João Carlos Gomes and Maria João Saraiva should be included in the author byline. João Carlos Gomes should be listed as the third author and Maria João Saraiva should be listed as the fourth author. Their affiliations are 4: Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal and 5: Molecular Neurobiology Unit, IBMC—Institute for Molecular and Cell Biology, University of Porto, Portugal.https://doi.org/10.1371/journal.pone.0221555The correct citation is: Talhada D, Gonçalves I, Gomes JC, Saraiva MJ, Reis Santos C, Ruscher K (2019) Transthyretin expression in the postischemic brain. PLoS ONE 14(9): e0221555. The updated author contributions are as follows:Conceptualization: Daniela Talhada, Karsten RuscherData curation: Daniela TalhadaFormal analysis: Daniela TalhadaFunding acquisition: Isabel Gonçalves, Cecília Reis Santos, Karsten RuscherInvestigation: Daniela Talhada, Karsten RuscherMethodology: Daniela Talhada, Karsten RuscherProject administration: Karsten RuscherResources: Karsten RuscherSupervision: Karsten RuscherValidation: Isabel Gonçalves, Cecília Reis Santos, João Carlos Gomes, Maria João Saraiva, Karsten RuscherWriting–original draft: Daniela TalhadaWriting–review & editing: Isabel Gonçalves, Cecília Reis Santos, João Carlos Gomes, Maria João Saraiva, Karsten RuscherThe raw data underlying Fig 1 and S2 Table are missing from the list of Supporting Information. The authors have provided the data as Supporting Information in S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.


Observou-se uma discordância de 15% entre LDL e não-HDL, o que foi similar a estudos prévios.6 No entanto, não foram identificadas diferenças anatômicas significativas na avaliação da gravidade da doença aterosclerótica. O uso prévio de estatinas tem um efeito mais significativo na redução de LDL em comparação a não-HDL, o que pode explicar a falta de associação.O presente estudo7 De fato, o presente estudo identificou discrepâncias na associação entre diabetes mellitus e níveis de LDL. Talvez o tamanho da amostra não tenha sido adequado para identificar diferenças anatômicas entre os grupos. O acompanhamento de pacientes com associações discrepantes poderia identificar um subgrupo de pacientes em alto risco para novos eventos cardiovasculares.Além disso, a sensibilidade dos níveis de LDL em identificar risco cardiovascular é menor no diabetes.8 Estudos anteriores já mostraram a eficácia desses medicamentos na redução de eventos cardiovasculares e apolipoprotein(a) em alguns grupos de pacientes.As diretrizes brasileiras já incluem metas de LDL e não-HDL, buscando identificar indivíduos com níveis adequados de LDL e alto risco residual para eventos cardiovasculares. Estudos prospectivos certamente ajudarão a identificar o subgrupo de pacientes que requeiram uma abordagem terapêutica mais intensa, e que provavelmente se beneficiariam de terapias mais caras e efetivas, como inibidores de PCSK9 e lomitapida. 1 Dyslipidemia is a risk and causal factor and is the focus of the therapy for primary and secondary prevention of CVDs.Cardiovascular diseases (CVDs) are the leading cause of mortality world.2 However, despite intensive use of lipid lowering agents, there remains a residual risk, a constant target of research and therapy.There is consensus and broad understanding of the causal mechanisms of low-density lipoproteins (LDL) in CVDs, and the benefit of the hypolipidemic therapy, with a magnitude of effect proportional to the reduction in serum levels.3 High non-HDL cholesterol levels help identify patients who despite having low serum LDL levels remain at high risk for cardiovascular events.4Recent evidence confirms that the initial event of atherogenesis is the retention of LDL and other particles in the vessel wall.5 retrospectively evaluated the anatomical characteristics of 574 patients diagnosed with acute coronary syndrome and correlated the findings with LDL and non-HDL serum levels. There was 15% disagreement between LDL and non-HDL, which was similar to previous studies.6 However, no significant anatomical differences were identified in the assessment of the severity of atherosclerotic disease. Prior use of statins may have a more significant effect on LDL reduction than non-HDL, which may explain the lack of association.The present study7 In fact, the present study reported discrepancies in the association between diabetes mellitus and LDL levels. Perhaps the sample size was not adequate enough to evidence anatomical differences between the groups. The follow-up of patients with discrepant associations could identify a subgroup at higher risk of new events.In addition, the sensitivity of LDL levels in identifying cardiovascular risk is reduced in diabetes.8 These drugs have already been shown to be effective in reducing cardiovascular events and apolipoprotein(a) in some groups of patients.The Brazilian guideline already includes both LDL and non-HDL targets, seeking to identify individuals with high residual risk of cardiovascular events despite adequate LDL levels. Prospective studies will help better identify the subgroup of patients who require more intense treatment approach, who would probably benefit from more expensive and effective therapies such as PCSK9 inhibitor and Lomitapide.


To identify the Brazilian cohorts that started either in the prenatal period or at birth, to describe their characteristics and the explored variables, and to map the cohorts with potential for studies on early determinants on health and the risk of falling ill on later stages of the life cycle. A scoping review was carried out. The articles were searched in the electronic databases PubMed and Virtual Health Library (VHL). The descriptors used were [ AND ) AND “Brazil”)]. The inclusion criteria were Brazilian cohorts that started the baseline in the prenatal period or at birth and with at least two follow-ups with the participants. In order to meet the concept of LCE, we excluded those cohorts whose follow-ups were restricted to the first year of life, as well as those that did not address biological, behavioral and psychosocial aspects, and cohorts with data collection of a single stage of the life cycle. The search step identified 5,010 articles. Eighteen cohorts were selected for descriptive synthesis. The median number of baseline participants was 2,000 individuals and the median age at the last follow-up was 9 years. Sample loss at the last follow-up ranged from 9.2 to 87.5%. Most cohorts monitored two phases of the life cycle . The Southern region had the highest number of cohorts. The main variables collected were sociodemographic and environmental aspects of the family, morbidity aspects, nutritional practices and lifestyle. We recommend the continuity of these cohorts, the approach to different social contexts and the performance of follow-ups with participants in different phases of the life cycle for the strengthening and expansion of life course epidemiology analyses in Brazil. Its purpose is to build and test theoretical models that might postulate paths that link exposures at different stages of the life course to later health outcomes2. These models explore the time and interactions of biological and psychosocial exposures to identify risks and protection processes throughout the life course4.Life course epidemiology (LCE) is a field that compromises the studies of biological, behavioral and psychosocial processes that occur throughout the life of individuals. It links the health conditions and the risk of illness of an adult to physical or psychosocial exposures that might have happened during pregnancy, infancy or adolescence, in the earlier stages of life or through generations5. These studies are generally conducted to assess the natural history of diseases, estimate disease frequency measures (incidence), identification of risk factors for health problems, prognosis and survival analysis7. Cohorts that collect information at different stages of their participants’ lives and with medium and long-term outcomes are excellent for testing explanatory models of LCE9, and it is possible to explore risk accumulation models and critical periods, in addition to investigating the mediating and modifying factors of the association between exposures and outcomes in study3.As such, cohort studies are a valuable tool for LCE, as they follow their participants from exposure to the occurrence of outcomes of interest4. They are mainly concentrated in high-income countries and differ from cohorts conducted in middle and low income countries by the greater number of follow-ups, follow-up of participants for longer periods and greater sophistication of the measures performed10. These cohorts, in middle- and low-income countries, offer valuable contributions due to the diversity of exposures and the different structures for disease determination11. In countries such as Brazil, with cultural diversity and regional inequality, they can offer contributions as valuable as cohorts from high-income countries. However, the research gaps of these studies in the country are not mapped, and a synthesis of information with the characteristics and outcomes studied by the main cohorts of this type is important in order to advance the studies of life course epidemiology throughout the country.Cohorts that start in the prenatal period or at birth offer a unique opportunity to assess the influence of early exposures on health throughout lifeThis study aims to describe the cohort studies initiated in the prenatal period or at birth conducted in Brazil, with the potential to study the early determinants of health and disease and the risk of falling ill in later stages of the life cycle. Through a scoping review, it was possible to describe the main methodological characteristics of these cohorts, as well as the variables studied, the location in the country and the needs related to epidemiological research of the life cycle in Brazil.12. We followed the following steps: identification of the research question , identification of relevant articles, selection of studies, data mapping and compilation, summary and reporting of results. The articles were searched in the electronic databases PubMed and Virtual Health Library (VHL). The descriptors were selected at the Medical Subject Headings (MeSH) with the following combination: [ AND ) AND “Brazil”)]. The search strategy was adapted for each database. All articles published as of June 16, 2018 were considered in the review.We conducted a scoping review to identify and map the available evidence on Brazilian cohorts with potential for life course epidemiology studies. This review is conducted to summarize and disseminate the research results and recognize research gaps in the available literature13. Two reviewers selected the titles and abstracts of the articles and read the full text of the eligible articles. Given that the scoping review aimed to map the evidence on a relevant topic, an evaluation of the quality of the evidence included in the review was not necessary12. Finally, from the interpretation of the results of this review, we presented recommendations to advance the studies of life course epidemiology in Brazil.The review included cohort studies conducted in Brazil that started the baseline of the study in the prenatal period or at birth and with at least two follow-ups with the participants. The studies excluded were those that described only the baseline and not the follow-ups performed. In order to meet the concept of LCE, we excluded those cohorts whose follow-ups were restricted to the first year of life, as