Browsing by Subject "HIV"

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  • Zusinaite, Eva; Ianevski, Aleksandr; Niukkanen, Diana; Poranen, Minna M.; Bjoras, Magnar; Afset, Jan Egil; Tenson, Tanel; Velagapudi, Vidya; Merits, Andres; Kainov, Denis E. (2018)
    There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can only be revealed after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which may be associated with potential side effects of these therapeutics. The current approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by mRNA, cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.
  • Kamara, David A.; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A.; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D.; Smith, Colette J.; DAD Study Grp; Ristola, Matti A (2014)
  • BEEHIVE Collaboration; Wymant, Chris; Blanquart, Francois; Golubchik, Tanya; Gall, Astrid; Bakker, Margreet; Bezemer, Daniela; Croucher, Nicholas J.; Hall, Matthew; Hillebregt, Mariska; Ong, Swee Hoe; Ratmann, Oliver; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Fransen, Katrien; Gourlay, Annabelle; Grabowski, M. Kate; Gunsenheimer-Bartmeyer, Barbara; Gunthard, Huldrych F.; Kivelä, Pia; Kouyos, Roger; Laeyendecker, Oliver; Liitsola, Kirsi; Meyer, Laurence; Porter, Kholoud; Ristola, Matti; van Sighem, Ard; Berkhout, Ben; Cornelissen, Marion; Kellam, Paul; Reiss, Peter; Fraser, Christophe (2018)
    Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of large between-and within-host diversity, including frequent indels, may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to pre-process reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with the user's choice of existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We used shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read whole-genome data produced with the Illumina platform, for sixty-five existing publicly available samples and fifty new samples. We show the systematic superiority of mapping to shiver's constructed reference compared with mapping the same reads to the closest of 3,249 real references: median values of 13 bases called differently and more accurately, 0 bases called differently and less accurately, and 205 bases of missing sequence recovered. We also successfully applied shiver to whole-genome samples of Hepatitis C Virus and Respiratory Syncytial Virus. shiver is publicly available from https://github.com/ChrisHIV/shiver.
  • Amele, S; Peters, L; Rodger, A; Lundgren, J; Rockstroh, J; Matulionyte, R; Leen, C; Jablonowska, E; Ostergaard, L; Bhagani, S; Sarcletti, M; Clarke, A; Falconer, K; Wandeler, G; Domingo, P; Maltez, F; Zaccarelli, M; Chkhartisvili, N; Szlavik, J; Stephan, C; Fonquernie, L; Aho, I; Mocroft, A; Group, ES (2021)
    Objectives: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe. Methods: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with >= 12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result >= 12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. Results: 1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir +/- ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir +/- RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir +/- RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin. Conclusions: Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.
  • Holmberg, Ville; Soini, Hanna; Kivelä, Pia; Ollgren, Jukka; Ristola, Matti (2019)
    Background: Tuberculosis (TB) is a major cause of death in HIV patients worldwide. Here we describe the epidemiology and outcome of HIV-TB co-infections in a high-income country with low TB incidence and integrated HIV and TB therapy according to European guidelines. Methods: This study was based on the HIV cohort of the Helsinki University Hospital which includes all HIV patients in the Helsinki region with a population of 1.5 million. Totally, 1939 HIV-positives who have been under follow-up between 1998 and 2015 were included. Results: TB was diagnosed in 53 (2.7%) of the HIV-patients. The TB incidence rate was higher in injecting drug users (IRR 3.15; 95% CI 1.33-7.52) and heterosexuals (IRR 3.46; 95% CI 1.64-7.29) compared to men having sex with men. The incidence rate was also higher in those born in Sub-Saharan Africa (IRR 3.53; 95% CI 1.78-7.03) compared to those born in Finland. There was a significant reduction in the total TB incidence rate of 59% per 6-year period between 1998 and 2015 (p <0.001). In injecting drug users there was a reduction in incidence rate from 1182 to 88 per 100,000 (p <0.001) and in people born in Sub-Saharan Africa from 2017 to 195 per 100,000 (p <0.001). Among the 53 HIV-TB co-infected cases, one female and 15 males died during follow up. HIV was the primary cause of death in five patients but none of the deaths were caused by TB. Conclusion: The incidence rate of tuberculosis among HIV-positives in Finland has been declining between 1998 and 2015. Among injecting drug users, the reduction is probably explained by harm reduction interventions and care in comprehensive care centers in Helsinki. The increased coverage of antiretroviral therapy is probably another main reason for the decline in TB incidence rates. Despite good treatment results for both HIV and TB, the all-cause mortality among Finnish males with HIV-TB was high, and common causes of death were intoxications and suicides.
