Primarily, this dissertation examined the extent to which churches have potential in preventing HIV/AIDS. Set in rural KwaZulu-Natal an area marked with both high levels of HIV prevalence and high religious participation, the study used the concept of social space as a framework within which the contribution of churches towards the prevention of further spread of the HIV infection can be understood. Unlike recent studies which have consistently shown that the contribution of churches in the prevention of further spread of HIV infection is likely to emanate from the churches‘ teaching on morality, this study has argued that the contribution of churches in minimizing risky sexual behaviours is likely to emanate from how churches balance their teachings on moral issues and the subsequent practice of social control on the one hand and the provision of social support on the other. This is particularly so because in African settings where behaviour is largely influenced by the prevailing circumstances within society, and where churches are significantly entrenched in the lives of individuals providing a variety of social support services, there is a strong likelihood that churches will have an impact on their adherents‘ behaviour as well. The social space concept, therefore, defines churches not only as institutions enforcing the moral code which churches emphasise but also as caring and integrating forces, providing social support for their members in time of need. The study investigated four churches representing three Christian religious denominations: the Mainline, the Pentecostal and the African Independent churches. In investigating these churches, it used two types of data: The Africa Centre Demographic surveillance Systems (ACDIS) data collected between 2002 and 2004 and the Ethnographic data collected in 2006 consisting of a total of 96 in-depth interviews, 11-13 services of each church type selected, 6-8 church- related activities (or groups in each church), 3 informal discussions with community members and a set of 2 conversational data from each church. The analysis is done in two parts. The first part of the analysis (Chapter Five) focuses on the existing quantitative ACDIS data, examining whether there exists a relationship between church affiliation, participation in church activities and sexual behaviours. The second part uses ethnographic data in order to provide explanations of the observed relationship. Overall, the study found that unlike church affiliation which had no influence on individual sexual behaviour, individuals who participated regularly in church activities were less likely to engage in behaviour that would put them at risk of acquiring the HIV infection. The study found, however, that there existed denominational differences and that churches where participation was high were the same churches likely to influence protective behaviour. The explanation provided from qualitative findings suggested that the ability of these churches to minimise risky sexual behaviour was found in the Intensive Social Spaces that churches and their members constructed. The study concluded that the ability of churches to minimise risky sexual behaviours resulted from an individual negotiating losing the benefits provided by fellow members of the church when she/he ceases to be a member. / Thesis (Ph.D.)-University of KwaZulul-Natal, Durban, 2013.

Background: Prevention of Mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) remains a significant challenge in resource-poor settings despite the advances in antiretroviral (ARV) treatment. HIV-1 infected individuals are able to achieve viral control naturally, however the underlying mechanisms of immunological control in children remains poorly understood. This study was conducted from 2006 to 2010 to investigate correlates of immune control in HIV-1 clade C infected mother-child pairs in the absence of ARVs. Genotypic and phenotypic viral characteristics, cellular immune responses to HIV-1 and host genetics were characterized and correlated with clinical markers of disease progression. Materials and Methods: To achieve the objectives of the study, three cohorts of mother-child pairs were investigated. The first cohort included 60 untreated mother-child pairs and a further ten uninfected children as controls. The second cohort comprised of ARV treated pairs (n=60). The third cohort consisted of 374 mothers and 374 children (infected, exposed uninfected, HIV negative). Plasma viral loads and absolute CD4+ T cell counts were routinely performed in all three cohorts. HIV-specific CD8+ T cell responses were analyzed by interferon gamma (IFN-γ) enzyme linked immunosorbent spot (ELISpot) assays. Viral replicative fitness was assessed using a green fluorescent protein reporter cell line (GFP).Multi-parameter flowcytometry allowed for the investigation of T cell regulation, exhaustion and activation using CD127/CD25, TIM-3/PD-1 and HLA-DR/CD38 markers respectively. IL-10 promoter single nucleotide polymorphisms (SNPs) at positions -592 and -1082 were determined by TaqMan allelic discrimination assays. Plasma IL-10 levels were measured using a luminex assay. Results: To describe the CTL responses elicited to various regions of the HIV proteome in HIV-infected treatment naïve children. Sixty children under one year of age in the untreated cohort were analyzed for CTL responses spanning the HIV genome, for which only 30 had detectable responses. There was no significant