En 2015, l’Organisation Mondiale de la Santé a mis en oeuvre des nouvelles lignes directrices sur la prévention de la transmission de la mère à l'enfant (PTME) du VIH recommandant à toutes les femmes enceintes et allaitantes séropositives, d'initier la trithérapie antirétrovirale à titre de traitement à vie (option B+). Cependant, il existe de plus en plus d'inquiétudes quant à l'efficacité de cette stratégie pour réduire réellement la transmission verticale du VIH à la lumière des défis programmatiques de sa mise en oeuvre ; on observe en particulier des niveaux sous-optimaux de suivi dans les soins chez le couple mère/enfant en Afrique sub-Saharienne. Notre thèse vise à évaluer, d’un point de vue de santé publique, l’engagement dans les soins du couple mère/enfant en prenant l’exemple du Mozambique, pays connu pour avoir l'une des prévalences du VIH les plus élevées au monde. Nous analysons, plus particulièrement trois aspects importants de l’engagement dans les soins : la cascade de soins prénatale, la rétention des femmes enceintes séropositives initiant la trithérapie antirétrovirale et la couverture dudépistage du VIH chez l’enfant exposé.Nous observons dans ce contexte mozambicain une couverture élevée du dépistage du VIH, une amélioration significative de la couverture du traitement antirétroviral au cours du temps et une meilleure acceptation du traitement chez les femmes enceintes séropositives. Cependant,la rétention dans les soins à la fin de la première année du traitement antirétroviral chez les femmes enceintes VIH+ et la couverture du dépistage du VIH chez les nourrissons exposés restent sous-optimales. Nous concluons que les interventions visant à améliorer l’engagementdans les soins du couple mère-enfant doivent être systématiquement encouragées. Enfin, nous soulignons la grande hétérogénéité des définitions des indicateurs utilisées dans les différents programmes de PTME.Ce travail met en évidence les lacunes dans l'engagement du couple mère-enfant dans les soins pour la PTME et ses conséquences sur l'élimination virtuelle de la transmission vertical du VIH. Nous soulignons également l’importance d’une approche consensuelle pour mesurer les indicateurs clés afin de permettre des comparaisons à l’échelle nationale et internationale. Les efforts visant à suivre les femmes sous traitement tout au long de leur vie, en veillant à ce que leurs nourrissons exposés au VIH reçoivent les soins attendus jusqu'à ce que leur statut VIH définitif soit déterminé, constituent la pierre angulaire de l’obtention d'une génération sans Sida pédiatrique d'ici 2030. / In 2015, the World Health Organization published new guidelines for the prevention of motherto- child transmission (PMTCT) of HIV and recommended that all seropositive pregnant and breastfeeding women be provided with lifelong anti-retroviral therapy (ART) (option B+).However, there are rising concerns about the effectiveness of the strategy in truly reducing the number of vertical HIV transmissions; there are indeed programmatic challenges related to its implementation; in particular, the sub-optimal levels of engagement in care of mother/infantpairs observed mainly in sub-Saharan Africa. The aim of the present thesis was to discuss, from a public health perspective, the programmatic challenges of engagement in care under option B+ strategy, with the example of Mozambique, a country known to have one of the highest HIVprevalence figures in the world. More specifically, we focused on three important aspects of engagement in care: the antenatal cascade of care, the maternal ART retention and the HIV exposed infant (HEI) testing coverage.We observed a high uptake of HIV testing, significant improvement in ART coverage over time and a better acceptance of ART at initiation in HIV+ pregnant women. Retention in care by the end of the first year of ART in HIV+ pregnant women and HIV testing coverage in HEI remainsub-optimal. Therefore, interventions to improve the mother-infant pair’s engagement in care should be systematically promoted. Finally, we underscore the considerable heterogeneity of definitions of outcomes used across various PMTCT programs.This work has highlighted the gaps in optimal engagement care of the mother-infant pair and its consequences on achieving virtual elimination of MTCT of HIV. We also highlighted the importance of having a consensus approach to measure PMTCT programme outcomes to allow national and international comparisons. Efforts to retain women under lifelong ART, ensuring their HIV-exposed infants receive the expected PMTCT services at the right moments along the continuum until final HIV status is determined, is the cornerstone of achieving an AIDS free generation by 2030.

