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 perte au suivi diminue grandement l’efficacité des interventions de prévention de la transmission mère-enfant du VIH en Afrique subsaharienne. Devrait-on donc choisir des traitements courts ou longs de pTME? Nous avons mené une revue systématique des études sur l’efficacité de traitements avec et sans composante anténatale et évalué l’impact de la perte au suivi sur leur efficacité. Nous avons trouvé qu’après ajustement pour la perte au suivi, les traitements avec composante anténatale ont encore une efficacité plus élevée à prévenir la TME. Les intervenants ne devraient pas craindre l’utilisation de traitements plus longs auprès de populations à risque de perte au suivi. Plus d’études sont nécessaires pour déterminer comment les interventions peuvent être adaptées au virage dans la pTME. / Loss to follow-up greatly decreases efficiency of MTCT interventions in sub-Saharan Africa. Should we therefore choose shorter pMTCT treatments over longer ones? We conducted a systematic review of studies on the efficiency of pMTCT treatments with or without an antenatal component. We found that after adjustment, treatments with an antenatal component still had a higher efficiency at decreasing MTCT despite loss to follow-up. Healthcare providers shouldn’t fear using longer treatments amongst populations at high risk of loss to follow-up. More studies are needed to determine how current interventions can be better adapted to the turnaround in pMTCT interventions.

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 perte au suivi diminue grandement l’efficacité des interventions de prévention de la transmission mère-enfant du VIH en Afrique subsaharienne. Devrait-on donc choisir des traitements courts ou longs de pTME? Nous avons mené une revue systématique des études sur l’efficacité de traitements avec et sans composante anténatale et évalué l’impact de la perte au suivi sur leur efficacité. Nous avons trouvé qu’après ajustement pour la perte au suivi, les traitements avec composante anténatale ont encore une efficacité plus élevée à prévenir la TME. Les intervenants ne devraient pas craindre l’utilisation de traitements plus longs auprès de populations à risque de perte au suivi. Plus d’études sont nécessaires pour déterminer comment les interventions peuvent être adaptées au virage dans la pTME. / Loss to follow-up greatly decreases efficiency of MTCT interventions in sub-Saharan Africa. Should we therefore choose shorter pMTCT treatments over longer ones? We conducted a systematic review of studies on the efficiency of pMTCT treatments with or without an antenatal component. We found that after adjustment, treatments with an antenatal component still had a higher efficiency at decreasing MTCT despite loss to follow-up. Healthcare providers shouldn’t fear using longer treatments amongst populations at high risk of loss to follow-up. More studies are needed to determine how current interventions can be better adapted to the turnaround in pMTCT interventions.

Background: Non-disclosure of HIV positive status to a partner threatens to reverse gains made in prevention of mother-to-child transmission (PMTCT) in resource limited settings. Determining the association between non-disclosure and infant HIV acquisition is important to justify focussing on disclosure as a strategy in PMTCT programmes. Objective: To determine the association between non-disclosure of HIV positive status to a partner and mother-to-child transmission (MTCT). Methods: Using a matched case-control design, we compared 34 HIV positive infants to 146 HIV negative infants and evaluated whether the mothers had disclosed their HIV status to their partner. Results: Non-disclosure was more frequent among cases (overall, 16.7%; cases, 52.8%; controls 7.6%), p<0.001 and significantly associated with MTCT (aOR 8.9 (3.0-26.3); p<0.0001), with male partner involvement partially mediating the effect of non-disclosure on MTCT. Conclusions: There is a need for PMTCT programs to focus on strategies to improve male partner involvement and partner disclosure without compromising the woman’s safety. / Health Studies / M. (Public Health)

