Student Number : 8044255 - PhD thesis - School of Pathology; Discipline Virology - Faculty of Health Sciences / Knowledge of the timing of mother-to-child transmission (MTCT) of HIV-1 is an important issue in reducing the risk of infant infection. Prior to giving birth therefore an HIV-1 positive mother should be provided with anti-HIV-1 drugs (antiretrovirals) during the shortest time possible to ensure both efficacy and minimal toxicity of the antiretrovirals to the newborn. However, in the absence of timeous administration of nevirapine (NVP) or zidovudine (AZT) to the mother at the onset of labour, infants are given post-exposure prophylaxis (PEP). Despite antiviral prophylaxis some infants still become infected. In an attempt to mimic the in vivo scenario we investigated, in Chapter Three, the replication ability of a primary isolate (M502L) in peripheral blood mononuclear cells (PBMC) isolated from healthy donors exposed to different concentrations of NVP or AZT either prior to or post-infection, but that reflected mean neonatal plasma concentrations measured following maternal dosing. In phytohaemagglutinin (PHA) stimulated cultures M502L exhibited some growth. Maintaining NVP and AZT in the culture medium resulted in decreased viral growth over time. In contrast to that expected certain donors demonstrated elevated p24 antigen levels in the presence of HIV-1 and NVP or AZT. This suggested that cells were more conducive to HIV-1 replication either because of cellular activation or due to cellular production of cytokines/chemokines. The in vitro study highlighted (i) the differential permissiveness of cells from different donors for HIV-1 infection, (ii) different abilities of antiretrovirals (ART) to circumvent infection in different individuals and (iii) immunomodulatory effects of ART in vitro. Commencing in Chapter Four we elected to investigate, in vivo, the immunomodulatory consequences of HIV-1 exposure and infection in two groups of HIV-1-exposed newborns whose mothers either received NVP at the onset of labour or who only received NVP as PEP within 72 hours of birth. Short-course antiretroviral drug regimens are known to reduce the risk of MTCT of HIV-1 but mechanisms affording protection of such interventions remain poorly defined. Since T-cell activation is an important factor in productive HIV-1 infection, we tested the hypothesis that single-dose NVP reduces immune activation, which in turn reduces the likelihood of transmission. We compared concentrations of cord and maternal blood plasma immune activation markers, neopterin, β2-microglobulin (β2-m) and soluble L-selectin (sL-selectin) in the two groups of HIV-1-exposed newborns and among HIV-unexposed controls. In utero exposure of the infant to HIV-1, regardless of NVP exposure, led to demonstrable increases in levels of immune activation markers, this being most notable in the presence of pre-existing infection. Contrary to what was hypothesized, immune activation was increased by pre-birth exposure to single-dose NVP, with this effect being enhanced in infants already infected at birth. Our data suggest that reductions in immune activation do not explain transmission prevention effects of single-dose NVP. Our data also suggest a biological explanation for why HIV-1 infected infants exposed perinatally to antiretroviral drugs might experience hastened disease progression, namely that the immunological mileau in some HIV-1 infected individuals treated with NVP favours increased HIV-1 replication. Cytokines and chemokines function to stimulate, or suppress cellular proliferation and differentiation and have unique immunomodulatory properties. Furthermore, they have the potential to protect against HIV-1 infection or to regulate HIV-1 replication. In Chapter Five we therefore questioned whether exposure to HIV-1 or NVP influences cytokine/chemokine levels of infants born to HIV-1 infected mothers. We compared levels of interleukin (IL)-7, IL-10, stromal cell-derived factor: SDF-1α (CXCL12), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage inflammatory protein-1α: MIP-1α (CCL3), macrophage inflammatory protein-1β: MIP-1β (CCL4) and regulated upon activation, normal T-cell expressed and secreted: RANTES (CCL5) of the two groups of HIV-1-exposed newborns and among the HIV-unexposed controls. HIV-1 exposure in the absence of single-dose NVP was not found to impact significantly on the levels of IL-7, IL-10, GM-CSF, CXCL12, CCL3, CCL4 or CCL5 and single-dose NVP had no appreciable effect on these cytokine/chemokine levels. Cord blood plasma levels of IL-7, CXCL12 and GM-CSF were found to be independent of mothers’ levels. Single-dose NVP reduced the ability of cord blood mononuclear cell (CBMC) to produce GM-CSF spontaneously. Maternal and infant (HIV-1 exposed NVP unexposed) IL-10 levels were significantly correlated. Significantly elevated levels of IL-10 were associated with pre-existing infection in NVP unexposed newborns. CCL3, CCL4 and CCL5 levels in NVP unexposed uninfected infants were not different from those of control infants but correlated significantly with IL-7 levels. HIV-1 specific cellular immune responses are elicited in a proportion of infants born to HIV-1 seropositive mothers and have been associated with protection from maternal HIV-1 transmission. In Chapter Six, levels of the immune activation markers neopterin, β2-m, sL-selectin, the immunomodulatory and haematopoietic factors IL-7, CXCL12, GM-CSF and the immunoregulatory cytokine IL-10 were examined amongst the group of newborns, that received NVP as PEP within 72 hours of birth, of which a proportion had specific cellular responses to HIV-1 envelope (Env) peptides. It was our aim to determine in infants that elicit HIV-1 specific cellular immune responses (Env+) and