difference in viral load between respondersand non-responders (p=0.2799). The responders predominantly targeted Nef (49%), Gag (17%) and Env (14%) regions. Markers of T cell exhaustion and regulation and theirrelationship to markers of disease progression, were next investigated as these parameters may explain the inability of T cells to effectively control HIV infection. T cell phenotyping compared treated, untreated and uninfected subgroups. In infected children, CD8+ T cells were significantly higher for both the inhibitory marker TIM-3 (p=0.001) and exhaustion marker PD-1 (p=0.0001) compared to uninfected children. Median expression of TIM-3 was higher on CD8+ T cells (46%) compared to CD4+ T cells (20%). TIM-3 and PD-1 expression on T cells were maintained at high levels over time. The frequency of absolute Tregs (p=0.0225) were found to be significantly higher in untreated compared to treated children. HLA-DR+CD38+ on CD8+ T cells were significantly up-regulated in untreated children compared to treated (p=0.002) and uninfected children (p=0.0177). HLA-DR+CD38+ was also significantly higher in children less than 6 months compared to older children on CD4+ (p=0.0437) and CD8+ T cells (p=0.00276). Interestingly, we observed a significant negative correlation between magnitude of CTL response and CD25+CD127- (p=0.0202; r=-0.7333) as well as HLA-DR+CD38+ (p=0.0408; r=-0.5516) on CD8+ T cells. IL-10 is an important immunoregulatory cytokine that has been shown to affect the outcome of chronic viral infections. IL-10 polymorphisms have previously been associated with IL-10 levels and HIV-1 outcomes in adults. Polymorphisms associated with different levels of IL-10 production and their relationship with transmission, markers of disease progression and immune responses were next investigated in this mother-child HIV transmission setting. Genetic analysis of IL-10 in cohort three revealed that HIV-1 acquisition was not associated with either IL10 -592 (AA/CA vs CC) or IL10 -1082 (AA/AG vs GG) single nucleotide polymorphisms (SNPSs). There was a significant association between IL10 -1082 and HIV-1 transmission (p=0.0012). No correlation was observed between IL10 -592 (p=0.4279) or IL10 -1082 SNPs (p=0.6361) and mortality rates in children. IL10 -592C was associated with an elevated magnitude of IFN-γ CD8+ T cell response compared to IL10 -529A (p=0.0071). We found a significant positive correlation between IL-10 plasma levels and viral loads (p=0.0068; r=0.4759) and the ages of the children (p=0.0312; r=0.1737). Conclusion: CD8+ T cell responses and viral fitness did not explain differences in disease progression in selected HIV-1 untreated clade C transmission pairs. T cell activation and regulatory markers influence CTL immune responses resulting in poor clinical outcome. IL10 -1082 polymorphisms may be used as a predictor of HIV-1 transmission. The association between increased IL-10 plasma levels and high viral loads suggest that IL-10 contributes to immune dysfunction in paediatric HIV-1 infection. This study has extended our understanding of immunological and genetic correlates of mother-to-child transmission and disease outcome in ARV naïve (naturally controlling) and HIV treated infected children. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.

By knowing the incidence of an infectious disease, we can ascertain the high risk factors of the disease as well as the e ectiveness of awareness programmes and treatment strategies. Since the work of Hugo Muench in 1934, many methods of estimating the force of infection have been developed, each with their own advantages and disadvantages. The objective of this thesis is to explore the di erent compartmental models of infectious diseases and establish and interpret the parameters associated with them. Seven models formulated to estimate the force of infection were discussed and applied to data obtained from CAPRISA. The data was agespeci c HIV prevalence data based on antenatal clinic attendees from the Vulindlela district in KwaZulu-Natal. The link between the survivor function, the prevalence and the force of infection was demonstrated and generalized linear model methodology was used i to estimate the force of infection. Parametric and nonparametric force of infection models were used to t the models to data from 2009 to 2010. The best tting model was determined and thereafter applied to data from 2002 to 2010. The occurring trends of HIV incidence and prevalence were then evaluated. It should be noted that the sample size for the year 2002 was considerably smaller than that of the following years. This resulted in slightly inaccurate estimates for the year 2002. Despite the general increase in HIV prevalence (from 54.07% in 2003 to 61.33% in 2010), the rate of new HIV infections was found to be decreasing. The results also showed that the age at which the force of infection peaked for each year increased from 16.5 years in 2003 to 18 years in 2010. Farrington's two parameter model for estimating the force of HIV infection was shown to be the most useful. The results obtained emphasised the importance of HIV awareness campaigns being targeted at the 15 to 19 year old age group. The results also suggest that using only prevalence as a measure of disease can be misleading and should rather be used in conjunction with incidence estimates to determine the success of intervention and control strategies. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2013.