  • Holmberg, Ville; Soini, Hanna; Kivelä, Pia; Ollgren, Jukka; Ristola, Matti (BioMed Central, 2019)
    Abstract Background Tuberculosis (TB) is a major cause of death in HIV patients worldwide. Here we describe the epidemiology and outcome of HIV-TB co-infections in a high-income country with low TB incidence and integrated HIV and TB therapy according to European guidelines. Methods This study was based on the HIV cohort of the Helsinki University Hospital which includes all HIV patients in the Helsinki region with a population of 1.5 million. Totally, 1939 HIV-positives who have been under follow-up between 1998 and 2015 were included. Results TB was diagnosed in 53 (2.7%) of the HIV-patients. The TB incidence rate was higher in injecting drug users (IRR 3.15; 95% CI 1.33–7.52) and heterosexuals (IRR 3.46; 95% CI 1.64–7.29) compared to men having sex with men. The incidence rate was also higher in those born in Sub-Saharan Africa (IRR 3.53; 95% CI 1.78–7.03) compared to those born in Finland. There was a significant reduction in the total TB incidence rate of 59% per 6-year period between 1998 and 2015 (p < 0.001). In injecting drug users there was a reduction in incidence rate from 1182 to 88 per 100,000 (p < 0.001) and in people born in Sub-Saharan Africa from 2017 to 195 per 100,000 (p < 0.001). Among the 53 HIV-TB co-infected cases, one female and 15 males died during follow up. HIV was the primary cause of death in five patients but none of the deaths were caused by TB. Conclusion The incidence rate of tuberculosis among HIV-positives in Finland has been declining between 1998 and 2015. Among injecting drug users, the reduction is probably explained by harm reduction interventions and care in comprehensive care centers in Helsinki. The increased coverage of antiretroviral therapy is probably another main reason for the decline in TB incidence rates. Despite good treatment results for both HIV and TB, the all-cause mortality among Finnish males with HIV-TB was high, and common causes of death were intoxications and suicides.
  • EuroSIDA Study Grp; Amele, S.; Ristola, M.; Mocroft, A.; Aho, I. (2019)
    Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.
  • Mikkola, Visa (Helsingin yliopisto, 2020)
    Tavoitteet: Itä-Euroopassa ja Keski-Aasiassa HIV-1-infektioiden ilmaantuvuus on noussut 57 % vuosina 2000−2015. Epidemiologista dataa on edelleenkin vähän. Lisäksi se on pääosin venäjänkielistä, eikä ole saatavilla kansainvälisten tietokantojen kautta. Suunnitelma: Keräsimme näytteitä ja epidemiologista dataa 328 HIV-tartunnan saaneelta, joista 91 % asui Venäjän Eteläisen federaatiopiirin alueella ja 9 % Pohjois-Kaukasian federaatiopiirin alueella. Menetelmät: Proteaasi-käänteiskopioijaentsyymi- (PRRT) ja integraasisekvessejä (IN) käytettiin viruksen alatyypin selvittämiseen sekä resistenssimutaatioiden ja lääkeherkkyyksien analysointiin. Fylogeneettisiä analyysejä käytettiin HIV:n ala-alatyyppien A6 ja A1 erottamiseen toisistaan. Tulokset: 303 (92 %) potilaan näytteet pystyttiin analysoimaan, näistä 32 %:lla infektio oli saatu huumeiden pistoskäytön kautta, 27 %:lla heteroseksissä ja 24 % infektioista oli nosokomiaalisia eli hoidon seurauksena tulleita. Miehillä huumeiden pistoskäyttö oli yleisin syy infektioille, naisilla heteroseksi. Tutkimuksessa todettiin eniten A6-viruksia (69 %), joita esiintyi erityisesti huumeita pistämällä käyttävillä sekä heteroseksin kautta saaduissa tartunnoissa. Tätä ja tulevia tutkimuksia varten luotiin A6-pol-referenssisekvenssi. Alatyypin B infektioita esiintyi erityisesti miehillä, joilla oli ollut miesten välistä seksiä. Alatyypin G infektiot olivat yhteydessä nosokomiaaliseen infektioon. Lääkeresistenssimutaatioita havaittiin PI-, NRTI-, NNRTI- ja INI-lääkeaineryhmiä kohtaan. Spesifisten mutaatioiden esiintyvyys korreloi tiettyjen HIV:n alatyyppien kanssa. Esimerkiksi ala-alatyyppi A6 yhteydessä esiintyi merkittävästi enemmän mutaatioita NRTI A62V sekä NNRTI G190S, kun taas alatyyppiin G korreloivat NRTI-lääkeaineryhmään liittyvät mutaatiot D67N ja M41L. Näytteissä havaittiin lääkeherkkyyden