those that lack the specific responses (Env-), whether these factors could predict transmission and whether the former group of infants exhibit unique immune features that might distinguish them from Env- non-responders. Our data suggested that none of the factors tested were predictive of HIV-1 transmission but confirmed that infants with cellular responses to HIV-1 envelope peptides were associated with lack of subsequent infection. In particular, our data demonstrated an association between HIV-1 specific cellular immune responses, lower maternal viral load and lack of infection suggesting that sustained exposure to antigen (reduced maternal viral load) may be responsible for the strong priming effect. Furthermore, an association between reduced GM-CSF levels and the presence of HIV-1 specific responses was demonstrated, which suggested therefore that newborn infants that elicited HIV-1 specific cellular immune responses exhibited different immune capabilities from those without responses. Finally, in Chapter Seven we looked at how immune activation and priming impact on thymic output of T-cells in newborn infants. Unfortunately, sample volumes of the two groups of HIV-1-exposed newborns used in the previous three Chapters became limited with the result that we chose to address these questions using anonymously collected cord blood samples from infants, some of which were used to supplement the placebo group of the the UNAIDS-sponsored clinical trial of short-course zidovudine-lamivudine (AZT-3TC). At the time the AZT-3TC trial was conducted short-course antiviral prophlyaxis was not the standard of care for the prevention of MTCT of HIV-1. The thymus is known to be essential for establishing diversity of the T-cell pool, and morphological thymic changes and effects on naïve T-cells and T-cell receptor excision circle (TREC) concentrations have been reported in studies of HIV-1 infected children and adults. As it is not known to what extent in utero exposure to HIV-1 and infection affects T-cell division in newborn infants, we elected to determine TREC levels of infants born to HIV-1 seropositive mothers that were not exposed to antiretrovirals. The impact of increased immune activation on TREC levels and the consequence of HIV-1 exposure or infection on circulating levels of IL-7 (raised levels indicative of T-cell depletion) was also investigated. HIV-1 exposure or infection did not result in significant losses of TREC. TREC levels were not affected by immune activation associated with HIV-1 exposure and infection and IL-7 levels were not raised. Infants that elicited HIV-1 specific cellular immune responses exhibit TREC levels that were similar to those of infants without HIV-1 specific responses. These data suggested that newborn infants of HIV-1 seropositive mothers demonstrated no altered thymopoietic ability compared to control infants. Furthermore, HIV-1 specific immune responses, (indicative of post-thymic memory T-cell expansion) did not influence thymic output measured in newborn infants. In conclusion, the in vitro study demonstrated that there is a high degree of variability between PBMC isolated from different donors with respect to viral replication and drug effectivity which suggests that these phenomena are likely to exist within patient (infant as well as adult) populations. While immune activation is considered central to productive infection we demonstrated that immune activation is increased by HIV-1 exposure and by single-dose NVP. Exposure to HIV-1 alone or with NVP did not influence birth levels of IL-7, IL-10, CXCL12, GM-CSF, CCL3, CCL4 and CCL5. Furthermore, levels of these factors did not predict infection outcome in the infant. Immune activation and haematopoietic growth factors are modulated independently of the mother but maternal factors such as IL-10 and exposure to single-dose NVP, which reduces responsiveness of CBMC, could impact on the infant. HIV-1 specific cellular immune responses at birth, which are elicited in a proportion of infants born to HIV-1 positive mothers, are of immunological significance and can predict lack of subsequent infection. Disturbances in thymic output are not readily detectable at birth when using TREC to assess de novo T-cell synthesis, alternatively there is a homeostatic balance between thymic output and peripheral T-cell proliferation in newborns of HIV-1 infected mothers. Overall our data suggests that (i) there are immune consequences of being born to an HIV-1 positive mother, (ii) short-course antiretroviral prophylaxis does impact on the developing immune system of the infant and (iii) while the direct effects of single-dose NVP are not disputed, there are indirect consequences of NVP exposure on immune cells. Despite the consequences of HIV-1 exposure or the result of being born to a HIV-1 seropositive mother or exposure to single-dose NVP, our data proposes that the immune system of newborn infants is capable of responding as demonstrated by the enhanced immune activation. It remains important to determine the correlates of immune protection for the development of novel immuno-therapeutic and vaccine strategies and maternal-infant transmission of HIV-1 provides a model which can address questions of protective immune processes. Understanding the influence of antiretrovirals on immune processes remains an important component of the drug mechanisms, (aside from their direct antiretroviral activity), that may underlie reductions in maternal-infant transmission of HIV-1. Furthermore, how antiretrovirals influence immune processes and immune development (together with exposure to HIV-1/consequences of being born to an HIV-1 seropositive mother), may impact on subsequent immune responsiveness to infectious organisms or childhood vaccines.