HIV/AIDS has been an obstacle to socio-economic development and a major cause of loss of human life. It has also caused vast inequities and frustration to the public health sector. One of the significant efforts made by the public health sector to combat the epidemic is the implementation of a mandatory HIV/AIDS testing policy to scale-up HIV treatment. This dissertation examines the impact of this policy on the human rights of people infected with and affected by HIV/AIDS. Coercive government policies aimed at controlling the AIDS pandemic often infringe on the rights of individuals known to be or suspected of living with HIV/AIDS and this decreases the effectiveness of public health measures. The research methodology involved the study of written literature and a comparative literature study of the law and practice obtaining in South Africa, Uganda and Canada. It revealed that voluntary testing is effective and suitable in South Africa. This dissertation aimed to show that any public health approach that aims to achieve a comprehensive prevention strategy must be consistent with respect for human rights as enshrined in regional and international human rights law. Public health and human rights should, therefore, not be regarded as opposing forces; rather they should be seen as a unified system of protection of human welfare under the Bill of Rights and the Constitution. The solution to the crisis lies not only in testing every single person but also requires a shift of focus to more pressing issues that include gender equality, stigma and discrimination; prioritizing human rights, institutional capacity and resources; and an end to extreme poverty. A human rights-based approach to HIV/AIDS testing, such as the Voluntary Counselling and Testing (VCT) is recommended. Therefore, failure to adhere to the core principles of testing - which are informed consent, counselling and confidentiality of the test result - will only hinder the global fight against HIV/AIDS. The rights of those affected by HIV/AIDS need to be protected in order to address public health imperatives. This can be done through the use of the law as an instrument of social change as well as education and awareness. Key words, HIV/AIDS, mandatory testing, Voluntary Counselling and Testing, public health, human rights-based approach.

The aim of this study was to explore and describe HIV and AIDS workplace programmes and policies (WPPs) in the tourism industry of Nelson Mandela Bay Municipality (NMBM) in South Africa. This study adopted a quantitative and qualitative approach, in other words, a mixed approach. The reason for using more than one method of inquiry was to obtain a deeper understanding of the tourism industry of NMBM in terms of examined behaviour, and of the meaning of occurrences in the industry. To gather qualitative data concerning HIV and AIDS programmes, key informant stakeholders in the tourism industry at global, national, provincial, and local levels were identified to conduct in-depth interviews. These respondents were selected using the non-probability sampling method of quota sampling. This is a type of stratified sampling in which the selection of the strata within the sample is not random, but rather is typically left to the discretion of the interviewer (Wienclaw, 2015). One respondent for each level of the industry was selected, resulting in four key informant stakeholders participating in the qualitative research component of this study. The initial criterion for participation in the quantitative portion for this study was that tourism businesses based in NMBM must be able to produce robust evidence of HIV and AIDS WPPs. The researcher selected the probability sampling method of stratified random sampling with proportional allocation. This technique considers the known characteristics of the population (Wienclaw, 2015). A database of tourism businesses was obtained from the local tourism organisation, who are members of the governing body for local tourism. This database was cleaned, to eliminate any data that did not meet the participation criterion for the study. Ten per cent of the total number of businesses in the cleaned database were sampled. The simplest approach to sampling is to merely randomly select from the population by, for example, having a computer choose names at random from a list, or by selecting names from a hat (Wienclaw, 2015). Therefore, every fifth business listed on the sampled database was selected to participate. Unfortunately, surveys tend to have notoriously low return rates, and people are frequently reluctant to give out information over the phone. This was also the case for most of the tourism businesses in the sample. When emailed or telephoned, they refused to participate for various reasons. Some stated that HIV does not affect their business; others reported that their businesses were too small and therefore they could not afford to implement these programmes. Some businesses were hearing about the WPP for the very first time, while several others responded with simple disinterest in participating. The findings of the study are that although tourism is viewed as an important industry that contributes to the economy, tourism businesses do not include any intervention programmes with which to respond to the threat of HIV and AIDS to their businesses. Additionally, there is neither leadership nor support from any level of the tourism industry, to create a conducive environment for the adoption of HIV and AIDS WPPs by tourism businesses. The primary reason for the lack of uptake of these programmes is ignorance across cascading levels of the tourism industry, which includes tourism businesses. Additionally, a number of perceived barriers, such as size of business, are cited as the reasons why tourism workplaces in the NMBM fail to participate in HIV and AIDS WPPs. It is anticipated that this study will create further awareness of HIV and AIDS WPPs, in an industry that seems to have limited knowledge about such programmes. This study will also provide guidance regarding the requirements to implement effective HIV and AIDS WPPs.

