Background: Tested independently, studies report that obesity and HIV infection and/or ART use in pregnancy are associated with adverse birth outcomes. However, there is limited data on the combined impact of these maternal factors on adverse birth outcomes. Given the high prevalence of obesity and HIV infection in Sub-Saharan Africa (SSA), understanding these associations is important. This study examined the association of the double burden of high maternal body mass index and HIV infection/ART use in pregnancy with adverse birth outcomes. Methods: Part A of this mini-dissertation presents the study protocol which outlines the rationale, aim and objectives of the study; the research methodology, analysis plan and ethical considerations. Part B is the literature review of studies conducted in SSA which investigated the relationship between BMI and HIV infection and adverse birth outcomes of interest. Part C is the journal-formatted manuscript which presents the results and discussion of the study findings in relation to other scholars. The referencing style used for the whole thesis is Vancouver as required by the journal chosen for the formatting of the manuscript. We used data collected from a large observational Prematurity Study that enrolled HIV-infected and HIV-uninfected women seeking antenatal care at Gugulethu MOU in Cape Town between April 2015 and October 2016. A subset of HIV-infected women who booked early (≤24weeks) was prospectively followed through delivery and was used to study gestational weight gain (GWG) and adverse birth outcomes. Data was obtained from review of medical records and study questionnaires. Logistic regression was used to compare birth outcomes by BMI status: preterm delivery (PTD), low/high birthweight (LBW/HBW) and small/large gestational age (SGA/LGA) between HIV-uninfected and -infected women; and between HIV-infected women who initiated ART before pregnancy and those who initiated ART during pregnancy. Using the subset of HIV-infected women who booked early (≤24weeks), we compared the adverse birth outcomes between low, adequate and high GWG. Results: Of the 2779 participants included in the analysis, 20% had normal BMI, 29% were overweight, 51% were obese and 39% were HIV-infected. Overall, there was no association between obese BMI and PTD (aOR 1.06, 95% CI 0.75-1.49). Instead, obese BMI was negatively associated with LBW (aOR 0.53; CI: 0.39-0.72) and SGA infants (aOR 0.55, 95% CI 0.41-0.75) compared to normal BMI women. Stratifying by HIV infection showed similar results for LBW (aOR 0.54; CI: 0.35-0.83) and SGA (aOR 0.60, 95% CI 0.38-0.94) in obese HIV-infected women compared to corresponding women with normal BMI. However, comparison of obese HIV-uninfected and obese HIV-infected women showed a higher incidence of LBW and SGA infants in obese HIV-infected women (12% vs 8%). The association of obese BMI and LBW and SGA in HIV-infected women did not differ by timing of ART initiation. In terms of HBW and LGA, overall, obese BMI was positively associated with HBW (aOR 2.00; CI: 1.13-3.57) and LGA infants (aOR 1.98, 95% CI 1.40-2.80) compared to normal BMI women. Stratifying by HIV infection also showed a positive association between obese BMI and HBW (aOR 2.54; CI: 1.17-5.53) and LGA (aOR 2.30; CI: 1.46-3.62) in HIV-uninfected women. Although a similar positive association was also obtained in obese HIV-infected women, the strength of this association was weaker for both HBW (aOR 1.41; CI: 0.59-3.34) and LGA (aOR 1.58; CI: 0.91-2.72). When the analysis was restricted to HIV-infected women by timing of ART initiation we found that obese women who initiated ART during pregnancy had 3-fold likelihood of having LGA infants (aOR 3.26; CI: 1.32-8.09) and those who initiated ART before pregnancy had a reversed effect (aOR 0.87; CI: 0.43-1.78) compared to respective normal BMI women. However, restricting the analysis to obese HIV-infected women only revealed a counter effect of the two conditions where the frequencies of both LGA and SGA are high. Abnormal gestational weight gain had no association with PTD, LBW, HBW and SGA. However, we showed that GWG lower than the IOM recommended values reduced the likelihood of having LGA infants (aOR 0.29; CI: 0.12-0.70) compared to adequate GWG. Conclusions: Obese HIV-infected women appear to be cushioned by their BMI against LBW and SGA when compared to normal BMI. However, comparison of these outcomes amongst women who are either obese or HIV-infected reveal a higher burden of both SGA and LGA infants in obese HIV-infected women, regardless of ART initiation status.