O presente trabalho tem por objetivo investigar e fundamentar teoricamente, a partir da teoria psicanalítica de orientação freud-lacaniana, como se dá a experiência da revelação do diagnóstico de HIV, para a parceria afetivo-sexual, em adolescentes e jovens adultos infectados por transmissão vertical. É absolutamente compreensível a relação que se estabelece no âmbito da Saúde, entre revelação do diagnóstico e cuidados preventivos. No entanto, a clínica psicanalítica com os pacientes envolvidos nesta problemática nos indica que a revelação do diagnóstico é, para o paciente, uma experiência que ultrapassa muito o ato de informar um dado, sendo, antes, uma experiência subjetiva da revelação de uma identidade herdada. Por esse motivo, percebemos ser fundamental uma compreensão dos processos psíquicos envolvidos na experiência da revelação do diagnóstico destes jovens, levando em conta a singularidade de cada caso. Partimos de duas hipóteses: a revelação do diagnóstico ao parceiro afetivo-sexual pode ser influenciada por como lhe foi revelado seu diagnóstico, ou seja, sua herança do HIV, transmitida por sua mãe; a angústia associada à experiência da revelação do diagnóstico de HIV por transmissão vertical para o parceiro pode ser uma resposta à fantasia de desamparo. Na tentativa de compreender esse cenário, elegemos alguns conceitos psicanalíticos como bússola, que podem contribuir para o cerzimento de articulações teórico-clínicas, são eles: tabu, transmissão, identificação, fantasia e angústia. Além disso, realizamos entrevistas semi-dirigidas com quatro pacientes, que tinham diagnóstico de HIV/aids por transmissão vertical. A análise das falas dos entrevistados foi realizada a partir do referencial psicanalítico, utilizando principalmente as teorias construídas por Freud e Lacan. A partir disso, pudemos concluir que guardar o diagnóstico de HIV como segredo implica resguardar a posição do sujeito em sua fantasia fundamental, que funciona de anteparo para a angústia e está diretamente ligada ao Outro. Nesse sentido a solução para ausência de sofrimento psíquico não seria nem direcionar o sujeito para a denúncia do segredo, nem tampouco, sugestioná-lo a manter o segredo a sete chaves. Neste momento, é fundamental compreender o lugar que o segredo encena na subjetividade dos jovens, por meio da escuta psicanalítica. Além disso, é imprescindível cuidar da resposta do psicanalista no âmbito institucional, como membro da equipe de saúde, defendendo um manejo delicado entre o tempo de cada sujeito e a importância da revelação do diagnóstico, uma vez que o paradigma da subjetividade pode ser uma alternativa competente para resolver uma problemática ainda muito incompreendida em serviços de saúde especializados em HIV/Aids / The present study aims to investigate and to formalize theoretically, according to the psychoanalytic theory of Freud and Lacan, how is the experience of the disclosure of HIV serostatus to an intimate partnership, for adolescents and young adults infected by mother-to-child-transmission. The connection established under Healths context, between the disclosure of HIV serostatus and preventive care is absolutely understandable. However, the psychoanalytic treatment of patients involved in this issue indicates that disclosure of HIV diagnosis is an experience that exceeds just the act of informing, it is actually a subjective experience of revelation of an inherited identity. For this reason, we consider that it is fundamental to understand which psychological processes are involved in the experience of disclosing the HIV diagnosis, taking into account the uniqueness of each case. We have two hypotheses: the disclosure of HIV diagnosis to the partner may be influenced by how the individual received its own diagnosis, that represents the heritage of HIV, transmitted by the mother; the anguish associated with the experience of disclosing the HIV diagnosis through mother-to-child-transmission to the partner may be a response to the fantasy of helplessness. In trying to understand this scenario, we elect some psychoanalytic concepts such as a compass, that can contribute to make the theoretical and clinical link, they are: taboo, transmission, identification, fantasy and angst. In addition, we conducted semi-structured interviews with four patients who were diagnosed with HIV/AIDS through mother-to-child-transmission. The analysis of the interviewed peoples speeches was done by the psychoanalytic theoretical basis, mainly using the theories constructed by Freud and Lacan. The course of this research allowed us to conclude that keep HIV diagnosis as a secret means to safeguard the position of the individual in its fundamental fantasy, which works as a screen for anxiety and is directly linked to the Other. In this context, the solution to the absence of psychological pain would be neither to guide the individual to denunciate its secret, nor suggests to keep the secret under lock and key. At this point, it is essential to understand the place that the secret stages in the subjectivity of young people, through the psychoanalytic listening. Moreover, it is also essential to take care of the psychoanalysts work in the health institution, as a member of the health team, protecting the delicate handling between the time of each subject and the importance of disclosure, since the paradigm of subjectivity can be a competent alternative to solve a misunderstood issue inside the HIV/Aids specialized health services