L'intégration du traitement et de la prévention des maladies chroniques non transmissibles (MNT) au sein des soins de santé primaires représente le principal défi à venir pour la santé publique et les systèmes de santé dans les pays à faible et moyen revenu comme l’Afrique du Sud. Il constitue le principal objectif de cette thèse. L’expérience de l'intégration de la prévention de la transmission du VIH de la mère à l'enfant (PTME) dans les soins de santé primaires (SSP) peut apporter des leçons importantes pour l'intégration de la prévention du diabète chez les femmes souffrant de diabète gestationnel récent (DSG) dans les SSP. Il a été estimé que le DSG touche plus de 9,1 % des grossesses en 2018 en Afrique du Sud. Le DSG augmente le risque de développer ultérieurement du diabète de type 2 (DT2). Le DSG multiplie par plus de 7 le risque de développer un DT2 ainsi que les risques de troubles métaboliques pour les bébés des femmes qui en sont atteintes. Cette thèse explore comment appliquer les leçons tirées de l’intégration de la PTME pour intégrer le dépistage du DSG et les initiatives de prévention du DT2 dans les soins de santé primaires de routine en Afrique du Sud. Le cadre conceptuel adapté pour cette thèse permet ainsi de comprendre les aspects de l’intégration au niveau du patient et du système de santé, englobant les contextes, les mécanismes et la mise en œuvre de l’intégration d’interventions préventives dans les services existants. L'étude s'inscrit dans le cadre du projet IINDIAGO, « Intervention intégrée du système de santé visant à réduire les risques de diabète de type 2 chez les femmes défavorisées après un diabète gestationnel en Afrique du Sud ». La thèse présente d’abord une revue narrative de l’impact de la PTME sur les services et les systèmes de soins de santé en Afrique subsaharienne (Article 1). Les résultats de cette revue montrent que la PTME a eu l’impact positif et négatif sur d’autres services de soins de santé et que son intégration dans les systèmes de santé est de plus en plus privilégiée. L’article 2 est une étude qualitative analysant l’histoire et l’expérience locales de l’intégration de la PTME dans les SSP de routine en Afrique du Sud de différents points de vue. Bien qu’elle ait constaté un fort soutien en faveur de l’intégration parmi tous les répondants, cette étude a fait état de multiples obstacles à la pleine intégration de la PTME dans les SSP, le post-partum en particulier. Les articles 3 et 4 ont utilisé les méthodes mixtes et révélé que l’intégration des services dans les SSP de routine, à base communautaire, pour dépister universellement le DSG et pour prévenir ou retarder le DT2 après le DSG, était perçue comme faisable, acceptable et nécessaire de toute urgence en Afrique du Sud. L’article 6 (dont le protocole est l’article 5) présentait une revue systématique et une méta-analyse sur la prise en charge intégrée du DSG et du DT2 dans le contexte de la multimorbidité en Afrique. Les 13 études incluses dans cette étude ont montré que la gestion intégrée du DSG et du DT2 dans le cadre de la multimorbidité était mise en œuvre avec succès, mais qu’elle nécessitait une formation et une supervision adéquates des infirmières, et la fourniture d’équipements et de médicaments additionnels au sein des systèmes de santé nationaux en Afrique. Les conclusions de cette thèse suggèrent que, bien qu’elle n’ait pas toujours été retenue, en raison de défis structurels et opérationnels, l’intégration complète plutôt que partielle des services de santé est considérée comme souhaitable et réalisable par les femmes, les travailleurs de la santé, les gestionnaires et les experts. L’intégration complète pourrait être idéale pour dépister, diagnostiquer et soigner les maladies chroniques, y compris le DSG et le DT2, au sein des SSP de routine et selon l’approche de la PTME dont les leçons d’intégration n’ont pas été adaptées à ce prochain défi de santé publique. / Integrating chronic, non-communicable diseases (NCDs) and their prevention into primary health care is the next major challenge for public health and health systems in low and middle-income countries like South Africa and is the primary focus of this thesis. The experience of integration of Prevention of Mother-to-Child Transmission (PMTCT) of HIV into primary health care (PHC) may have important lessons for integrating prevention of diabetes among women with recent gestational diabetes (GDM) into PHC. GDM was estimated to affect more than 9.1% of pregnancies in 2018 in South Africa. GDM increases the risk of developing subsequent type 2 diabetes (T2DM) more than 7-fold as well as increasing the risks of metabolic disorders for the babies of women who had GDM. This thesis conducted a systematised narrative synthesis, a systematic review and a convergent mixed methods study using primarily qualitative methods in South Africa (focus on Cape Town, Western Cape) to explore how to apply lessons from PMTCT integration in order to integrate GDM screening and T2DM prevention initiatives into routine PHC in South Africa. The adapted conceptual framework for this thesis enables to understand both patient-level and health system-level aspects of integration and encompassing the contexts, mechanisms and implementation for integrating preventive interventions in the existing services. The study was nested in the IINDIAGO project, “Integrated health system intervention aimed at reducing type 2 diabetes risks in disadvantaged women after gestational diabetes in South Africa”. The thesis first presents a narrative review of the impact of PMTCT on health care services and systems in sub-Saharan Africa (Paper 1). This review findings show that PMTCT has had positive and negative impacts on other health care services and that its integration into health systems is increasingly favored. Paper 2 qualitatively documented the local history and experience of PMTCT integration into routine PHC in South Africa from different perspectives. Though it found strong support for integration among all respondents (N=20), this study reported multiple barriers for the full integration of PMTCT into PHC, especially in postpartum. Papers 3 and 4 used mixed methods and highlighted that integrating services within routine, community-based PHC to universally screen GDM and to prevent or delay of T2DM after GDM, was perceived as feasible, acceptable and urgently needed in South Africa – but that it is not currently occurring at a satisfactory level, despite international and national guidelines. The fifth article is a published protocol for Paper 6, a systematic review and meta-analysis on the integrated management of GDM and T2DM in the context of multimorbidity in Africa. This was a study in which all 13 included studies showed that integrated management of GDM and T2DM within multimorbidity was successfully implemented but it required adequate training and supervision of nurses, provision of additional equipment and drugs to the existing resources within national health systems in Africa. This thesis concludes that although not always opted for, due to structural and operational challenges, the full instead of partial integration of health services to screen, diagnose and care for chronic diseases including GDM and T2DM into routine PHC, following the PMTCT approach, was seen as both desirable and feasible by women, health workers, managers, and experts. However, the lessons learned through the history of PMTCT and its integration have not been adapted to this next public health challenge.

