Thesis (Ph.D.(Public Health))--University of the Witwatersrand, Faculty of Health Sciences, 2012. / Measuring HIV incidence has proved challenging over the years. A number of serological HIV assays have been proposed, and among these, the BED Capture Enzyme Immunoassay (CEIA) is one of the more widely used. Although the assay performs well among known seroconverting panels, it has been shown to classify some long term infected patients as being recently infected. Information on the performance of the BED assay among low CD4 cell count patients and those on antiretroviral therapy is limited. The risk of onwards transmission of HIV has been reported to be elevated around the seroconversion period compared to the chronic stage of infection. RNA viral load has been reported as the strongest predictor of HIV transmission compared to other HIV markers. Understanding how these markers influence the relationship between the likelihood of being recently infected and the BED assay might help in understanding some of the shortcomings of the BED assay. The main aim of this study was to understand the properties of the BED assay. The performance of the BED assay among advanced HIV disease patients and the influence of ART on BED levels once patients started treatment was investigated. The BED assay and CD4 cell count were used to quantify the risk of in utero and intrapartum transmission to their infants among women believed to have seroconverted during pregnancy. The influence of viral load, haemoglobin and mid-upper arm circumference was investigated on the relationship between the probability of being recently infected and BED ODn levels. Methods Cryopreserved plasma samples from HIV patients on the national antiretroviral treatment (ART) rollout programme at Tygerberg Hospital HIV clinic, South Africa, iv were used to investigate the effect of ART on BED ODn levels once patients commenced treatment. Mixed effect logistic regression models accounting for multiple readings per patient were used. To investigate the risk associated with seroconversion during pregnancy HIV seropositive women who had just given birth were classified into mutually exclusive groups according to their likelihood of having recently seroconverted using BED and CD4 cell count levels. Multinomial logistic regression models adjusting for other factors were used to assess the risk of MTCT in utero and intra-partum infection comparing these groups. To investigate the relationship between BED ODn levels and the probability of being recently infected, BED data from known HIV infected women and women who seroconverted over a 2 year period was used. Fractional polynomial regression models that allow for non-linear functions to be fitted were used, and the influence of viral load, haemoglobin and mid-upper arm circumference was assessed through multi-variable models. Data from the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) project, a double blinded treatment-placebo trial was used for these last two objectives. Results Patients with very low CD4 cell counts were more likely to test false recently infected according to the BED assay than other patients. ART changed BED ODn kinetics among HIV patients on treatment. Over half of advanced disease stage patients were likely to be classified as being recently infected according to the BED assay 2 years into ART treatment. v Women who seemed to have seroconverted during pregnancy had elevated risk of transmitting HIV in-utero compared to chronic HIV patients. BED and CD4 cell count were not predictive of risk of intra-partum infections attributed to seroconversion during pregnancy. The relationship between the probability of being recently infected with HIV and BED ODn levels was described better using Fractional Polynomial regression models than using a linear model in BED ODn or a model in which the BED ODn was categorised. Viral load and haemoglobin were important independent predictors of incident infections. Conclusions If the BED assay is to be used for HIV incidence estimations patients on ART should be accounted for. The BED assay together with other HIV serological markers can be used as prognostic tools to assess the risk of HIV transmission. The risk of in-utero transmission of HIV is higher among women who seroconvert during pregnancy. Repeat HIV testing among pregnant women may help in identifying women who seroconvert during pregnancy, and these women will benefit from Prevention of Mother-to-Child transmission (PMTCT) programmes. It was found that additional markers such as viral load and haemoglobin did not alter the relationship between the probability of having been recently infected and BED ODn.