O presente trabalho tem por objetivo investigar e fundamentar teoricamente, a partir da teoria psicanalítica de orientação freud-lacaniana, como se dá a experiência da revelação do diagnóstico de HIV, para a parceria afetivo-sexual, em adolescentes e jovens adultos infectados por transmissão vertical. É absolutamente compreensível a relação que se estabelece no âmbito da Saúde, entre revelação do diagnóstico e cuidados preventivos. No entanto, a clínica psicanalítica com os pacientes envolvidos nesta problemática nos indica que a revelação do diagnóstico é, para o paciente, uma experiência que ultrapassa muito o ato de informar um dado, sendo, antes, uma experiência subjetiva da revelação de uma identidade herdada. Por esse motivo, percebemos ser fundamental uma compreensão dos processos psíquicos envolvidos na experiência da revelação do diagnóstico destes jovens, levando em conta a singularidade de cada caso. Partimos de duas hipóteses: a revelação do diagnóstico ao parceiro afetivo-sexual pode ser influenciada por como lhe foi revelado seu diagnóstico, ou seja, sua herança do HIV, transmitida por sua mãe; a angústia associada à experiência da revelação do diagnóstico de HIV por transmissão vertical para o parceiro pode ser uma resposta à fantasia de desamparo. Na tentativa de compreender esse cenário, elegemos alguns conceitos psicanalíticos como bússola, que podem contribuir para o cerzimento de articulações teórico-clínicas, são eles: tabu, transmissão, identificação, fantasia e angústia. Além disso, realizamos entrevistas semi-dirigidas com quatro pacientes, que tinham diagnóstico de HIV/aids por transmissão vertical. A análise das falas dos entrevistados foi realizada a partir do referencial psicanalítico, utilizando principalmente as teorias construídas por Freud e Lacan. A partir disso, pudemos concluir que guardar o diagnóstico de HIV como segredo implica resguardar a posição do sujeito em sua fantasia fundamental, que funciona de anteparo para a angústia e está diretamente ligada ao Outro. Nesse sentido a solução para ausência de sofrimento psíquico não seria nem direcionar o sujeito para a denúncia do segredo, nem tampouco, sugestioná-lo a manter o segredo a sete chaves. Neste momento, é fundamental compreender o lugar que o segredo encena na subjetividade dos jovens, por meio da escuta psicanalítica. Além disso, é imprescindível cuidar da resposta do psicanalista no âmbito institucional, como membro da equipe de saúde, defendendo um manejo delicado entre o tempo de cada sujeito e a importância da revelação do diagnóstico, uma vez que o paradigma da subjetividade pode ser uma alternativa competente para resolver uma problemática ainda muito incompreendida em serviços de saúde especializados em HIV/Aids / The present study aims to investigate and to formalize theoretically, according to the psychoanalytic theory of Freud and Lacan, how is the experience of the disclosure of HIV serostatus to an intimate partnership, for adolescents and young adults infected by mother-to-child-transmission. The connection established under Healths context, between the disclosure of HIV serostatus and preventive care is absolutely understandable. However, the psychoanalytic treatment of patients involved in this issue indicates that disclosure of HIV diagnosis is an experience that exceeds just the act of informing, it is actually a subjective experience of revelation of an inherited identity. For this reason, we consider that it is fundamental to understand which psychological processes are involved in the experience of disclosing the HIV diagnosis, taking into account the uniqueness of each case. We have two hypotheses: the disclosure of HIV diagnosis to the partner may be influenced by how the individual received its own diagnosis, that represents the heritage of HIV, transmitted by the mother; the anguish associated with the experience of disclosing the HIV diagnosis through mother-to-child-transmission to the partner may be a response to the fantasy of helplessness. In trying to understand this scenario, we elect some psychoanalytic concepts such as a compass, that can contribute to make the theoretical and clinical link, they are: taboo, transmission, identification, fantasy and angst. In addition, we conducted semi-structured interviews with four patients who were diagnosed with HIV/AIDS through mother-to-child-transmission. The analysis of the interviewed peoples speeches was done by the psychoanalytic theoretical basis, mainly using the theories constructed by Freud and Lacan. The course of this research allowed us to conclude that keep HIV diagnosis as a secret means to safeguard the position of the individual in its fundamental fantasy, which works as a screen for anxiety and is directly linked to the Other. In this context, the solution to the absence of psychological pain would be neither to guide the individual to denunciate its secret, nor suggests to keep the secret under lock and key. At this point, it is essential to understand the place that the secret stages in the subjectivity of young people, through the psychoanalytic listening. Moreover, it is also essential to take care of the psychoanalysts work in the health institution, as a member of the health team, protecting the delicate handling between the time of each subject and the importance of disclosure, since the paradigm of subjectivity can be a competent alternative to solve a misunderstood issue inside the HIV/Aids specialized health services

