Master of Public Health - MPH / Background: Globally, it is estimated that about 1.8 million adolescents (aged 10–19 years) were living with HIV in 2015. In Kenya an estimated 133,455 adolescents were living with HIV in 2015, of which 75% (105,679) were in need of antiretroviral therapy (ART). Among adolescents on ART in 2016, 63% reported viral suppression; which is far below the UNAIDS targets of 90%. Viral suppression (having less than 1000 copies of viral RNA/ml of blood) is a key indicator of HIV treatment success, and is associated with better quality of life and reductions in HIV incidence at a population level. Homabay County recorded the highest HIV prevalence (26%) and the highest number of adolescents living with HIV in Kenya (15,323) in 2015. By the end of June 2017 5,709 adolescents were initiated on ART in Homabay County. Despite the successes in initiating HIV positive adolescents on ART, little is known about the factors that are associated with viral suppression. The current study investigated the factors associated with viral suppression among adolescents initiated on ART before November 30, 2017 in Homabay County, Kenya. Methods: A descriptive cross-sectional study was conducted among 925 adolescents registered on ART for at least 6 months and with at least one documented viral load in the last 12 months, in six health facilities in Homabay County. Data was extracted from the electronic medical records and exported into an excel spreadsheet. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to viral suppression using Stata 12.0.

Effective antiretroviral therapy (ART) is essential for viral suppression (VS) in HIV-infected patients. However, there is a lack of nationally representative data on types of ART regimens used and their impact on VS. This thesis used self-reported interview and abstracted medical record from 2009 Medical Monitoring Project (MMP) to study ART regimen type and related health outcomes. Results showed that 88.6% of HIV-infected adults in care was prescribed ART, and about half took regimens designated as ‘preferred’ according to U.S ART guidelines. Among MMP participants prescribed ART, 62.7% achieved durable VS, 77.8% achieved recent VS, 83.5% were 100% dose-adherent, and 17.1% reported side effects. Multivariate regression analyses revealed that although ART was critical for VS, there were minor differences in health outcomes among the major ART classes in the U.S. ART guidelines or six most-commonly used regimens. This study could be potentially useful for future strategic planning of HIV care.

In sub-Saharan Africa, women are disproportionately affected by HIV. Sustained adherence to lifelong antiretroviral therapy (ART) is needed to ensure their own health and prevent transmission of HIV to their partners and their children. However, non-adherence to ART remains a substantial challenge with many associated risk factors. Travel is often reported in the qualitative literature as a barrier to ART adherence among women living with HIV, but few quantitative studies have explored this association. This research aimed to describe travel in the past year among mothers living with HIV in the Long-term Adherence and Care Engagement (LACE) study, to explore factors associated with travel, and to investigate the associations between travel and i) self-reported adherence, and ii) HIV viral load. Part A of this dissertation is the study protocol that introduces the need for this research and presents how the research will be carried out. Part B is a narrative literature review. The review summarises and synthesises existing research relating to HIV treatment and travel in sub-Saharan Africa, giving context to the dissertation. Part C is the journal “ready” manuscript. This section presents an analysis of data from the LACE study, a cross-sectional survey of women living with HIV approximately four years after they had started ART during pregnancy in Gugulethu, Cape Town. At the LACE study visit, data on short-term travel patterns (stayed away from home for 3 or more nights) in the past year and self-reported adherence in the past 30 days (using a validated three-item scale) were collected through structured questionnaires, and a blood specimen was tested for HIV viral load. Poisson regression models with robust standard errors were used to explore factors associated with travel (any versus none), self-reported adherence (100% versus <100%), and viral suppression (≤50 copies/mL). Results were reported as crude risk ratios (RR) and adjusted risk ratios (aRR) with 95% confidence intervals (CI). The results showed that among 353 women enrolled in the LACE study (mean age 32.6 years, 48% employed, 38% married/cohabiting, median 44 months postpartum) 23% (n=81) reported travelling in the past year. Of the women who travelled, most went to the Eastern Cape (90%) and travelled 1-2 times during the year (93%). Women who travelled were more likely to be married/cohabiting than women who had not travelled (aRR = 1.45; 95% Cl: 0.97 - 2.16). Only 9% of women who travelled (7 of 81) reported difficulty with ART adherence due to travel. Overall, 59% of women reported 100% adherence in the past 30 days: 52% of women who had travelled in the past year versus 61% of those who had not travelled (aRR = 0.83; 95% Cl: 0.66-1.04). Only 56% of the cohort were virally suppressed: 60% and 55% of those who had and had not travelled in the past year, respectively (aRR = 1.10; 95% Cl: 0.89-1.36). Travel in the past year was not significantly associated with self-reported adherence or viral suppression in crude or adjusted analyses. These results highlight that poor adherence and viremia were very common in this cohort of women, four years after starting ART in pregnancy. Almost a quarter of women reported travel in the past year but only a v few reported difficulties with adherence related to travel and we found no association between travel in the past year, self-reported adherence in the past 30 days or viremia. Further research is needed to understand adherence patterns during periods of travel and interventions are clearly needed to support women's long-term adherence to ART.