Thesis (Master of Nursing)--Cape Peninsula University of Technology, 2019 / The HIV/AIDS epidemic is a public health concern worldwide. An estimated 36.9 million people are living with HIV/AIDS with about two million new infections annually. An approximate ten million people have died of AIDS-related causes since the beginning of the epidemic. Sub-Saharan Africa (SSA) is the most affected sub-region, with approximately 71% of all People Living with HIV/AIDS (PLHWA) from mid-2016. In SSA, the epidemic has become a socioeconomic burden on developing countries. The literature review established a high prevalence of HIV/STIs among mineworkers and in mining communities, despite the increase in education on HIV/AIDS prevention in the media and public fora. The aim of the study was to explore and describe the knowledge and experiences of mineworkers on the prevention of HIV/AIDS in a mining community in Ghana. An exploratory, descriptive and contextual design was applied. Data collection was done using semi-structured individual interviews. The population in this study was mineworkers who come from other districts and regions in Ghana to live in the catchment community without their families because of employment. Seventeen (17) participants were interviewed, after purposive sampling was done. Interview transcriptions and manual coding were done by the researcher using Microsoft Word. The raw data was coded and sorted into themes and sub-themes and analysed by using Braun and Clarke's six-phase framework for thematic analysis. The Health Belief Model (HBM), a theoretical framework was applied to the study to predict and explain whether a person will perform an action necessary for preventing a HIV/AIDS or not. Findings from this study revealed that although there has been an increase in education on HIV/AIDS across the country and through workplace HIV/AIDS programmes, mineworkers lacked knowledge of HIV/AIDS, as they still had misconceptions about HIV/AIDS, especially regarding the mode of transmission and preventive measures. A strong recommendation was made to embark on a continuous and intensive HIV/AIDS education programme that will be focused on the knowledge needs of mineworkers to dismiss the misconceptions and improve their knowledge level. This will empower them to know the benefits of prevention and ultimately change their behaviour.

Youth engage in high-risk sexual behaviors, placing them at risk for human immunodeficiency virus, sexually transmitted infections, unintended pregnancy, and other unwanted sexual and reproductive health (SRH) outcomes. Alarmingly, Black and Hispanic/Latinx adolescents who are houseless are more likely to engage in high-risk sexual behaviors and are disproportionately affected by these outcomes. Sex education can equip Black and Hispanic/Latinx adolescents who are houseless with the knowledge and skills to protect their SRH. Disturbingly, sex education is not mandated to be taught in all U.S. schools. Therefore, it is critical for parents to provide sex education to their teens. However, most parents do not possess the knowledge and skills to educate their teens about sex education. Specifically, parent-child communication about the topic may be lacking. Research shows that parent-child communication regarding sex and dating is associated with fewer risky sexual behaviors. Thus, parents must be armed with the knowledge and skills necessary to help them effectively communicate evidence-based sex education topics to their teens. Borrowing from the case study methodology, the overarching purpose of this dissertation was to elicit parental input for the design, feasibility, and content of a potential parent-based sex education program among parents living or who lived in homeless shelters and transitional housing in New York City (NYC). Specifically, this study aimed to (i) conduct a scoping review on parent-based sex education interventions that include parental involvement in the program and parental input in the planning or design process; (ii) administer needs assessment questionnaires to collect information on program input and parental attitudes, beliefs, and views about sex education and the program; and (iii) conduct semi-structured qualitative interviews to further collect specific information on program input and understand parental attitudes, beliefs, and views about sex education and the program. The scoping review of the literature confirmed the absence of parent-based sex education programs in homeless shelters and transitional housing in the country. From the needs assessment questionnaires and semi-structured interviews, participants highlighted the need for an accessible, convenient, and flexible parent-based sex education program. Furthermore, parents yearned for interactive and fun ways of learning sex education topics with various participants. Lastly, study participants endorsed comprehensive and inclusive information about life skills and sex education being included in the parent-based program.