As medidas preventivas da transmissão vertical do HIV podem efetivamente reduzir as taxas da infecção nas crianças. No entanto, são necessárias a participação e adesão das mães ao tratamento. Buscando compreender as crenças que influenciam o comportamento das mães portadoras do HIV em relação às medidas profiláticas da transmissão vertical, desenvolvemos este estudo qualitativo. Foram entrevistadas 14 mulheres portadoras do HIV cujos filhos nasceram no município de Ribeirão Preto e tinham no mínimo 6 meses de vida. Os dados foram tratados de acordo com o método da Análise de Conteúdo e interpretados utilizando-se como referencial teórico o Modelo de Crenças em Saúde (Rosenstock, 1974), composto pelas dimensões susceptibilidade percebida, severidade percebida, benefícios percebidos e barreiras percebidas. Na análise emanaram categorias que evidenciam as contradições da epidemia da aids: na susceptibilidade percebida emergiram “invulnerabilidade antes da gravidez", “o pré-natal" e “susceptibilidade da criança"; quanto à severidade da doença – “subestimação do HIV" e “medo da morte"; “crescer saudável" e “não ser como eu", foram os benefícios percebidos pelas mães; em relação às barreiras possíveis, encontramos a “descrença na existência do vírus", “dificuldades financeiras" e “omissão do diagnóstico". Alguns aspectos das crenças podem ser considerados tanto como facilitadores como dificultadores da adesão materna, dependendo do contexto sócio-econômico e cultural em que vive a mãe. Conhecer a percepção das mães acerca das crenças que motivam os seus comportamentos proporciona aos profissionais de saúde maior compreensão desses comportamentos, permitindo ainda a possibilidade de elaboração de um planejamento mais efetivo de cuidados dentro de um contexto culturalmente significativo, com maior probabilidade de promover a adesão da clientela. / Prevention measures for the mother-to-child transmission of the HIV virus may effectively reduce infection rates in children. However, for such effectiveness to come true, mothers have to comply with the treatment. This study was carried out aiming to understand the beliefs which influence the HIV positive mothers’ behaviors towards prevention methods against mother-to-child transmission. Fourteen HIV infected women whose children were at least 6 months old and all born in Ribeirão Preto county were interviewed. Data were studied according to the Content Analyses method and interpreted using as a theoretical reference the Health Belief Model (Rosenstock, 1974), formed by the following dimensions: perceived susceptibility, perceived severity, perceived benefits and perceived obstacles. As we analyzed those data we came up with some under categories showing the AIDS epidemic paradox: in the perceived susceptibility appeared: “invulnerability prior to pregnancy"; “pre delivery"; “a child’s susceptibility" as for the disease seriousness. “Underestimation of the HIV virus";" fear of death"; “healthy growing up"; and “not the same as me" were the benefits mentioned by the mothers. As for the possible barriers, we found things like: “disbelief in the virus existence"; “financial problems"; “diagnosis omission". Some aspects of the beliefs may be considered both helpers and trouble-makers for a mother’s adhesion, varying according to the social, economic and cultural environment the mother lives in. Getting to know a mother’s perception regarding the beliefs motivating their behaviors provides the health professionals a higher understanding of such behaviors, allowing the possibility of making up an effective care plan within the context culturally meaningful, with a higher probability of promoting patients’ adhesion.

A principal via de infecção pelo HIV-1 em crianças é a transmissão materno-infantil (TMI). Estimativas para taxas de TMI do HIV-1 são de 3% entre gestantes sob terapia antirretroviral e de 25 a 30% para as não tratadas. Apesar da exposição viral durante a gestação, a maioria dos recém-nascidos não são verticalmente infectados, o que sugere a existência de barreiras protetoras à TMI do HIV-1. Diversos fatores podem estar associados com a TMI do HIV-1. Polimorfismos genéticos são descritos em associação com a infecção pelo HIV-1, incluindo os dos antígenos leucocitários humanos (HLA). A molécula HLA-G tem sido implicada nas interações imunológicas materno-fetais e é expressa em células da placenta, especificamente nos citotrofoblastos extravilosos, que formam a camada responsável pela interface entre os tecidos fetais e maternos. Este estudo avaliou os polimorfismos de inserção e deleção de 14pb do HLA-G na TMI do HIV-1. Participaram do estudo, 86 duplas de mães e filhos, sendo 58 duplas de mãe-filho em que a TMI do HIV-1 não ocorreu e 28 duplas em que a TMI ocorreu. Os resultados mostraram maior frequência