Magister Public Health - MPH / In 2018, it was estimated that 33,000 adolescent girls and 4,200 adolescent boys were HIV-positive in South Africa. The Free State province reports that 89% of people living with HIV are diagnosed; 72% of those diagnosed are receiving antiretroviral therapy (ART); of which 93% have achieved viral suppression (< 1000 RNA copies/mL). Thabo Mofutsanyane District has the highest HIV prevalence in the Free State province. A retrospective, quantitative cross-sectional study was conducted to determine the predictors of viral suppression among adolescents on ART in Thabo Mofutsanyane District Municipality, Free State province, South Africa. Data for all adolescents, aged 10–19 years, receiving ART in 2019 (N = 6 300) was extracted from Tier.net electronic database into an Excel spread sheet and exported into Statistical Package for the Social Sciences – Version 26 (SPSS v 26) for analysis.

Background: Rates of care retention and maintenance of viral suppression differ by location in the Unites States due the varying public health policies and infrastructures. As a result, it is imperative to determine the rates of retention and viral suppression as well as factors associated with these changes during the prenatal and postpartum period in the state of Georgia Methods: Data on 161 HIV infected women was collected from birth certificate records and the enhanced HIV/AIDS Reporting System (eHARS). Multivariate logistic regression was used to determine the association between sociodemographic as well as clinical variables and outcome variables of retention, viral suppression and care engagement during and after pregnancy. Results: Women were more likely to be retained in care during pregnancy (79.50%) than during the postpartum period (55.28%). Women were also more likely to achieve viral suppression during pregnancy (68.94%) than during the postpartum period (49.69%). Approximately 43% of women engaged in HIV care within 90 days of giving birth. Women who were retained in HIV Care prior to pregnancy were more likely to be retained during pregnancy (95%) and the postpartum period (76%) than women diagnosed during pregnancy or not retained in care prior to pregnancy. Conclusion: Women face a myriad of challenges that make retention and viral suppression difficult. It is important that we utilize technology to help improve treatment received in the postpartum period.