well as those that did not address biological, behavioral and psychosocial aspects, and cohorts with data collection of a single stage of the life cycle. We considered as stages of the life cycle the perinatal period (between the 22nd week of gestation and six days of life), childhood (between the first week of life and six years of age), school age (between 6 and 12 years), adolescence (between 12 and 18 years) and adulthood (18 years or more)The following information was extracted from the selected studies: geographic location of the cohort ; year of beginning of the cohort (baseline); type of cohort according to the age of baseline participants, divided into birth (recruitment of participants started at birth) and prenatal (recruitment initiated during pregnancy); type of cohort regarding the time of occurrence of exposure and outcome and the beginning of the study, divided into prospective (exposure data were collected at the beginning of the study and the outcome has not yet occurred), retrospective  and ambispective (exposure data were collected in the past and the outcome has not yet occurred); type of data used in the cohort, divided into primary  and secondary ; reference base of the sample, divided into hospital-based  and population-based (representative or convenience); number of participants in the baseline; number of participants in the last follow-up; average age of the participants in the last follow-up; total number of follow-ups with participants; mean age of participants in each follow-up; information collected at each stage of the life cycle.These data were complemented with information extracted from publications from the list of references of selected articles, as well as from electronic pages of cohort studies, from contacting via e-mail researchers of these studies and consultations with databases of dissertations and theses. Finally, a descriptive analysis of the main characteristics of the cohorts included in the review was performed.The search stage identified 5,010 articles in the databases, excluding 1,678 duplicated ones. After reading the titles and abstracts, 2,904 articles were excluded because they did not meet the eligibility criteria. After reading the full text, 428 articles from 79 cohort studies conducted in Brazil initiated in the prenatal period or at birth with at least two follow-ups with the participants were identified. Of these 79 cohorts, 41 with follow-ups only during the first year of life and five that did not address biological, behavioral and psychosocial aspects were excluded. Due to the interest in analyzing cohorts that explored effects of exposures that occurred in the perinatal period, childhood, adolescence and in later stages of the life cycle, fifteen cohorts with data collection of a single stage of the life cycle were excluded. At the end, 18 cohorts were selected (n = 345 articles). The flowchart of the review steps is illustrated in 14, 15 started at birth14 and three, at the prenatal period31. All cohorts were prospective and collected primary data. Ten cohorts20 had a representative sample of the baseline reference population, seven cohorts30 used a convenience sample, and a single cohort was hospital-based23. The number of baseline participants ranged from 189 to 7,747 individuals . The mean age at the last follow-up ranged from 2 to 30 years (median of 9 years) and the number of follow-ups ranged from 2 to 11 (median of 4), as observed in Of the 18 cohorts identified29 and investigated more frequently morbidity and lifestyle data. Six cohorts followed participants in the early adulthood26, with data collection of morbidity, dietary practices, anthropometric measurements, cognition, lifestyle and human capital. The information collected less frequently in adulthood was mental health. Of the total cohorts, 14 collected biological material (blood and/or feces)14 at some point in the life cycle  in at least one of the follow-ups. The most frequent information collected in the perinatal period were characteristics of the moment of delivery, of the newborn, morbidity and life habits of the pregnant woman, while the least frequent was the mental health of the mother. The most investigated characteristics of the participant in childhood were morbidity, dietary practices and breastfeeding, and the least frequent was vaccination. The cohorts that followed up with the participants at school age collected more frequently morbidity data and less frequently, information on oral health. Five cohorts followed participants in adolescencefe cycle .14; it included 239 children born between 2000–2001 and carried through three additional follow-ups  for mercury exposure analysis. Loss at the last follow-up regarding this cohort was 59.3% in relation to the number of baseline participants. The most recent cohort of the Northern region was conducted in the state of Acre, known as the Maternal-Infant study in Acre (Mina), which began between July 2015 and June 2016 in the municipality of Cruzeiro do Sul15. The Mina cohort consisted of all live birth infants living in the urban area of the municipality , of which 588 had data collected in the prenatal period (up to the second trimester of pregnancy). This cohort performed three follow-ups with the children so far  and the loss of follow-up at 24 months was 28.6%.16. These children were monitored every three months during their first two years, in the period between 1989 and 1993, for records of diarrheal diseases, dietary information and anthropometric measurements. This cohort performed a total of nine follow-ups , with loss at the last follow-up of 59.3%. The cohort conducted in five municipalities of Pernambuco , started in 1993, included 549 live birth infants between January 1993 and August 199417. This cohort performed eight follow-ups  and had a loss in the last follow-up of 60.5% of the participants. Two population-based cohorts were identified in the city of São Luís, Maranhão. The first, started in 1997, included 2,691 single live birth infants and carried through two follow-ups with participants (between 7 and 9 years and between 18 and 19 years), with loss in follow-up between 18 and 19 years of age of 75.3%18. The second cohort was initiated in 2010, known as Brisa São Luís, and included 5,166 live birth infants at baseline, of which 1,447 had data collected in prenatal care20. To date, Brisa São Luís has monitored children between 13 and 30 months, with 36% of losses compared to baseline. In Bahia, there is a cohort in the municipality of Feira de Santana since April 200419; it included 1,309 live birth infants, performed ten follow-ups with the participants  and had a loss of 48.7% in the last follow-up.In the Northeastern region, five cohorts were identified. The cohort of Fortaleza, in Ceará, began in 1989 and included 189 children born in the favela of Gonçalves Dias21, 199422 and 201024, and one was hospital-based, started in 200123. The Ribeirão Preto cohort started in 1978 included 6,764 single live birth infants, performed three follow-ups  and had 69.5% of loss in the last follow-up. The one started in 1994 included 2,846 single live birth infants and carried through two follow-ups with participants (between 9 and 11 years and between 22 and 24 years), with loss in follow-up between 78,1 and 19 years of age of 75.3%. The cohort started in 2010, known as Brisa Ribeirão Preto, included 2,443 single live birth infants of that year, of which 1,417 had data collected in the prenatal period. To date, it has monitored children between 13 and 30 months of life, with loss of follow-up of 46%. The Ribeirão Preto cohort started in 2001, known as the Gesta-Álcool Project, monitored 449 pregnant women in the third trimester of pregnancy and conducted two follow-ups with the participants (between 6 and 7 years and between 11 and 12 years), with a loss of 87.5% in the last follow-up.In the Southeast region, four cohorts were identified, all in the city of Ribeirão Preto, in the state of São Paulo. Three were population-based, started in 197825. Subsequent and still ongoing cohorts involved 5,249 births in 1993 with 11 follow-ups 26; 4,231 births in 2004 with seven follow-ups 29 and, in the most recent cohort, 4,226 prenatal recruitments in 2015 with four follow-ups to date . The losses in the last follow-up of the Pelotas cohorts of 1982, 1993, 2004 and 2015 were, respectively, 37.4%, 21.8%, 15.8% and 9.2%. The other three cohorts identified were the one in São Leopoldo, started in 200127, in Pelotas started in 200228 and in Porto Alegre started in 200830. The São Leopoldo cohort recruited 500 mother-child pairs between October 2001 and June 2002 and carried out four follow-ups with the participants , with loss at the last follow-up of 38.6%. The Pelotas cohort included all 2,741 live birth infants between September 2002 and May 2003 in the urban area of the municipality and followed a random sample of 30% (n = 973) at 1, 3 and 6 months of life and at 8 years of age, with a loss of 36.7% at the last follow-up. The Porto Alegre cohort started with 715 pregnant women recruited in the third week of pregnancy and performed three follow-ups , with 33.6% loss at the last follow-up.In the Southern region of the country, seven cohorts were identified, all in the state of Rio Grande do Sul. We highlight the population-based cohorts of Pelotas, given the high number of individuals recruited, the greater number of follow-ups with the participants and for having followed their participants from birth to adolescence and early adult life. Of the 345 articles selected in this systematic review, 75% corresponded to publications derived from these cohorts. The first cohort of Pelotas was initiated in 1982 and involved 5,914 children, with nine follow-ups to date 25, 199326 and 200429, the Ribeirão Preto cohorts of 197821 and 199422 and the São Luís cohort of 199718. The losses of follow-up were related to not knowing the whereabouts of the participants, to internal migration and refusals to further participation. The most explored variables were related to sociodemographic, environmental and domestic family data, maternal morbidity and lifestyle, additional morbidity data, breastfeeding and nutritional practices during infancy, morbidity during school age, morbidity and lifestyle during adolescence and aspects of integral health during adulthood.The Brazilian cohorts identified, initiated in the prenatal or birth period, were prospective and collected primary data. To date, few have followed participants in adolescence (n = 6) and adulthood (n = 5). Six cohorts stood out by the largest number of baseline participants, the comprehensive approach to the health of children, adolescents and adults and by accompanying participants in more phases of the life cycle: the Pelotas birth cohorts of 198233, allowing for intergenerational analyses. On the other hand, the prenatal and birth cohorts of middle and low-income countries frequently present difficulties related to lack of financial resources, early death of children and internal migration, and infrequent follow-up of participants in more advanced stages of the life cycle12.In high-income countries, prenatal and birth cohorts, in addition to accompanying their participants for a prolonged time, are not limited to single-generation individuals; it also includes their descendants34. Sample size and follow-up losses were weak points of most identified cohorts. Reducing the loss of follow-up over time represents a challenge, since differential losses between exposed and unexposed groups tend to introduce biases in