Thesis (MScMedSc))--Stellenbosch University, 2012. / Includes bibliography / ENGLISH ABSTRACT: Despite the availability of Hepatitis B virus (HBV) vaccination for over three decades, this infection remains a major public health problem. Whilst the WHO recommends giving a birth dose of the vaccine, in South Africa, routine infant HBV vaccination commences at six weeks of age. This schedule is based on data from the pre-HIV era which showed transmission occurred via the horizontal, rather than the vertical route. In the era of HIV however, maternal HIV co-infection may release HBV from immune control, resulting in higher HBV loads and increasing the risk of vertical transmission. The aim of this study was to determine the prevalence and character of HBV infection in HIV-exposed infected and uninfected infants. Residual plasma samples from routine HIV nucleic acid testing of 1000 HIV-exposed infants aged between 0 and 18 months from the Western Cape were tested. Samples were tested for HBsAg by ELISA (Murex HBsAg Version 3) and confirmed by neutralisation. HBV DNA was quantified using an in-house real-time PCR assay. Infants with HBsAg positive samples were followed up and a blood sample was collected from mother and child. Those HBsAg positive samples were tested for HBeAg/antiHBe (Diasorin) and HBsAg negative samples were tested for antiHBs. HBV DNA was quantified. The surface gene was sequenced and the HBV genotype determined by phylogenetic analysis using HepSEQ (www.hepseq.org.uk). Whole genome sequencing was also performed. Of 1000 samples tested, four samples were positive for HBsAg and/or HBV DNA, indicating a prevalence of HBV transmission of 0.4%. At follow-up, two of three infected infants were positive for HBsAg, with HBV viral loads of greater than 108 IU/ml. The third infant was found to have cleared his infection and the fourth child was lost to follow up. These infected infants had all received HBV vaccination. All four mothers were HBeAg positive. Sequencing analysis showed the HBV strains from the two infants and four mothers belonged to subgenotype A1. The two mother-child paired sequences were identical. The data from this study shows that vertical transmission of HBV infection in HIV-exposed infants from the Western Cape is occurring, despite vaccination. Data from the Western Cape, showing an HBV prevalence of 3.4% in HIV-infected pregnant women, and those presented here suggest a vertical transmission rate of HBV of 12%. This is despite the widespread use of tenofovir and lamivudine in HIV-infected women with low CD4 counts. This study provides data supporting calls to bring HBV vaccination closer to the time of birth. Further work is urgently needed to confirm these findings and to determine the rates of transmission in HIV-unexposed infants. / AFRIKAANSE OPSOMMING: Ten spyte van die beskikbaarheid van die Hepatitis B virus (HBV) inenting vir meer as drie dekades, hierdie infeksie bly 'n groot openbare gesondheid probleem. Terwyl die WGO aan beveel dat'n geboorte dosis van die entstof, in Suid-Afrika, roetine baba HBV inenting op die ouderdom van ses weke gegee word. Hierdie skedule is gebaseer op data van die pre-MIV era wat getoon het dat die oordrag plaasgevind het via die horisontale, eerder as die vertikale roete. In die era van MIV egter, moeder MIV ko-infeksie kan HBV vrylaat van immuun beheer, wat lei in hoër HBV vlakke en die verhoging van die risiko van vertikale oordrag. Die doel van hierdie studie was om die voorkoms en karakter van die HBV infeksie in MIV-besmette en onbesmette babas te bepaal. Residuele plasma monsters van roetine-MIV-nukleïensuur toetse van 'n 1000 MIV-blootgestelde babas tussen die ouderdomme van 0 en 18 maande van die Wes-Kaap was getoets. Monsters was getoets vir HBsAg deur ELISA (Murex HBsAg Version 3) en bevestig deur neutralisering. HBV DNA is gekwantifiseer deur gebruik te maak van 'n in-huis real-time PCR assay. Babas met HBsAg positiewe monsters was opgevolg en 'n bloedmonster is versamel van moeder en kind. Die HBsAg positiewe monsters was getoets vir HBeAg/antiHBe (Diasorin) en HBsAg negatiewe monsters was getoets vir antiHBs. HBV DNA was gekwantifiseer. Die oppervlak gene volgorde en genotipes was bepaal deur filogenetiese analise met behulp van HepSEQ (www.hepseq.org.uk). Die hele genoom-volgordebepaling was ook uitgevoer. Van die 1000 monsters wat getoets was, was vier monsters positief vir HBsAg en of HBV DNA, dit dui op 'n voorkoms van HBV oordrag van 0.4%. By op volg, twee van die drie besmette babas was positief vir HBsAg, met HBV