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2017-09-22T19:16:04Z No. of bitstreams: 1 Alcino A C Golega.pdf: 7388772 bytes, checksum: 8eb5fba312dc9dc756493466ca4bf72a (MD5) / Made available in DSpace on 2017-09-22T19:16:06Z (GMT). No. of bitstreams: 1 Alcino A C Golega.pdf: 7388772 bytes, checksum: 8eb5fba312dc9dc756493466ca4bf72a (MD5) Previous issue date: 2017-08-25 / By 2013, UNAIDS has updated its global targets for the year 2020 for HIV-positive people; In which 90% of infected people are tested and will know that they are HIV, 90% of HIV-positive people are receiving ARV treatment, and that 90% of those people must achieve viral suppression to end the transmission of the epidemic by 2030 A The cascade of HIV continuous care is commonly represented as a bar chart that counts the number of individuals engaged in providing services to People Living with HIV / AIDS at all stages of ongoing care. The loss of individuals occurs at different points, which means that the number of people observed in each stage of the cascade is smaller than in the previous one. The objective of this study is to evaluate the steps of the continuous care of patients assisted in a public service specialized in HIV / AIDS (SAE - adult), in Santos, São Paulo, between 2009 and 2013. Methodology: This study was designed according to as standards for the construction of the Continuous Care Cascade for HIV patients, as recommended by the Brazilian Ministry of Health. It is a mixed study of Temporal and Longitudinal series, Transverse, successive and sequential cross-sections are drawn up in continuous care, represented by columns, for the years 2009 to 2013; For study purposes the study population are all HIV patients enrolled in SECRAIDS, from January 2, 2009 to December 30, 2013. Results: A total of 1,179 patients enrolled in SAE - (224), 2010 (253), 2011 (240), 2012 (216) and 2013 (246), we observed that even with a heterogeneous population, we perceive a certain homogeneity in the distribution of socio-demographic factors. In relation to sex we have a predominance of the masculine in relation to the feminine, in all the years and a variation in the reason of sex, that goes of 1.7 until 3 men for each woman. Regarding the category of exposure, each year presents the heterosexual form as preponderant with more than 50% of the cases. Regarding the age group, we noticed that the age group of 30 to 39 holds the largest number of people in every year. In the category of schooling the subgroup with more than 10 years of study concentrates the largest contingent of people. In relation to race / color, it presents above 60% of the cases of race / color White and in average 33% of browns and blacks. However, in the case of the Marital State, the subgroup Singular, more than 50% of the cases, followed by married / amassed with 30% of the cases. Although linkage to service and access to treatment increased during the period, there was a significant decrease in viral suppression. Viral suppression is directly linked to the quality of service offered to HIV patients, since it is directly linked to the link that the service establishes for this patient, as well as the possibility of performing an integral treatment and also linked to the correct use of the medication. Thus we can add that it is necessary, a good adhesion of the patient to the service, the proposed treatment, the support offered, the continuous monitoring, the withdrawal of the medication, that is, the correct use and therapeutic control, that must be studied in other works. / Em 2013 a UNAIDS, atualizou suas metas globais para o ano de 2020 para as pessoas HIV-positivas; em que 90% das pessoas infectadas são testados e saberão que são HIV, 90% das pessoas HIV-positivas estejam tratamento com ARV, e que 90% dessas pessoas devem alcançar a supressão viral, para assim acabar com a transmissão da epidemia até 2030 A cascata do cuidado contínuo do HIV é comumente representada como um gráfico de barras que contabiliza o número de indivíduos inseridos na prestação de serviços às Pessoas Vivendo com HIV/Aids em todas as etapas do cuidado contínuo. A perda de indivíduos ocorre em diferentes pontos, o que faz com que o número de pessoas observadas em cada etapa da cascata seja menor que na anterior. O objetivo deste trabalho é avaliar as etapas de cuidado contínuo dos pacientes atendidos em serviço público especializado em HIV/Aids (SAE ¿ adulto), no município de Santos, São Paulo, entre 2009 e 2013. Metodologia: Este estudo foi construído de acordo com as normas da construção da Cascata de Cuidado Contínuo para os pacientes HIV, nos moldes recomendados pelo Ministério da Saúde do Brasil. É um estudo misto, longitudinal de Série Temporal. Foram elaborados cortes transversais, sucessivos e sequenciais nos cuidados contínuos, representados por colunas, para os anos de 2009 a 2013; para fins desse estudo a população de estudo são todos os pacientes portadores do HIV