Masters of Public Health - see Magister Public Health / Introduction: Mother-to-child transmission (MTCT) is the cause of most HIV acquisition among children. Prevention of mother-to-child transmission (PMTCT) of HIV programs aim to enable pregnant women to attain viral suppression so that they are unlikely to pass HIV to the foetus in utero or during birth, and to the neonate during breastfeeding. The Option B+ treatment regimen - initiating pregnant and breastfeeding women, diagnosed with HIV, on lifelong triple antiretroviral therapy (ART) regardless of their WHO clinical stage – was introduced in 2013 in Zambia but to date, no evaluation of this program has been done. Study Aim: The current study described factors associated with adherence and retention in care(RIC) among postnatal women initiated on ART during the antenatal and postnatal period at five PMTCT centres in Lusaka District, Zambia in 2017 and 2018. Methodology: A quantitative, retrospective cohort analysis of 311 postnatal women who were initiated on option B+ regimen at five PMTCT centres in Lusaka District between 1 January 2017 and 30 April 2018 was done. Adherence to treatment was measured by analysing data on patients’ missed clinic appointments and self-reported missed medication doses. Kaplan-Meier survival analysis was used to calculate RIC at 6, 12, 18, and 24 months. Bivariate analysis was conducted to determine the significance of associations between adherence and RIC, and sociodemographic and clinical characteristics, respectively. Results: Retention in care decreased over time, from 92% at the time of delivery to 81%, 77%, 74% and 70% at 6, 12, 18 and 24 months postnatal, respectively. Higher retention in care was observed amongst married women (p=0.012); who stayed within one kilometer from the health facility (p=0.018); whose spouses were on ART (p=0.027); who knew their HIV status before pregnancy (p=0.005); who were commenced on ART in the first trimester (p=<0.001); and the postnatal period (p=<0.001); who were on other medication, in addition to ART (p=0.001); who did not miss a dose of medication in the week before the last appointment (p=<0.001); and who did not miss any clinic appointment since commencing ART (p=<0.001). Half of the study participants (50.2%; n=155) reported optimal adherence (did not miss a scheduled clinic appointment since commencing ART). Optimal adherence to ART was significantly associated with women who lived within 1 km from the health facility (p=0.012) and who had a treatment supporter (p=0.030). Conclusion: Half of the study participants had optimal adherence to their scheduled clinic visits since enrolment into the Option B+ program, and 30% were lost to follow up over the first two years. Staying closer to the health facility where the woman received ART, knowing one’s HIV status before pregnancy or earlier in pregnancy, and initiating ART earlier in pregnancy, increased the likelihood of optimal adherence to ART and RIC at 24 months postnatal. Additionally, having a treatment supporter increased the likelihood of optimal adherence.

Master of Public Health - MPH / Background: Zimbabwe has one of the highest HIV prevalence rates in sub-Saharan Africa, with the adult prevalence rate at 15%. The HIV prevalence is highest among adult women, at 18%. Mother-to-child transmission is the second leading cause of HIV in Zimbabwe. Therefore, provision of anti-retroviral therapy to pregnant women is important in reducing mother-to-child transmission. In 2012, the World Health Organisation formally adopted ART guidelines known as "Option B Plus", where triple therapy is provided to pregnant women for life, regardless of CD4 count. Zimbabwe subsequently adopted Option B Plus in September 2013. However, the success of ART depends on adherence to treatment. Lack of adherence to treatment leads to an increased risk of opportunistic infections and drug resistance, which is costly to treat. The aim of the study was to explore pre-and post-partum barriers to anti-retroviral therapy for HIV-positive women initiated onto Option B Plus in Harare, Zimbabwe. Methodology: Descriptive qualitative methods were used to explore the barriers to ART adherence for pre-and post-partum HIV-positive women initiated onto Option B Plus in Harare, Zimbabwe. In-depth, semi-structured interviews were conducted in Shona with 20 non-adherent pre-and post-partum HIV-positive women and four key informants who are health workers from two identified health facilities (Edith Opperman Polyclinic and Kuwadzana Polyclinic). The interviews were recorded, transcribed and translated into English. The data was analysed using inductive thematic analysis. Results: Health facility and individual factors emerged as barriers to adherence. Heavy workload and staff shortages, negative health worker attitude, cost of accessing health facilities, medicine shortages and detrimental health facility policies were all health facility related barriers identified by both key informants and the women. Individual barriers were related to difficulty in navigating the early days after diagnosis and treatment, stigma, intimate partner dynamics and religion. Conclusion: Despite free, decentralised provision of ART, barriers to adherence still exist. Many of the barriers have been articulated in previous research that focused on prevention of- mother-to-child transmission regimens, as well as ART regimens for the general population. The fact that the barriers remain suggests that the barriers are complex and addressing them will require tackling social constraints such as stigma and gender roles that pose a significant barrier to adherence.