virale vlakke van groter as 108 IE/ml. Die derde baba was gevind dat sy infeksie opgeklaar het en die vierde kind was verlore as gevolg van op volg. Hierdie besmette babas het almal HBV inenting ontvang. Al vier moeders was HBeAg positief. Volgordebepaling analise het getoon die HBV stamme van die twee babas en vier moeders behoort aan subgenotype A1. Die twee moeder-kind gepaarde rye was homoloë. Die data van hierdie studie toon dat die vertikale oordrag van HBV infeksie in MIV-blootgestelde babas van die Wes-Kaap vind plaas, ten spyte van inenting. Data van die Wes-Kaap, wat 'n HBV voorkoms van 3.4% in MIV-besmette swanger vroue, en dié wat hier aangebied is dui op 'n vertikale oordrag koers van 12% van die HBV. Dit is ten spyte van die wydverspreide gebruik van tenofovir en lamivudine in MIV-geïnfekteerde vroue met 'n lae CD4-telling. Hierdie studie bied data wat ondersteunende oproepe van HBV inenting nader aan die tyd van die geboorte bring. Verdere werk is dringend nodig om die bevindinge te bevestig en die pryse van die oordrag in MIV-blootgestelde babas te bepaal. / National Health Laboratory Service Research Trust / Poliomyelitis Research Foundation (PRF) / Harry Crossley Foundation / Stellenbosch University

La transmission mère-enfant (TME) du VIH-1 est un des enjeux majeurs de la pandémie. Une meilleure compréhension de la réponse des lymphocytes T cytotoxiques CD8+ (LTC) VIH-spécifiques lors de la grossesse facilitera le design de stratégies optimales pour diminuer la TME. Notre objectif est donc de caractériser l’amplitude et la diversité de la reconnaissance antigénique des LTC VIH-spécifiques avant, pendant et après la grossesse chez des femmes infectées par le VIH-1. Nos résultats montrent pour la première fois que l’initiation et la progression de la grossesse, à elles seules, n'ont que peu d’influence sur l’amplitude et la diversité de la reconnaissance antigénique des réponses LTC en termes de production d’IFN‐. Ces résultats indiquent que les femmes infectées par le VIH conservent une immunocompétence durant leur grossesse, du moins dans le contexte d’un traitement antirétroviral efficace. Ceci pourrait éventuellement aider à promouvoir l’immunisation comme stratégie pour prévenir la TME du VIH‐1. / Mother-to-child transmission (MTCT) of HIV-1 is one of the major issues of the pandemic. Characterization of HIV-specific immunity during pregnancy, especially cytotoxic CD8+ T lymphocytes (CTL), will lead to a better understanding of HIV pathogenesis and facilitate design of optimal strategies to prevent MTCT. Our objective is to describe the magnitude and the breadth of antigen recognition of HIV-specific CTL responses before, throughout and after pregnancy in a group of HIV-infected women. Our results revealed for the first time that initiation of pregnancy by itself doesn’t change the magnitude of CTL responses in terms of IFN- production. These findings support the fact that HIV-infected women maintain immunocompetence throughout gestation, at least in the context of effective antiretroviral treatment. These results provide a novel understanding of the dynamics of HIV-specific CTL responses during pregnancy and may help to promote maternal immunization as a strategy to prevent MTCT of HIV-1.

La transmission mère-enfant du VIH-1 (TME) représente le principal mode d’infection chez l’enfant et se produit durant la grossesse (in utero, IU), l’accouchement (intrapartum, IP) ou l’allaitement (postpartum, PP). Les mécanismes qui sous-tendent le passage du VIH-1 à travers le placenta et les muqueuses intestinales du nouveau-né sont encore très peu décrits. « Dendritic cell-specific ICAM-grabbing non-integrin » (DC-SIGN) et son homologue DC-SIGN « related » (DC-SIGNR) sont des récepteurs d’antigènes exprimés au niveau du placenta et capables de capter et de transmettre le VIH-1 aux cellules adjacentes. Ils pourraient donc participer au passage trans placentaire du VIH-1 et le polymorphisme génétique affectant l’expression ou modifiant l’interaction avec le virus aurait une influence sur la TME du VIH-1. Afin d’explorer cette hypothèse, nous avons procédé à une analyse exhaustive du polymorphisme de DC-SIGN et DC-SIGNR dans la population du Zimbabwe. Par la suite, nous avons déterminé l’association entre le polymorphisme de DC-SIGN et DC-SIGNR et la TME du VIH-1 dans une cohorte d’enfants nés de mères VIH-positives à Harare, au Zimbabwe. Enfin, nous avons défini l’impact fonctionnel des mutations associées. Les enfants homozygotes pour les haplotypes H1 et H3 dans le gène de DC-SIGNR sont 4 