matriculados no SAE - adulto, no período de 02 de janeiro de 2009 à 30 de dezembro de 2013. Resultados: Foram estudados um total de 1.179 pacientes matriculados no SAE - adulto, referente aos anos de 2009 (224), 2010 (253), 2011 (240), 2012 (216) e 2013 (246), observamos que mesmo possuindo uma população heterogênea, percebemos uma certa homogeneidade na distribuição dos fatores sócio demográficos. Em relação ao sexo temos uma predominância do masculino em relação ao feminino, em todos os anos e uma variação na razão de sexo, que vai de 1,7 até 3 homens para cada mulher. Em relação a categoria de exposição, todos os anos apresenta a forma heterossexual como preponderante com mais de 50% dos casos. Em relação a faixa etária, notamos que a faixa de 30 a 39 anos detém o maior número de pessoas em todos os anos. Na categoria de escolaridade o subgrupo com mais de 10 anos de estudo concentra o maior contingente de pessoas. Em relação a raça/cor, apresenta acima de 60% dos casos da raça/cor Branca e em média 33% de pardos e pretos. Entretanto quanto ao Estado Marital, majoritariamente o subgrupo Solteiro, acima de 50% dos casos, seguido por casados/amasiados com 30% dos casos. Embora a vinculação ao serviço e acesso ao tratamento tenham aumentado no período, houve expressiva queda na supressão viral. A Supressão Viral está diretamente ligada a qualidade do serviço oferecido aos pacientes HIV, pois está diretamente ligado ao vínculo que o serviço estabelece a este paciente, além da possibilidade de realizar um tratamento integral e também ligado ao uso correto da medicação. Assim podemos acrescentar que é necessário, uma boa adesão do paciente ao serviço, ao tratamento proposto, ao suporte oferecido, o acompanhamento contínuo, a retirada da medicação, ou seja, o uso correto e controle terapêutico, que devem ser estudados em outros trabalhos.

Introduction. Après 40 ans de recherche, l’éradication de la pandémie mondiale à VIH n’est pas encore à notre portée. Si le Canada a connu une raréfaction des cas de transmissions verticales, en 2019 on compte plus de 1,8 million d’enfants infectés par le VIH. Durant l’infection à VIH, la thérapie antirétrovirale (TAR) et les réponses immunitaires à médiation cellulaire, y compris celles véhiculées par les lymphocytes T cytotoxiques CD8+ (CTL), jouent aussi un rôle important dans la limitation de la réplication virale. L’atteinte et le maintien d’une suppression virale soutenue (SVS) sous l’effet de la TAR sont associés à une limitation de taille du réservoir cellulaire du VIH pédiatrique. Si l’on possède beaucoup d’informations sur le développement et l’évolution des réponses immunitaires à médiation cellulaire dirigées contre le VIH chez l’adulte, ce n’est pas le cas au niveau pédiatrique. Cette thèse avait pour but de caractériser la complexité phénotypique et fonctionnelle de la réponse antivirale des cellules CD8+ chez les enfants et les adolescents infectés par le VIH-1. Objectifs : Caractériser les réponses anti-VIH-1 à médiation cellulaire chez les enfants et les adolescents infectés. Mesurer la réponse immunitaire dirigée spécifiquement contre la protéine Gag du VIH-1. Nous avons aussi étudié l’expression des marqueurs d’épuisement des cellules T chez l’enfant et l’adolescent infectés verticalement, ainsi que le transcriptome des cellules T CD8+ effectrices mémoires. Résultats : Les enfants et les adolescents sont capables de développer des réponses à médiation cellulaire dirigées spécifiquement contre le VIH-1, et cela malgré une longue période sous TAR. Les réponses observées sont influencées par l’âge et la proportion de vie cumulative sous SVS (cPLUS). Les réponses IFN- spécifiques au VIH sont augmentées avec l'âge en termes d'amplitude et de spectre de reconnaissance antigénique et sont diminuée avec une cPLUS plus faible, ce qui pourrait refléter une exposition moindre aux antigènes du VIH. Les mécanismes de l'expansion quantitative des réponses des lymphocytes T sont différents de ceux qui conduisent à l'élargissement du spectre de reconnaissance des antigènes viraux par les lymphocytes T de l’hôte. L’âge et la cPLUS exerçaient une influence sur l’expression des récepteurs inhibiteurs, ce qui pourrait contribuer à la difficulté d’atteindre et de maintenir une SVS ainsi que la progression plus rapide de l’infection chez les enfants vivant avec le VIH. Comparativement aux lymphocytes T CD4+, des fréquences plus élevées de lymphocytes T CD8+ exprimaient des récepteurs inhibiteurs et exprimaient un plus grand nombre de récepteurs différents. Cette tendance était influencée par l'âge. Cela indique que les lymphocytes T CD8+ sont plus épuisés que les lymphocytes T CD4+, ce qui pourrait contribuer à la persistance du VIH de l'enfance à l'âge adulte sous TAR. Cependant, les corrélations des fréquences de cellules exprimant des récepteurs inhibiteurs avec l'ampleur des réponses immunitaires à médiation cellulaire spécifiques au VIH suggèrent fortement que