alentuma: 14,5 % PI-, 29,6 % NNRTI-, 27,1 % NNRTI- ja 8,2 % INI-ryhmän lääkkeitä kohtaan. Yhteenveto: Tutkimuksessa havaittu HIV-1 alatyyppijakauma Venäjällä on merkittävästi erilainen kuin Saksassa. A6 oli yleisin tutkimuksen näytteissä havaittu alatyyppi samoin kuin muissakin Venäjälle sijoittuvissa tutkimuksissa on kuvattu. Alatyyppiä G esiintyi poikkeuksellisen paljon tämän tutkimuksen näytteissä verrattuna muihin Venäjältä julkaistuihin tutkimuksiin, mikä viittaa paikalliseen epidemiaan. HIV-1:n resistenssitestauksen yleistyminen parantaisi HIV-lääkehoidon tehokkuutta sekä toisi lisätietoa Venäjän HIV-epidemiasta. (271 sanaa)
  • GBD 2017 Mortality Collaborators (2018)
    Background Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systetns, sample registration systetns, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings Globally, 18.7% (95% uncertainty interval 18.4-19.0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58.8% (58.2-59.3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48.1 years (46.5-49.6) to 70.5 years (70.1-70.8) for men and from 52.9 years (51.7-54.0) to 75.6 years (75.3-75.9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49.1 years (46.5-51.7) for men in the Central African Republic to 87.6 years (86.9-88.1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216.0 deaths (196.3-238.1) per 1000 livebirths in 1950 to 38.9 deaths (35.6-42.83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5.4 million (5.2-5.6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult tnales, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, wotnen, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing. Copyright C) 2018 The Author(s). Published by Elsevier Ltd.
  • Hay, Simon I.; Abajobir, Amanuel Alemu; Abate, Kalkidan Hassen; Abbafati, Cristiana; Abbas, Kaja M.; Abd-Allah, Foad; Abdulle, Abdishakur M.; Abebo, Teshome Abuka; Abera, Semaw Ferede; Aboyans, Victor; Abu-Raddad, Laith J.; Ackerman, Ilana N.; Adedeji, Isaac A.; Adetokunboh, Olatunji; Afshin, Ashkan; Aggarwal, Rakesh; Agrawal, Sutapa; Agrawal, Anurag; Kiadaliri, Aliasghar Ahmad; Ahmed, Muktar Beshir; Aichour, Amani Nidhal; Aichour, Ibtihel; Aichour, Miloud Taki Eddine; Aiyar, Sneha; Akinyemiju, Tomi F.; Akseer, Nadia; Al Lami, Faris Hasan; Alahdab, Fares; Al-Aly, Ziyad; Alam, Khurshid; Alam, Noore; Alam, Tahiya; Alasfoor, Deena; Alene, Kefyalew Addis; Ali, Raghib; Alizadeh-Navaei, Reza; Alkaabi, Juma M.; Alkerwi, Ala'a; Alla, Francois; Allebeck, Peter; Allen, Christine; Al-Maskari, Fatma; AlMazroa, Mohammad AbdulAziz; Al-Raddadi, Rajaa; Alsharif, Ubai; Kivimaki, Mika; Lallukka, Tea; Meretoja, Atte; Meretoja, Tuomo J.; Weiderpass, Elisabete; GBD 2016 DALYs HALE Collaborators (2017)
    Background Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings The highest globally observed HALE at birth for both women and men was in Singapore, at 75.2 years (95% uncertainty interval 71.9-78.6) for females and 72.0 years (68.8-75.1) for males. The lowest for females was in the Central African Republic (45.6 years [42.0-49.5]) and for males was in Lesotho (41.5 years [39.0-44.0]). From 1990 to 2016, global HALE increased by an average of 6.24 years (5.97-6.48) for both sexes combined. Global HALE increased by 6.04 years (5.74-6.27) for males and 6.49 years (6.08-6.77) for females, whereas HALE at age 65 years increased by 1.78 years (1.61-1.93) for males and 1.96 years (1.69-2.13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2.3% [-5.9 to 0.9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16.1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
  • GBD 2017 DALYs & HALE Coll (2018)