à 6 fois plus à risque de contracter le VIH-1 par voie IU et IP. H1 et H3 contiennent la mutation du promoteur p-198A et la mutation de l’intron 2, int2-180A, et des études fonctionnelles nous ont permis de démontrer que p-198A diminue l’activité transcriptionnelle du promoteur de DC-SIGNR et l’expression des transcrits d’ARNm dans le placenta, alors que int2-180A modifie le répertoire d’isoformes de DC-SIGNR vers une proportion diminuée d’isoformes membranaires. Les enfants porteurs des haplotypes H4 et H6 de DC-SIGN sont 2 à 6 fois plus à risque de contracter le VIH-1 par voie IU. Ces haplotypes contiennent deux mutations du promoteur (p-336T/C et p-201C/A) et quatre mutations codant pour un changement d’acide aminé dans l’exon 4 (R198Q, E214D, R221Q ou L242V) associées à un risque augmenté de transmission IU, IP et PP du VIH-1. Des études fonctionnelles ont démontré que les mutations du promoteur diminuent l’expression de DC-SIGN dans les macrophages placentaires. Toutefois, l’exposition IU au VIH-1 module le niveau d’expression de DC-SIGN, résultant en des niveaux d’expression similaires entre les macrophages des porteurs des allèles sauvages et mutés. Les mutations de l’exon 4 augmentent l’affinité de DC-SIGN pour le VIH-1 et sa capacité à capturer et à transmettre le virus aux lymphocytes T, favorisant possiblement la dissémination du VIH-1 à travers le placenta. L’association entre les mutations de DC-SIGN et la transmission IP et PP du VIH-1 suggèrent qu’il aurait aussi un rôle à jouer dans les muqueuses intestinales de l’enfant. Notre étude démontre pour la première fois l’implication de DC-SIGN et DC-SIGNR dans la TME du VIH-1. L’augmentation des capacités de capture et de transmission de DC-SIGN résulte en une susceptibilité accrue de l’enfant à l’infection au VIH-1 et concorde avec un rôle dans la dissémination transplacentaire. Toutefois, la diminution préférentielle des transcrits membranaires de DC-SIGNR au placenta augmente la TME du VIH-1 et laisse croire à son implication via un autre mécanisme. Ces mécanismes pourraient aussi s’appliquer à d’autres pathogènes reconnus par DC-SIGN et DC-SIGNR et transmis de la mère à l’enfant. / Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. MTCT of HIV-1 can occur during pregnancy (in utero, IU), delivery (intrapartum, IP) or breastfeeding (postpartum, PP). Dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN) and its homolog DC-SIGN related (DC-SIGNR) are attachment receptors for HIV-1 and are expressed in the placenta. They have been implicated in viral capture and transmission to T cells. To investigate the potential role of DC-SIGN and DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 4-fold increased risk of IU and 6-fold increased risk of IP HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU and IP HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers. Infants carrying H4 and H6 haplotypes in DC-SIGN gene were more likely to be HIV-1-infected during pregnancy. These haplotypes contain promoter variants (p-336T/C and p-201C/A) and exon 4 variants (R198Q, E214D, R221Q and L242V) that were all significantly associated with increased risk of MTCT of HIV-1. Compared with wild-type sequence, the promoter variants reduced both the DC-SIGN transcription in vitro and expression (2-fold) in placental macrophages of HIV-1-unexposed infants. However, in HIV-1-exposed infants, the level of DC-SIGN expression in placental macrophages was similar in infants carrying either the promoter wild-type or variant sequences. Exon 4 variants increased HIV-1 capture and transmission to T cells in vitro. Association between DC-SIGN SNPs and HIV-1 IP and PP infection also suggests that DC-SIGN plays an important role in intestinal mucosa. This is the first study reporting on functional impact of DC-SIGN and DC-SIGNR natural polymorphisms on HIV-1 transmission from mother-to-child. Decreased levels of expression of membrane DC-SIGNR isoforms at the placental endothelial cell surface increased child susceptibility to HIV-1. Presence of DC-SIGN variants increasing its affinity for the virus augmented child susceptibility to HIV-1 and may favour viral dissemination across the placental barrier. This study provides compelling evidence to support an important role of DC-SIGN and DC-SIGNR in various modes of MTCT of HIV-1 and shed light on the possible mechanisms involved in HIV-1 passage from mother-to-infant. These findings raise the possibility that similar mechanisms may operate with other human pathogens known to interact with DC-SIGN and DC-SIGNR.

