Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil

Detalhes bibliográficos
Autor(a) principal: Lima, Yanna Andressa Ramos de
Data de Publicação: 2014
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFG
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/5589
Resumo: HIV-1 mother-to-child-transmission (MTCT) is a multifactorial event associated mainly with maternal viral load. Thus, the molecular epidemiology of HIV-1 and the evaluation of factors associated with MTCT in pregnant women are crucial for epidemic understanding and monitoring in this population. Objectives: To assess the frequency of recent seroconversion cases among newly diagnosed, antiretroviral (ARV) naïve pregnant women and evaluation of pregnancy outcomes and transmitted drug resistance (TDR) in this group; to compare sociodemographical, clinical, genetic diversity of the virus and resistance among young and adult pregnant women. Methods: HIV-1-infected pregnant women (n = 250) were recruited during antenatal care conducted by the Program for the Protection of Pregnant Women from Goias State (PPPW/GO). Recent cases of seroconversion were identified by BED-CEIA among naïve pregnant women and confirmed by ambiguous nucleotide calls. Pol gene (protease/PR and 2/3 of the reverse transcriptase/RT) was sequenced from plasma samples. Resistance mutations were evaluated by Calibrated Population Resistance tool and Stanford HIV-1 and International AIDS Society-USA (IAS-USA) databases. Viral subtypes were assigned by REGA software and phylogenetic analyzes with reference sequences. Results: Cases of recent seroconversion (RS) were identified in 16.6% of 95 newly diagnosed, ARV-naïve pregnant women. Medians of CD4+ cell count and viral load were 530 cells/μL and 8,796.5 copies/mL, respectively. Nine patients with RS probably seroconverted during pregnancy. One case of MTCT was observed among pregnant women with RS. Incident cases presented a predominance of isolates assigned as subtype B. There was no difference regarding the distribution of non-B subtypes. The amont of 250 pregnant women recruited were divided into two distinct age groups: adolescents and young (96/250, 38%) and adult women (154/250, 62%). When compared with the adult group, young women had fewer previous pregnancies and they were diagnosed mainly in the current pregnancy. One case of MTCT was identified in both groups (2/250, 0.8%). The CD4+ cell counts were similar between both groups. Viral load was significantly higher among ARV-naïve pregnant adolescents (15-19 years) when compared with the group of ARV-naïve pregnant adults (>24 years). Young pregnant women previously exposed to ARVs were less likely to have viral load <1,500 copies / mL. The distribution of HIV-1 subtypes was similar in both groups and recombinant subtypes with similar recombination points were identified among both groups. The frequency of transmitted resistance was similar between young and adult women (9.5% and 7.1%, respectively). The frequency of secondary resistance was higher among adult pregnant women compared with younger women (21.8% and 12.8%, respectively). Conclusions: Recent seroconversion during pregnancy associated with moderate levels of transmitted resistance may contribute to vertical transmission of HIV-1. Preventive measures should include adolescents and young women as an attempt to control the vertical transmission of HIV-1 in Central Western region, Brazil.
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spelling Stefani, Mariane Martins de Araújohttp://lattes.cnpq.br/5581414958714905http://lattes.cnpq.br/5615495396989670Lima, Yanna Andressa Ramos de2016-05-20T13:41:52Z2014-07-02LIMA, Y. A. R. Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil. 2014. 138 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2014.http://repositorio.bc.ufg.br/tede/handle/tede/5589HIV-1 mother-to-child-transmission (MTCT) is a multifactorial event associated mainly with maternal viral load. Thus, the molecular epidemiology of HIV-1 and the evaluation of factors associated with MTCT in pregnant women are crucial for epidemic understanding and monitoring in this population. Objectives: To assess the frequency of recent seroconversion cases among newly diagnosed, antiretroviral (ARV) naïve pregnant women and evaluation of pregnancy outcomes and transmitted drug resistance (TDR) in this group; to compare sociodemographical, clinical, genetic diversity of the virus and resistance among young and adult pregnant women. Methods: HIV-1-infected pregnant women (n = 250) were recruited during antenatal care conducted by the Program for the Protection of Pregnant Women from Goias State (PPPW/GO). Recent cases of seroconversion were identified by BED-CEIA among naïve pregnant women and confirmed by ambiguous nucleotide calls. Pol gene (protease/PR and 2/3 of the reverse transcriptase/RT) was sequenced from plasma samples. Resistance mutations were evaluated by Calibrated Population Resistance tool and Stanford HIV-1 and International AIDS Society-USA (IAS-USA) databases. Viral subtypes were assigned by REGA software and phylogenetic analyzes with reference sequences. Results: Cases of recent seroconversion (RS) were identified in 16.6% of 95 newly diagnosed, ARV-naïve pregnant women. Medians of CD4+ cell count and viral load were 530 cells/μL and 8,796.5 copies/mL, respectively. Nine patients with RS probably seroconverted during pregnancy. One case of MTCT was observed among pregnant women with RS. Incident cases presented a predominance of isolates assigned as subtype B. There was no difference regarding the distribution of non-B subtypes. The amont of 250 pregnant women recruited were divided into two distinct age groups: adolescents and young (96/250, 38%) and adult women (154/250, 62%). When compared with the adult group, young women had fewer previous pregnancies and they were diagnosed mainly in the current pregnancy. One case of MTCT was identified in both groups (2/250, 0.8%). The CD4+ cell counts were similar between both groups. Viral load was significantly higher among ARV-naïve pregnant adolescents (15-19 years) when compared with the group of ARV-naïve pregnant adults (>24 years). Young pregnant women previously exposed to ARVs were less likely to have viral load <1,500 copies / mL. The distribution of HIV-1 subtypes was similar in both groups and recombinant subtypes with similar recombination points were identified among both groups. The frequency of transmitted resistance was similar between young and adult women (9.5% and 7.1%, respectively). The frequency of secondary resistance was higher among adult pregnant women compared with younger women (21.8% and 12.8%, respectively). Conclusions: Recent seroconversion during pregnancy associated with moderate levels of transmitted resistance may contribute to vertical transmission of HIV-1. Preventive measures should include adolescents and young women as an attempt to control the vertical transmission of HIV-1 in Central Western region, Brazil.A transmissão vertical do HIV-1 é um evento multifatorial em que a carga viral materna desempenha importante papel. Assim, a epidemiologia molecular do HIV-1 em gestantes e a avaliação de fatores associados com a transmissão vertical são cruciais para a compreensão e monitoramento da epidemia nessa população. Objetivos: Avaliação da frequência de casos de soroconversão recente entre gestantes recém-diagnosticadas, virgens de tratamento e avaliação dos desfechos da gestação nesse grupo e da frequência de resistência transmitida. Comparação entre os fatores sociodemográficos, clínicos, de diversidade genética do vírus e perfil de resistência entre gestantes jovens e adultas. Métodos: Gestantes infectadas por HIV-1 (n=250) foram recrutadas durante o pré-natal realizado pelo Programa de Proteção à Gestante/GO. Os casos de soroconversão recente em pacientes virgens de tratamento com diagnóstico recente foram identificados pelo teste imunoenzimático BED-CEIA e confirmados pela análise molecular de bases ambíguas em pol. O gene pol (protease/PR e 2/3 da transcriptase reversa/RT) foi sequenciado a partir de amostras de plasma. As mutações de resistência foram avaliadas pela ferramenta Calibrated Population Resistance tool e pelos bancos de dados Stanford HIV-1 Database e International AIDS Society-USA (IAS-USA). Os subtipos virais foram definidos pelo software REGA e análises filogenéticas com sequências de referência. Resultados: Casos de soroconversão recente (SR) foram identificados em 16,6% das 95 gestantes recém-diagnosticadas e virgens de tratamento. A mediana da contagem de células CD4+ foi 530 células/μL e da carga viral foi 8796,5 cópias/mL. Nove pacientes com SR (82%) provavelmente soroconverteram durante a gestação. Um caso de transmissão vertical foi observado entre as gestantes com SR. Os casos incidentes apresentaram predomínio de isolados com subtipo B. Não houve diferença com relação à distribuição dos outros subtipos. As 250 gestantes recrutadas foram divididas em dois grupos etários distintos: adolescentes e jovens (96/250, 38%) e adultas (154/250, 62%). Quando comparadas com as adultas, as gestantes jovens apresentaram menor número de gestações prévias e foram diagnosticadas principalmente na gestação atual. Um caso de transmissão vertical da infecção foi identificado em cada um dos grupos (2/250, 0,8%). A contagem de células CD4+ foi similar entre ambos os grupos. O grupo de gestantes adolescentes (15-19 anos), virgens de tratamento, apresentou carga viral significativamente mais alta que o grupo de gestantes adultas. As gestantes jovens previamente expostas aos ARVs tinham menor probabilidade de apresentar carga viral <1500 cópias/mL. A distribuição de subtipos do HIV-1 foi similar em ambos os grupos e foram identificados subtipos recombinantes com ponto de recombinação similar entre os dois grupos. A frequência de resistência transmitida foi similar entre as gestantes jovens e adultas (9,5% e 7,1%, respectivamente). A frequência de resistência secundária foi maior entre as gestantes adultas quando comparadas com as gestantes jovens (21,8% e 12.8%, respectivamente). Conclusões: A soroconversão recente na gestação associada com níveis moderados de resistência transmitida pode contribuir para a transmissão vertical do HIV-1. Políticas preventivas devem incluir a população de adolescentes e jovens como tentativa de controlar a transmissão vertical do HIV-1, na região Centro-Oeste do Brasil.Submitted by Cláudia Bueno (claudiamoura18@gmail.com) on 2016-05-19T17:45:53Z No. of bitstreams: 2 Tese - Yanna Andressa Ramos de Lima - 2014.pdf: 3948681 bytes, checksum: 03820f7151617bba515baa141492f753 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-05-20T13:41:52Z (GMT) No. of bitstreams: 2 Tese - Yanna Andressa Ramos de Lima - 2014.pdf: 3948681 bytes, checksum: 03820f7151617bba515baa141492f753 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2016-05-20T13:41:52Z (GMT). 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dc.title.por.fl_str_mv Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