Thesis (M.Med. (Family Medicine)) -- University of Limpopo, 2017 / Objectives: To assess adherence to Isoniazide Prevention Therapy (IPT) among HIV positive patients in Rethabile Community Health Centre in the Capricorn District of the Limpopo Province. Methods: A cross-sectional study with qualitative and quantitative data collection methods was conducted among HIV positive patients in Rethabile Community Health Centre from January 2013 to December 2013. Consecutive sampling was used to select 90 participants. Adherence was assessed using patient self-rated adherence to IPT, and confirmed by urine tests for isoniazid metabolites. Data was collected using an interviewer administered questionnaire. Information was also obtained from health care works regarding the perception about reason for non- adherence to IPT. Data was analysed using STATA software and thematic analysis. Results: Self-rated adherence to IPT among the participant was 80% where as urine test was positive for Isoniazid metabolites in 73%. While 84% of participants reported that transportation was the main reason for non adherence, 70% also reported distance from the health care as their main reasons for non-adherence to IPT. However, health care providers reported that many patients do not adhere to treatment due to: Lack of money for transport, missed clinic appointment due to rain and fear of losing jobs, use of traditional medicine, wrong belief about IPT, medicine side effects and alcohol consumption. Conclusion: Self – rate adherence to IPT was suboptimal and appears over – estimated among study participants. Interventions to improve adherence to IPT must ensure easy access to healthcare facilities, address wrong perceptions and promote healthy social behaviours

Thesis (DPhil)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Disabled adolescents are vulnerable to HIV infection particularly in countries like South Africa which has one of the largest HIV epidemics in the world. Like able-bodied adolescents, adolescents with disabilities are at a critical stage of their psychosocial and sexual development. They may be at risk of sexual abuse as perpetrators may believe that they are incapable of defending themselves or reporting the crime to the authorities. Deaf or hard of hearing adolescents are vulnerable to HIV/AIDS due to similar risk factors to other disabled adolescents. They also face difficulties in communicating with hearing people and receiving information in sign language, and they share characteristics with minority ethnic groups, which make them hard to reach for HIV prevention campaigns. There is a paucity of research in South Africa investigating the role of schools for Deaf and hard of hearing adolescents in delivering appropriate HIV and sexuality education to their learners. This thesis is an exploratory study and investigates HIV prevention issues for Deaf or hard of hearing adolescents in South Africa. More specifically, I aim to determine the ways in which participants believe schools, health systems and other organizations contribute or fail to contribute to the HIV/AIDS prevention needs of Deaf and hard of hearing adolescents. The study includes qualitative interviews with employees of Deaf organizations, educators of Deaf and hard of hearing adolescents, parents of Deaf and hard of hearing adolescents and Deaf and hard of hearing adolescents themselves in relation to sexuality and HIV related issues. Results indicate that Deaf organizations have an interest in the HIV prevention needs of the Deaf community and in Deaf schools. However they have experienced obstacles in delivering HIV education to learners. These obstacles include communication barriers as well as the fact that religious environments in some of the schools may not always be experienced as conducive to HIV education. Although all educators of Deaf and hard of hearing adolescents interviewed in the previous phase of the study were aware that their learners are at risk of HIV/AIDS, some educators of Deaf and hard of hearing adolescents were constrained by the same issues of morality and religious conviction discussed in the first phase. Some participants had made efforts to produce appropriate HIV and sexuality materials for Deaf learners. Parents of Deaf and hard of hearing adolescents were affected by communication barriers with their children but seemed unaware of the religious ethos of many of the schools their children attended. The