The study reports on the perceptions of the midwives and pregnant women of the PMTCT of HIV programme at the antenatal care and maternity ward at the Johan Heyns Community Health Centre. A qualitative approach was adopted to conduct the study. Purposive sampling was used to select participants and was informed by social behavioural theories. Data was collected using interviews and analysed using thematic categorisation. The findings show that at the first PMTCT encounter participants had little to no knowledge of the PMTCT programme, generally displayed a lack of interest, experienced emotional distress, and fear at the thought of having to disclosing their HIV-positive status to their partners/family and had certain trepidations about participating in the PMTCT programme. The participants’ perception on their roles was that their roles were interlinked, midwife needs the recipients (pregnant woman) and pregnant woman needs the provider (midwife) therefore one cannot do PMTCT without the other. The study recommends that the capacity building of pregnant women be optimised, that PMTCT awareness campaigns for women of childbearing age should be a priority and PMTCT skills to be prerequisite for midwives deployed to ANC clinics and maternity ward units. / Health Studies / M.A. (Social Behaviour Studies in HIV/AIDS)

Introdução: O cenário da epidemia da AIDS vem se modificando no Brasil e no mundo e o perfil epidemiológico das pessoas vivendo com HIV/AIDS vem sofrendo sucessivas alterações desde a década de 80. Embora os homens representem em números absolutos, o maior número de notificações do total de casos de AIDS, a velocidade de crescimento da epidemia é maior entre as mulheres. O Brasil tem uma resposta à epidemia de DST/AIDS reconhecida internacionalmente, baseada nos princípios do SUS à universalidade, à equidade e à integralidade na assistência. Um dos capítulos desta resposta é a prevenção da transmissão vertical do HIV. O tema que vem ganhando importância na medida em que a AIDS recebe status de doença crônica e as mulheres soropositivas podem fazer as suas escolhas reprodutivas. A prevenção da transmissão vertical do HIV contempla testagem para diagnóstico precoce, terapia antirretroviral durante a gravidez e o parto, terapia antirretroviral para o recém-nascido e a não amamentação. Objetivo- Conhecer como as ações de prevenção e controle da transmissão vertical do Vírus da Imunodeficiência Humana são percebidas pelas gestantes e puérperas atendidas pelo Programa Estadual de DST/AIDS, e sua satisfação, ou insatisfação, em relação à assistência recebida. Método- Nossa amostra foi composta por 14 mulheres, sendo 13 soropositivas para o HIV que engravidaram e tiveram pelo menos um filho no contexto da soropositividade e uma, soronegativa para o HIV e mãe adotiva de uma criança soropositiva. Para a coleta de dados foi utilizada a metodologia qualitativa, com base em entrevistas individuais, semiestruturadas, realizadas em 2010. Resultados - Não houve aconselhamento para a testagem de nenhuma mulher da amostra. As mulheres apresentaram, no geral, uma falta de identificação com o perfil de pessoas que podem se infectar com o HIV, sendo surpreendidas com o diagnóstico. Oito pais apresentaram status sorológico desconhecido, sendo que três negaram-se à testagem. Há dificuldades por parte das mulheres, para promoverem relações sexuais protegidas com o uso do preservativo masculino. Os efeitos adversos dos antirretrovirais são descritos como obstáculo importante à adesão ao tratamento. O alojamento conjunto foi o cenário das piores vivências dentre toda a assistência recebida, destaque dado ao tema aleitamento materno. Há uma lacuna entre as demandas das mulheres em produzir e relatar as suas narrativas e a inexistência de espaços de escuta, seja individualmente na relação com o profissional médico, seja em grupos. Conclusões - A ausência do aconselhamento como espaço de abordagem e esclarecimentos, informações e escolhas, dificulta uma ação mais oportuna para a redução da transmissão vertical do HIV. As mulheres comuns não são atingidas pelas informações sobre HIV/AIDS oferecidas pelas campanhas para prevenção da infecção. O uso do preservativo para evitar a infecção ainda é uma decisão masculina. As mulheres raramente encontram interlocução entre os profissionais, para tirarem suas dúvidas e planejarem sua vida reprodutiva de forma mais segura. Apesar da falta de discussão sobre o planejamento terapêutico, a via de parto e os cuidados com o bebê, as mulheres seguem a prescrição e seguem com seus medos e suas dúvidas / Introduction: The scenario of the AIDS epidemic has been changing in Brazil and worldwide, and epidemiological profile of people living with HIV / AIDS has undergone successive changes since the 80\'s. Although men represent in absolute numbers, the highest number of notifications of all cases of AIDS, the epidemic growth rate is higher among women. Brazil has a response to the epidemic of STD / AIDS internationally recognized principles of the SUS: universality, equity and integrity in service. One of the elements of this response is the prevention of vertical transmission of HIV. The theme that is gaining importance, as AIDS gets the status of chronic disease and HIV positive women can make their own reproductive choices. The prevention of vertical transmission of HIV includes testing for early diagnosis, antiretroviral therapy during pregnancy and delivery, antiretroviral therapy for the newborn and not breastfeeding. Objective -To study how the prevention and control of vertical transmission of human immunodeficiency virus are perceived by pregnant women and new mothers assisted by the State Program of STD / AIDS, and their satisfaction or dissatisfaction in relation to care received. Methods -Our sample consisted of 14 women, 13 HIV-positive pregnant and who had at least one child in the context of being HIV positive and one was seronegative for HIV and an adoptive mother of an HIV positive child. To collect data we used the qualitative methodology, based