PhD (Health Sciences) / Department of Advanced Nursing Science / Background: Family-centred approaches to Prevention of Mother-to-Child Transmission (PMTCT) interventions present an important direction for sustainability and prevention of pediatric infections while improving overall family health. Despite numerous opportunities to sustain and expand the existing PMTCT interventions, Mother-to-Child Transmission (MTCT) still occurs. This is evidenced by the number of under-five children who are admitted in hospital being infected by the Human Immunodeficiency Virus (HIV) between the ages of 6 weeks to 18 months, whereas the Polymerase Chain Reaction (PCR) results was non-reactive at six weeks. Purpose: The purpose of this study was to develop a strategy to enhance family-centered interventions for PMTCT sustainability in the selected districts of Limpopo Province, South Africa. Phase 1: The study was conducted in phases. In Phase 1, which was empirical, the following objectives: to explore the risks that contribute to MTCT between the ages of 6 weeks and 18 months; to explore the perceptions of family members regarding family support in PMTCT interventions; and to explore the factors that affect the provision of family support in PMTCT interventions. Phase 2: was development of the strategy and validation of the strategy. Methods: The exploratory sequential mixed method was used to conduct the study, where qualitative data were collected and analyzed first; followed by collecting, analyzing and interpreting the quantitative data. The population comprised the following groups: mothers of babies between 6 weeks and 18 months who are living with HIV/AIDS, family members were represented by male partners, grandmothers or mother’s in_-law and health care professionals working at the PHC Heath Centers v or clinics rendering PMTCT services. In the qualitative design, participants were selected by non-probability purposive sampling and data were collected through one-to-one interview and focus group discussions. Data were analyzed utilizing the open-coding method. In the quantitative design, participants were selected by using simple random sampling and data were collected by means of self-administered survey questionnaires with structured close-and open-ended questions. The population were midwives from Capricorn, Mopani and Vhembe districts PHC clinic. Data were analyzed using the Statistical Package for the Social Sciences (SPSS), Version 22 and descriptive statistics. In Phase 2, findings from the data were used to develop an intervention strategy. The strategy was developed through the use of Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis. The developed strategy was validated by using a quantitative design. / NRF

This study aimed to identify factors affecting women’s utilisation of the prevention of mother-to-child transmission (PMTCT) of HIV, evaluate the quality of PMTCT services, describe health outcomes of mothers and infants and to identify factors that influence mother-to-child transmission (MTCT) of HIV. Structured interviews were conducted with 384 women who had utilised PMTCT services. Information was also obtained from the health records of these women and of their infants. Better educated women, who had male partners and were self-employed were more likely to use PMTCT services. Being unmarried, poor and feeling stigmatised made it difficult for women to use these services. Respondents were satisfied with PMTCT services except that clinics sometimes had no medications. The health care workers followed the Ethiopian guidelines during HIV testing and counseling but not when prescribing treatment. Although the respondents’ CD4 cell counts improved, their clinical conditions did not improve. The MTCT rate was significantly higher if infants did not receive ARVs, had APGAR scores below seven, weighed less than 2.5kg at birth, were born prematurely, and if their mothers had nipple fissures. PMTCT services could be improved if more women used these services, health care workers followed the national guidelines when prescribing ARVs, clinics had adequate supplies of medicines, all infants received ARVs, and mothers’ nipple fissures could be prevented. Antenatal care should help to avoid premature births of infants weighing less than 2.5kg and having APGAR scores below 7. Future research should compare formula feeding versus breastfeeding of infants with HIV-positive mothers / Health Studies / D. Litt. et Phil. (Health Studies)

This study aimed to identify factors affecting women’s utilisation of the prevention of mother-to-child transmission (PMTCT) of HIV, evaluate the quality of PMTCT services, describe health outcomes of mothers and infants and to identify factors that influence mother-to-child transmission (MTCT) of HIV. Structured interviews were conducted with 384 women who had utilised PMTCT services. Information was also obtained from the health records of these women and of their infants. Better educated women, who had male partners and were self-employed were more likely to use PMTCT services. Being unmarried, poor and feeling stigmatised made it difficult for women to use these services. Respondents were satisfied with PMTCT services except that clinics sometimes had no medications. The health care workers followed the Ethiopian guidelines during HIV testing and counseling but not when prescribing treatment. Although the respondents’ CD4 cell counts improved, their clinical conditions did not improve. The MTCT rate was significantly higher if infants did not receive ARVs, had APGAR scores below seven, weighed less than 2.5kg at birth, were born prematurely, and if their mothers had nipple fissures. PMTCT services could be improved if more women used these services, health care workers followed the national guidelines when prescribing ARVs, clinics had adequate supplies of medicines, all infants received ARVs, and mothers’ nipple fissures could be prevented. Antenatal care should help to avoid premature births of infants weighing less than 2.5kg and having APGAR scores below 7. Future research should compare formula feeding versus breastfeeding of infants with HIV-positive mothers / Health Studies / D. Litt. et Phil. (Health Studies)