Deaf and hard of hearing adolescents knew they could be at risk of HIV/AIDS. Some displayed poor knowledge of HIV transmission. There are a number of issues to be addressed if schools for Deaf and hard of hearing learners are to provide adequate HIV/AIDS prevention information to their learners. / AFRIKAANSE OPSOMMING: Gestremde adolessente is kwesbaar vir MIV-infeksie veral in lande soos Suid-Afrika wat een van die grootste MIV-epidemies ter wêreld het. Soos nie-gestremde adolessente is gestremde adolessente in 'n kritieke stadium van hul psigososiale en seksuele ontwikkeling. Oortreders van seksuele misbruik mag gestermde adolessente beskou as sagte teikens aangesien daar die persepsie is dat hulle minder in staat is om hulself te verdedig of minder geneig is om `n misdaad by die owerhede te rapporteer. Dowe of hardhorende adolessente is kwesbaar vir MIV / VIGS vir redes war soortgelyk is aan die van ander gestremde adolessente. Dowe of hardhorende adolessente vind dit problematies om met horende (nie-gestremde) mense te komminikeer, inligting in gebaretaal te ontvang, en deel eienskappe met etniese minderheidsgroepe wat dit moeilik maak om hulle deur middel van MIV voorkomingsveldtogte te bereik. Daar is 'n gebrek aan navorsing in Suid-Afrika oor die rol wat skole vir dowe en hardhorende adolessente speel in die lewering van geskikte MIV en seksualiteitsopvoeding. Hierdie proefskrif verken en ondersoek kwessies met betrekking tot MIV-voorkoming onder dowe en hardhorende adolessente in Suid-Afrika. Meer spesifiek was die doel van hierdie studie om vas te stel wat deelnemers se persepsies is oor die bydrae of gebrek aan bydrae van skole, gesondheids-en ander organisasies tot die behoeftes van dowe en hardhorende adolessente wanneer dit kom by die voorkoming van MIV/ VIGS. Gedurende die studie is kwalitatiewe onderhoude met die volgende deelnemers gevoer: die werknemers van organisasies vir dowes; die onderwysers van dowes, ouers van dowe en hardhorende adolessente. Die onderhoude het hoofsaaklik gehandel oor seksualiteit en MIV-verwante kwessies onder gehoor gestremde adolessente. Die studie het bevind dat organisasies vir dowes `n belangstelling toon in die behoeftes van dowe gemeenskappe en skole vir dowes wanneer dit kom by MIV-voorkomming. Hulle het dit egter met tye problematies gevind om leerders op te voed oor MIV weens verskeie hindernisse. Hierdie hindernisse sluit in kommunikasie-hindernisse sowel as die godsdienstige etos wat wat in sommige skole teenwoordig is en wat nie altyd bevorderlik is tot MIV-onderrig nie. Alhoewel al die opvoeders van dowe en hardhorende adolessente gedurende die vorige fase van die studie aangedui het dat hul wel bewus is van leerders se risiko vir MIV/VIGS word sommige van hulle beperk deur bogenoemde kwessies van moraliteit en godsdienstige oortuiging. Sommige deelnemers het daarop gedui dat hul pogings aangewend het om geskikte materiaal te produseer wat spreek tot MIV en seksualiteit onder dowe leerders. Ouers van dowe en hardhorende adolessente was bewus van en word beïnvloed deur kommunikasie-hindernisse, maar was nie bewus van die godsdienstige etos van die skole wat hul kinders bywoon nie. Dowe en hardhorende adolessente was bewus daarvan dat hulle die risiko loop om MIV / vigs op te doen, maar dit blyk dat sommige min kennis dra oor MIV-oordrag. Daar is 'n aantal kwessies wat aangespreek moet word voordat skole vir dowes en hardhorendes instaat sal wees om geskikte MIV/VIGS voorkomingsprogramme aanbied te bied wat voldoen aan die behoeftes van leerders.

Thesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: In 2007, AIDS caused an estimated 2.1 millions deaths worldwide; about 70% in sub-Saharan Africa. HIV preferentially targets activated CD4 T cells, expressing the major HIV receptor CD4, as well as the major chemokine coreceptors CCR5 and CXCR4. These coreceptors play a prominent role during HIV cell entrance phase, HIV transmission and also disease progression. They have been found to be differentially expressed by CD4 T cell subsets. Tuberculosis coinfection may enhance immune activation in vivo thus accelerating HIV disease progression and has become a major challenge in the control of TB in Africa. Introduction of HAART has reduced disease progression to AIDS, as well as risk of further morbidity and mortality. HAART results in a rapid decline of viral load and an initial increase of peripheral CD4 count, however little is known on the effect