Background: In 2016, Khayelitsha reported almost 89% viral load (VL) suppression but less than 56% completion on routine quarterly reports, casting doubt on the validity of reported suppression. Objectives: To assess the validity of reported VL suppression as a measure of progress towards the 90-90-90 target and identify barriers to routine VL completion. Methods: A retrospective cohort study including all patients on antiretroviral treatment (ART) in Khayelitsha with a routine VL expected between 1 July 2015 and 30 June 2016 was conducted. ART programme and laboratory data were obtained and a sample of 1 035 patient folders were reviewed. Suppression was calculated using laboratory data and compared to reported suppression. A VL cascade from “expected” to “done”, “filed”, “noted” and “captured” was constructed to reflect the steps a VL must complete to be included in reported suppression and successful progression to each step was estimated. Logistic regression models were used to calculate adjusted odds ratios (aOR) with 95% confidence intervals (95%CI) for completion among different patient groups. Results: Using laboratory data, VL suppression was estimated to be 82%, 87%, 89% and 91% at the 50, 200, 400 and 1 000 copies/mL thresholds respectively, but reported suppression would have been 80%, 86%, 88% and 89% at those thresholds. Of 22 991 patients with a routine VL due in the study period, 84% were done, 79% filed, 76% noted, and 55% captured. Routine VL were more likely to be done among children< 15 years old (aOR 1.89, 95%CI 1.45–2.48) and pregnant women (aOR 1.90, 95%CI 1.28–2.81) compared to adult men, adjusted for facility. Conclusion: Despite low reported completion, actual completion was high and reported suppression was similar to suppression calculated using laboratory data, thus providing an accurate measure of progress towards the 90-90-90 target. More work is needed to reach the 16% of patients missed by routine testing. Most of the VL done were available to the clinician at the next assessment, and further research is needed to assess how effectively these VL results are used in clinical decision-making.

Sex workers have a higher risk of acquiring and transmitting HIV as a result of social, structural, biomedical and behavioural factors. Many recent studies have highlighted that sex workers and other key populations experience higher levels of depression compared to the general population. Evidence is also emerging that mental health issues such as depression are related to HIV risk behaviour as well as the social and structural factors that leave sex workers vulnerable to bio-behavioural risks. The study protocol is described in Part A of this mini-dissertation. The study from which these data were derived is discussed in detail. Particular attention is placed on the use of respondent-driven sampling as a probabilistic method to estimate population proportion for hidden populations. The primary outcome, depression, and how it is measured through the Patient Health Questionnaire 9, is discussed in detail. The objective of measuring the prevalence of depression and assessing how it relates to risk factors is noted. The protocol argues that most research on sex workers focuses only on social, structural and bio-behavioural risk factors and rarely includes intrapersonal factors such as mental health. Based on this gap, it is argued that this research will help elucidate how depression, as an intrapersonal factor, relates to HIV risk. The literature review in Part B expands the argument that mental health in general and depression in particular are not given the attention they deserve as there are very few studies that measure mental health variables and even fewer that attempt to make any link between mental health, bio-behavioural risk and social vulnerabilities. The journal article in Part C offers empirical evidence that depression is higher among female sex workers than the general population and that depression is strongly associated with bio-behavioural and social risk factors. The article argues for more integration of mental health in research and programme implementation among sex workers.

Background: The associations between common variants in the fat mass- and obesity-associated (FTO) gene and obesity-related traits may be age-dependent and may differ by sex. The present study aimed to assess the association of FTO rs9939609 with body mass index (BMI) and the risk of obesity from childhood to adolescence, and to determine the age at which the association becomes evident. Methods: Totally 757 obese and 2,746 non-obese Chinese children aged 6-18 years were genotyped for FTO rs9939609. Of these, a young sub-cohort (n = 777) aged 6-11 years was reexamined 6 years later. Obesity was defined using the sex- and age-specific BMI cut-offs recommended by the International Obesity Task Force. Results: The associations of FTO rs9939609 with BMI and obesity did not appear until children reached 12-14 years. The variant was associated with an increased BMI in boys (β = 1.50, P = 0.004) and girls (β = 0.97, P = 0.018), respectively. Thereafter, the magnitude of association increased in girls at ages 15-18 years (β = 2.02, P0.05). Age was found to interact with the variant on BMI (P<0.001) and obesity (P = 0.042) only in girls. In the sub-cohort, the associations of FTO rs9939609 with BMI (β = 1.07, P = 0.008) and obesity (OR = 2.09, 95% CI: 1.12, 3.91) were only observed 6 years later (ages 12-18 years) in girls, even after adjusting for baseline BMI. Conclusions: The association between FTO rs9939609 and obesity-related traits may change from childhood to adolescence in Chinese individuals, and the association may start as early as age 12 years, especially in girls.