de genótipo deleção/deleção em mães pertencentes ao grupo TMI positiva, sem utilização de antirretrovirais (p=0,05). Foi observada associação significante entre conhecimento prévio da soropositividade, realização de pré-natal, utilização de antirretrovirais na gestação e não amamentação com a prevenção da TMI (p<0,05). Nesse contexto, a enfermagem pode contribuir com ações que envolvem o pré-natal, parto e puerpério, por meio de aconselhamento quanto à realização do teste anti- HIV-1 no pré-natal, utilização adequada de antirretrovirais e promoção de práticas ideais de alimentação infantil. Adicionalmente, o estudo contribui para a ampliação de conhecimentos da enfermagem sobre a temática do HLA-G na TMI, e destaca a importância de que a enfermagem, fundamentada em ciências biológicas, esteja envolvida na produção de conhecimentos e tecnologias, o que reflete na melhoria da prestação do cuidado ao paciente. / The main way of HIV-1 infection in children is mother-child transmission (MTCT). TMI rates estimates for HIV-1 are 3% in pregnant women in antiretroviral therapy and 25 to 30% for untreated ones. Despite the viral exposure during pregnancy, most newborns are not vertically infected, suggesting the existence of protective barriers to TMI of HIV-1. Several factors may be associated with MTCT of HIV-1. Genetic polymorphisms are described in association with HIV-1, including the human leukocyte antigens (HLA). The molecule HLA-G has been implicated in maternal-fetal immune interactions and is expressed in placenta cells, particularly in extravillous cytotrophoblasts, forming the layer responsible for the interface between fetal and maternal tissues. This study evaluated the HLA-G 14pb insertion and deletion polymorphisms in MTCT of HIV-1. Participated in the study 86 mother-child pair, 58 mother-child pairs in which the MTCT did not occur and 28 doubles in which the MTCT occurred. The results showed a higher frequency of genotype deletion/deletion in mothers in which MTCT occurred belonging to the group without using antiretroviral (p=0.05). Significant association was observed between prior knowledge of seropositivity, conducting prenatal, use of antiretroviral during pregnancy and not breastfeeding to the prevention of MTCT (p <0.05). In this context, nursing can contribute to actions involving prenatal, birth and postpartum, conducting counseling for the conduct of HIV testing during prenatal care, proper use of antiretroviral and promotion of optimal infant feeding practices. Additionally, the study contributes to the expansion of nursing knowledge about the topic of HLA-G in MTCT, and highlights the importance of nursing, grounded in basic sciences, is involved in the production of knowledge and technology, which reflects improvement in the provision of patient\'s care.

Purpose and rationale: In 2012, an estimated 9,500 infants in Ethiopia were born with HIV. Mortality for these infants is high, and preventing infection offers the best hope for reducing the childhood death rates. Effective measures exist which can reduce the likelihood of a child acquiring HIV from its mother to less than 2%, and the necessary anti-retroviral medications are free and accessible to Ethiopian women. However, Prevention of Mother to Child Transmission of HIV (PMTCT) efforts in the country have not kept pace with the global reduction in infant infections over the last decade, and the Ethiopian MTCT rate was still 20% in 2012. Although a large number of women are getting tested for HIV during pregnancy, only 41% of eligible women in the country complete PMTCT therapy. The purpose of this exploratory study was to elicit the perspectives of HIV+ mothers on the unique socio-contextual factors which affect them during pregnancy, both positively and negatively, including the beliefs, attitudes, cultural norms and individuals who have influence over their reproductive health decisions. Methods: The mixed-methods study was done at a community level in Addis Ababa, Ethiopia. With the assistance of several large networks of people living with HIV (PLHIV), PLHIV mothers who have a child at least one year of age were recruited by mixed purposeful sampling; various socio-economic demographics were represented. In-depth interviews, focus groups and surveys were then completed in Amharic with a research assistant translating to English. Results: 98 women in total took part in the study: 23 completed interviews, 28 participated in focus groups, and 49 completed additional surveys. The greatest barriers to PMTCT completion identified were: feelings of hopelessness and carelessness, a general lack of understanding of the efficacy of ARVs, negative religious influences, stigma and poverty. The strongest facilitators to PMTCT use expressed by the women were: PLHIV peer support, faith, and gaining hope. It was recommended that PLHIV mothers be utilized in all PMTCT planning and interventions in the future. Implications: Program managers and health officials can build on these findings to modify existing PMTCT programs and to develop innovative and effective new PMTCT interventions. This will ultimately result in increased PMTCT uptake and adherence amongst HIV + pregnant women and a reduction in infant HIV transmission.