of HAART in regulation of coreceptor expression, immune activation status and CD4 T cell subset distribution in HIV infection and HIV/TB coinfection. This study is a cross-sectional analysis of coreceptor expression, immune activation status and CD4 T cell subpopulation distribution in South African HIV and HIV/TB coinfected patients before and after ARV. A total of 137 South African individuals were investigated, comprising 15 healthy normal donors (healthy subgroup), 10 patients with active pulmonary tuberculosis (PTB subgroup), 33 HIV-1 positive patients without active PTB (HIV subgroup), 23 positive patients with active PTB (HIV/PTB subgroup), 36 HIV-1 positive patients on ARV (HIV on ARV subgroup) and 20 HIV-1 positive patients with active PTB on ARV (HIV/PTB on ARV subgroup). CD4 absolute count and plasma viral load were determined for all donors. Freshly isolated PBMC were classified by flow cytometry into the following CD4+ T lymphocyte subsets: naïve (CD45+, CD27+), effector memory (CD45-, CD27-), central memory (CD45-, CD27+), and effector (CD45+, CD27-). Coreceptor expression and activation status was assessed by CCR5, CXCR4 and CD38 expression on CD4 T cell subsets. HIV, TB and HIV/TB coinfection was associated with a decrease in percentage CCR5+ T cells as compared to healthy controls, with the HIV/TB group showing the most extensive decrease. In treatment naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 as determined by mean fluorescence intensity in HIV/TB co-infection compared to HIV infection alone. The percentage of antigen-experienced cells was higher in the HIV/TB co-infected group compared to the HIV group. The percentage of naïve T cells was decreased in both the HIV infected and the HIV/TB co-infected groups compared to healthy controls. HIV patients with more than 6 months of ARV showed decreased CCR5 and CD38 surface level expression in the HIV and the HIV/ TB co-infected subgroups. An increased percentage of naïve T cells was observed in the HIV infected subgroup, but not in the HIV/TB subgroup, similarly, a decreased percentage of antigen-experienced cells was observed in the HIV subgroup, but not in the HIV/TB co-infected subgroup. A positive correlation was found between CCR5 and CD38 expression, and CXCR4 and CD38 expression (Spearman coefficient of correlation respectively: r=0.59, p<0.001 and r=0.55, p<0.001). Furthermore we found plasma viral load positively associated with CD38 expression (r=0.31, p<0.001) and percentage activated CCR5+ expressing CD4 T cells positively related to viral load (r=0.31, p<0.001). Percentage naïve CD4 T cells was positively associated with CD4 count (r=0.60, p<0.001) and negatively correlated to viral load (r=-0.42, p<0.001). These results indicate that TB coinfection exacerbates certain aspects of dysregulation of CD4 T cell homeostasis and activation caused by HIV infection. In addition, ARV-associated decrease in coreceptor expression, immune activation status and a normalisation of CD4 T cell subset distribution was observed in HIV infected individuals, but not in HIV/TB coinfection. Despite viral suppression after ARV treatment, the decline in the immune activation marker CD38 and coreceptor CCR5 expression, increase in percentage naïve CD4 T cells and decrease of antigen-experienced cells did not reach the levels displayed in the healthy control group. This may indicate that ongoing (albeit reduced) T cell immune activation may occur in the presence of ARV. Further longitudinal studies are needed to closely monitor immune activation during ARV treatment. This study highlighted an association of TB disease with immune activation in HIV infection, the importance of T-cell activation in HIV pathogenesis and its impact on ARV treatment. Further studies are needed to identify causative factors that may lead to a persistent immune activation status during ARV treatment, and how TB coinfection confounds normal responses to ARV. / AFRIKAANSE OPSOMMING: In 2007 was ongeveer 2.1 miljoen sterftes wêreldwyd veroorsaak deur VIGS; ongeveer 70% in Sub-Sahara Afrika. CD4 T selle is die hoof teiken van MIV, aangesien dit die primêre CD4 reseptor, sowel as een of beide van die vernaamste chemokien koreseptore CCR5 en CXCR4 vrystel. Hierdie koreseptore speel ‘n prominente rol wanneer die MIV die sel binnedring, asook tydens MIV oordrag en verloop van die siekte. Dit word ook deur verskillende fraksies van CD4 T selle vrygestel. Gelyktydige TB