1 surveillance using molecular epidemiology to study and monitor HIV-1 outbreaks among intravenous drug users (IDUs) in Athens and Bucharest

Background: A significant increase in HIV-1 diagnoses was reported among Injecting Drug Users (IDUs) in the Athens (17-fold) and Bucharest (9-fold) metropolitan areas starting 2011. Methods: Molecular analyses were conducted on HIV-1 sequences from IDUs comprising 51% and 20% of the diagnosed cases among IDUs during 2011-2013 for Greece and Romania, respectively. Phylodynamic analyses were performed using the newly developed birth-death serial skyline model which allows estimating of important epidemiological parameters, as implemented in BEAST programme. Results: Most infections (>90%) occurred within four and three IDU local transmission networks in Athens and Bucharest, respectively. For all Romanian clusters, the viral strains originated from local circulating strains, whereas in Athens, the local strains seeded only two of the four sub-outbreaks. Birth-death skyline plots suggest a more explosive nature for sub-outbreaks in Bucharest than in Athens. In Athens, two sub-outbreaks had been controlled (Re< 1.0) by 2013 and two appeared to be endemic (Re~ 1). In Bucharest one outbreak continued to expand (Re> 1.0) and two had been controlled (Re< 1.0). The lead times were shorter for the outbreak in Athens than in Bucharest. Conclusions: Enhanced molecular surveillance proved useful to gain information about the origin, causal pathways, dispersal patterns and transmission dynamics of the outbreaks that can be useful in a public health setting. © 2015 Elsevier B.V

Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group

Objectives: Gender-related factors can influence management decisions, treatment outcomes and the overall long-term wellbeing of people living with HIV (PLWH). The Women Against Viruses in Europe (WAVE) Working Group was established to promote the health and wellbeing of women living with HIV (WLWH). WAVE is part of the European AIDS Clinical Society (EACS) and organizes annual workshops to discuss different issues in the management of WLWH. Methods: In 2016, 34 WAVE members including community representatives, HIV clinicians and researchers met to discuss standards of care for WLWH and to review current guidelines. Participants focused on three different themes: (1) access to and engagement and retention in care; (2) monitoring of women on antiretroviral therapy and management of comorbidities; and (3) review of EACS treatment guidelines. Results: Five priority areas for optimizing the care of WLWH were identified: (1) psychosocial aspects of HIV diagnosis and care; (2) mental health and wellbeing; (3) pharmacokinetics, toxicity and tolerability of antiretroviral therapy; (4) coinfections and comorbidities; and (5) sexual and reproductive health. WAVE recommendations are provided for each of these areas, and gaps in knowledge and needs for changes in currently existing standards are discussed. Conclusions: This position statement provides an overview of the key recommendations to optimize the care of WLWH that emerged during the 2016 WAVE workshop

Immunisation practices in centres caring for children with perinatally acquired HIV: A call for harmonisation

Background Current national immunisation schedules differ between countries in terms of vaccine formulation, timing of vaccinations and immunisation programme funding and co-ordination. As a result, some HIV infected paediatric population may be left susceptible to vaccine preventable infections. Vaccines used in healthy population should be subjected to high quality ethical research and be explicitly validated for use in children with special vaccination needs such as those infected with HIV. This survey was completed to assess current vaccination practices and attitudes toward vaccination among pediatricians who care for vertically HIV infected children. Methods An online questionnaire was completed by 46 experts in paediatric HIV-infection from the Paediatric European Network for Treatment of AIDS (PENTA). Data were collected between November 2013 and March 2014. Results 46 units looking after 2465 patients completed the questionnaire. The majority of units (67%) reported that common childhood immunisation were administered by the family doctor or local health services rather than in the HIV specialist centre. Vaccination histories were mostly incomplete and difficult to obtain for 40% of the studied population. Concerns were reported regarding the use of live attenuated vaccines, such as varicella and rotavirus, and these were less frequently recommended (61% and 28% of the units respectively). Monitoring of vaccine responses was employed in a minority of centres (41%). A range of different assays were used resulting in diverse units of measurement and proposed correlates of protection. Conclusion Vaccination practices for perinatally HIV-infected children vary a great deal between countries. Efforts should be made to improve communication and documentation of vaccinations in healthcare settings and to harmonise recommendations relating to additional vaccines for HIV infected children and the use of laboratory assays to guide immunisation. This will ultimately improve coverage and vaccine induced immunity in this vulnerable patient group

The immunological and virological consequences of planned treatment interruptions in children with HIV infection

Contains fulltext : 126098.pdf (publisher's version ) (Open Access)OBJECTIVES: To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV. DESIGN: This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children. METHODS: HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks. RESULTS: In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naive and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA. CONCLUSIONS: PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naive CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART

Potential adjustment methodology for missing data and reporting delay in the HIV surveillance system, European Union/European Economic Area, 2015

Accurate case-based surveillance data remain the key data source for estimating HIV burden and monitoring prevention efforts in Europe. We carried out a literature review and exploratory analysis of surveillance data regarding two crucial issues affecting European surveillance for HIV: missing data and reporting delay. Initial screening showed substantial variability of these data issues, both in time and across countries. In terms of missing data, the CD4+ cell count is the most problematic variable because of the high proportion of missing values. In 20 of 31 countries of the European Union/European Economic Area (EU/EEA), CD4+ counts are systematically missing for all or some years. One of the key challenges related to reporting delays is that countries undertake specific one-off actions in effort to capture previously unreported cases, and that these cases are subsequently reported with excessive delays. Slightly different underlying assumptions and effectively different models may be required for individual countries to adjust for missing data and reporting delays. However, using a similar methodology is recommended to foster harmonisation and to improve the accuracy and usability of HIV surveillance data at national and EU/EEA levels. © The authors, 2018