cohort studies6.Some methodological characteristics and difficulties of the identified cohorts were observed. Most monitored two phases of the life cycle . Although there is a requirement for immediate results to satisfy and stimulate the funders and participants of the study, it is known that the most important results from the perspective of the life cycle are those that analyze the influence of early exposures on health and well-being in later stages of life and with repeated measures at different stages of an individual’s life36. In addition to this investment of time, effort and intellectual contribution, keeping a cohort study running is quite costly. The adequacy of funding might determine the timespan of the study. Cohort studies are often funded by government agencies and international organizations, and therefore are vulnerable to political and governmental priorities, or by local research foundations that do not guarantee the sustainability and availability of long-term financial resources37.The development process of cohort studies is challenging. The implementation of a cohort requires close collaboration between the institutions involved, health professionals and families, as well as laborious logistics for the correct execution of the phases of the study , including quality control procedures in all stages38 The possibility of verifying the nature of the associations between exposures and outcomes in different contexts and comparing results between existing cohorts is another advantage40. Brazilian cohorts have the potential to further contribute the scientific capacity of the country, with the training of researchers and improvement of the process of collecting and analyzing data11, in addition to assisting decision makers in the analysis of health determinants and in strengthening the health care provided41.The development of cohorts in Brazil is important for several reasons. New exposures resulting from demographic, epidemiological, nutritional and institutional transitions in the country create a demand for new investigations on its effects on the health of the Brazilian population.7. This argument is justified by providing opportunities for collection of new risk information and recruiting underrepresented participants in existing studies, but faces serious budgetary challenges required by cohorts of this size42. On the other hand, other authors44 argue that representativeness is not necessary to determine the relationship between environmental or genetic factors and the risk of disease. These scholars suggest strategies for combining data from existing cohorts44 and with the formation of national and international cohort consortia43. A systematic review study of European cohorts concluded that a network of coordinated cohort studies, following a harmonized general protocol with a perspective of joint interpretation of data, would increase the scientific impact and international collaboration interest in these researches45.In view of the importance of cohorts initiated in the prenatal period and at birth in Brazil, the dichotomy between the development of new cohorts or investment in existing cohorts is discussed. International authors advocate the establishment of new population-based cohorts in countries with socioeconomic and racial/ethnic diversity, with annual follow-ups and evaluation of exposures of greater local relevance for multiple health outcomesThe cohorts with a representative population of Pelotas, Ribeirão Preto and São Luís correspond to the birth cohorts with the greatest potential to study biological, behavioral, social and genetic precursors of chronic diseases in Brazil. The ones in Pelotas are the largest population-based birth cohort studies in low- and middle-income countries with nearly four decades of work, more than 20,000 individuals studied throughout life, regular assessments in childhood and adolescence, and smaller rates of loss at follow-up. The birth cohorts of Ribeirão Preto and São Luís, initiated in partnership with the same group of researchers, studied about 17,000 and 7,000 individuals, respectively, and foresee more follow-ups with their participants. Located in a region with distinct sociocultural characteristics and lacking research, the Mina cohort, in Cruzeiro do Sul, Acre, also has the potential to contribute to life cycle studies in Brazil, since it is the first cohort initiated in with an integral approach to children’s health in the Amazon region.In conclusion, this review identified cohorts initiated in the prenatal period and at birth in Brazil with potential for life course epidemiology studies. These cohorts differ in sample size, number of follow-ups and phase of the life cycle in which individuals were monitored, as well as rates of loss of follow-up. It is recommended that the Brazilian cohorts initiated in the prenatal period and at birth have enough participants to perform analyses of the effect of early determinants on health outcomes in the short, medium and long term. In addition, in order to expand the epidemiology analyses of the life course in Brazil, it is necessary that the existing cohorts contemplate different social contexts and follow-ups with the participants at different stages of life. 1. O seu propósito é construir e testar modelos teóricos que postulem caminhos que liguem as exposições em diferentes fases do curso da vida a resultados posteriores de saúde2. Esses modelos exploram o tempo e as interações de exposições biológicas e psicossociais para identificar riscos e processos de proteção ao longo do ciclo vital4.A epidemiologia do ciclo vital (ECV) estuda os processos biológicos, comportamentais e psicossociais que ocorrem ao longo da vida dos indivíduos e que ligam a saúde do adulto e o risco de adoecer a exposições físicas ou psicossociais que aconteceram durante a gravidez, infância, adolescência, nas etapas precoces da vida adulta ou através de gerações5. Esses estudos são conduzidos geralmente para a avaliação da história natural de doenças, estimação de medidas de frequência de doenças (incidência), identificação dos fatores de risco de agravos de saúde, prognóstico e análise de sobrevida7. As coortes que coletam informações em diferentes estágios da vida de seus participantes e com desfechos em médio e longo prazo são ótimas para testar modelos explicativos da ECV9, sendo possível explorar modelos de acumulação de risco e períodos críticos, além de investigar os fatores mediadores e modificadores da associação entre exposições e desfechos em estudo3.Os estudos de coorte, por acompanharem seus participantes desde a exposição até a ocorrência do desfecho de interesse, são uma ferramenta valiosa para a ECV4. Elas estão principalmente concentradas nos países de alta renda e se diferenciam das coortes realizadas em países de renda média e baixa pelo maior número de acompanhamentos, seguimento dos participantes por períodos mais prolongados e maior sofisticação das medidas realizadas10. Essas coortes, em países de média e baixa renda, oferecem contribuições valiosas em virtude da diversidade de exposições e das diferentes estruturas de determinação de doenças11. Em países como o Brasil, com diversidade cultural e desigualdade regional, podem oferecer contribuições tão valiosas quanto as coortes de países de alta. No entanto, não estão mapeadas as lacunas de pesquisa desses estudos no país, sendo oportuna uma síntese de informações com as características e desfechos estudados pelas principais coortes desse tipo para se avançar nos estudos de epidemiologia do ciclo vital no território nacional.As coortes que se iniciam no período pré-natal ou no nascimento oferecem uma oportunidade única para avaliar a influência de exposições precoces sobre a saúde ao longo da vidaO presente estudo tem como objetivo descrever os estudos de coorte iniciados no período pré-natal ou no nascimento realizados no Brasil, com potencial para estudar os determinantes precoces de saúde e doença e o risco de adoecer em etapas posteriores do ciclo vital. Por meio de uma revisão de escopo, foi possível descrever as principais características metodológicas dessas coortes, as variáveis estudadas, a localização no território nacional e as necessidades relacionadas à pesquisa epidemiológica do ciclo vital no Brasil.12. Seguimos as seguintes etapas: identificação da questão de pesquisa , identificação dos artigos relevantes, seleção dos estudos, mapeamento dos dados e compilação, resumo e relato dos resultados. A busca dos artigos foi realizada nas bases de dados eletrônicas PubMed e Biblioteca Virtual em Saúde (BVS). Os descritores foram selecionados no Medical Subject Headings (MeSH) com a seguinte combinação: [ AND ) AND “Brazil”)]. A estratégia de busca foi adaptada para cada base de dados. Foram considerados na revisão todos os artigos publicados até a data de 16 de junho de 2018.Realizou-se uma revisão de escopo para identificar e mapear as evidências disponíveis sobre coortes brasileiras com potencial para estudos de epidemiologia do ciclo vital. Essa revisão é conduzida para resumir e divulgar os resultados da pesquisa e reconhecer lacunas de pesquisa na literatura existente13. Dois revisores realizaram a seleção dos títulos e resumos dos artigos e fizeram a leitura do texto completo dos artigos elegíveis. Como a revisão de escopo objetivou mapear as evidências sobre um tópico relevante, uma avaliação da qualidade das evidências incluídas na revisão não foi necessária12. Por fim, a partir da interpretação dos resultados da presente revisão, foram apresentadas recomendações para se avançar nos estudos de epidemiologia do ciclo vital no Brasil.Foram incluídos na revisão os estudos com delineamento de coorte realizados no Brasil que iniciaram a linha de base do estudo no período pré-natal ou no nascimento e com pelo menos dois acompanhamentos com os participantes. Não foram incluídos os que descrevem só a linha de base e não os acompanhamentos realizados. Para atender ao conceito de ECV, foram excluídas aquelas coortes cujos acompanhamentos foram restritos ao primeiro ano de vida, as coortes que não abordaram aspectos biológicos, comportamentais e psicossociais e as coortes com coleta de informações em um único estágio do ciclo vital. Foram considerados estágios do ciclo vital o período perinatal (entre a 22ª semana de gestação e os seis dias de vida), infância (entre a primeira semana de vida e os seis anos de idade), idade escolar (entre 6 e 12 anos), adolescência (entre 12 e 18 anos) e vida adulta (18 anos ou mais)As seguintes informações foram extraídas dos estudos selecionados: localização geográfica da coorte ; ano de início da coorte (linha de base); tipo de coorte conforme a idade dos participantes na linha de base, dividido em nascimento (recrutamento dos participantes iniciado no momento do nascimento) e pré-natal (recrutamento iniciado durante a gestação); tipo de coorte quanto ao momento de ocorrência da exposição e do desfecho e o início do estudo, divido em prospectiva (os dados de exposição foram coletados no início do estudo e o desfecho ainda não ocorreu), retrospectiva  e ambispectiva (os dados de exposição foram coletados no passado e o desfecho ainda não ocorreu); tipo de dados utilizados na coorte, divididos em primários  e secundários ; base de referência da mostra, dividida em hospitalar  e populacional (representativa ou de conveniência); número de participantes na linha de base; número de participantes no último acompanhamento; idade média dos participantes no último acompanhamento; número total de acompanhamentos realizados com os participantes; idade