GB virus C (GBV-C) is a common, apathogenic virus that can inhibit human immunodeficiency virus (HIV) replication in vitro. Persistent coinfection with GBV-C has been associated with improved survival among HIV-infected adults while loss of GBV-C viremia has been associated with poor survival. If GBV-C does inhibit HIV replication, it is possible that GBV-C infection may reduce mother-to-child-transmission (MTCT) of HIV. This study investigated whether maternal or infant GBV-C infection was associated with reduced MTCT of HIV infection. The study population consisted of 1,783 pregnant women from three Bangkok perinatal HIV transmission studies (1992-94, 1996-7, 1999-2004). We tested plasma collected at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If maternal GBV-C RNA was detected, the four- or six-month infant specimen was tested for GBV-C RNA. Rates of MTCT of HIV in GBV-C-infected and GBV-C-uninfected women and infants were compared using multiple logistic regression as were associations with MTCT of GBV-C and prevalence of GBV-C infection. The prevalence of GBV-C infection (i.e. presence of RNA or antibody) was 33% among HIV-infected women and 15% among HIV-uninfected women. Forty-one percent of GBV-C-RNA-positive women transmitted GBV-C to their infants. Only two of 101 (2.0%) GBV-C-RNA-positive infants acquired HIV infection compared to 162 (13.2%) of 1,232 of GBV-C-RNA-negative infants (RR 0.15, p<0.0001). This association remained after adjustment for maternal HIV viral load, antiretroviral prophylaxis, CD4+ count and other covariates. MTCT of HIV was not associated with presence of maternal GBV-C RNA or maternal GBV-C antibody. Maternal receipt of antiretroviral therapy was associated with increased MTCT of GBV-C, as was high GBV-C viral load, vaginal delivery and absence of infant HIV infection. GBV-C infection among women was independently associated with more than one lifetime sexual partner, intravenous drug use and HIV-infection. We observed a higher prevalence of GBV-C infection among HIV-infected compared to HIV-uninfected pregnant women in Thailand, likely due to common risk factors. Antiretroviral therapy appears to increase MTCT of GBV-C. Infant GBV-C acquisition, but not maternal GBV-C infection, was significantly associated with reduced MTCT of HIV. Mechanisms for these later two associations are unknown. / Bhanich Supapol W, Remis RS, Raboud J, Millson M, Tappero J, Kaul R, Kulkarni P, McConnell MS, Mock PA, Culnane M, McNicholl J, Roongpisuthipong A, Chotpitayasunondh T, Shaffer N, Butera S. 2008. Reduced mother-to-child transmission of HIV associated with infant but not maternal GB virus C infection. J Infect Dis 197(10):1369-1377. Bhanich Supapol W, Remis RS, Raboud J, Millson M, Tappero JW, Kaul R, Kulkarni P, McConnell MS, Mock PA, McNicholl JM, Vanprarar N, Asavapiriayanont S, Shaffer N, Butera ST. 2009. Mother-to-child transmission of GB virus C in a cohort of women coinfected with GB virus C and HIV in Bangkok, Thailand. J Infect Dis 200:227-235.

Mother-to-child transmission (MTCT) of HIV is the most significant source of HIV infection in young children. As the HI virus has been identified in cell-free and cell-associated compartments of breast milk, it is clear that breast milk is one of the ways in which mother-to-child transmission of HIV can take place in addition to in utero and intrapartum transmission. While breastfeeding carries the risk of HIV transmission, not breastfeeding carries significant health risks for infants and young children, such as an increased risk of diarrhoea and pneumonia, morbidity and mortality. When an HIV-positive mother decides to breastfeed her baby, pasteurisation of expressed breast milk (EBM) could be a possible infant-feeding option to limit transmission of the HI virus through breast milk, since this method has shown to effectively inactivate HIV type 1. Three methods of pasteurisation of human milk were investigated in this study: Holder pasteurisation, flash-heating and Pretoria pasteurisation. The systematic review is a helpful method to summarise the best-quality empirical evidence of the benefits and limitations of a specific method, such as heat treatment, and to provide recommendations for future research. Therefore, the aim of this study was to critically synthesise by means of a systematic review the best available existing evidence and to provide a clear overview of the effectiveness of heat treatment of EBM as an in-home procedure to inactivate the HI virus, and in so doing limit mother-to-child transmission of HIV. This study provides the clinical practitioner with accessible information on the effectiveness of heat treatment of EBM as an in-home procedure in terms of (1) safety, inactivation of the HI virus and retaining the protective and nutritional value of the EBM; (2) feasibility as an in-home procedure; and (3) acceptability by the mothers and their communities. This information could be used to improve clinical practitioners‟ knowledge and include it in their health education to contribute to the prevention of mother-to-child transmission. This study is based on the framework of the model for evidence-based clinical decisions of Haynes, Devereaux and Guyatt (2002). The search strategy was conducted in March/April 2009. The initial search resulted in 574 articles. After thorough screening of potentially relevant studies on heat treatment of EBM, the studies that met the inclusion criteria were critically appraised and scored based on their methodological qualities using standardised instruments. After 6 months, the search was updated. The search obtained 1 article. The final sample involved 12 articles. Conclusions were integrated and synthesised as a basis for developing a clear overview of the best available existing evidence. Finally, the findings of the study were synthesised and the research was evaluated, a conclusion was given, limitations were identified and recommendations were formulated for nursing practice, education and research. The bottom-line answer concluded that heat treatment of EBM should be emphasised as a safe alternative for feeding exposed infants (those of an HIV-positive mother, those of uncertain HIV status or during weaning if the mother cannot afford formula or cow‟s milk), but should be supported with appropriate information to the individual mother, her family and the community. Overall it can be concluded that existing evidence of the effectiveness (in terms of safety, feasibility and acceptability) of heat treatment of EBM, particularly Pretoria pasteurisation, used as a simple in-home procedure, is insufficient, and further research is required. / Thesis (M.Cur.)--North-West University, Potchefstroom Campus, 2010