This thesis develops novel statistical methodology for estimating the incidence and the prevalence of Human Immunodeficiency Virus (HIV) using routinely collected surveillance data. The robust estimation of HIV incidence and prevalence is crucial to correctly evaluate the effectiveness of targeted public health interventions and to accurately predict the HIV- related burden imposed on healthcare services. Bayesian CD4-based multi-state back-calculation methods are a key tool for monitoring the HIV epidemic, providing estimates of HIV incidence and diagnosis rates by disentangling their competing contribution to the observed surveillance data. Improving the effectiveness of public health interventions, requires targeting specific age-groups at high risk of infection; however, existing methods are limited in that they do not allow for such subgroups to be identified. Therefore the methodological focus of this thesis lies in developing a rigorous statistical framework for age-dependent back-calculation in order to achieve the joint estimation of age-and-time dependent HIV incidence and diagnosis rates. Key challenges we specifically addressed include ensuring the computational feasibility of proposed methods, an issue that has previously hindered extensions of back-calculation, and achieving the joint modelling of time-and-age specific incidence. The suitability of non-parametric bivariate smoothing methods for modelling the age-and-time specific incidence has been investigated in detail within comprehensive simulation studies. Furthermore, in order to enhance the generalisability of the proposed model, we developed back-calculation that can admit surveillance data less rich in detail; these handle surveillance data collected from an intermediate point of the epidemic, or only available on a coarse scale, and concern both age-dependent and age-independent back-calculation. The applicability of the proposed methods is illustrated using routinely collected surveillance data from England and Wales, for the HIV epidemic among men who have sex with men (MSM).

L'incidence de l'infection par le VIH, définie comme le nombre de sujets nouvellement infectés par le VIH au cours du temps, est le seul indicateur permettant réellement d'appréhender la dynamique de l'épidémie du VIH/SIDA. Sa connaissance permet de prévoir les conséquences démographiques de l'épidémie et les besoins futurs de prise en charge, mais également d'évaluer l'efficacité des programmes de prévention. Jusqu'à très récemment, l'idée de base pour estimer l'incidence de l'infection par le VIH a été d'utiliser la méthode de rétro-calcul à partir des données de l'incidence du SIDA et de la connaissance de la distribution de la durée d'incubation du SIDA. L'avènement, à partir de 1996, de nouvelles combinaisons thérapeutiques très efficaces contre le VIH a contribué à modifier la durée d'incubation du SIDA et, par conséquent, à augmenter la difficulté d'utilisation de la méthode de rétro-calcul sous sa forme classique. Plus récemment, l'idée d'intégrer des informations sur les dates de diagnostic VIH a permis d'améliorer la précision des estimations. La plupart des pays occidentaux ont mis en place depuis quelques années un système de surveillance de l'infection à VIH. En France, la notification obligatoire des nouveaux diagnostics d'infection VIH, couplée à la surveillance virologique permettant de distinguer les contaminations récentes des plus anciennes a été mise en place en mars 2003. L'objectif de ce travail de thèse est de développer de nouvelles méthodes d'estimation de l'incidence de l'infection par le VIH capables de combiner les données de surveillance des diagnostics VIH et SIDA et d'utiliser les marqueurs sérologiques recueillis dans la surveillance virologique dans le but de mieux saisir l'évolution de l'épidémie dans les périodes les plus récentes. / The knowledge of the dynamics of the HIV/AIDS epidemic is crucial for planning current and future health care needs. The HIV incidence, i.e. the number of new HIV infections over time, determines the trajectory and the extent of the epidemic but is difficult to measure. The backcalculation method has been widely developed and used to estimate the past pattern of HIV infections and to project future incidence of AIDS from information on the incubation period distribution and AIDS incidence data. In recent years the incubation period from HIV infection to AIDS has changed dramatically due to increased use of antiretroviral therapy, which lengthens the time from HIV infection to the development of AIDS. Therefore, it has become more difficult to use AIDS diagnosis as the basis for back-calculation. More recently, the idea of integrating information on the dates of HIV diagnosis has improved the precision of estimates. In recent years, most western countries have set up a system for monitoring HIV infection. In France, the mandatory reporting of newly diagnosed HIV infection, coupled with virological surveillance to distinguish recent infections from older, was introduced in March 2003. The goal of this PhD thesis is to develop new methods for estimating the HIV incidence able to combine data from monitoring HIV and AIDS diagnoses and use of serologic markers collected in the virological surveillance in order to better understand the evolution of the epidemic in the most recent periods.