dc.title.alternative.eng.fl_str_mv HIV-1 mother-to-child transmission, antiretroviral resistance and genetic diversity among pregnant women from Central Western, Brazil
title Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
spellingShingle Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
Lima, Yanna Andressa Ramos de
HIV-1
Gestantes
Soroconversão recente
Resistência aos antirretrovirais
Diversidade genética
HIV-1
Pregnant woman
Recent seroconversion
Antiretroviral resistance
Genetic diversity
IMUNOLOGIA::IMUNOGENETICA
title_short Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
title_full Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
title_fullStr Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
title_full_unstemmed Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
title_sort Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil
author Lima, Yanna Andressa Ramos de
author_facet Lima, Yanna Andressa Ramos de
author_role author
dc.contributor.advisor1.fl_str_mv Stefani, Mariane Martins de Araújo
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5581414958714905
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5615495396989670
dc.contributor.author.fl_str_mv Lima, Yanna Andressa Ramos de
contributor_str_mv Stefani, Mariane Martins de Araújo
dc.subject.por.fl_str_mv HIV-1
Gestantes
Soroconversão recente
Resistência aos antirretrovirais
Diversidade genética
topic HIV-1
Gestantes
Soroconversão recente
Resistência aos antirretrovirais
Diversidade genética
HIV-1
Pregnant woman
Recent seroconversion
Antiretroviral resistance
Genetic diversity
IMUNOLOGIA::IMUNOGENETICA
dc.subject.eng.fl_str_mv HIV-1
Pregnant woman
Recent seroconversion
Antiretroviral resistance
Genetic diversity
dc.subject.cnpq.fl_str_mv IMUNOLOGIA::IMUNOGENETICA
description HIV-1 mother-to-child-transmission (MTCT) is a multifactorial event associated mainly with maternal viral load. Thus, the molecular epidemiology of HIV-1 and the evaluation of factors associated with MTCT in pregnant women are crucial for epidemic understanding and monitoring in this population. Objectives: To assess the frequency of recent seroconversion cases among newly diagnosed, antiretroviral (ARV) naïve pregnant women and evaluation of pregnancy outcomes and transmitted drug resistance (TDR) in this group; to compare sociodemographical, clinical, genetic diversity of the virus and resistance among young and adult pregnant women. Methods: HIV-1-infected pregnant women (n = 250) were recruited during antenatal care conducted by the Program for the Protection of Pregnant Women from Goias State (PPPW/GO). Recent cases of seroconversion were identified by BED-CEIA among naïve pregnant women and confirmed by ambiguous nucleotide calls. Pol gene (protease/PR and 2/3 of the reverse transcriptase/RT) was sequenced from plasma samples. Resistance mutations were evaluated by Calibrated Population Resistance tool and Stanford HIV-1 and International AIDS Society-USA (IAS-USA) databases. Viral subtypes were assigned by REGA software and phylogenetic analyzes with reference sequences. Results: Cases of recent seroconversion (RS) were identified in 16.6% of 95 newly diagnosed, ARV-naïve pregnant women. Medians of CD4+ cell count and viral load were 530 cells/μL and 8,796.5 copies/mL, respectively. Nine patients with RS probably seroconverted during pregnancy. One case of MTCT was observed among pregnant women with RS. Incident cases presented a predominance of isolates assigned as subtype B. There was no difference regarding the distribution of non-B subtypes. The amont of 250 pregnant women recruited were divided into two distinct age groups: adolescents and young (96/250, 38%) and adult women (154/250, 62%). When compared with the adult group, young women had fewer previous pregnancies and they were diagnosed mainly in the current pregnancy. One case of MTCT was identified in both groups (2/250, 0.8%). The CD4+ cell counts were similar between both groups. Viral load was significantly higher among ARV-naïve pregnant adolescents (15-19 years) when compared with the group of ARV-naïve pregnant adults (>24 years). Young pregnant women previously exposed to ARVs were less likely to have viral load <1,500 copies / mL. The distribution of HIV-1 subtypes was similar in both groups and recombinant subtypes with similar recombination points were identified among both groups. The frequency of transmitted resistance was similar between young and adult women (9.5% and 7.1%, respectively). The frequency of secondary resistance was higher among adult pregnant women compared with younger women (21.8% and 12.8%, respectively). Conclusions: Recent seroconversion during pregnancy associated with moderate levels of transmitted resistance may contribute to vertical transmission of HIV-1. Preventive measures should include adolescents and young women as an attempt to control the vertical transmission of HIV-1 in Central Western region, Brazil.
publishDate 2014
dc.date.issued.fl_str_mv 2014-07-02
dc.date.accessioned.fl_str_mv 2016-05-20T13:41:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv LIMA, Y. A. R. Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil. 2014. 138 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2014.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/5589
identifier_str_mv LIMA, Y. A. R. Transmissão vertical, resistência aos antirretrovirais e diversidade genética do HIV-1 em gestantes infectadas do Centro-Oeste do Brasil. 2014. 138 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2014.
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