média dos participantes em cada acompanhamento; principais informações coletadas em cada fase do ciclo vital.Esses dados foram complementados com informações extraídas de publicações da lista de referências dos artigos selecionados, de páginas eletrônicas dos estudos de coortes, por contato via endereço eletrônico com pesquisadores dos estudos e consultas a bancos de dissertações e teses. Por fim, realizou-se uma análise descritiva das principais características das coortes incluídas na revisão.A etapa de busca identificou 5.010 artigos nas bases de dados, sendo excluídos 1.678 artigos duplicados. Após leitura dos títulos e resumos, foram excluídos 2.904 artigos por não atenderem aos critérios de elegibilidade. Após leitura do texto completo, foram identificados 428 artigos de 79 estudos de coorte realizadas no Brasil iniciadas no período pré-natal ou no nascimento e com pelo menos dois acompanhamentos com os participantes. Dessas 79 coortes, foram excluídas 41 com acompanhamentos restritos ao primeiro ano de vida e cinco que não abordaram aspectos biológicos, comportamentais e psicossociais. Devido ao interesse em analisar coortes que exploram os efeitos de exposições que acontecem no período perinatal, infância, adolescência e em fases posteriores do ciclo de vida, foram excluídas quinze coortes com coleta de informações em um único estágio do ciclo vital. Ao final, foram selecionadas 18 coortes (n = 345 artigos). O fluxograma das etapas da revisão está ilustrado na 14, 15 iniciaram-se no nascimento14 e três coortes iniciaram-se no período pré-natal31. Todas as coortes foram prospectivas e coletaram dados primários. Dez coortes20 tiveram uma amostra representativa da população de referência na linha de base, sete coortes30 utilizaram uma amostra de conveniência e uma única coorte foi de base hospitalar23. O número de participantes na linha de base variou de 189 a 7.747 indivíduos (mediana de 2.000). A média de idade no último acompanhamento variou de 2 a 30 anos (mediana de 9 anos) e o número de acompanhamentos variou de 2 a 11 (mediana de 4), conforme observado na Das 18 coortes identificadas29 e investigaram mais dados de morbidade e estilo de vida. Seis coortes acompanharam os participantes na fase precoce da vida adulta26, com coleta de dados de morbidade, práticas alimentares, medidas antropométricas, cognição, estilo de vida e capital humano. A informação menos frequentemente coletada na fase adulta foi saúde mental. Do total de coortes, 14 realizaram coletaram material biológico (sangue e/ou fezes)14 em algum momento do ciclo vital  em pelo menos um dos acompanhamentos. As informações mais frequentes coletadas no período perinatal foram características do momento do parto, do recém-nascido, morbidade e hábitos de vida da gestante, enquanto a menos frequente foi a saúde mental da mãe da criança. As características mais investigadas do participante na infância foram morbidade, práticas alimentares e aleitamento materno, e a menos frequente foi a vacinação. As coortes que realizaram acompanhamento com os participantes na idade escolar coletaram com maior frequência dados de morbidade e em menor frequência, informações sobre saúde bucal. Cinco coortes acompanharam os participantes na adolescêncialo vital .14, foi formada por 239 crianças nascidas em 2000–2001 e realizou mais três acompanhamentos  para análise de exposição de mercúrio. A perda no último acompanhamento dessa coorte foi de 59,3% em relação ao número de participantes da linha de base. A coorte mais recente da região Norte foi realizada no Acre, conhecida como estudo Materno-Infantil no Acre (Mina), iniciada entre julho de 2015 e junho de 2016 no município de Cruzeiro do Sul15. A coorte Mina foi formada por todos os nascidos vivos residentes na zona urbana do município (n = 1.195), dos quais 588 tiveram dados coletados no período pré-natal (até o segundo trimestre de gestação). Essa coorte realizou três acompanhamentos com as crianças até o momento  e a perda de acompanhamento aos 24 meses foi de 28,6%.A 16. Essas crianças foram acompanhadas a cada três meses durante os dois primeiros anos de vida, no período entre os anos de 1989 e 1993, para registros de doenças diarreicas, informações dietéticas e medidas antropométricas. Essa coorte realizou um total de nove acompanhamentos , com perda no último acompanhamento de 59,3%. A coorte realizada em cinco municípios de Pernambuco , iniciada em 1993, incluiu 549 nascidos vivos entre janeiro de 1993 e agosto de 199417. Essa coorte realizou oito acompanhamentos  e teve perda no último acompanhamento de 60,5% dos participantes. Foram identificadas duas coortes de base populacional realizadas no município de São Luís, no Maranhão. A primeira, iniciada no ano de 1997, incluiu 2.691 nascidos vivos únicos e realizou dois acompanhamentos com os participantes (entre os 7 e 9 anos e entre os 18 e 19 anos), com perda no acompanhamento entre os 18 e 19 anos de 75,3%18. A segunda coorte foi iniciada em 2010, conhecida como Brisa São Luís, e incluiu 5.166 nascidos vivos na linha de base, dos quais 1.447 tiveram dados coletados no pré-natal20. Até o momento, a Brisa São Luís acompanhou as crianças na faixa etária entre 13 e 30 meses, com 36% de perdas em relação à linha de base. Na Bahia, tem-se a coorte no município de Feira de Santana, iniciada em abril de 200419, que incluiu 1.309 nascidos vivos, realizou dez acompanhamentos com os participantes  e teve perda de 48,7% no último acompanhamento.No Nordeste, identificaram-se cinco coortes. A coorte de Fortaleza, no Ceará, teve início no ano de 1989 e incluiu 189 crianças nascidas na favela de Gonçalves Dias21, 199422 e 201024, e uma foi de base hospitalar, iniciada em 200123. A coorte de Ribeirão Preto iniciada em 1978 incluiu 6.764 nascidos vivos únicos, realizou três acompanhamentos  e teve 69,5% de perda no último acompanhamento. A de 1994 recrutou 2.846 nascidos vivos únicos, realizou dois acompanhamentos com os participantes (entre os 9 e 11 anos e entre os 22 e 24 anos), com perda de 78,1% no último acompanhamento. A coorte iniciada no ano de 2010, conhecida como Brisa Ribeirão Preto, incluiu 2.443 nascidos vivos únicos do referido ano, dos quais 1.417 tiveram dados coletados no período pré-natal. Até o momento, ela acompanhou as crianças entre 13 e 30 meses de vida, com perda de acompanhamento de 46%. A coorte de Ribeirão Preto iniciada em 2001, conhecida como Projeto Gesta-Álcool, acompanhou 449 gestantes no terceiro trimestre de gestação e realizou dois acompanhamentos com os participantes (entre os 6 e 7 anos e entre os 11 e 12 anos), com perda de 87,5% no último acompanhamento.Na região Sudeste, foram identificadas quatro coortes, todas no município de Ribeirão Preto, no estado de São Paulo. Três foram de base populacional, iniciadas em 197825. As coortes subsequentes e ainda em curso envolveram 5.249 nascimentos no ano de 1993 com 11 acompanhamentos 26; 4.231 nascimentos no ano de 2004 com sete acompanhamentos 29 e, na coorte mais recente, 4.226 recrutamentos no período pré-natal no ano de 2015 com quatro acompanhamentos até o momento 31. As perdas no último acompanhamento das coortes de Pelotas de 1982, 1993, 2004 e 2015 foram, respectivamente, 37,4%, 21,8%, 15,8% e 9,2%. As outras três coortes identificadas foram a de São Leopoldo iniciada em 200127, a de Pelotas iniciada em 200228 e a de Porto Alegre iniciada em 200830. A coorte de São Leopoldo recrutou 500 pares mãe-filho entre outubro de 2001 e junho de 2002 e realizou quatro acompanhamentos com os participantes , com perda no último acompanhamento de 38,6%. A coorte de Pelotas incluiu todos os 2.741 nascidos vivos entre setembro de 2002 e maio de 2003 na área urbana do município e acompanhou uma amostra aleatória de 30% (n = 973) aos 1, 3 e 6 meses de vida e aos 8 anos de idade, com perda de 36,7% no último acompanhamento. A coorte de Porto Alegre iniciou-se com 715 gestantes recrutadas na terceira semana de gestação e realizou três acompanhamentos , com 33,6% de perda no último acompanhamento.Na região Sul do país, identificaram-se sete coortes, todas no estado do Rio Grande do Sul. Destacam-se as coortes de base populacional de Pelotas, pelo elevado número de indivíduos recrutados, pelo maior número de acompanhamentos com os participantes e por terem acompanhado seus participantes desde o nascimento até a adolescência e o início da vida adulta. Dos 345 artigos selecionados na presente revisão sistemática, 75% corresponderam a publicações derivadas dessas coortes. A primeira coorte de nascimentos de Pelotas foi iniciada em 1982 e envolveu 5.914 crianças, com nove acompanhamentos até o momento 25, 199326 e 200429, as coortes de Ribeirão Preto de 197821 e 199422 e a coorte de São Luís de 199718. As perdas de acompanhamento relacionaram-se à não localização dos participantes do estudo, ao movimento migratório dentro do próprio país e às recusas. As variáveis mais exploradas foram os dados sociodemográficos, ambientais e domésticos da família, morbidade e estilo de vida maternos, dados de morbidade, aleitamento materno e práticas alimentares na infância, morbidade na idade escolar, morbidade e estilo de vida na adolescência e aspectos de saúde integral na fase adulta.As coortes brasileiras identificadas, iniciadas no período pré-natal ou nascimento, foram do tipo prospectivas e coletaram dados primários. Até o momento, poucas acompanharam os participantes na adolescência (n = 6) e na fase adulta (n = 5). Destacaram-se seis coortes pelo maior número de participantes na linha de base, pela abordagem integral da saúde da criança, do adolescente e do adulto e por acompanhar os participantes em mais fases do ciclo de vida: as coortes de nascimento de Pelotas de 198233, permitindo as análises entre gerações. Já as coortes de pré-natal e nascimento de países de renda média e baixa apresentam com frequência dificuldades relacionadas à falta de recursos financeiros, morte precoce de crianças e migração interna, sendo pouco frequente o acompanhamento dos participantes em fases mais avançadas do ciclo vital12.Nos países de alta renda, é frequente que as coortes de pré-natal e nascimento, além de acompanhar por tempo prolongado seus participantes, não se limitem aos indivíduos de uma única geração, incluindo também seus descendentes34. O tamanho da amostra e as perdas de acompanhamento foram pontos fracos da maioria das coortes identificadas. Diminuir a perda de acompanhamento ao longo do tempo representa um desafio, já que perdas diferenciais entre os grupos expostos e não expostos tendem a introduzir vieses nos estudos de coorte6.Foram observadas algumas características e dificuldades metodológicas das coortes identificadas. A maioria realizou acompanhamentos em duas fases do ciclo vital . Embora exista a exigência de resultados imediatos para satisfazer e estimular os financiadores e participantes do estudo, é sabido que os resultados mais importantes na perspectiva do ciclo vital são aqueles que analisam a influência das exposições precoces sobre a saúde e bem-estar em estágios posteriores da vida e com medidas repetidas em diferentes fases da vida de um indivíduo36. Além desse investimento de tempo, esforço e contribuição intelectual, manter um estudo de coorte em funcionamento é bastante custoso. O financiamento em níveis adequados e em longo prazo pode definir se o estudo poderá se estender no tempo. Frequentemente os estudos de coorte são financiados por agências do governo e organizações internacionais, sendo vulneráveis às prioridades políticas e governamentais, ou por fundações de pesquisa locais que não garantem a