    Background How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. Methods We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Sociodemographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Findings Globally, from 1990 to 2017, life expectancy at birth increased by 7.4 years (95% uncertainty interval 74-7.8), from 65.6 years (65.3-65- 8) in 1990 to 73.0 years (72.7-73.3) in 2017. The increase in years of life varied from 5.1 years (5.0-5.3) in high SDI countries to 12.0 years (11.3-12.8) in low SDI countries. Of the additional years of life expected at birth, 26.3% (20.1-33.1) were expected to be spent in poor health in high SDI countries compared with 11.7% (8.8-15.1) in low-middle SDI countries. HALE at birth increased by 6.3 years (5.9-6.7), from 57.0 years (54.6-59.1) in 1990 to 63.3 years (60.5-65.7) in 2017. The increase varied from 3.8 years (3.4-4.1) in high SDI countries to 10.5 years (9.8-11.2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1.0 year (0.4-1.7) in Saint Vincent and the Grenadines (62.4 years [59.9-64.7] in 1990 to 63.5 years [60.9-65.8] in 2017) to 23.7 years (21.9-25.6) in Eritrea (30.7 years [28.9-32.2] in 1990 to 54.4 years [51.5-57.1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1.4 years (0.6-2.3) in Algeria to 11.9 years (10.9-12.9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75.8 years [72.4-78.7]) and males (72.6 years [69 " 8-75.0]) and the lowest estimates were in Central African Republic (47.0 years [43.7-50.2] for females and 42.8 years [40.1-45.6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41.3% (38.8-43.5) for communicable diseases and by 49"8% (47.9-51.6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40.1% (36.8-43.0), although age-standardised DALY rates decreased by 18.1% (16.0-20.2). Interpretation With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low S DI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.
  • Wang, Haidong; Abajobir, Amanuel Alemu; Abate, Kalkidan Hassen; Abbafati, Cristiana; Abbas, Kaja M.; Abd-Allah, Foad; Abera, Semaw Ferede; Abraha, Haftom Niguse; Abu-Raddad, Laith J.; Abu-Rmeileh, Niveen M. E.; Adedeji, Isaac Akinkunmi; Adedoyin, Rufus Adesoji; Adetifa, Ifedayo Morayo O.; Adetokunboh, Olatunji; Afshin, Ashkan; Aggarwal, Rakesh; Agrawal, Anurag; Agrawal, Sutapa; Kiadaliri, Aliasghar Ahmad; Ahmed, Muktar Beshir; Aichour, Amani Nidhal; Aichour, Ibthiel; Aichour, Miloud Taki Eddine; Aiyar, Sneha; Akanda, Shafqat; Akinyemiju, Tomi F.; Akseer, Nadia; Al-Eyadhy, Ayman; Al Lami, Faris Hasan; Alabed, Samer; Alahdab, Fares; Al-Aly, Ziyad; Alam, Khurshid; Alam, Noore; Alasfoor, Deena; Aldridge, Robert William; Alene, Kefyalew Addis; Alhabib, Samia; Ali, Raghib; Alizadeh-Navaei, Reza; Aljunid, Syed M.; Alkaabi, Juma M.; Alkerwi, Ala'a; Alla, Francois; Allam, Shalini D.; Allebeck, Peter; Kivimaki, Mika; Meretoja, Atte; Meretoja, Tuomo J.; Weiderpass, Elisabete; GBD 2016 Mortality Collaborators (2017)
    Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0.5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Sociodemographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86.9 years (95% UI 86.7-87.2), and for men in Singapore, at 81.3 years (78.8-83.7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
  • Rossi, Katriina (Helsingin yliopisto, 2020)
    HIV-1 is a lentivirus causing a serious immunodeficiency disease called AIDS to almost 38 million people in the world. Like all retroviruses, HIV has an ability to insert a copy of its genome into the host cell DNA thus having a lifelong effect on the host cell. Two identical copies of single-stranded RNA are first reverse transcribed, and then a protein called integrase inserts the DNA into the genome of T-cells of the human immune system. Studies have shown that in some retroviruses the integrase protein has a unique integration pattern favoring certain areas of the host cell genome. For example, active transcription units or promoter units are found to attract integration activity. On the other hand, with nuclear localization signals in its structure and an ability to attach to the human genome, it raises a question if the integrase could have additional functions. Regulating certain gene expression levels could support viral replication and the survival of the virus. The aim of the study was to determine whether integration sites differ from integrase genomic contact sites, which could be an indication of integrase’s additional role. Study was started by method optimization. Two chromatin fragmentation methods, sonication and endo-exonuclease