ces cellules n'étaient pas fonctionnellement épuisées. L’âge et la cPLUS exerçaient une influence déterminante sur l’expression de certains gènes. L’exploitation de technologies récentes pour l’étude du transcriptome des cellules T CD8+ mémoires au niveau unicellulaire nous ont permis d’obtenir une grande quantité de données à partir qu’un faible échantillon de cellules. Les participants avec une longue cPLUS avaient une fréquence plus grande de cellules exprimant CD69 et exprimant des gènes stimulés par l'interféron (ISG). Cependant, chez ces patients, on observait également une expression moindre des gènes associés à l’épuisement. Conclusion. Nous avons apporté des réponses quant aux mécanismes de la réponse immunitaire pédiatrique, mais aussi d’identifier les facteurs qui peuvent l’influencer. Cependant, l’écriture de la thèse a révélé une carence importante dans la compréhension des mécanismes de l’immunité au niveau pédiatrique au niveau de la littérature. Pour dépasser les limites des études pédiatriques, il existe un besoin constant de mettre en place des techniques de suivi immunitaire réalisables sur de petits échantillons biologiques. / Introduction. After 40 years of research, the eradication of the global HIV pandemic is not yet within our reach. While Canada has experienced a decline in cases of vertical transmission, in 2019 there were more than 1.8 million children infected with HIV. During HIV infection, antiretroviral therapy (ART) and cell-mediated immune responses, including those mediated by CD8+ cytotoxic T lymphocytes (CTL), also play an important role in limiting viral replication. The achievement and maintenance of sustained viral suppression (SVS) under the effect of ART are associated with a limitation in the size of the cellular reservoir of HIV at the pediatric level. While there is a lot of information on the development and evolution of cell-mediated immune responses against HIV, this is not the case at the pediatric level. This thesis aimed to characterize the phenotypic and functional complexity of the antiviral response of CD8+ cells in children and adolescents infected with HIV-1. Objectives: To characterize cell-mediated anti-HIV-1 responses in infected children and adolescents. To measure the immune response directed specifically against the Gag protein of HIV-1. To study the expression of T cell exhaustion markers in vertically infected children and adolescents, as well as the transcriptome of effector memory CD8+ T cells. Results: Children and adolescents are able to develop cell-mediated responses specifically directed against HIV, despite SVS under ART. The immune responses observed are influenced by age and the proportion of cumulative life on SVS (cPLUS). HIV-specific IFN- responses are increased with age in terms of amplitude and antigen recognition spectrum and are decreased with lower cPLUS, which may reflect shorter exposure to HIV antigens. Two distinct mechanisms of T cell responses were observed. On one hand quantitative expansion of T cell responses and on the other hand the broadening of the T cells spectrum of viral antigens recognition. Age and cPLUS exerted an influence on the expression of inhibitory receptors, which could contribute to the difficulty of achieving and maintaining SVS as well as the more rapid progression of infection in children living with HIV. Compared to CD4+ T cells, higher frequencies of CD8+ T cells expressed inhibitory receptors and expressed more different type of receptors. This trend was influenced by age. This indicates that CD8+ T cells are more depleted than CD4+ T cells, which may contribute to the persistence of HIV from childhood to adulthood on ART. However, correlations of frequencies of cells expressing inhibitory receptors with the magnitude of HIV-specific cell-mediated immune responses strongly suggest that these cells were not functionally exhausted but rather recently activated. Age and cPLUS exerted a determining influence on the expression of certain genes. The exploitation of recent technologies for the study of the transcriptome of memory CD8+ T cells at the single-cell level has enabled us to obtain a large amount of data from only a small biological sample. Participants with long cPLUS had a higher frequency of cells expressing CD69 and ISGs. However, in these patients, there was also a lower expression of genes associated with exhaustion. Conclusion. We have provided answers as to the mechanisms of the pediatric immune response but also identify the factors that can influence it. However, the writing of the thesis revealed an important deficiency in the understanding of the immunity mechanisms at the pediatric level in current literature. To overcome limits in pediatric studies, there is a constant need to set up immune monitoring techniques that can be performed on small biological samples Keywords: HIV, perinatal infection, inhibitory receptors, immune response, sustained viral suppression.