sustentabilidade e disponibilidade de recurso financeiro em longo prazo37.O processo de desenvolvimento dos estudos de coorte mostra-se desafiador. A implantação de uma coorte requer uma estreita colaboração entre as instituições envolvidas, os profissionais de saúde e as famílias, assim como uma logística laboriosa para a correta execução das fases do estudo , incluindo procedimentos de controle de qualidade em todas as etapas38. A possibilidade de verificar a natureza das associações entre exposições e desfechos em diferentes contextos e comparar resultados entre coortes existentes é outra vantagem40. As coortes brasileiras têm o potencial de desenvolver a capacidade científica do país, com a formação de pesquisadores e aprimoramento do processo de coleta e análises de dados11, além de auxiliar tomadores de decisão na análise de determinantes de saúde e no fortalecimento dos cuidados à saúde prestados41.O desenvolvimento de coortes no Brasil é importante por diversas razões. As novas exposições decorrentes das transições demográfica, epidemiológica, nutricional e assistencial vivenciadas pelo país demandam novas investigações sobre seus efeitos na saúde da população brasileira7. Esse argumento é justificado por oportunizar a coleta de novas informações de risco e recrutar participantes sub-representados em estudos existentes, mas esbarra em sérios desafios orçamentários requeridos por coortes desse porte42. Em contrapartida, outros autores44 argumentam que a representatividade não é necessária para determinar a relação entre fatores ambientais ou genéticos e o risco de doença. Esses últimos sugerem estratégias de combinação de dados de coortes já existentes44 e com a formação de consórcios de coorte nacionais e internacionais43. Um estudo de revisão sistemática de coortes europeias concluiu que uma rede de estudos de coorte coordenados, seguindo um protocolo geral harmonizado e com perspectiva de uma interpretação conjunta de dados, aumentaria o impacto científico e o interesse de colaboração internacional por essas pesquisas45.Tendo em vista a importância de coortes iniciadas no período pré-natal e ao nascimento no Brasil, coloca-se em discussão a dicotomia entre o desenvolvimento de novas coortes ou investimento nas coortes já existentes. Autores internacionais defendem a instauração de novas coortes de base populacional em países com diversidade socioeconômica e racial/étnica, com acompanhamentos anuais e avaliação das exposições de maior relevância local para múltiplos desfechos de saúdeAs coortes com população representativa de Pelotas, Ribeirão Preto e São Luís correspondem às coortes de nascimento com maior potencial de estudar precursores biológicos, comportamentais, sociais e genéticos das doenças crônicas no Brasil. As de Pelotas são os maiores estudos de coorte de nascimentos de base populacional em países de baixa e média renda, com quase quatro décadas de trabalho, mais de 20.000 indivíduos estudados ao longo da vida, avaliações regulares na infância e adolescência e as taxas mais baixas de perda de acompanhamento dos participantes. As coortes de nascimento de Ribeirão Preto e São Luís, iniciadas em parceria com o mesmo grupo de pesquisadores, estudaram cerca de 17.000 e 7.000 indivíduos, respectivamente, e preveem mais acompanhamentos com seus participantes. Localizada em uma região com características socioculturais distintas e que carece de pesquisas, a coorte Mina, em Cruzeiro do Sul, no Acre, também possui potencial para contribuir para estudos de ciclo de vida no Brasil, uma vez que é a primeira coorte iniciada no nascimento, com abordagem integral da saúde da criança, na região amazônica.Em conclusão, a presente revisão identificou coortes iniciadas no período pré-natal e ao nascimento no Brasil com potencial para estudos de epidemiologia do ciclo vital. Essas coortes diferem quanto ao tamanho da amostra, número de acompanhamentos e fase do ciclo vital em que os indivíduos foram acompanhados, bem como taxas de perdas de acompanhamentos. Recomenda-se que as coortes brasileiras iniciadas no período pré-natal e no nascimento tenham número de participantes suficiente para realizar análises do efeito de determinantes precoces em resultados de saúde em curto, médio e longo prazo. Além disso, para que se ampliem as análises de epidemiologia do ciclo vital no Brasil, é necessário que as coortes existentes contemplem diferentes contextos sociais e realizem acompanhamentos com os participantes em diferentes fases da vida.


To estimate the prevalence of high-risk human papillomavirus (HR-HPV) anal infection and associated factors in human immunodeficiency virus (HIV) positive patients in Medellín.Descriptive cross-sectional study in 300 HIV-positive patients, adults, with history of anal intercourse, treated in two health care services of Medellín 2017–2018. We conducted a structured survey on sociodemographics, sexual behavior and medical history. HPV was detected in anal swabs tested by the COBAS 4800 system. Exploratory data analysis of risk factors associated with HR-HPV was conducted by chi-square test of independence and both raw and adjusted prevalence ratios used the Poisson regression model, at a 95% confidence interval.The high-risk HPV had a prevalence of 82.7%; HPV16 had a prevalence of 32.7%, HPV18 a prevalence of 21.7% and other HPV types scored 78.3%. The high-risk HPV prevalence in women was of 68.2% and 83.8% in men. The risk factors associated with high-risk HPV after adjustment were age under 30 years, elementary education, casual sex partners, and first sexual activity before 18 years old.The high incidence of high-risk HPV, along with the occurrence of coinfections by multiple types in the study population shows their susceptibility to develop some type of anal intra-epithelial neoplasia. It is important to establish sexual health programs focused on primary health care. Anal intercourse and high number of sexual partners are important risk factors in the direct transmission of the virus, through the contact with the squamous epithelium and the anal transitional zone. Likewise, human immunodeficiency virus (HIV) concomitant infection and the use of highly active antiretroviral therapy (HAART) increase the survival rate of patients, promote HPV persistence and progress intraepithelial lesions. Thus, anal cancer is one of the most important non-AIDS-defining cancers 6 .The etiology of anal cancer is associated with the persistent infection by the human papillomavirus (HPV), present in more than 80% of the cases. The most frequent virus is the 16 genotype, detected in nearly 70% of biopsies 9 . Epidemiological, pathogenical and clinical characteristics of the anal cancer are similar to those of cervical cancer. This leads to the incorporation of several strategies for early detection of anal cancer: anal cytology, high resolution anoscopy (HRA) and biopsy 10 , which are contemplated by the anal cancer early detection program proposed in the United States for the high-risk population, HIV-positive people included 11 .The prevalence of HPV infection in the anal canal is high for HIV-positive people, and even greater in men who have sex with men, where rates range between 40% and 92% 13 .Colombia lacks structured protocols for the prevention of anal neoplasia, despite the increasing trend of HIV infection. According to the Colombian Ministry of Health, 46,348 new HIV cases were reported in 2013, rising up to 61,147 in 2015, which equals a 0.1% prevalence. These figures account for a population at risk of infection by HPV and premalignant lesions in the anal canal 14 . This study estimates the prevalence of high-risk HPV infection in the anal canal in HIV-positive patients and its relation with epidemiological, clinical and sexual behavior factors. These evidences can support the importance of establishing diagnosis and treatment protocols for anal intra-epithelial neoplasia (AIN) within this specific population.The cases of anal cancer are reported within the colon and rectal cancer group in Colombia, according to the CIE 10-C21 classification. It hides the extent of the problem, as it prevents the availability of epidemiological information regarding the behavior of the anal neoplasia and HPV infection, important data to implement prevention and early-detection programs Descriptive study conducted with 300 participants over 18 years old, HIV-positive and with a history of anal intercourse, selected out of 2,000 patients treated in two health care services offering HIV programs in Medellín. These services referred patients to the Cytology Service of the School of Microbiology from Universidad de Antioquia, where they were invited to join the research from June 2016 to December 2018.The referred patients received information on the research. Each individual answered a structured questionnaire, previously validated in form and content and subjected to pilot testing. The questionnaire was divided into survey blocks: sociodemographic characteristics, risk factors, sexual behavior, signs and symptoms and information about the tests.The evaluated factors were: sexual partner, being considered as regular sexual partner those with whom a stable affective relationship is maintained; and as casual sexual partner those with whom casual sex happens, without affection; in such case, there may be one or several partners. Tobacco or alcohol consumption: those who consume these substances or had done it in the past, regardless of frequency. Condom use: frequent or regular condom use. AIN symptoms: rectal pain, rectal bleeding, feeling of lumps in the rectum or abnormal rectum discharges the participant may had experienced at some point in life. History of benign lesion, and any anal or perianal lesion, such as anal fissures, fistulas, warts or abscesses.16 . The remaining material in the cervical brush was deposited in a vial filled with Thin Prep PreservCyt solution, orbitally shaken for several seconds for cells to be obtained. This sample was analyzed in the Infection and Cancer Group of Universidad de Antioquia using the COBAS 4800® system (Roche Diagnostics), that simultaneously identifies the types HPV16 and HPV18 along with the other 12 high-risk genotypes . This method amplifies a 200bp segment of the HPV L1 gene, identified by genotype-specific PCR fluorescent oligonucleotides probes in real time 17 . The results of the sample were: either positive or negative for HPV16, HPV18 or other high-risk genotypes. The results were informed to each participant and to the health care service providing treatment.An anal swab was collected from each participant, by a cervical brush, and the samples were deposited in microscope slides, according to the guidelines of Darragh T et al. We realized a descriptive analysis with median and mode measures of central tendency, and inter-quartile range as measure of dispersion. We created three HPV groups, one for the 16 genotype, one for the 18 genotype and one for others HR-HPV, determining the frequencies according to the sociodemographic characteristics. We investigated the correlation, by comparing the risk factor occurrence to HPV infection, using the Chi-square test of independence, the Fisher’s exact test and Chi-square distribution. The raw prevalence ratios were calculated at a significance level of 0.05.We proposed three Poisson regression models, having the presence or absence of HR-HPV as the outcome variable, the first one including HPV16, the second including HR-HPV18 and the third one encompassing all high-risk genotypes. We included the factors at p < 0.25 in the model with bivariate