treatment, were tested in order to achieve optimal sized DNA fragments for ChIP-sequencing. Two cell lines were infected with HIV-1. Genomic DNA was collected for integration site sequencing. Integrase genomic contact sites were studied with ChIP-sequencing. Next generation sequencing for both, integration sites and integrase genomic contact sites, was carried out by an outsource biotechnology company. Sequences were processed with bioinformatics platforms, such as Galaxy and Homer. Study of the effects of transfected integrase was also initiated by transfection method optimization. Treatment with endo-exonuclease resulted in correctly sized DNA fragments when DNA was first purified. In a cell lysate, a correct ratio of MNase and cells was not found, although several cell lysis methods and buffers were tried. This is why actual integrase genomic contact site samples were fragmented by sonication. In MRC-5 cell line, integration site sequencing resulted in over 2 M reads with 289 aligned, unique integration sites. Integrase genomic contact site sequencing resulted in 1.8E+6 Bowtie mapped reads. A brief analysis of the sequences including sequence visualization, comparison of localization in the genome and GO terms, showed that integrase genomic contact sites have certain patterns that differ from integration sites. Therefore, it was confirmed that the study is repeatable, as the results were in line with the study conducted several years earlier. These results also suggest that method optimization had been successful. As bioinformatics methods were used with default parameters only, more attention should be payed when sequences are analyzed more deeply. This will offer a more thorough understanding of the functions of integrase.
  • Nobre, Nuno; Pereira, Marco; Roine, Risto P.; Sutinen, Jussi; Sintonen, Harri (2018)
    We examined how HIV-related self-stigma was associated with different domains of quality of life (QoL), as measured by the World Health Organization Quality of Life in HIV-infected persons instrument (WHOQOL-HIV-Bref), and health-related quality of life (HRQoL) as measured by the generic 15D (15-dimensional measure of HRQoL), to identify the factors associated with self-stigma of people living with HIV (PLWH). The study sample included 440 patients living with HIV followed at the Infectious Disease Clinic of Helsinki University Hospital. Participants with more severe self-stigma reported significantly lower QoL and HRQoL. Male gender, cohabiting with a partner, and disclosure of HIV status were associated with less self-stigma; high education level and financial difficulties were associated with greater self-stigma. Having lived longer with HIV, being unemployed, and living alone were also predictors of self-stigma via financial difficulties. The findings suggest that self-stigma is a complex and multidimensional phenomenon that impacts the HRQoL of PLWH. Psychosocial interventions to enhance the well-being of PLWH are increasingly needed. Copyright (C) 2017 Association of Nurses in AIDS Care
  • Rautila, Kanerva (Helsingin yliopisto, 2018)
    Tutkimuksessa selvitettiin hiv-tartunnan saaneiden somalialais- ja venäläistaustaisten maahanmuuttajien terveydentilaa, elämänlaatua, terveyspalvelujen käyttöä sekä syrjintä- ja hoitokokemuksia Suomessa verrattuna maahanmuuttajiin, joilla ei ole todettu hiv-infektiota. Tutkimuksen kirjallisuuskatsauksessa käydään läpi hiv-infektioiden esiintyvyyttä maahanmuuttajilla Suomessa ja Euroopassa, testaus- ja seulontakäytäntöjä sekä tarkastellaan hiv-infektion vaikutusta elämänlaatuun ja mielenterveyteen. Hiv-positiiviset maahanmuuttajat ovat ryhmä, josta on niukalti tutkimustietoa Suomessa. Kyseessä on havainnoiva poikkileikkaustutkimus, jossa haastateltiin Helsingin Yliopistollisen sairaalan infektiotautien poliklinikan hiv-positiivisia maahanmuuttajataustaisia potilaita rakenteellisen kyselykaavakkeen avulla. Tietoja verrattiin Terveyden ja hyvinvoinninlaitoksen Maahanmuuttajien terveys ja hyvinvointi tutkimuksen aineiston hiv-negatiivisten maahanmuuttajiin. Tutkimuksessa selvisi, ettei