on individual interviews, semi-structured, conducted in 2010. Results - There was no counseling for the testing of any women in the sample. Women had, overall, a lack of identification with the profile of people who can become infected with HIV, being surprised by the diagnosis. Eight male partners had unknown HIV status, and three refused to be tested. There are difficulties, for women, to promote safe sex with condom use. Adverse effects of antiretroviral drugs are described as barrier to treatment adherence. Rooming-in was the scene of the worst experiences among all the care received, highlighting the theme of breastfeeding. There is a gap between women\'s demands to produce and report their stories and the lack of opportunities to listen, either individually in relation to the medical professional, either in groups. Conclusions - The lack of counseling as a space for dialogue and explanations, information and choices, hampers a more timely action to reduce vertical transmission of HIV. The \"ordinary\" women are not affected by information about HIV / AIDS provided by the campaigns to prevent infection. The use of condoms to prevent infection is still a male decision. Women are rarely have the opportunity to with professionals, to expose their questions and plan their reproductive lives more safely. In this setting of lack ofparticipation on treatment planning, delivery or baby care, women follow the \"prescription\" and move on with their fears and doubts

Introdução: O cenário da epidemia da AIDS vem se modificando no Brasil e no mundo e o perfil epidemiológico das pessoas vivendo com HIV/AIDS vem sofrendo sucessivas alterações desde a década de 80. Embora os homens representem em números absolutos, o maior número de notificações do total de casos de AIDS, a velocidade de crescimento da epidemia é maior entre as mulheres. O Brasil tem uma resposta à epidemia de DST/AIDS reconhecida internacionalmente, baseada nos princípios do SUS à universalidade, à equidade e à integralidade na assistência. Um dos capítulos desta resposta é a prevenção da transmissão vertical do HIV. O tema que vem ganhando importância na medida em que a AIDS recebe status de doença crônica e as mulheres soropositivas podem fazer as suas escolhas reprodutivas. A prevenção da transmissão vertical do HIV contempla testagem para diagnóstico precoce, terapia antirretroviral durante a gravidez e o parto, terapia antirretroviral para o recém-nascido e a não amamentação. Objetivo- Conhecer como as ações de prevenção e controle da transmissão vertical do Vírus da Imunodeficiência Humana são percebidas pelas gestantes e puérperas atendidas pelo Programa Estadual de DST/AIDS, e sua satisfação, ou insatisfação, em relação à assistência recebida. Método- Nossa amostra foi composta por 14 mulheres, sendo 13 soropositivas para o HIV que engravidaram e tiveram pelo menos um filho no contexto da soropositividade e uma, soronegativa para o HIV e mãe adotiva de uma criança soropositiva. Para a coleta de dados foi utilizada a metodologia qualitativa, com base em entrevistas individuais, semiestruturadas, realizadas em 2010. Resultados - Não houve aconselhamento para a testagem de nenhuma mulher da amostra. As mulheres apresentaram, no geral, uma falta de identificação com o perfil de pessoas que podem se infectar com o HIV, sendo surpreendidas com o diagnóstico. Oito pais apresentaram status sorológico desconhecido, sendo que três negaram-se à testagem. Há dificuldades por parte das mulheres, para promoverem relações sexuais protegidas com o uso do preservativo masculino. Os efeitos adversos dos antirretrovirais são descritos como obstáculo importante à adesão ao tratamento. O alojamento conjunto foi o cenário das piores vivências dentre toda a assistência recebida, destaque dado ao tema aleitamento materno. Há uma lacuna entre as demandas das mulheres em produzir e relatar as suas narrativas e a inexistência de espaços de escuta, seja individualmente na relação com o profissional médico, seja em grupos. Conclusões - A ausência do aconselhamento como espaço de abordagem e esclarecimentos, informações e escolhas, dificulta uma ação mais oportuna para a redução da transmissão vertical do HIV. As mulheres comuns não são atingidas pelas informações sobre HIV/AIDS oferecidas pelas campanhas para prevenção da infecção. O uso do preservativo para evitar a infecção ainda é uma decisão masculina. As mulheres raramente encontram interlocução entre os profissionais, para tirarem suas dúvidas e planejarem sua vida reprodutiva de forma mais segura. Apesar da falta de discussão sobre o planejamento terapêutico, a via de parto e os cuidados com o bebê, as mulheres seguem a prescrição e seguem com seus medos e suas dúvidas / Introduction: The scenario of the AIDS epidemic has been changing in Brazil and worldwide, and epidemiological profile of people living with HIV / AIDS has undergone successive changes since the 80\'s. Although men represent in absolute numbers, the highest number of notifications of all cases of AIDS, the epidemic growth rate is higher among women. Brazil has a response to the epidemic of STD / AIDS internationally recognized principles of the SUS: universality, equity and integrity in service. One of the elements of this response is the prevention of vertical transmission of HIV. The theme that is gaining importance, as AIDS gets the status of chronic disease and HIV positive women can make their own reproductive choices. The prevention of vertical transmission of HIV includes testing for early diagnosis, antiretroviral therapy during pregnancy and delivery, antiretroviral therapy for the newborn and not breastfeeding. Objective -To study how the prevention and control of vertical transmission of human immunodeficiency virus are perceived by pregnant women and new mothers assisted by the State Program of STD / AIDS, and their satisfaction or dissatisfaction in relation to care received. Methods -Our sample consisted of 14 women, 13 HIV-positive pregnant and who had at least one child in the context of being