Adherence to antiretroviral therapy is crucial to ensure viral suppression. In the scientific community it is widely accepted that an adherence level of at least 90% is necessary to achieve viral suppression. This study uses pharmacy refill records to describe antiretroviral adherence in HIV-positive patients in Ugu District and to describe pharmacy refill records as reliable monitoring method of antiretroviral therapy. In total, 61 patients’ records were reviewed. Overall, 82% of participants (n=50) achieved an optimum adherence level of at least 90%. Although 38% (n=19) of these participants did not show any related viral suppression. A statistically significant relationship between adherence and viral suppression was not demonstrated. Therefore, pharmacy refill records cannot be recommended as an alternative method of monitoring response to antiretroviral therapy, but laboratory tests including CD4 cell count and or viral load must be combined to pharmacy refill method for monitoring of antiretroviral therapy in HIV-positive patients / Health Studies / M.A. (Public Health)

De nombreuses études ont montré que les enfants traités précocement ne sont pas capables de développer une réponse à médiation cellulaire contre le VIH [1]. Cependant, le rebond viral observé après la rémission prolongée du cas du « bébé du Mississippi » pose de nombreuses questions quant à la capacité de ces enfants à développer une réponse immunitaire VIH spécifique malgré une suppression virale à long terme [2, 3]. Nous avons étudié cinq cas ayant un profil similaire au « bébé du Mississippi » qui ont été identifiés précédemment [4]. L’objectif de ce projet était de déterminer si les enfants traités précocement développent une réponse immunitaire à médiation cellulaire contre le VIH qui est quantitativement et/ou qualitativement différente de celle retrouvée chez les enfants traités plus tard. Cette étude a permis de montrer que l’amplitude et la diversité des réponses LTC des enfants traités précocement est plus faible que celle observée chez des enfants traités plus tard ou non traités. / Several studies have shown early treated children are not able to develop a cell-mediated response [1]. However, the viral rebound after prolonged remission in the case of the "Mississippi baby" raises many questions about the ability of these children to develop a specific immune response despite HIV viral suppression in the long term [2, 3]. We currently have five cases with a similar profile to the "Mississippi baby" that were identified previously [4]. The objective of this project is to determine whether early treated children develop an immune cell-mediated response against HIV that is quantitatively and/or qualitatively different from that found in children treated later. This study showed that the magnitude and diversity of CTL responses of children treated early is lower than that observed in children treated later if possible.

Adherence to antiretroviral therapy is crucial to ensure viral suppression. In the scientific community it is widely accepted that an adherence level of at least 90% is necessary to achieve viral suppression. This study uses pharmacy refill records to describe antiretroviral adherence in HIV-positive patients in Ugu District and to describe pharmacy refill records as reliable monitoring method of antiretroviral therapy. In total, 61 patients’ records were reviewed. Overall, 82% of participants (n=50) achieved an optimum adherence level of at least 90%. Although 38% (n=19) of these participants did not show any related viral suppression. A statistically significant relationship between adherence and viral suppression was not demonstrated. Therefore, pharmacy refill records cannot be recommended as an alternative method of monitoring response to antiretroviral therapy, but laboratory tests including CD4 cell count and or viral load must be combined to pharmacy refill method for monitoring of antiretroviral therapy in HIV-positive patients / Health Studies / M.A. (Public Health)