Globally, ~17 million women and ~2.1 million children are living with HIV. Sub-Saharan Africa accounts for 70% of HIV-infected (HIV+) persons. Mother-To-Child Transmission of HIV (MTCT) during pregnancy, delivery and breastfeeding, is the main route of HIV infection in children. The World Health Organisation recommends lifelong antiretroviral therapy (ART) for all HIV+ pregnant and breastfeeding mothers to prevent MTCT, and breastfeeding for ≥24 months for optimal child health in resource limited settings (Option B+ strategy). Initiation of ART in HIV+ adults is associated with a 2-6% decrease in areal bone mineral density (aBMD) regardless of ART regimen, but data are limited in pregnant and lactating women. Tenofovir, a preferred first-line drug in Option B+ ART regimen, is associated with 1-2% greater decreases in aBMD. Pregnancy and lactation are associated with physiological changes in maternal bone mineral density, but most evidence shows that this is recovered after cessation of breastfeeding. The hypothesis of this thesis is that ART may accentuate the normal process of bone mobilisation during pregnancy and lactation, leading to bone loss that is not recovered in the mother and/or compromised infant growth and bone mineral accretion. The primary objective of this research was to investigate if HIV+ women experience greater reductions in bone mineral compared to HIV-uninfected (HIV-) counterparts. Two groups of pregnant women, 95 HIV+ on ART (Tenofovir-Lamivudine-Efavirenz, previously ART naïve) and 96 HIV- were followed prospectively in Kampala, Uganda. Data were collected at 36 wks gestation (PG36), 2 (PP2) and 14 wks postpartum (PP14). Dual-energy x-ray absorptiometry was used to measure bone phenotype (aBMD, bone mineral content (BMC), bone area (BA), and size-adjusted BMC (SA-BMC, adjusted for height or length, weight and BA) of the whole body (WB) and lumbar spine (LS) in mother-baby pairs, and total hip (TH) in mothers. The primary outcome was the difference between groups in % change (± SE) in maternal LS aBMD between PP2 and PP14. Secondary outcomes included changes in maternal markers of bone formation (P1NP and BAP) and resorption (CTX), serum 25-hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), plasma and urine concentrations of creatinine (Cr), calcium (Ca), phosphate (PO4) and magnesium (Mg), urine mineral:creatinine ratios, TmCa/GFR and TMP/GFR, respectively), breastmilk mineral composition (Ca, P, Na, K and Na/K ratio); and infant growth Z-scores and bone mineral. Statistical models were adjusted for potential confounders. Median maternal age was 24.5 (IQR 21.1, 26.9) yrs. Mean gestation was 40.9±1.8 wks and not significantly different between groups. All women were breastfeeding at PP2 and PP14. More HIV+ women reported exclusive breastfeeding (PP2: 82.9% v 58.7%, p=0.0008; PP14: 86.7% v 66.2%, p=0.002). Body weight was 4-5% lower in HIV+ women. By PP14, mean duration of ART was 29.3±5.1 wks, adherence was > 95%, and the median CD4 count was 403 (IQR 290-528) cells/mm3. Maternal aBMD decreased between PP2 and PP14 at all skeletal sites in both groups as expected in lactation. Reductions in LS aBMD were not significantly different between groups (-1.8±0.4% vs -2.5±0.4%, p=0.3). However, HIV+ women had a significantly greater reduction in TH aBMD which persisted after adjustment for body size (-3.7±0.3% vs -2.7±0.3%, p=0.04). Median serum 25(OH)D was 67.4 nmol/L (IQR 54.8, 83.7) at PG36 and 57.6 nmol/L (48.7, 70.1) at PP14 with no significant difference between groups. Changes in 25(OH)D and PTH from PG36 to PP14 were not significantly different between groups (25(OH)D: -13.9±4.1% vs -11.1±3.1%; PTH: +60.0±6.4% vs +57.6±6.4%; both p > 0.05). However, HIV+ women had 33-35% greater plasma PTH concentrations at both PG36 and PP14. Bone formation and resorption markers increased in both groups between PG36 and PP14. HIV+ women had greater increases (CTX: +74.6±5.9% vs +56.2±5.9%; P1NP: +100.3±5.0% vs +72.6±5.0%; BAP: +67.2±3.6% vs +57.1±3.6%, all p < 0.05). They also had a greater decrease in plasma Ca (-6.6±0.5% vs-3.8±0.5%, p≤0.0001) and greater increase in plasma phosphate (+14.4±2.0% vs +7.7±2.0%, p=0.02). Changes in plasma Cr and Mg, TmP/GFR and urine mineral:creatinine ratios were not significantly different between the groups. However, at both PG36 and PP14, HIV+ had significantly lower mean plasma Ca (PG36: -1.0±0.5%; PP14: -4.1±0.6%) and TmP/GFR (PG36: -11.4±3.1%; PP14: -7.2±3.0%) but higher PTH (PG36: +33.0±7.0%; PP14: +35.3±7.6%) compared to HIV- women (all p < 0.05). Mean breastmilk Ca decreased between PP2 and PP14, and the changes were not different between the groups (-19.9±3.0% vs -24.2±3.1%, p=0.3). There were no significant changes in breastmilk phosphorus (P) in both groups, but HIV+ women had significantly higher concentrations (PP2: +9.7±3.8%, p=0.01; PP14:+9.6±3.5 %, p=0.007). Breastmilk P was significantly correlated with maternal plasma [CTX] in a separate ANCOVA model (β = +0.13±0.04% per 1% increase in CTX, p=0.0003). Mean breastmilk Na, K concentrations and Na/K decreased between PP2 and PP14 in both groups. However, HIV+ women had a smaller decrease in breastmilk Na (-44.3±8.9% vs -72.6±9.0%, p=0.03). They also had a trend towards smaller reduction in Na/K ratio (-22.2±9.3% vs -46.6.6±9.5%, p=0.07). Babies born to HIV+ mothers (HIV-exposed infants, HEI) had significantly lower gains in weight +53.0±1.4% vs +57.5±1.4%, p=0.02) compared to HIV-unexposed infants (HUI), and also lower weight-for-age (-0.47±0.16, p=0.003) and length-for-age (-0.53±0.18, p=0.005) Z-scores at PP14. HEI had a slower gain in WB BMC (+51.2±1.9% vs +57.3±1.9%, p=0.02), but the difference was not significant after adjustment for body size (-6.0±3.5% vs -7.6±3.8%, p=0.2); showing that the bone mineral accretion was appropriate for achieved infant size. In contrast, HEI had a greater increase in LS BMC (+29.5±1.7% vs +24.4±1.7%, p=0.03), a difference which remained after size-adjustment (+9.4±5.8% vs +4.3±6.2%, p=0.02). This is the first study to compare changes in maternal aBMD and bone metabolism between HIV+ mothers on Option B+ ART and HIV- counterparts. The results show a greater reduction in TH aBMD in Ugandan HIV+ women on Option-B+ ART compared to HIV- in the first three months of lactation, consistent with their greater increases in bone turnover markers, lower TmP/GFR and plasma phosphate, and higher breastmilk phosphorus concentration. Also, HEI have slower growth and whole body bone mineral accretion compared to HUI. It is important to determine if these changes are temporary or have long-term consequences for the bone health of the mother and child.

Study Objective The objectives of this study are: (1) to explore the impact of the national consolidated guidelines for Option B+ PMTCT on the work of healthcare professionals at both clinical and management levels (including nurses, physicians and management) (2) to understand pregnant HIV-positive women views and experiences with ART for life, as a way to better manage the Option B+ PMTCT programme within state hospitals Research Questions The following research questions will be used to explore both perceptions of healthcare professionals and patients: 1.How have the national consolidated guidelines for Option B+ PMTCT affected the work of healthcare professionals? 2.What are pregnant HIV-positive women’s views and experiences about going on lifetime treatment with ARVs? / ABSTRACT Background. South Africa’s National Department of Health has adopted World Health Organization’s (WHO) 2013 consolidated guidelines on the use of ARVs for treatment and prevention of HIV infection. The guidelines include changes for prevention of mother to child transmission (PMTCT) through Option B+. Option B+ aims to reduce the HIV prevalence rate amongst these women by placing them on ART for life, no matter their CD4 count. As a result, in January 2015, these guidelines were implemented for the PMTCT programme at RMMCH. Little is known about the impact of these new guidelines on the work of healthcare professionals in state hospitals. Most importantly, no research has focused on how these changes have affected adherence for the patients. Purpose. The purpose of this research project is (1) to explore the impact of the Option B+ PMTCT programme on the work of healthcare professionals, and (2) to understand pregnant HIV-positive women views and experiences with ART for life, as a way to better manage the Option B+ PMTCT programme. Methods. A qualitative study design is used with a phenomenological approach. The methodology uses demographic questionnaires and semi-structured interviews with healthcare professionals and patients. The study is situated in Johannesburg, South Africa. Findings. The findings demonstrate that work has changed and become difficult to manage for all healthcare professionals because of (1) the need for strengthening indicators for tracking to decrease loss to follow-up (LTFU); (2) inconsistency in delivery of counseling and support services and the need for communication across clinical departments; and (3) the lack of compassion and understanding by service providers. The difficult healthcare environment has affected overall views and experiences of pregnant HIV-positive women going on ART for life. All 55 patient participants responded that they chose to take the fixed-dose combination (FDC) for life to protect the health of the baby and felt ART for life can be stopped after giving birth. Conclusion. Implications for future research include the need to address changes within the healthcare system at both clinical and management levels. It is crucial to incorporate the perspective of patients in policy implementation; uptake and adherence are key indicators in informing whether the Option B+ PMTCT programme is being adapted into state hospitals effectively. There needs to be extensive research on how to strengthen indicators for long term scalability and sustainability of the programme. Future evaluations need to address, will interdisciplinary collaboration within hospitals improve the management and understanding of Option B+? / Thesis / Master of Science (MSc)