HIV positive and one was seronegative for HIV and an adoptive mother of an HIV positive child. To collect data we used the qualitative methodology, based on individual interviews, semi-structured, conducted in 2010. Results - There was no counseling for the testing of any women in the sample. Women had, overall, a lack of identification with the profile of people who can become infected with HIV, being surprised by the diagnosis. Eight male partners had unknown HIV status, and three refused to be tested. There are difficulties, for women, to promote safe sex with condom use. Adverse effects of antiretroviral drugs are described as barrier to treatment adherence. Rooming-in was the scene of the worst experiences among all the care received, highlighting the theme of breastfeeding. There is a gap between women\'s demands to produce and report their stories and the lack of opportunities to listen, either individually in relation to the medical professional, either in groups. Conclusions - The lack of counseling as a space for dialogue and explanations, information and choices, hampers a more timely action to reduce vertical transmission of HIV. The \"ordinary\" women are not affected by information about HIV / AIDS provided by the campaigns to prevent infection. The use of condoms to prevent infection is still a male decision. Women are rarely have the opportunity to with professionals, to expose their questions and plan their reproductive lives more safely. In this setting of lack ofparticipation on treatment planning, delivery or baby care, women follow the \"prescription\" and move on with their fears and doubts

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-20T16:29:39Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) CIENCIAS MEDICAS GABRIELA AVILA.pdf: 1035117 bytes, checksum: 1e557cad3ea706ebe746a5080324d310 (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-20T16:29:50Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) CIENCIAS MEDICAS GABRIELA AVILA.pdf: 1035117 bytes, checksum: 1e557cad3ea706ebe746a5080324d310 (MD5) / Made available in DSpace on 2017-09-20T16:29:50Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) CIENCIAS MEDICAS GABRIELA AVILA.pdf: 1035117 bytes, checksum: 1e557cad3ea706ebe746a5080324d310 (MD5) Previous issue date: 2017 / Universidade Federal Fluminense / O padrão da epidemia da infecção pelo vírus da imunodeficiência humana (HIV) entre crianças modificou-se substancialmente nos últimos anos, com declínio no número de novas infecções na população pediátrica após a implementação, em 1994, do protocolo PACTG 076 (Pediatric Aids Clinical Trials Group 076). Posteriormente, o impacto da terapia antirretroviral combinada durante a gestação, primariamente para diminuir a morbidade na mãe, apresentou o benefício adicional da redução das taxas de TVHIV. Este estudo é uma série de casos, cujo objetivo é conhecer o perfil clínico-epidemiológico das gestantes infectadas pelo HIV atendidas no Serviço de Infectologia do Hospital Universitário Antônio Pedro no período de 1998 a 2013, o resultado de suas gestações ea taxa de transmissão vertical do HIV. Foram investigadas 115 gestantes, que resultaram em 152 gestações, através da seleção mediante consulta ao registro de atendimento no ambulatório de Serviço de Infectologia do HUAP. A média de idade das gestantes atendidas foi de 26 anos (desvio padrão - DP = 2,1) e 57,9% eram brancas. A idade gestacional média na primeira consulta foi de 22,8 semanas gestacionais (DP = 7,8). Embora a maioria já soubesse ser portadora do HIV, 46,4% foram diagnosticados em mulheres que não tinham conhecimento do seu estado sorológico. A percentagem de gestações consideradas em imunossupressão grave (CD4 + <200 células / mm3) caiu de 17,9% antes de iniciar a terapêutica anti-retroviral para 8,9% na consulta pré-parto. Houve também um aumento na proporção de mulheres grávidas que atingiram uma carga viral não detectada, de 10,4% para 37,9%. A taxa de transmissão vertical do HIV foi de 1,6%., corroborando para a importância do acompanhamento pré-natal adequado e do tratamento com antirretrovirais potentes, fundamentais para a saúde das gestantes e para prevenção da transmissão do HIV aos recém-nascidos. / The pattern of the human immunodeficiency virus (HIV) epidemic among children has changed substantially in recent years, with a decline in the number of new infections in the pediatric population following the implementation in 1994 of the PACTG 076 protocol (PEDIATRIC AIDS CLINICAL TRIALS GROUP 076). Subsequently, the impact of combination antiretroviral therapy during pregnancy, primarily to reduce maternal morbidity, had the additional benefit of reducing maternal-fetal transmission rates of the virus. This study is a series of cases, whose objective is to know the clinical-epidemiological profile of HIV-infected pregnant women attended the Infectious Disease Department of the Antônio Pedro University Hospital from 1998 to 2013, the outcome of their pregnancies and the vertical HIV transmission rate. 115 pregnant women, resulting in 152 pregnancies, were investigated through the selection by consulting medical records. The mean age of the pregnant women attended was 26 years (standart deviation - ST = 2.1), 57.9% of them were white. The mean gestational age at the first outpatient clinic was 22.8 gestational weeks (ST = 7.8). Although most of them already knew to be HIV carrier, 46.4% were diagnosed in women who were unaware of their serological status. The percentage of pregnancies considered in severe immunosuppression (CD4+ < 200 cells/mm3) fell from 17.9% before starting antiretroviral therapy to 8.9% in the prepartum consultation. There was also an increase in the proportion of pregnant women who achieved an undetected viral load, from 10.4% to 37.9%. The vertical HIV transmission rate was 1.6%, corroborating the importance of adequate prenatal care and treatment with potent antiretroviral drugs, which are essential for the health of pregnant women and for the prevention of HIV transmission to newborns.

Made available in DSpace on 2014-07-29T15:26:22Z (GMT). No. of bitstreams: 1 Tese Keila Correia de Alcantara.pdf: 2967378 bytes, checksum: abcf75d777805ea6de3323b7586a4654 (MD5) Previous issue date: 2010-10-31 / Introduction: The spread of the aids epidemic among young women and HIV-1 mother-tochild transmission (MTCT) represent important public health issues. In this context, prenatal care represents a unique opportunity for the early diagnosis of young women and for the implementation of full preventive strategies to HIV-1MTCT. Objectives: To study immunological, virological, clinical and epidemiological characteristics and to identify factors associated with HIV-1MTCT among HIV-1 pregnant women/infants recruited in Goias State. Material and methods: Cohort 1: 41 pregnant HIV/AIDS: infant pairs (April/2000-August/2001) were recruited and prospectively followed up at two regional reference centers-Mother-Infant Hospital (HMI/SUS) and Hospital Dr. Anuar Auad (HAA/HDT/SUS). Cohort 2: 172 HIV/AIDS pregnant women and 149 exposed children were recruited at the Institute of diagnosis and prevention (IDP/APAE) and prospectively followed up at HAA/HDT/SUS. The following tests were performed: maternal viral load, CD4+ T cell counts, HIV-1env/gag subtypes by heteroduplex mobility assay/HMA (cohort 1) and pol (protease and reverse transcriptase-PR/RT) sequencing for resistance profile, subtypes identification and phylogeography analysis for subtype C (cohort 2). Infants born to HIV-1/aids mothers were evaluated by plasma viral RNA and CD4+ T cell counts. Seroreversion of exposed- uninfected children was followed by sequential ELISA tests for IgG anti HIV-1. Results: Patients from cohorts 1 and 2 presented similar social-demographic and clinical profiles. The median age was 26 years; 15-41 years), lower educational level predominated and most were diagnosed during pregnancy (90%). Over 80% received ARV prophylaxis. One case of MTCT was observed in cohort 1 which was associated with short prophylaxis and long labor period. Exposed-uninfected infants born to symptomatic mothers seroreverted earlier. Cohort 2 included 80% of all HIV-1 infected pregnant women from Goias state in that period. The early prophylaxis and undetectable viral load predominated among previously diagnosed patients (p<0.05). One ARV naive patient presented transmitted drug resistance; 10 ARV experienced patients presented secondary drug resistance: 6 under MTCT prophylaxis, 4 under HAART. MTCT was observed in 3/149 (2.01%) cases and late diagnosis, vaginal delivery, brastfeeding and lack of oral ZDV were observed. Among MTCT cases resistance mutations were not detected. HMA env/gag (cohort 1) and pol sequencing (cohort 2) results showed mostly subtype B followed by subtypes F1, C and recombinants, mainly BF1. HIV-1 subtype C was identified only among pregnant women from cohort 2 which together with recombinants BC represented around 20% of the isolates. Subtype C and BC recombinants were isolated in interior municipalities of Goias state located close to the main highways that connect south/southern to north (BR153), northeast (BR020) and South/west (BR369/BR070). Phylogenetic/ phylogeographic analysis showed a subtype C clado, clusters (aLTR &#8805; 0.85) with sequences from Southern states and from Sao Paulo and evidences of multiple introductions. Conclusion: Our results indicate the importance of prenatal care for the early diagnosis/prevention of HIV-1 vertical transmission. However late diagnosis and missed opportunities to fully prevent transmission were associated with vertical transmission. Multiple introductions and the dissemination of HIV-1 subtype C by heterosexual contact in interior cities highlight the importance of monitoring the genetic diversity and the impact of subtype C dissemination in the interior of Brazil. Note: superscript + is where it appears and the program does not copy. / Introdução: O avanço da epidemia de aids em mulheres jovens e a transmissão materno-infantil do HIV-1 (TMI) representam importantes temas de saúde pública. Neste contexto, a assistência pré-natal representa uma oportunidade única para o diagnóstico da infecção pelo HIV-1 e implementação precoce de medidas profiláticas para TMI. Objetivos: Estudar as características imunológicas, virais, clínicas, epidemiológicas e identificar fatores associados à transmissão materno-infantil do HIV-1 entre gestantes infectadas pelo HIV-1/filhos recrutados no estado de Goiás. Material e métodos: Coorte 1: 41 pares mães HIV/aids-filhos (abril/2000-agosto/2001) recrutados e acompanhados prospectivamente em dois centros de referência regionais (Hospital Materno Infantil/HMI/SUS; Hospital Dr. Auar Auad/HAA/HDT/SUS). Coorte 2: 172 mães HIV/aids-149 filhos recrutados no Instituto de Diagnóstico e Prevenção/IDP/APAE e acompanhados prospectivamente no HAA/HDT/SUS. Foram avaliados viremia plasmática materna, contagem de células T CD4+, subtipos de HIV-1 nas regiões env/gag pelo ensaio da mobilidade de heteroduplex (HMA) para coorte 1 e sequenciamento gene pol (protease e transcriptase reversa-PR/RT) para