This thesis is focused on a situation of sexually transmitted infections in Prague (and in The Czech Republic shallowly) and analyzes this issue relatively to the social epidemiology. The thesis tries to identify the most vulnerable groups of a population. These groups contain homosexual men, individuals having unprotected sex and promiscuous people. Further more, the thesis tries to identify a relation between a high-risk factor and an exposition of a particular infection. For example, it was found out that sexual related risks are mostly determinated by a sexual behavior and a region where the individuals come from. Also, men are more vulnerable group of people than women according to findings of this thesis. A gonorrhoea infection is the most reported sexually transmitted infection in Prague (59,1 % of all cases). Syphilis is the second most common infection of this kind. The highest prevalence of sexually transmitted infections was reported for people with (finished or unfinished) basic education. This group of people represents 14,3 % of all reported cases. Its prevalence is 67,7 patients per ten thousand individuals. A group of people aged 20 - 29 years is another group with high prevalence. Further identification of a sexual behavior in The Czech Republic was one of the main goals of this...

Since the earliest reported cases of HIV/AIDS probably in 1959 in Africa, there has been a consistent progression in the new HIV/AIDS infection cases. In South Africa, Gauteng, records one of the highest HIV/AIDS prevalence rates in the country. The Department of Health (DOH) South Africa conducts ongoing studies on HIV/AIDS at provincial levels; these studies monitor the prevalence of HIV/AIDS amongst pregnant women attending antenatal clinics, as a tool for determining and monitoring the prevalence, trends, patterns and spread of the disease in the general population. This study analyses sentinel and spatial data collected from the (DOH) and Statistics South Africa (StatsSA) respectively, and depicts them in the form of spatial maps, and then critically analyses the spatial patterns that occur. The research findings would hopefully contribute to the overall knowledge of HIV/AIDS and provide framework and relevant literature for further investigation. / Geography / M.Sc. (Geography)

Since the earliest reported cases of HIV/AIDS probably in 1959 in Africa, there has been a consistent progression in the new HIV/AIDS infection cases. In South Africa, Gauteng, records one of the highest HIV/AIDS prevalence rates in the country. The Department of Health (DOH) South Africa conducts ongoing studies on HIV/AIDS at provincial levels; these studies monitor the prevalence of HIV/AIDS amongst pregnant women attending antenatal clinics, as a tool for determining and monitoring the prevalence, trends, patterns and spread of the disease in the general population. This study analyses sentinel and spatial data collected from the (DOH) and Statistics South Africa (StatsSA) respectively, and depicts them in the form of spatial maps, and then critically analyses the spatial patterns that occur. The research findings would hopefully contribute to the overall knowledge of HIV/AIDS and provide framework and relevant literature for further investigation. / Geography / M.Sc. (Geography)

Text in English / Previous studies have reported a high prevalence of HIV and AIDS among adolescent girls. It is estimated that there are 5,24 million people living with HIV/AIDS (PLWHA). These estimates would mean that about 2.36 million people living with HIV/AIDS would be young women and girls aged 15-24 years. The latest household survey conducted by the Human Science Research Council (HSRC) revealed that the prevalence of HIV is three to seven fold in girls and young women aged 15-24 than boys and young men (HSRC 2014) This resurgence in HIV incidence is occurring at a time when it is believed the epidemic has reached a plateau following aggressive behavioural, biomedical and structural interventions by the Department of Health, Non-Governmental Organizations (NGO) and civil society in general. A probability sampling method, involving a random selection of elements was used to select 130 young women and girls aged 18-24 presenting at Dr George Mukhari Academic Hospital by simple random sampling. Data were collected by self-administering questionnaires. High unemployment and greater age-disparity in the relationships were found to have a direct correlation with HIV incidence in the population under study. This study also shows that inconsistent condom use, low rate of medical male circumcision of male partners, coupled with lower HIV counselling and testing than the national average, was associated with new HIV infections, in spite of high level of condom availability, knowledge of HIV issues and an exposure to an array of behavioural change communication interventions. / Health Studies / M.A. (Public Health)