The benefits of breastfeeding are well known. It has been shown that HIV is transmitted through breast milk. The HIV epidemic is threatening exclusive breastfeeding in South Africa. It is important that mothers make the right infant feeding choice. There are three basic infant feeding methods available for HIV infected mothers namely; breastfeeding, replacement feeding or formula feeding and heat treatment of breast milk. There are many risk factors for the transmission of HIV through breast milk. Exclusive breastfeeding may reduce the risk of mother-to-child-transmission, compared with mixed feeding. This can only take place when breastfeeding is done safely and not mixed with other food or drinks. There are many factors that influence a mother's decision to breastfeed, for example personal, social, cultural factors, facilities, environmental factors, knowledge about breastfeeding, mass media and friends. There are also many sources of information about infant feeding methods. The aim of this study was to determine which factors influence the decision on the early infant feeding choice of women who delivered at the Lower Umfolozi District War Memorial Hospital in Empangeni, KwaZulu-Natal. This may help to understand what factors health professionals should focus on in promoting appropriate infant feeding methods. A structured questionnaire was completed by a 100 women and focus group discussions were held with 22 women who delivered at the Lower Umfolozi District War Memorial Hospital. Most of the mothers (72%) did choose breastfeeding, and 58% of these mothers intended to breastfeed for only six months. The majority of the women (97%) received counseling about their infant feeding method, mostly from a health care worker at the clinic. One-third of the women (33%) were influenced by health care professionals on deciding on their infant feeding method and 44% of the participants indicated that no-one influenced them and that they decided themselves. In the focus group discussions the fear of transmission of HIV through breast milk was stated as an important reason why mothers should choose replacement feeding. In conclusion the most important results are that significantly more HIV-infected mothers chose replacement feeding as infant feeding method, and mothers who chose breastfeeding were significantly older than mothers who selected replacement feeding and they made their infant feeding decision significantly earlier than those who chose replacement feeding. According to the focus group discussion results the communities also felt that the HIV-infected mothers should not breastfeed their infants due to the fact that the virus can be transmitted through breast milk. Health professionals should still provide all the necessary information about exclusive breastfeeding for the first six months, even where the prevalence of HIV is high. In most of these areas replacement feeding will not be acceptable, feasible, affordable, sustainable and safe, due to lack of safe water, sanitation and the poor socio-economic status of these people. The dangers of mixed feeding should be emphasized. Most of the women in this study received information from health care workers and family. It is important that family members are included when information is given to women of child-bearing age. Health care workers need appropriate training to ensure that they give the right messages about safe infant feeding to the mothers. / Thesis (M.Sc. (Dietetics)--North-West University, Potchefstroom Campus, 2009.

Mother-to-child transmission (MTCT) of HIV is the most significant source of HIV infection in young children. As the HI virus has been identified in cell-free and cell-associated compartments of breast milk, it is clear that breast milk is one of the ways in which mother-to-child transmission of HIV can take place in addition to in utero and intrapartum transmission. While breastfeeding carries the risk of HIV transmission, not breastfeeding carries significant health risks for infants and young children, such as an increased risk of diarrhoea and pneumonia, morbidity and mortality. When an HIV-positive mother decides to breastfeed her baby, pasteurisation of expressed breast milk (EBM) could be a possible infant-feeding option to limit transmission of the HI virus through breast milk, since this method has shown to effectively inactivate HIV type 1. Three methods of pasteurisation of human milk were investigated in this study: Holder pasteurisation, flash-heating and Pretoria pasteurisation. The systematic review is a helpful method to summarise the best-quality empirical evidence of the benefits and limitations of a specific method, such as heat treatment, and to provide recommendations for future research. Therefore, the aim of this study was to critically synthesise by means of a systematic review the best available existing evidence and to provide a clear overview of the effectiveness of heat treatment of EBM as an in-home procedure to inactivate the HI virus, and in so doing limit mother-to-child transmission of HIV. This study provides the clinical practitioner with accessible information on the effectiveness of heat treatment of EBM as an in-home procedure in terms of (1) safety, inactivation of the HI virus and retaining the protective and nutritional value of the EBM; (2) feasibility as an in-home procedure; and (3) acceptability by the mothers and their communities. This information could be used to improve clinical practitioners‟ knowledge and include it in their health education to contribute to the prevention of mother-to-child transmission. This study is based on the framework of the model for evidence-based clinical decisions of Haynes, Devereaux and Guyatt (2002). The search strategy was conducted in March/April 2009. The initial search resulted in 574 articles. After thorough screening of potentially relevant studies on heat treatment of EBM, the studies that met the inclusion criteria were critically appraised and scored based on their methodological qualities using standardised instruments. After 6 months, the search was updated. The search obtained 1 article. The final sample involved 12 articles. Conclusions were integrated and synthesised as a basis for developing a clear overview of the best available existing evidence. Finally, the findings of the study were synthesised and the research was evaluated, a conclusion was given, limitations were identified and recommendations were formulated for nursing practice, education and research. The bottom-line answer concluded that heat treatment of EBM should be emphasised as a safe alternative for feeding exposed infants (those of an HIV-positive mother, those of uncertain HIV status or during weaning if the mother cannot afford formula or cow‟s milk), but should be supported with appropriate information to the individual mother, her family and the community. Overall it can be concluded that existing evidence of the effectiveness (in terms of safety, feasibility and acceptability) of heat treatment of EBM, particularly Pretoria pasteurisation, used as a simple in-home procedure, is insufficient, and further research is required. / Thesis (M.Cur.)--North-West University, Potchefstroom Campus, 2010