identificar mutações de resistência aos antirretrovirais e subtipos do HIV-1 e análise filogeográfica das seqüências do subtipo C da coorte 2. As crianças filhas de mães HIV/aids foram submetidas a testes para quantificação do RNA HIV-1 plasmático e das células T CD4+. Nas crianças não infectadas a sororreversão foi acompanhada sequencialmente por ELISA para IgG anti HIV-1/2. Resultados: As pacientes da coorte 1 e 2 apresentaram características sócio-demográficas e clínicas semelhantes. A mediana de idade foi 26 anos (variação 15-41 anos), a maioria tinha baixa escolaridade e foi diagnosticada durante a gestação (90%). Mais de 80% recebeu profilaxia ARV para TMI. Na coorte 1 foi observado um caso de TMI associado a curta exposição à profilaxia e longo trabalho parto. Entre crianças expostas/nãoinfectadas a sororreversão foi mais rápida entre os nascidos de mães sintomáticas. A coorte 2 representou 80% do total de gestantes HIV-1+ do Estado de Goiás no período. A introdução precoce da profilaxia e viremia indetectável predominaram nas pacientes com diagnóstico anterior à gestação (p<0.05). Uma paciente virgem de tratamento apresentou resistência transmitida; 10 pacientes apresentaram resistência secundária: 6 sob profilaxia, 4 sob HAART. Entre os casos de TMI (3/149; 2.01%) observamos diagnóstico tardio, parto vaginal, amamentação e ausência do AZT oral e mutações de resistência não foram detectadas. Resultados do HMA (coorte 1) e do sequenciamento automatizado (coorte 2) em gestantes de Goiás mostraram a circulação dos subtipos B, F1 e recombinantes, principalmente BF1 nas regiões env/gag e pol do HIV-1. O subtipo C só foi detectado na coorte 2 e juntamente com os recombinantes BC representaram em torno de 20% dos isolados. HIV-1 subtipo C, originado do sul do país, foi detectado em gestantes de municípios do interior de Goiás por onde passam importantes vias de ligação sul-norte (BR153), sul-nordeste (BR020) e sulcentro-oeste/Mato Grosso (BR070/BR364). Análises filogenética/filogeográfica do subtipo C mostraram um clado monofilético formado por sequencias de Goias e da região Sul e de São Paulo e evidências de múltiplas introduções em Goiás. Conclusão: Nossos resultados indicam que o programa pré-natal de alta cobertura em Goiás representa uma importante oportunidade para diagnósttico e prevenção precoce de transmissão vertical do HIV-1. Entretanto os 3 casos de TMI observamos diagnóstico tardio e perda de oportunidade para a profilaxia completa da transmissão vertical do HIV-1. Múltiplas introduções e a disseminação do subtipo C por contato heterossexual no interior indicam a necessidade de monitoramento da diversidade genética e do impacto da disseminação do subtipo C no interior do Brasil. OBS: + está sobrescrita onde aparece e o programa não copia.

<p>The study aimed to assess the level of adherence and to identify the barriers to adherence and the motivations for good adherence to antiretroviral therapy, amongst women who commenced treatment while pregnant at research clinics in Molepolole, Mochudi, Lobatse and Gaborone.</p>

La transmission mère-enfant (TME) du VIH-1 est un des enjeux majeurs de la pandémie. Une meilleure compréhension de la réponse des lymphocytes T cytotoxiques CD8+ (LTC) VIH-spécifiques lors de la grossesse facilitera le design de stratégies optimales pour diminuer la TME. Notre objectif est donc de caractériser l’amplitude et la diversité de la reconnaissance antigénique des LTC VIH-spécifiques avant, pendant et après la grossesse chez des femmes infectées par le VIH-1. Nos résultats montrent pour la première fois que l’initiation et la progression de la grossesse, à elles seules, n'ont que peu d’influence sur l’amplitude et la diversité de la reconnaissance antigénique des réponses LTC en termes de production d’IFN‐. Ces résultats indiquent que les femmes infectées par le VIH conservent une immunocompétence durant leur grossesse, du moins dans le contexte d’un traitement antirétroviral efficace. Ceci pourrait éventuellement aider à promouvoir l’immunisation comme stratégie pour prévenir la TME du VIH‐1. / Mother-to-child transmission (MTCT) of HIV-1 is one of the major issues of the pandemic. Characterization of HIV-specific immunity during pregnancy, especially cytotoxic CD8+ T lymphocytes (CTL), will lead to a better understanding of HIV pathogenesis and facilitate design of optimal strategies to prevent MTCT. Our objective is to describe the magnitude and the breadth of antigen recognition of HIV-specific CTL responses before, throughout and after pregnancy in a group of HIV-infected women. Our results revealed for the first time that initiation of pregnancy by itself doesn’t change the magnitude of CTL responses in terms of IFN- production. These findings support the fact that HIV-infected women maintain immunocompetence throughout gestation, at least in the context of effective antiretroviral treatment. These results provide a novel understanding of the dynamics of HIV-specific CTL responses during pregnancy and may help to promote maternal immunization as a strategy to prevent MTCT of HIV-1.