Introduction Globally, the population of older adults is ageing rapidly, due to increased longevity and decreasing fertility rates. With the rapidly accelerating growth of this ageing population in low-to-middle income countries, the health systems are not well resourced to manage this rapid growth that are required to accommodate older multimorbid populations. Multimorbidity presents as an elevated risk for the health and wellbeing of older populations and occurs when more than one chronic condition is present. Globally pain is a common symptom among older adults that impairs health with severe consequences especially when multimorbidity is present. Some evidence has shown that living under poverty-stricken conditions is associated with increased pain, particularly among vulnerable populations such as older adults. There is limited evidence in Cape Town on the relationship between living in low-to middle income areas and poverty indicators such as making financial trade-offs for survival with increased reports of pain in older adults. Methods In this cross-sectional analysis, adults aged 60 years and above seeking care from four selected primary health care clinics and health clubs were enrolled in an ongoing longitudinal study (Wellbeing Study). Data was used from an existing study that commenced in March 2018. Data were collected using a multidimensional geriatric instrument called the Check-Up Self-Report (interRAI). The researcher assessed the relationship between financial trade-offs made for survival (as a proxy for poverty) and pain in the last three days (as a proxy for pain) overall, and according to study sites. Permission for the parent study was sought and granted by the University of Cape Town's Health Research Ethics Committee (UCT-HREC, Ref: 790/2017) as well as by the Western Cape Department of Health. Results The results highlighted that overall and by site, no associations were observed between pain and financial trade-offs after adjusting for various health-related variables (aOR: 1.17, 95% CI: 0.97 – 1.42). Of the 1813 older adults included in this analysis (64% female, median age 68 years (IQR: 64-74)) 51% reported making financial trade-offs and 46% reported experiencing pain in the last three days. Overall, a moderate proportion of participants (27%) reported daily pain, which was categorised as not severe (11%), severe (12%) and excruciating (4%). When assessed by site a significantly higher proportion of participants reported daily pain in Khayelitsha (43%) and Woodstock (40%). Conclusion In this study the need to make financial trade-offs for survival and pain were prevalent in this population. Although an association was not found between making financial trade-offs and recent pain, the results provided valuable information that can drive future research studies and policy. The use of this multidimensional tool which collects information from various health categories and provides broad and less in-depth data may have played a role in the nullified results. Further research is needed to evaluate the association of poverty indicators on pain in this population using more detailed pain and poverty assessment tools.

Includes bibliographical references. / [Background] South Africa has one of the highest prevalences of HIV-infection in women of reproductive age and a high rate of unplanned pregnancy. It is important to explore contraceptive use in HIV-positive women to better understand how to facilitate service delivery to those women wishing to avoid pregnancy. While it is critical to emphasise condom use, information is needed on the factors that contribute to nonbarrier contraceptive use (NBCU) and its prevalence among HIV-positive women in order to afford women the opportunity to choose to have maximum dual method protection to prevent both infection and unwanted pregnancy. While there is literature on people living with AIDS and contraceptive use from other areas of the world, there is little quantitative research conducted in a South African context, although there is evidence of a high proportion of unwanted pregnancy among HIVpositive women in this setting. [ Rationale and Justification for Research ] Information is needed to understand the factors that contribute to NBCU by HIVpositive women, including the prevalence of these determinants. By better understanding the obstacles to non-barrier contraceptive use, both HIV and reproductive health services will better be able to provide more appropriate contraceptive health care to HIV-positive women. [ Aims ] The aim of this study is to determine the prevalence of NBCU and the types of methods used innon-pregnant, HIV-positive women, and to determine the factors that influence the choice of NBCU. [ Objectives ] To determine the prevalence of NBCU in a population of HIV-positive South African females; To determine what factors influence NBCU in women infected with HIV, including whether or not NBCU changes after an HIV-positive diagnosis; To compare the NBCU prevalence among HIV-positive women who want children in the future to 8 those who do not want children in the future, and who are currently on antiretroviral therapy (ART) to those who are not currently on ART; To determine what factors influence NBCU for particular subsets of women, including those with and without fertility intentions in the next 12 months and women currently on and not on ART; To determine the unmet need for non-barrier contraception in HIV-positive women. [ Methods ] This study will form a part of a larger cross-sectional study, which collected data on the fertility intentions and the utilization of HIV and reproductive health services of 459 HIV-seropositive men and women from the peri-urban informal settlement of Gugulethu, located outside of Cape Town, from May to September 2006. Data was collected by trained fieldworkers through the use of a standardised quantitative survey instrument. A qualitative study consisting of in-depth interviews and focus groups with HIV-infected men was also conducted as part of the larger research project. After being cleaned, data was transferred to STATA Release 10 (STATACorp, College Station, USA) where bi-variate and multi-variate statistical analysis was performed. [ Ethics ] The Ethical Review Committee of the World Health Organisation and the Research Ethics Committee of the University of Cape Town, the research partners in this study, granted ethical approval to the larger cross-sectional study to which this sub-study is part. All participants who agreed to the voluntary interview provided informed consent, and although the risk of personal harm was very low, effort was put forth to minimise non-maleficence.