infeksie mag immuunaktivering in vivo verhoog en dus die siekeproses versnel. MIV het ‘n groot uitdaging geword in die beheer van TB in Afrika. Bekendstelling van HAART het die ontwikkeling van VIGS vertraag, asook die risiko van verdere morbiditeit en mortaliteit. HAART veroorsaak ‘n vinnige afname in virale lading ‘n toename in CD4 telling, hoewel die spesifieke invloed van HAART op die regulering van koreseptor vrystelling, immuunaktivering en verspreiding van CD4 fraksies in MIV en MIV/TB infeksies nog onduidelik is. Hierdie studie het gepoog om koreseptor vrystelling, immuunaktiveringstatus en die verspreiding van CD4 subpopulasies in pasiënte met MIV en MIV/TB voor en na ARV behandeling te ondersoek. ‘n Totaal van 137 Suid-Afrikaanse individue is ondersoek en die studiegroep het bestaan uit 15 normale persone (gesonde subgroep), 10 pasiënte met aktiewe pulmonale TB (PTB subgroup), 33 MIV positiewe pasiënte sonder PTB (MIV subgroep), 23 MIV positiewe pasiënte met aktiewe PTB (MIV/PTB subgroep), 36 MIV positiewe pasiënte op ARV (MIV op ARV subgroep) en 20 MIV positiewe pasiënte met aktiewe PTB op ARV (MIV/PTB op ARV subgroep). Absolute CD4 telling en virale ladings was bepaal vir alle deelnemers. Vars geïsoleerde perifere bloed mononukleêre selle is geklassifiseer deur middel van vloeisitometrie as die volgende CD4 T limfosiet subgroepe: naïewe selle (CD45+, CD27+), effektor geheueselle (CD45-, CD27-), sentrale geheueselle (CD45-, CD27+), en effektor selle (CD45+, CD27-). Koreseptor vrystelling en aktivering was beoordeel volgens CCR5, CXCR4 en CD38 vrystelling op CD4 T sel subgroepe. HIV, TB en MIV/TB ko-infeksie is geassosieer met ‘n afname in die persentasie CCR5+ T selle, vergeleke met gesonde kontroles, waar die MIV/TB subgroep die grootste afname getoon het. In onbehandelde pasiënte het die CD4 T selle verhoogde vrystelling van CCR5 en CD38 op die oppervlakte getoon en dit is bevestig deur die gemiddelde fluoresserende vii intensiteit in die MIV/TB subgroep vergeleke met die subgroep met slegs MIV. Die MIV/TB subgroep het verder ook ‘n verhoogde persentasie totale geheue T selle getoon vergeleke met die MIV subgroep. Die persentasie naïewe T selle was egter verlaag in beide die MIV en MIV/TB subgroepe vergeleke met normale kontroles. MIV pasiënte wat langer as 6 maande op ARV behandeling was in beide die MIV en MIV/TB subgroepe, het ‘n verlaagde vrystelling van CCR5 en CD38 op die oppervlakte van die CD4 selle getoon. ‘n Verhoogde persentasie naïewe T selle het in die MIV subgroep voorgekom, maar nie in die MIV/TB subgroup nie. ‘n Soortgelyke tendens is gevind waar die persentasie totale geheueselle verlaag was in die MIV subgroep, maar nie in die MIV/TB subgroep nie. ‘n Positiewe korrelasie is gevind tussen CCR5 en CD38 vrystelling, asook CXCR4 en CD38 vrystelling (Spearman korrelasie koëffisiënt: r=0.59, p<0.001 en r=0.55, p<0.001 onderskeidelik). Verder het die plasma virale lading ‘n positiewe assosiasie getoon met CD38 vrystelling (r=0.31, p<0.001) en die persentasie geaktiveerde CCR5+ vrystellende CD4 T selle met virale lading (r=0.31, p<0.001). Die persentasie naïewe CD4 T selle het ‘n positiewe assosiasie getoon met CD4 telling (r=0.60, p<0.001) en ‘n negatiewe korrelasie met virale lading (r=-0.42, p<0.001). Volgens hierdie resultate vererger TB ko-infeksie sekere aspekte van die disregulasie van CD4 T selhomeostase en aktivering as gevolg van MIV infeksie. Verder kon ‘n ARVgeassosieerde afname in koreseptor vrystelling, immuunaktivering en normalisering van CD4 T sel fraksies bespeur word in die MIV subgroep, maar nie in die MIV/TB subgroep nie. Ten spyte van virale onderdrukking veroorsaak deur ARV behandeling, het die afname in die immuunmerker CD38 en koreseptor CCR5, toename in die persentasie naïewe CD4 selle en afname in totale geheue CD4 T selle nie die vlakke van die normale kontrolegroep bereik nie. Dit is moontlik dat volgehoue verlaagde T sel immuunaktivering nog steeds mag plaasvind in die teenwoordigheid van ARV. Verdere longitudinale studies is nodig om immuunaktivering tydens ARV behandeling te monitor. Hierdie studie het die belangrikheid van T sel aktivering in MIV patogenese en dit impak daarvan op ARV behandeling beklemtoon. Verdere studies is nodig om moontlike oorsake of bydraende faktore te identifiseer wat tot volgehoue immuunaktivering tydens ARV behandeling kan lei, asook tot mate waartoe TB ko-infeksie kan inmeng met die normale werking van ARV behandeling.