hiv-infektio ollut merkittävä hiv-positiivisten maahanmuuttajien elämänlaatuun tai syrjintäkokemuksiin vaikuttava tekijä. Hiv-infektio sen sijaan vaikutti tutkittavien tyytyväisyyteen omaan terveyteensä sekä selviytymiseen päivittäisistä toimista. Lisäksi hiv-positiiviset käyttivät ja kokivat enemmän tarvetta mielenterveyspalveluille ja heillä oli enemmän vakavia masennus- ja ahdistusoireita kuin hiv-negatiivisilla maahanmuuttajilla. Tutkimuksessa korostui erityisesti hiv-positiivisten maahanmuuttajamiesten riski masennus- ja ahdistusoireisiin. Hiv-positiiviset tutkittavat olivat kuitenkin tyytyväisempiä saamaansa hoitoon ja kokivat vähemmän tyydyttymätöntä lääkärinhoidon tarvetta. Tutkimus onnistui saamaan tietoa ryhmästä, josta on hyvin vähän tutkimustietoa saatavilla Suomessa. Toisaalta tutkimuksen pieni otoskoko ja tutkittujen maahanmuuttajaryhmien kulttuuriset erityispiirteet rajoittavat tulosten yleistettävyyttä. Jatkotutkimuksissa tulisi selvittää mitkä tekijät lisäävät hiv-positiivisten maahanmuuttajien riskiä sairastua mielenterveysongelmiin, miten niitä voitaisiin ehkäistä sekä miten mielenterveyspalveluja voitaisiin kehittää. (193 sanaa)
  • Meuwissen, Pieter J.; Stolp, Bettina; Iannucci, Veronica; Vermeire, Jolien; Naessens, Evelien; Saksela, Kalle; Geyer, Matthias; Vanham, Guido; Arien, Kevin K.; Fackler, Oliver T.; Verhasselt, Bruno (2012)
  • Laurila, Minni (University of Helsinki, 2000)
  • Achhra, Amit C.; Mocroft, Amanda; Ross, Michael; Ryom-Nielson, Lene; Avihingsanon, Anchalee; Bakowska, Elzbieta; Belloso, Waldo; Clarke, Amanda; Furrer, Hansjakob; Lucas, Gregory M.; Ristola, Matti; Rassool, Mohammed; Ross, Jonathan; Somboonwit, Charurut; Sharma, Shweta; Wyatt, Christina; INSIGHT START Study Grp (2017)
    The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4(+) (cellsimm(3)) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m(2), calculated by CI94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 056 (95% CI 0.003-1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21-2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84-4.97) versus non-Blacks (1.05, 95% CI 0.33-1.77) (P <0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55-1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
  • Tiittala, Paula; Kivelä, Pia; Liitsola, Kirsi; Ollgren, Jukka; Pasanen, Sini; Vasankari, Tuula; Ristola, Matti (2018)
    Migrants are disproportionately affected by HIV in many European countries, including Finland. We aimed to compare the HIV-related knowledge, attitudes and practices (KAP) of young asylum seekers to those of the general young adult population. Two cross-sectional surveys were conducted among 20- to 25-year-old young adults: The TIE study among asylum seekers (n=47) and the World AIDS Day 2014 study among the general population (n=485). Important gaps in HIV KAP were identified especially among the young asylum seekers. For the general young adult population, previous HIV testing was associated with female gender, better HIV knowledge and increased sexual activity. Health education concerning HIV needs to be further enforced among young adults in Finland. Due to poorer HIV knowledge, young asylum seekers might be especially vulnerable to HIV. The asylum process is a window of opportunity for health education and HIV testing.
  • EuroSIDA study; Mocroft, Amanda; Lundgren, Jens D.; Rockstroh, Juergen K.; Aho, Inka; Peters, Lars (2020)
    Background. The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear. Methods. Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (antiHCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment). Results. A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNApositive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6-13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7-8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global P = .33). Hypertension (22.2%; 95% CI, 17.5%-26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%-29.7%) had the largest population-attributable fractions for DM. Conclusions. HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized.