Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS

Detalhes bibliográficos
Autor(a) principal: Leticia Penna Braga
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/BUOS-ASXL8D
Resumo: Background: Antiretroviral therapy (ART) has led to increased life expectancy and has given to HIV infection chronic characteristics, bringing up new challenges for long-term ART use. Over the years, the number of antiretroviral drugs at the pharmaceutical market has increased, allowing modifications in the ART. However, multiple antiretroviral drug modifications increase probability of HIV in developing mutations. HIV could get resistance to antiretroviral drugs from the same therapeutic class, and salvage therapy could be necessary. This study aimed at investigate ART modifications in HIV-infected adults, initiating ART between 2001 and 2005 in three HIV/AIDS referral centers in Belo Horizonte (MG). Method: Non-concurrent cohort study (historical cohort) from three HIV/AIDS referral centers in Belo Horizonte (MG), Brazil. It included treatment nave HIV-infected adults who had their first ART prescription between 2001 and 2005, followed up for at least one year and for a maximum of five years. The main endpoint was ART modifications defined as at least one drug alteration in the triple combined ART or addition to monotherapy or dual therapy with zidovudine (ZDV). Modifications in first ART were evaluated in the first year of treatment. Also, first, second and third ART modifications were assessed in a 5-year follow-up, between 2001 and 2010. For the analysis of first ART modification, all patients from initial cohort were considered (Population 1, n=247). For the analysis of second ART modification, all patients from Population 1, who had at least one ART modification were considered (Population 2, n=119). For the analysis of third ART modification, all patients from Population 2, who had at least a second ART modification were considered (Population 3, n=51). Exposure variables were sociodemographic characteristics, clinical, related to ART and to health care. Descriptive analysis was performed to characterize studied population and ART modifications profile. Pearson's qui-square test was performed to compare frequencies of ART modification in different population categories. The outcome was also describe by incidence of patients who had ART modified expressed in 100 persons-month. Kaplan-Meier curves were employed to describe ART durability in population categories. Multivariate logistic regression analysis was used to evaluate factors associated to first ART modification in the first year of treatment. Cox proportional hazard model was performed to evaluate the hazard ratio of first, second and third ART modifications during five years of follow-up. Results: 247 patients enrolled at initial cohort. 119 (48.2%) patients modified ART at least once and 51 (25.6%) modified at least two times. One patient modified ART five times. The vast majority of modifications occurred in the first year of treatment (53.8%), in protease inhibitor (PI)-based regimens, and the main reason for modification was adverse drug reactions. Among patients who modified ART, median time for first, second and third modifications were 10.7, 13.4 and 5.1 months, respectively. Non-nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens had higher durability when used as first, second and third ART option. Patients who started ART with PI-based regimens had 3.46 higher chance of having at least one ART modification than those who started 10 ART with NNRTI-regimens (odds ratio [OR]=3.46; IC95%=2.02 - 5.92), in the first year of treatment. Over five years, female sex, have AIDS-defining illness before ART and start ART with PI-based regimens or monotherapy or dual therapy with ZDV were risk factors for ART modification (hazard ratio [HR]=1.67; CI95%=1.08 - 2.57; HR=1.59; CI95%=1.01 - 2.51; HR=2.50; CI95%=1.54 - 4.04 e HR=11.45; IC95%=4.28 - 30.63, respectively]. It was not verified any variable statistically associated to second ART modification. Patients who had more than four medical visits per year were at higher risk of third ART modification (HR=7.12; CI95%=1.95 - 26.07), as well as those who start third ART with PI-based regimens (HR=4.84; CI95%=1.32 - 17.83). Conclusions: PI-based regimens are not well tolerated and are more modified due to adverse drug reactions. Delay in ART start makes treatment more complex and it is associated to ART modifications in the first year of treatment. Monitoring the adverse reactions to antiretroviral drugs at any stage of treatment is essential to avoid modifications in ART, contributing to ART effectiveness.
id UFMG_dae9e6a94e7a20ddcf5ede936879900e
oai_identifier_str oai:repositorio.ufmg.br:1843/BUOS-ASXL8D
network_acronym_str UFMG
network_name_str Repositório Institucional da UFMG
repository_id_str
spelling Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDSHIV/aidsEstudo de coorteTerapia antirretroviralModificaçõesEfetividadeAIDS (Doença)HIV (Virus)Terapia antirretroviralDoenças sexualmente transmissiveisBackground: Antiretroviral therapy (ART) has led to increased life expectancy and has given to HIV infection chronic characteristics, bringing up new challenges for long-term ART use. Over the years, the number of antiretroviral drugs at the pharmaceutical market has increased, allowing modifications in the ART. However, multiple antiretroviral drug modifications increase probability of HIV in developing mutations. HIV could get resistance to antiretroviral drugs from the same therapeutic class, and salvage therapy could be necessary. This study aimed at investigate ART modifications in HIV-infected adults, initiating ART between 2001 and 2005 in three HIV/AIDS referral centers in Belo Horizonte (MG). Method: Non-concurrent cohort study (historical cohort) from three HIV/AIDS referral centers in Belo Horizonte (MG), Brazil. It included treatment nave HIV-infected adults who had their first ART prescription between 2001 and 2005, followed up for at least one year and for a maximum of five years. The main endpoint was ART modifications defined as at least one drug alteration in the triple combined ART or addition to monotherapy or dual therapy with zidovudine (ZDV). Modifications in first ART were evaluated in the first year of treatment. Also, first, second and third ART modifications were assessed in a 5-year follow-up, between 2001 and 2010. For the analysis of first ART modification, all patients from initial cohort were considered (Population 1, n=247). For the analysis of second ART modification, all patients from Population 1, who had at least one ART modification were considered (Population 2, n=119). For the analysis of third ART modification, all patients from Population 2, who had at least a second ART modification were considered (Population 3, n=51). Exposure variables were sociodemographic characteristics, clinical, related to ART and to health care. Descriptive analysis was performed to characterize studied population and ART modifications profile. Pearson's qui-square test was performed to compare frequencies of ART modification in different population categories. The outcome was also describe by incidence of patients who had ART modified expressed in 100 persons-month. Kaplan-Meier curves were employed to describe ART durability in population categories. Multivariate logistic regression analysis was used to evaluate factors associated to first ART modification in the first year of treatment. Cox proportional hazard model was performed to evaluate the hazard ratio of first, second and third ART modifications during five years of follow-up. Results: 247 patients enrolled at initial cohort. 119 (48.2%) patients modified ART at least once and 51 (25.6%) modified at least two times. One patient modified ART five times. The vast majority of modifications occurred in the first year of treatment (53.8%), in protease inhibitor (PI)-based regimens, and the main reason for modification was adverse drug reactions. Among patients who modified ART, median time for first, second and third modifications were 10.7, 13.4 and 5.1 months, respectively. Non-nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens had higher durability when used as first, second and third ART option. Patients who started ART with PI-based regimens had 3.46 higher chance of having at least one ART modification than those who started 10 ART with NNRTI-regimens (odds ratio [OR]=3.46; IC95%=2.02 - 5.92), in the first year of treatment. Over five years, female sex, have AIDS-defining illness before ART and start ART with PI-based regimens or monotherapy or dual therapy with ZDV were risk factors for ART modification (hazard ratio [HR]=1.67; CI95%=1.08 - 2.57; HR=1.59; CI95%=1.01 - 2.51; HR=2.50; CI95%=1.54 - 4.04 e HR=11.45; IC95%=4.28 - 30.63, respectively]. It was not verified any variable statistically associated to second ART modification. Patients who had more than four medical visits per year were at higher risk of third ART modification (HR=7.12; CI95%=1.95 - 26.07), as well as those who start third ART with PI-based regimens (HR=4.84; CI95%=1.32 - 17.83). Conclusions: PI-based regimens are not well tolerated and are more modified due to adverse drug reactions. Delay in ART start makes treatment more complex and it is associated to ART modifications in the first year of treatment. Monitoring the adverse reactions to antiretroviral drugs at any stage of treatment is essential to avoid modifications in ART, contributing to ART effectiveness.Introdução: O advento da terapia antirretroviral (TARV) contribuiu para o aumento da expectativa de vida das pessoas infectadas pelo vírus HIV. A infecção pelo HIV atualmente se configura como doença crônica transmissível, trazendo novos desafios para o tratamento de longa duração. Ao longo dos anos, aumentaram as opções de medicamentos antirretrovirais no mercado farmacêutico, possibilitando a conduta de modificações na TARV. Modificações recorrentes na TARV aumentam a probabilidade de desenvolvimento de mutações do vírus HIV. O vírus pode adquirir resistência aos antirretrovirais da mesma classe terapêutica, sendo necessária a utilização de terapia de resgate. O objetivo deste estudo foi estudar a ocorrência de modificações da TARV em pessoas com HIV que iniciaram tratamento entre os anos de 2001 e 2005 em três serviços de serviços públicos de referência para atendimento a pessoas com HIV/aids na cidade de Belo Horizonte (MG). Método: Estudo de coorte prospectivo não concorrente (coorte histórica) conduzido em três centros de referência para tratamento de HIV/aids em Belo Horizonte (MG), Brasil. Incluiu adultos com HIV, com 18 anos de idade ou mais, que tiveram a primeira prescrição de TARV entre 2001 e 2005, sendo acompanhados por no mínimo 1 ano e por até 5 anos. O principal desfecho avaliado foi a modificação da TARV definida como a substituição de pelo menos um medicamento de terapia tripla ou acréscimo de pelo menos um medicamento à monoterapia ou terapia dupla contendo zidovudina (AZT). Foram avaliadas as modificações da TARV inicial no primeiro ano de tratamento e a primeira, segunda e terceira modificações da TARV ao longo de cinco anos de acompanhamento, entre 2001 e 2010. Para análise da primeira modificação, foram considerados todos os pacientes da amostra da coorte inicial (População 1, n=247). Para a análise da segunda modificação, foram considerados todos os pacientes da População 1 que apresentaram pelo menos uma modificação da TARV (População 2, n=119). Para a análise da terceira modificação, foram considerados todos os pacientes da População 2 que apresentaram pelo menos uma segunda modificação da TARV (População 3, n=51). As variáveis de exposição incluíram características sociodemográficas, clínicas, relacionadas à TARV e à utilização de serviços de saúde. Análise descritiva foi realizada para caracterizar a população e o perfil de modificações da TARV. O desfecho foi descrito por meio de frequência de modificações nos diferentes estratos da população, que foram comparadas pelo teste do qui-quadrado de Pearson. O desfecho também foi descrito por meio da incidência de modificações por 100 pessoas-mês. Curvas de Kaplan-Meier foram utilizadas para descrever a durabilidade dos esquemas antirretrovirais nos diferentes estratos da população. Análise de regressão logística multivariada foi realizada para verificar fatores associados à modificação da TARV inicial no primeiro ano de tratamento. Modelo de riscos proporcionais de Cox foi utilizado para verificar os fatores de risco para modificação da primeira, segunda e terceira TARV, ao longo de cinco anos. Resultados: 247 pacientes formaram a amostra final do estudo de coorte. 119 (48,2%) pacientes modificaram a TARV pelo menos uma vez e 51 (25,6%) modificaram pelos menos duas vezes. Um paciente modificou a TARV cinco vezes. A 8 maioria das modificações aconteceu no primeiro ano de tratamento (53,8%), em esquemas contendo inibidores de protease (IP), tendo como principal motivo as reações adversas. Dentre os pacientes que modificaram a TARV, o tempo mediano para primeira, segunda e terceira modificação foi de 10,7; 13,4 e 5,1 meses, respectivamente. Esquemas contendo inibidores da transcriptase reversa não análogos de nucleosídeo (ITRNN) apresentaram maior durabilidade quando utilizados como primeira, segunda ou terceira TARV. Pacientes que iniciaram a TARV com esquemas contendo IP possuem chance 3,46 vezes maior de ter pelo menos uma modificação da TARV do que pacientes que iniciaram TARV com esquemas contendo ITRNN [odds ratio (OR)=3,46; IC95%=2,02 - 5,92], no primeiro ano de tratamento. Ao longo de cinco anos de acompanhamento, ser do sexo feminino, apresentar diagnóstico relacionado à aids no início do tratamento, iniciar TARV com esquemas contendo IP ou com monoterapia/terapia dupla contendo AZT são fatores de risco para primeira modificação da TARV [hazard ratio (HR)=1,67; IC95%=1,08 - 2,57; HR=1,59; IC95%=1,01 - 2,51; HR=2,50; IC95%=1,54 - 4,04 e HR=11,45; IC95%=4,28 - 30,63, respectivamente]. Nenhum fator esteve estatisticamente associado à segunda modificação da TARV. Pacientes que apresentaram média de mais de quatro consultas médicas por ano apresentaram maior risco de modificação da terceira TARV (HR=7,12; IC95%=1,95 - 26,07) e aqueles que iniciaram a terceira TARV com esquemas contendo IP apresentaram risco 4,84 vezes o risco dos pacientes que iniciaram a terceira TARV com esquemas contendo ITRNN (HR=4,84; IC95%=1,32 - 17,83). Conclusões: Esquemas contendo IP são menos tolerados e mais modificados devido às reações adversas associadas a esta classe terapêutica. O início tardio da TARV torna o tratamento mais complexo e está associado à modificação da TARV no primeiro ano de tratamento. O monitoramento das reações adversas aos antirretrovirais em qualquer fase do tratamento é imprescindível para garantir a efetividade do tratamento.Universidade Federal de Minas GeraisUFMGCristiane Aparecida Menezes de PaduaLeticia Penna Braga2019-08-14T22:25:26Z2019-08-14T22:25:26Z2016-08-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/1843/BUOS-ASXL8Dinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2019-11-14T20:46:46Zoai:repositorio.ufmg.br:1843/BUOS-ASXL8DRepositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2019-11-14T20:46:46Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
title Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
spellingShingle Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
Leticia Penna Braga
HIV/aids
Estudo de coorte
Terapia antirretroviral
Modificações
Efetividade
AIDS (Doença)
HIV (Virus)
Terapia antirretroviral
Doenças sexualmente transmissiveis
title_short Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
title_full Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
title_fullStr Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
title_full_unstemmed Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
title_sort Incidência e fatores associados às modificações da Terapia Antirretroviral em pessoas com HIV/AIDS
author Leticia Penna Braga
author_facet Leticia Penna Braga
author_role author
dc.contributor.none.fl_str_mv Cristiane Aparecida Menezes de Padua
dc.contributor.author.fl_str_mv Leticia Penna Braga
dc.subject.por.fl_str_mv HIV/aids
Estudo de coorte
Terapia antirretroviral
Modificações
Efetividade
AIDS (Doença)
HIV (Virus)
Terapia antirretroviral
Doenças sexualmente transmissiveis
topic HIV/aids
Estudo de coorte
Terapia antirretroviral
Modificações
Efetividade
AIDS (Doença)
HIV (Virus)
Terapia antirretroviral
Doenças sexualmente transmissiveis