Includes bibliographical references. / Pesticide exposure has been increasingly associated with adverse respiratory health effects including asthma and allergy. However, few studies have been conducted among women and workers in developing countries. South Africa is one of the largest users of pesticides on the continent and the Western Cape is one of the main agricultural areas in the country, with uncontrolled use posing an increased health risk to farm workers. This study focused on determining the association between pesticide exposure (predominantly organophosphates and carbamates) and the presence of allergy and asthma among women farm workers and residents. A cross-sectional study was conducted on 211 women including those working and living on farms (farm dwellers, n=121) and those residing in neighbouring farm areas (town dwellers, n=90). Outcome measurements included the abbreviated European Community Respiratory Health questionnaire, fractional exhaled nitric oxide (FeNO) levels and immunological tests (a positive Phadiatop test indicating atopy and quantification of specific IgE to house dust mite, storage mite and spider mite). The outcome variables included doctor diagnosed asthma, adult onset asthma, current asthma, allergic sensitisation, allergic airway inflammation and the asthma symptom score. The asthma symptom score was a continuous outcome generated as the sum of positive responses to four questions on asthma symptoms in the last 12 months including wheeze with breathlessness, woken up with chest tightness, attack of shortness of breath at rest and woken by attack of coughing. The asthma symptom score values ranged from from 0 for no symptoms to 4 for all symptoms.

The authors regret the order and address of corresponding authors of the original article were given incorrectly. The correct order of all authors is as follows: Jie Weng1, Mengyun Tu1, Peng Wang, Xiaoming Zhou, Chuanyi Wang, Xinlong Wan, Zhiliang Zhou, Liang Wang, Xiaoqun Zheng, Junjian Li, Chan Chen**, Zhiyi Wang**, Zhibin Wang*. The correct corresponding author at: Institute of Bioscaffold Transplantation and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. This reflects the fact that Zhibin Wang was the main contributing corresponding author to the original article. The authors would like to apologise for any inconvenience caused.

Clinical trials had provided evidence for the benefit effect of antihypertensive treatments in preventing future cardiovascular disease (CVD) events; however, the association between hypertension, whether treated/untreated or controlled/uncontrolled and risk of mortality in US population has been poorly understood. A total of 13,947 US adults aged ≥18 years enrolled in the Third National Health and Nutrition Examination Survey (1988-1994) were used to conduct this study. Mortality outcome events included all-cause, CVD-specific, heart disease-specific and cerebrovascular disease-specific deaths, which were obtained from linked 2011 National Death Index (NDI) files. During a median follow-up of 19.1 years, there were 3,550 all-cause deaths, including 1,027 CVD deaths. Compared with normotensives, treated but uncontrolled hypertensive patients were at higher risk of all-cause (HR = 1.62, 95%CI = 1.35-1.95), CVD-specific (HR = 2.23, 95%CI = 1.66-2.99), heart disease-specific (HR = 2.19, 95%CI = 1.57-3.05) and cerebrovascular disease-specific (HR = 3.01, 95%CI = 1.91-4.73) mortality. Additionally, untreated hypertensive patients had increased risk of all-cause (HR = 1.40, 95%CI = 1.21-1.62), CVD-specific (HR = 1.77, 95%CI = 1.34-2.35), heart disease-specific (HR = 1.69, 95%CI = 1.23-2.32) and cerebrovascular disease-specific death (HR = 2.53, 95%CI = 1.52-4.23). No significant differences were identified between normotensives, and treated and controlled hypertensives (all p > 0.05). Our study findings emphasize the benefit of secondary prevention in hypertensive patients and primary prevention in general population to prevent risk of mortality later in life.

Tardive dyskinesia (TD) is a side effect of antipsychotic medications used to treat schizophrenia (SCZ) and other mental health disorders. No study has previously used pyrosequencing to quantify DNA methylation levels of the DLGAP2 gene; while the quantitative methylation levels among CpG sites within a gene may be correlated. To deal with the correlated measures among three CpG sites within the DLGAP2 gene, this study analyzed DNA methylation levels of the DLGAP2 gene using a linear mixed model (LMM) in a Chinese sample consisting of 35 SCZ patients with TD, 35 SCZ without TD (NTD) and 34 healthy controls (HCs) collected in Beijing, China. The initial analysis using the non-parametric Kruskal-Wallis test revealed that three groups (TD, NTD and HC) had significant differences in DNA methylation level for CpG site 2 (p = 0.0119). Furthermore, the average methylation levels among the three CpG sites showed strong correlations (all p values < 0.0001). In addition, using the LMM, three groups had significant differences in methylation level (p = 0.0027); while TD, NTD and TD + NTD groups showed higher average methylation levels than the HC group (p = 0.0024, 0.0151, and 0.0007, respectively). In conclusion, the LMM can accommodate a covariance structure. The findings of this study provide first evidence of DNA methylation levels in DLGAP2 associated with SCZ with TD in Chinese population. However, TD just showed borderline significant differences to NTD in this study.