analysis. The confidence intervals were set at 95% and the statistical significance p < 0.05, both for bivariable and multivariable determinants. The statistical analyses were performed in the Stata Release 15 and EpiData 3.1 version software.This research was authorized by the Bioethics Committee of the Facultad Nacional de Salud Pública de la Universidad de Antioquia under an act dated July 9, 2015, which was updated by the act no. CI00328, dated August 9, 2018. According to the Resolution no. 8430 issued by the Colombian Ministry of Health, this research was classified as greater than minimal risk. The principles of data confidentiality, handling and custody were based on the Declaration of Helsinki and on The Council for International Organizations of Medical Sciences (CIOMS) guidelines. The participants signed off an informed consent form.Of the 300 participants, 92.7% were men. The average age was 39 years old for men and 45 years old for women. Among participants, 49.7% were aged between 30 and 50 years old. Ninety five percent lived in the urban area and 84.5% had a middle-low socioeconomic status, 56% attended college and 54% were covered by the contributory health care system   .The HR-HPV infection prevalence (of at least one of the detectable genotypes by the exam) was of 82.7%, 95%CI 78.2–87.1; VPH16 prevalence was of 32,7%, 95%CI 27.2–38.1; VPH18 prevalence was of 21.7%, 95%CI 16.8–26.5 and other genotypes prevalence was of 78.3%, 95%CI 73.5–83.2. The prevalence of HPV infection by multiple genotypes, three or more, was 10.3%, 95%CI 6.72-13.94 .The bivariate analysis shows the prevalence of infection by the HPV types that the exam detects. The occurrence of HR-HPV, HPV16 and other types of HR-HPV was higher in men under 30 years old, insured by the contributory regime, middle-high stratum and who had completed higher education. The infection by HPV18 y > 2HPV was greater in the middle-low stratum. Despite the low number of participants residing in the rural area, the HPV genotypes distribution was similar in both places of residence, with the exception of HPV18, which was notoriously smaller in the rural area (6.7%) than the urban (22.5%)   .The average age of first sexual intercourse was 15 years old and 17 years old for the first anal intercourse, without significant difference per gender. The average time elapsed since HIV diagnosis was 6.9 years. Of the participants, 98.7% were receiving HAART therapy. Those with casual sexual partners presented higher risk of infection by HPV16. Those who had sex in exchange for money at some point, tobacco users and those who had not frequently used condoms presented a higher risk of HPV18 infection. The infection by HR-HPV was related to: casual sexual partners, regular sexual partners, first sex intercourse before 18 years old, history of 10 plus sexual partners and history of benign lesions, such as anal fissures, ulcers, abscesses and fistulas. Having a HIV diagnosis in the past three years or more was a protective factor against infection by HR-HPV, HPV16 and HPV18   .The infection by HPV16 was related to age in the multivariate analysis using the Poisson regression model. The risk of infection reduced as the participants’ ages increased, especially over 50 years old, age in which the risk was lower than 50%; and the risk of infection was also related to having a casual sexual partner. The model was adjusted by gender. The infection by HPV18 was related to age, presenting the same pattern as HPV16, with the risk being lowered to 60% over 50 years old. The infection by HPV18 was also associated with sex in exchange for money, infrequent use of condoms and history of benign anal lesions. The infection by HR-HPV was connected to the educational level, the individuals with higher education and a sexual partner, whether regular or casual, presented a lower risk once this gender and age connection was adjusted   .18 . The larger proportion of men in the study is due to the fact that they are, in large account, homosexuals, engaged in anal intercourse, from which they contracted HIV. In addition, in the male population anal intercourse is increasingly common, whether they are homo or bisexuals 19 .The main sociodemographic characteristics of the participants are comparable with those of the HIV-positive patients at national level, which supports the representativeness of the sample, although it was not randomly selected. The majority of participants are insured by the contributory health care system, live in the urban area and over 75% are men 21 ; in Japan, a rate of 76% found in 421 MSM 22 ; in China, a rate of 61% found 212 MSM 23 and in Korea, a rate of 47% found in 201 men with the same characteristics 24 . In South Africa, Muller et al. 26 reported a prevalence of 58% found in 191 MSM, 81% found in HIV-positives and 39% in HIV-negative individuals, emphasizing the disparity in infection occurrence according to the serological status of participants. Studies show that this infection is 4 to 10 times more frequent in MSM than in heterosexual men, and the presence of HIV increases the risk.The oncogenic HPV prevalence rate found in the 300 HIV-positive participants was 82.7%, which is higher than globally reported rates. Studies carried out in the Asian region report rates in HIV-positive men ranging between 45% and 74% in Taiwan 28 research in Puerto Rico shows, with 79% of prevalence in 239 HIV-positive participants and a low proportion of heterosexual men 28 . In the United States (USA), an incidence higher than 74% in MSM HIV-positive was found 29 . These rates are similar to those in this study. The high HR-HPV prevalence in MSM HIV-positive indicates a higher risk of anal cancer in this population group because the HIV infection increases their susceptibility to reinfections, persistence and infection reactivation by HPV 30 . Both are sexually transmitted diseases (STD), thus the associated risk behaviors for HIV can also influence the HPV infection 23 .The incidence of HR-HPV in the American continent also varies, as the Medina et al. 31 , a rate lower than the one found in the USA (76%), where the rate almost doubled those of HPV cervical, both for HIV-positive and HIV–negative women 8 . In this study, the women proportion was low and, yet, the occurrence of HR-HPV in the anal canal was close to that reported in the USA. Also, the proportion of women who engaged in anal intercourse was similar in Brazil, USA and in this research. This emphasizes the need to assess other determinant aspects on anal infection by HPV in this population, such as history of gynecologic malignancies, an association supported by research conducted with women presenting uterinecervix neoplasias 32 .Studies focused on women are scarce, reporting variable infection rates. Of 138 Brazilian HIV-positive women, 43% tested positive for oncogenic HPV 4 . The prevalence of 16 and 18HPV in this study was slightly higher than what was found in studies where variable prevalence’s are reported. In the USA, the infection rates by HR-HPV were of 47%, by HPV16 of 28%, by VPH18 were of 11%; in Italy, the infection rates by HPV16 were of 27% and by HPV18 of 14%; in Puerto Rico, where the same commercial exam for viral DNA detection we used was employed, a similar rate for other HPV types was found (79%), and rates were slightly lower for the 16 and 18 genotypes, with 28% and 16%, respectively 28 . The HPV18 rates found in this study are higher than what were found by other studies, showing possible greater importance of this genotype in our environment. The dissimilar results can show that HR-HPV distribution varies within the different MSM groups and according to the HIV status. Other explanation is the peculiar characteristics of each study population.The 16 and 18 HPV genotypes have a major involvement in the carcinogenesis, as they were detected in 85% and 7%, respectively, of invasive anal cancer biopsies. Their presences at this anatomical area are a risk factor for anal cancer in itself, as it increases when multiple genotypes are found 34 , but the commercial kits used vary on their ability to identify the viral genotypes. This can lead to minimal differences in prevalence, especially regarding multiple types infections 29 . The COBAS 4800 method used in this study can only specifically detect HPV16 and 18, but is unable to determine possible multiple infections of the 12 other genotypes.The diagnosis exams employed in the different analyzed studies were based on PCR, a high-sensitivity and specificity test for detection of the virus 24 . In contrast, studies that included HIV population only, men or MSM only, regardless of their serological status, found high prevalence. Same results were reported by studies carried out in urology clinics, HIV clinics, etc 25 . These aspects have a decisive effect on the prevalence in groups with specific characteristics and also explains the high infection rates in this study, which included participants presenting the two major risk factors in the etiology of HPV infection: the immunodeficiency caused by HIV and anal intercourse.Likewise, distinctive characteristics of the study population and of the study itself can influence the findings. Studies with samplings smaller than 200 individuals reported low prevalence of HR-HPV 35 , where the main risk factor was history of STD, use of hallucinogens and presence of warts. Glick et al. 36 reported results similar to those of this study regarding the change of partners, by finding that, for each additional partner in the past three months, the infection prevalence increased 24% and the incidence, 32%. Also, Natera et al. 37 observed the risk increases if an individual has more than two sexual partners.Regarding the HR-HPV risk factors for HIV-positive patients explored in this study, the higher risk was found in individuals with casual sexual partners and first sexual intercourse before 18 years old. These factors are different from those found in other studies, such as the one conducted by Chia-Chun Lin, et al. in Taiwan 21 ; in Korea, 34% were women, of which 47.3% were 50 years old or older, an age where HPV infection significantly decreases; besides, 70% had not attended college, and proportion of homo/bisexual men was of 66.2% 23 . In the study conducted with Brazilian women, 52.2% of participants had anal intercourse once in their lifes 31 , while in this study, all participants were compliant with the criteria. In this same sense, in this study, the men proportion was high, the majority was receiving HAART therapy, all were HIV-positive and had anal intercourse as inclusion criteria.The higher prevalence of HR-HPV found in this study differs from other studies, probably due to the differences in the characteristics of the study population. In Taiwan, 51.4% were receiving HAART therapy and 33.3% engaged in anal intercourse 33 worked as a protective factor, and the HAART therapy 22 was not significant in the statistical model we used. Thus, these variables must be analyzed in detail by further studies, because of their implication to the progression of AIN.It was difficult to compare the HPV infection incidence found with other studies, probably due to the sociodemographic and clinical differences among the participants, along with the inclusion criteria in each study. Yet, we were able to observe that age, educational level, anal receptive intercourse, casual sex partners and first sexual activity under the age of 18 are predictive factors for risk of HR-HPV infection. However, the time elapsed since the HIV diagnosis Using exams that analyze other HR-HPV genotypes altogether hinders an individual analysis. Thus, we could not extract the incidence data for each one of them in the study population, which would make the study richer.Being a cross-sectional study, we were able to explore the possible risk factors implicated in the anal infection by oncogenic HPV. However, analytical epidemiologic studies are required to deepen the subject and detect the critical aspects to which prevention campaigns must aim. The viral detection method used did not identify the other 12 types of oncogenic HPV. Thus, the coinfections prevalence may be higher than reported because of the possible presence of more than one HPV strain in the participants. While the HIV infection status  are greatly important aspects for HPV infection, satisfactory up-to-date data were not available to be included in the analysis.22 . The strong presence of other oncogenic virus types, such as 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 in the anal canal of these patients shows the need to further explore the role they play in carcinogenesis. Such aspects must be considered in primary prevention strategies currently considered towards this population.The findings of this research allow a baseline of the HR-HPV infection in the anal canal of the HIV-positive population, which was unknown up to now in the Colombian context. The high prevalence of HR-HPV infection and, especially of the 16 and 18 types of evidence the strong exposure to these virus genotypes to which the HIV-positive population engaged in anal intercourse is subjected to. Consequently, the findings point to the risk of anal neoplasia and its possible progression to anal cancer; especially considering the multiple genotypes infections, which suggest their persistence over time, increasing the risk  2 .El cáncer anal es un tema de interés para la salud pública, en particular en la población VIH positiva, en quienes se reporta incidencias ajustadas por edad de 30 por 100.000 años-persona en mujeres y de 130 en hombres que tienen sexo con hombres (HSH) 3 . Las relaciones sexuales anales y el alto recambio de parejas sexuales son factores de riesgo importantes para la transmisión directa del virus al entrar en contacto con el epitelio escamoso y zona de transición anal. Asimismo, la infección concomitante por el virus de inmunodeficiencia humana (VIH) y el uso de terapia antirretroviral altamente efectiva (HAART) aumentan la tasa de sobrevivencia de los pacientes, favorece la persistencia del VPH, la instauración y progresión de las lesiones intraepiteliales. Por esta razón, el cáncer anal es uno de los cánceres no definitorios de SIDA más importante 6 .La etiología del cáncer anal se asocia a la infección persistente por el virus del papiloma humano (VPH), presente en más del 80,0% de los casos. Es más frecuente el genotipo 16, detectado aproximadamente en el 70,0% de las biopsias 9 . Características epidemiológicas, patogénicas y clínicas para el cáncer anal son similares a las de cáncer del cuello uterino. Eso lleva a la incorporación de estrategias de detección precoz para el cáncer anal: citología anal, anoscopia de alta resolución (AAR) y biopsia 10 , las cuales se encuentran contempladas en el programa de detección precoz para cáncer anal propuesto en Estados Unidos, a poblaciones de alto riego, entre ellas, personas VIH positivas 11 .La prevalencia de la infección por VPH en canal anal es alta en personas VIH positivas; y aún mayor en los hombres que tienen sexo con hombres, donde las cifras oscilan entre el 40,0% y 92,0% 13 .Colombia no cuenta con protocolos estructurados para la prevención de la neoplasia anal a pesar de que la infección por VIH tiende a crecer. Según estadísticas del Ministerio de Salud de Colombia, se reportaron 46.348 casos nuevos de VIH en el 2013, aumentando a 61.147 en el 2015, que corresponde a una prevalencia de 0,1%. Estas cifras dan cuenta de una población en riesgo de infectarse por VPH y de desarrollar lesiones premalignas en canal anal 14 . Esta investigación tuvo como objetivo estimar la prevalencia de la infección por VPH de alto riesgo oncogénico en canal anal de pacientes VIH positivos y la relación con factores epidemiológicos, clínicos y de comportamiento sexual. Esas evidencias poden sustentar la importancia de establecer protocolos de diagnóstico y de tratamiento de Neoplasia Intraepitelial Anal (NIA) en esta población en específico.Los casos de cáncer anal se reportan en el grupo de cáncer de colon y recto en Colombia, según la clasificación CIE 10-C21. Eso hace difícil visibilizar la magnitud del problema pues impide disponer de información epidemiológica en lo referente al comportamiento de la neoplasia anal y la infección por VPH, datos importantes al momento de implementar programas de prevención y detección precoz Estudio descriptivo, realizado en 300 participantes mayores de 18 años con diagnóstico previo de VIH e historia de relaciones sexuales anales, seleccionados de una población de 2.000 pacientes atendidos en dos instituciones de salud que cuentan con programas de VIH en Medellín. Estas instituciones remitieron a los pacientes al Servicio de Citología de la Escuela de Microbiología de la Universidad de Antioquia, en donde fueron invitados a participar en la investigación de junio de 2016 a diciembre de 2018.Los pacientes remitidos fueron sensibilizados con información acerca de la investigación. Cada individuo respondió una encuesta estructurada dirigida, previamente validada por apariencia y contenido y sometida a prueba piloto. La encuesta fue dividida por los bloques de preguntas: características sociodemográficas, factores de riesgo, conductas sexuales, signos y síntomas y conocimientos sobre la citología.Los factores evaluados fueron: pareja sexual, se tomó como pareja permanente a aquella con la que se tiene una relación estable mediada por el afecto, y como pareja ocasional, con la/s que se tiene relaciones sexuales eventuales sin involucrar sentimientos afectivos; en tal caso puede ser una o varias parejas ocasionales. Exposición a tabaco o bebidas alcohólicas: quienes consumen estas sustancias o lo hicieron en el pasado, independientemente de la frecuencia del consumo. Uso del condón: uso frecuente o de manera regular del mismo. Los síntomas relacionados con NIA: dolor rectal, sangrado rectal, sensación de masa en el ano o secreciones anormales en la zona, que el participante haya podido tener en algún momento de su vida. Antecedente de lesiones benignas, a toda lesión en la región anal o perianal como fisuras, fístulas, condilomas o abscesos.16 . El remanente del citocepillo se depositó en un vial con solución de ThinPrep PreservCyt, agitándose circularmente durante varios segundos para la obtención de células. Esta muestra fue evaluada en el laboratorio del Grupo Infección y Cáncer de la Universidad de Antioquia por la prueba COBAS® 4800 (Roche Diagnostics), la cual identifica en forma simultánea los genotipos VPH16 y VPH18 y en conjunto los otros 12 genotipos de alto riesgo . Este método amplifica un segmento de 200pb del gen L1 del VPH, identificado con sondas de oligonucleótidos fluorescentes específicas de genotipo en PCR en tiempo real 17 . El resultado de la prueba se reportó: positivo o negativo para VPH16, VPH18 y otros genotipos de alto riesgo. Los resultados del examen fueron informados a cada participante y a la institución tratante.A cada participante se le tomó muestra de exfoliado anal utilizando citocepillo ginecológico, la muestra se extendió en láminas de vidrio para citología, siguiendo las recomendaciones de Darrag T et al Se realizó análisis descriptivo mediante medidas de tendencia central como mediana y moda, de dispersión como rango intercuartílico. Se conformaron tres grupos de VPH, uno para el genotipo 16, otro para el genotipo 18 y el otro para el resto de VPH-AR, determinando las frecuencias según las características socio-demográficas. Se exploró la relación, a través de la comparación de la frecuencia de los factores de riesgo con la infección por VPH, mediante la prueba Chi cuadrado de independencia, exacta de Fisher y la prueba Chi cuadrado de tendencia lineal. Se calcularon razones de prevalencia cruda con un nivel de significación de 0,05. Se plantearon tres modelos de regresión Poisson, tomando como variable de desenlace la presencia o ausencia de VPH-AR, el primero incluyó VPH16, el segundo VPH18 y el tercero todos los genotipos de alto riesgo. Se incluyeron los factores con p < 0,25 en los modelos en el análisis bivariado. Los intervalos de confianza se establecieron en el 95% y la significación estadística en el p <0,05, tanto para determinaciones bivariadas como multivariadas. El análisis estadístico se realizó en los programas Stata, Versión 15 y EPidat versión 3.1.Esta investigación contó con el aval del Comité de Bioética de la Facultad Nacional de Salud Pública de la Universidad de Antioquia en el acta del 9 de julio de 2015 y actualizado en el acta CI00328 del 9 de agosto del 2018. Según la Resolución 8430 del Ministerio de Salud de Colombia, la investigación se catalogó como de riesgo mayor al mínimo. Los principios de confidencialidad, manejo y custodia de la información fueron basados en la declaración de Helsinki y las normas de The Council for International Organizations of Medical Sciences (CIOMS). Los participantes firmaran el termo de consentimiento informado.El 92,7% de los 300 participantes eran hombres. La mediana de edad fue 39 años para hombres y 45 años para mujeres. El 49,7% tenían entre 30 y 50 años. El 95,0% residían en zona urbana, el 84,5% pertenecían al nivel socioeconómico medio-bajo y el 56,0% habían accedido a educación superior; el 54,0% pertenecían al régimen contributivo de salud   .La prevalencia global de infección por VPH-AR  fue 82,7%, IC95% 78,2–87,1, VPH16 de 32,7%, IC95% 27,2–38,1, VPH18 de 21,7%, IC95% 16,8–26,5 y para otros genotipos 78,3%, IC95% 73,5–83,2. La prevalencia de infección por VPH con múltiples genotipos, tres o más, fue de 10,3%, IC95% 6,72–13,94 .El análisis bivariado muestra la prevalencia de infección por los tipos de VPH que detecta la prueba. La frecuencia de VPH-AR, VPH16 y otros tipos de VPH-AR fue mayor en hombres menores de 30 años, del régimen contributivo, estrato medio-alto y con educación superior. La infección por VPH18 y > 2VPH se encontró en mayor proporción en estrato medio bajo. A pesar del bajo número de participantes residentes en el área rural, la distribución de los genotipos de VPH fue similar en ambas zonas de residencia, con excepción del VPH 18 que fue notoriamente menor en la zona rural  respecto a la urbana    .La mediana de edad de inicio de relaciones sexuales fue 15 años y para el inicio de relaciones anales de 17 años, sin diferencias estadísticas significativas por sexo. La mediana del tiempo del diagnóstico de VIH fue 6,9 años. El 98,7% de los participantes recibían HAART. El mayor riesgo de infección por VPH16 ocurrió en personas con pareja ocasional. La infección por VPH18 se presentó con mayor riesgo entre personas que tuvieron sexo por dinero alguna vez en su vida, consumidores de tabaco y quienes no usaban el condón permanentemente en sus relaciones sexuales. La infección por VPH-AR se relacionó con: tener pareja sexual ocasional, pareja permanente, inicio de relaciones sexuales antes de 18 años, historia de más de 10 parejas sexuales y con antecedentes de lesiones benignas como fisuras, ulceras, abscesos y fístulas en el ano. Tener un diagnóstico de VIH hace tres años o más, fue factor protector tanto para la infección por VPH-AR, como para VPH 16 y 18   .La infección por VPH16 estuvo en función de la edad en el análisis multivariado por regresión de Poisson. El riesgo de la infección fue menor a medida que aumentó la edad de los participantes, especialmente después de los 50 años, edad en la cual el riesgo fue menor del 50%; también estuvo en función de tener pareja sexual ocasional. El modelo fue ajustado por sexo. La infección por VPH18 estuvo en función de la edad, con el mismo patrón que VPH16, disminuyendo el riesgo en un 60%, después de los 50 años. La infección por VPH18 se asoció también con tener sexo por dinero, no usar condón de forma permanente y tener antecedentes de lesiones anales benignas. La infección por un VPH-AR estuvo en función del nivel educativo, siendo menor el riesgo en personas con educación superior y tener pareja sexual ya sea permanente u ocasional; una vez ajustada esta relación por sexo y edad   .18 . Asimismo, la mayor proporción de hombres en el estudio se puede explicar por el hecho de que fueron pacientes en un alto porcentaje homosexuales, con práctica de relaciones anales, mecanismos por el cual adquirieron la infección por VIH. Además, porque en la población masculina son cada vez más comunes las relaciones anales ya sean homo/bisexuales 19 .Las principales características sociodemográficas de los participantes son comparables a las de los pacientes con VIH a nivel nacional; esto respalda la representatividad de la muestra, a pesar de no haber sido seleccionada aleatoriamente. La mayoría pertenece al régimen contributivo de salud, reside en zona urbana y más del 75,0% son hombres 21 , en Japón, prevalencias del 76,0% en 421 HSH 22 , en China del 61,0% en 212 HSH 23 y en Corea de 47,0% en 201 hombres con las mismas características 24 . En Sur África, Muller et al 26 reportan una prevalencia de 58,0% en 191 HSH, 81,0% en VIH positivos y 39,0% en VIH negativos, destacando la diferencia en la frecuencia de la infección según el estado serológico de los participantes. Estudios muestran que esta infección es entre cuatro y 10 veces más frecuente en HSH que en los hombres heterosexuales, riesgo que se incrementa con la condición de VIH 27 .La prevalencia de VPH oncogénico hallada en los 300 participantes VIH positivos fue del 82,7%, superior a las reportadas en el ámbito mundial. Los estudios realizados en la Región Asiática presentan cifras en hombres con VIH que oscilan entre 45,0 y 74,0% en Taiwán 28 en Puerto Rico, con un 79,0% en 239 participantes con VIH y una proporción de hombres heterosexuales baja 28 . En Estados Unidos (EU), se encontró una frecuencia superior al 74,0% en HSH, VIH positivos 29 . Estas cifras son similares a las del presente estudio. La alta prevalencia de VPH AR en los HSH-HIV positivos indican un riesgo mayor de desarrollar cáncer anal de este grupo poblacional, debido a que la infección por VIH incrementa la susceptibilidad para reinfecciones, persistencia y reactivación de infección por VPH 30 . Ambas son infecciones de transmisión sexual (ITS), así las conductas asociadas al riesgo de adquirir VIH también pueden influir en la infección por VPH 23 .La frecuencia de VPH-AR en el continente americano también es variable, como lo muestra el estudio de Medina et al 31 , cifra menor a la hallada en EU , donde este valor casi duplicaba a la del VPH en el cérvix, tanto de mujeres positivas como negativas para VIH 8 . En la presente investigación, la proporción de mujeres fue baja y, sin embargo, la frecuencia de VPH-AR en el canal anal fue similar a la reportada en EU. Asimismo, la proporción de mujeres que practicaban sexo anal fue similar en Brasil, EU y en éste. Eso resalta la necesidad de evaluar en esta población otros aspectos determinantes para la infección anal por VPH, como tener antecedentes de neoplasias ginecológicas, cuya asociación ha sido sustentada en investigaciones realizadas con mujeres con neoplasias cervicouterinas 32 .Son escasos los estudios con la población femenina, los cuales reportan frecuencias de infección variables. En 138 mujeres brasileñas VIH positivas, el 43,0% fue positiva para VPH oncogénicos 4 . La prevalencia de VPH16 y 18 en este estudio fue ligeramente superior a la observada en otras investigaciones donde se reportan prevalencias variables. La infección por múltiples VPH-AR fue de 47,0%, VPH16, 28,0% y VPH18, 11,0% 29 en EU; se encontró VPH16 en 27,0% y VPH18 en 14,0% en Italia 33 ; en Puerto Rico, donde emplearon la misma prueba comercial para la detección del ADN viral que se utilizó en la presente investigación, reportaron una frecuencia similar para otros tipos de VPH , y levemente inferior para los genotipos 16 y 18 con 28,0% con 16,0%, respectivamente 28 . Las cifras de VPH 18 halladas en el presente estudio son superiores a las de las investigaciones analizadas, mostrando una posible importancia mayor de este genotipo en nuestro medio. Los resultados disímiles pueden indicar que la distribución de los VPH-AR varía en los distintos grupos de HSH y de acuerdo a su estado de HIV. Otra explicación, son las características propias de cada población evaluada.Los genotipos 16 y 18 del VPH tienen gran implicación en la génesis del cáncer, pues éstos se han detectado en biopsias de cáncer anal invasor en un 85,0% y 7,0% respectivamente. Su presencia en este sitio anatómico, por sí mismo, se constituye en un factor de riesgo para el desarrollo cáncer anal, el cual se incrementa cuando se encuentran múltiples genotipos 34 , pero los kits comerciales utilizados varían en su capacidad para discriminar los genotipos virales. Esto puede dar lugar a diferencias mínimas en la prevalencia, especialmente para las infecciones por múltiples tipos 29 . El método COBAS 4800 del presente estudio solo detecta de forma específica el VPH 16 y 18, pero no permite determinar posibles infecciones múltiples entre los 12 genotipos restantes,Las pruebas de diagnóstico empleadas en los diferentes estudios analizados se fundamentan en la PCR, prueba con alta sensibilidad y especificidad para la detección del virus 24 . Por el contrario, aquellos estudios que incluyeron únicamente población VIH, solo hombres o HSH, independientemente de su estado serológico, hallaron altas prevalencias. Iguales resultados reportaron aquellas investigaciones realizadas en clínicas urológicas, clínicas de VIH, etc 25 . Estos aspectos tienen un efecto decisivo en la prevalencia en los grupos con características específicas y también explica el porqué de las altas cifras de infección en el presente estudio, donde se incluyeron participantes que cumplían con los dos factores de riesgo de mayor peso en la etiología de la infección por VPH: la inmunodeficiencia dada por el VIH y el sexo anal.De igual manera, características propias de la población de estudio y de la investigación en sí pueden influir en las cifras halladas. Estudios con una muestra menor de 200 individuos reportaron prevalencias bajas de VPH-AR 35 , donde el principal factor de riesgo fue tener historia de ITS, uso de drogas alucinógenas y presencia de verrugas. Glick et al 36 reportaron resultados similares al de la presente investigación con respecto al recambio de pareja, al encontrar que por cada compañero adicional en los últimos tres meses, la prevalencia de la infección aumentó en un 24,0% y la incidencia en un 32,0%. Asimismo, Natera et al 37 observaron que el riesgo aumenta si se tiene más de dos compañeros sexuales.En cuanto a los factores de riesgo explorados para la infección por VPH-AR en pacientes con HIV del presente estudio, el mayor riesgo fue en personas con pareja ocasional e inicio de relaciones sexuales antes de los 18 años. Esos factores son diferentes a los encontrados por otros estudios, como el realizado por Chia-Chun Lin, et al en Taiwán 21 ; en Corea, el 34,0% eran mujeres, de las cuales el 47,3% tenían 50 años o más, edad donde la infección por VPH disminuye significativamente; además, el 70,0% no habían accedido a educación universitaria, y la proporción de hombres homo/bisexuales era del 66,2% 23 . En el estudio realizado en mujeres brasileñas, 52,2% de las participantes habían tenido sexo anal alguna vez en su vida 31 , mientras que en la presente investigación, todas las participantes cumplían con este criterio. En este mismo sentido, en el presente estudio, el porcentaje de hombres fue alto, la mayoría recibía terapia HAART, todos eran VIH positivos y tenían sexo anal como criterio de inclusión.La mayor prevalencia de VPH-AR hallada en este estudio difiere de otras investigaciones, probablemente debido a las diferencias en las características de la población objeto. En Taiwán, el 51,4% recibía HAART y el 33,3% practicaban sexo anal 33 se comportó como un factor protector y la terapia HAART 22 no fue significativa en el modelo estadístico aplicado. Por tanto, estas variables deberán ser evaluadas en futuros estudios a profundidad, debido a su implicación en la progresión a la NIA.Hubo dificultades para comparar las frecuencias de infección por VPH halladas con los otros estudios, debido probablemente a las diferencias sociodemográficas y clínicas de los participantes, así como los criterios de inclusión en cada uno de los estudios. Asimismo, se pudo observar que la edad, el nivel educativo, las prácticas sexuales ano-receptivas, tener pareja sexual ocasional e iniciar vida sexual antes de la mayoría de edad son factores que predicen el riesgo de infección por VPH-AR. No obstante, el tiempo que llevan con el diagnóstico de VIH El tener pruebas que analizan los genotipos de otros VPH AR en conjunto no permite hacer un análisis de éstos por separado. Así, no se pudo tener el dato de la frecuencia de cada uno de ellos en la población analizada, lo cual daría mayor riqueza al estudio.Al ser un estudio transversal, permitió hacer una exploración de los posibles factores de riesgo implicados en la infección anal por VPH oncogénico. Sin embargo, se requiere de estudios epidemiológicos analíticos que profundicen en el tema con el fin de detectar los aspectos críticos en los cuales se deben dirigir las campañas de prevención. El método de detección viral empleado no permitió discriminar entre los otros 12 tipos de VPH oncogénico. Por lo tanto, la prevalencia de co-infecciones puede ser mayor a la reportada debido a la posibilidad de existencia de más de un VPH de estos otros tipos en los participantes. Si bien el estado de la infección del VIH  son aspectos de gran importancia para la infección por VPH, no se disponían de datos actualizados suficientes para incluirlos en el análisis.22 . La fuerte presencia de otros tipos oncogénicos del virus tales como 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 y 68, en el canal anal de estos pacientes revela la necesidad de profundizar en el papel que están desempeñando estos genotipos en la génesis del cáncer. Estos aspectos deben considerarse en las estrategias de prevención primaria que se evalúan actualmente para esta población.Los hallazgos de esta investigación permiten una línea base sobre la infección por VPH-AR en canal anal de la población con VIH, información hasta ahora desconocida en el contexto colombiano. La alta prevalencia para la infección por VPH-AR y en especial los tipos 16 y 18 evidencian la fuerte exposición que tiene la población VIH positiva con relaciones anales a estos genotipos de virus. Consecuentemente, apuntan para el riesgo de neoplasias anales y su posible progresión a cáncer anal; en especial si se tiene en cuenta las infecciones por múltiples genotipos, que sugieren persistencia de éstos por periodos prolongados, incrementando en mayor medida el riesgo