description Background: Antiretroviral therapy (ART) has led to increased life expectancy and has given to HIV infection chronic characteristics, bringing up new challenges for long-term ART use. Over the years, the number of antiretroviral drugs at the pharmaceutical market has increased, allowing modifications in the ART. However, multiple antiretroviral drug modifications increase probability of HIV in developing mutations. HIV could get resistance to antiretroviral drugs from the same therapeutic class, and salvage therapy could be necessary. This study aimed at investigate ART modifications in HIV-infected adults, initiating ART between 2001 and 2005 in three HIV/AIDS referral centers in Belo Horizonte (MG). Method: Non-concurrent cohort study (historical cohort) from three HIV/AIDS referral centers in Belo Horizonte (MG), Brazil. It included treatment nave HIV-infected adults who had their first ART prescription between 2001 and 2005, followed up for at least one year and for a maximum of five years. The main endpoint was ART modifications defined as at least one drug alteration in the triple combined ART or addition to monotherapy or dual therapy with zidovudine (ZDV). Modifications in first ART were evaluated in the first year of treatment. Also, first, second and third ART modifications were assessed in a 5-year follow-up, between 2001 and 2010. For the analysis of first ART modification, all patients from initial cohort were considered (Population 1, n=247). For the analysis of second ART modification, all patients from Population 1, who had at least one ART modification were considered (Population 2, n=119). For the analysis of third ART modification, all patients from Population 2, who had at least a second ART modification were considered (Population 3, n=51). Exposure variables were sociodemographic characteristics, clinical, related to ART and to health care. Descriptive analysis was performed to characterize studied population and ART modifications profile. Pearson's qui-square test was performed to compare frequencies of ART modification in different population categories. The outcome was also describe by incidence of patients who had ART modified expressed in 100 persons-month. Kaplan-Meier curves were employed to describe ART durability in population categories. Multivariate logistic regression analysis was used to evaluate factors associated to first ART modification in the first year of treatment. Cox proportional hazard model was performed to evaluate the hazard ratio of first, second and third ART modifications during five years of follow-up. Results: 247 patients enrolled at initial cohort. 119 (48.2%) patients modified ART at least once and 51 (25.6%) modified at least two times. One patient modified ART five times. The vast majority of modifications occurred in the first year of treatment (53.8%), in protease inhibitor (PI)-based regimens, and the main reason for modification was adverse drug reactions. Among patients who modified ART, median time for first, second and third modifications were 10.7, 13.4 and 5.1 months, respectively. Non-nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens had higher durability when used as first, second and third ART option. Patients who started ART with PI-based regimens had 3.46 higher chance of having at least one ART modification than those who started 10 ART with NNRTI-regimens (odds ratio [OR]=3.46; IC95%=2.02 - 5.92), in the first year of treatment. Over five years, female sex, have AIDS-defining illness before ART and start ART with PI-based regimens or monotherapy or dual therapy with ZDV were risk factors for ART modification (hazard ratio [HR]=1.67; CI95%=1.08 - 2.57; HR=1.59; CI95%=1.01 - 2.51; HR=2.50; CI95%=1.54 - 4.04 e HR=11.45; IC95%=4.28 - 30.63, respectively]. It was not verified any variable statistically associated to second ART modification. Patients who had more than four medical visits per year were at higher risk of third ART modification (HR=7.12; CI95%=1.95 - 26.07), as well as those who start third ART with PI-based regimens (HR=4.84; CI95%=1.32 - 17.83). Conclusions: PI-based regimens are not well tolerated and are more modified due to adverse drug reactions. Delay in ART start makes treatment more complex and it is associated to ART modifications in the first year of treatment. Monitoring the adverse reactions to antiretroviral drugs at any stage of treatment is essential to avoid modifications in ART, contributing to ART effectiveness.
publishDate 2016
dc.date.none.fl_str_mv 2016-08-11
2019-08-14T22:25:26Z
2019-08-14T22:25:26Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/BUOS-ASXL8D
url http://hdl.handle.net/1843/BUOS-ASXL8D
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
_version_ 1823248007110328320