HIV is a prominent infection in society and its health implications are seen in the paediatric wards daily. Despite its multi-system effect on the body, it particularly results in many respiratory infections. Effective understanding of the disease profile and management of patients with HIV relies on correct statistics and proper use of resources. Since the introduction of anti-retrovirals in 2004 in South Africa, the impact of HIV/AIDS on respiratory disease needs to be re-evaluated. The purpose of the study is to understand the disease profile of children with HIV/AIDS with regard to the presence of respiratory conditions with which they present, the need for chest physiotherapy and their health status. Of the 125 patients recruited in this study 55% were boys, average age was 20.55 months (SD= 23.64), average length of hospital stay of 2 ½ weeks (mean=18.76, SD=19.19), 80% discharged and 9.6% died. The most common respiratory conditions presented included bacterial pneumonia (66.4%), tuberculosis (48%) and pneumocystis jirovecii pneumonia (23.2%). The least common condition was lymphoid interstitial pneumonitis (4.8%). Two thirds of the children (68.8%) presented with a high burden of disease. Physiotherapy treatment was indicated for 96% of the patients mainly due to excess secretions and poor air entry. About forty percent (40.8%) of children were taking anti-retrovirals with an average length of use of 9.81 months (SD=11.61). Three out of four (75%) mothers were not involved in a PMTCT program. The analysis of immune status revealed a mean CD4 percentage 17.33% (SD=10.96), CD4 absolute 631.36 cell/mm3 (SD=610.36) and viral load 2.6 million copies /ml (SD=9.08 million copies/ml). A higher burden of disease was related to the use of anti-retrovirals, a lower immunity, female patients, longer length of hospital stay and incidences of mortality occuring at later periods of hospital stay. Results of this study highlight the characteristics of respiratory disease burden among children with HIV in a South African setting in a post HAART era.

Ph.D., Faculty of health Sciences, University of the Witwatersrand, 2011 / The rate of HIV infection in South Africa remains high despite the continued efforts to prevent its transmission. Conversely, the rate of AIDS related mortality has been on the decline since the country introduced its comprehensive care and treatment plan. Among other things, the comprehensive plan seeks to coordinate activities to prevent further infection and facilitate health and social support services for the infected and affected. Despite this, South Africa has an increasing number of people living with HIV (PLWH) and is home to the largest population of HIV infected people in the world. Consequently, there is a growing shift of focus of HIV/AIDS response programmes from issues of survival and death prevention to the quality of survival of PLWH. This point accentuates the need for patient evaluation of their wellbeing and quality of life in the context of the country’s HIV/AIDS response services. There are HIV-specific quality of life assessment tools like the WHOQOL-HIV, but these tools are subject to cultural variations and have not been validated across South Africa’s multicultural society. The available tools are often too long and cannot be used in routine care and support of PLWH. In the absence of validated and efficient quality of life assessment tools, there is over reliance on biomedical markers of HIV/AIDS like the CD4 cell count and viral load. These biomedical indicators do not provide a complete view of the impact of the disease given the multidimensional consequences of HIV and AIDS. With the above background, this study sought to firstly explore the health related quality of life (HRQOL) and the experiences of PLWH in seeking care and support services, and secondly, to validate the ability of the WHOQOL-HIV instrument to measure the health related quality of life of PLWH among the three cultural groups in Limpopo Province over a specified time period. The study was divided into two, with the first and second studies using qualitative and quantitative research approaches respectively. Both studies divided their participants into three groups, with each group representing each of the three main ethnic groups in Limpopo Province (Pedi, Tsonga and Venda). The qualitative study used focus group discussions (FGDs) iii to solicit information and grounded theory to guide its participant selection, number of FGDs conducted and the interpretation of its findings. The second study was a longitudinal follow up of participants in the three groups from the point of treatment initiation over 12 months. In the second study, there were three points of data collection (baseline, six and twelve months). The participants were conveniently selected and interviewed repeatedly with the WHOQOL-HIV and MOS-HIV instruments. The study findings were mostly presented in tables and t-tests and ANOVA were used to compare quality of life scores in different groupings while correlation and limits of agreements were used to establish instrument validity. Item-total correlation coefficient and alpha if item deleted, was used to explore the possibility of shortening the WHOQOL-HIV instrument in an attempt to suggest a shorter and more user friendly version of the instrument. The key findings of the qualitative study are that the quality of life of PLWH in Limpopo is determined by three groups of factors (physical, mental and external). The frequency and severity of these factors are determined by the participants’ duration on treatment, disclosure of their HIV status and socioeconomic status. The physical factors were mostly constituted by biological symptoms of the disease. The most commonly cited symptoms were diarrhoea, pain and fatigue. The study also noted marked differences in the occurrence of the symptoms through the trajectory of the disease revealing four main stages: pre-treatment; treatment initiation; early treatment; and treatment maintenance stages. The study also noted that the impact of the determinants of the quality of life on an individual is influenced by intervening factors which can be altered by a set of modifying factors. In all, the quality of life determinants identified by this study replicates those that constitute the WHOQOL-HIV instrument. This finding hence obviates the need for the modification of existing quality of life instruments to suit the three South African ethnic groups investigated by this study. The quantitative study showed high reliability of the WHOQOL-HIV among the three ethnic groups with alpha ranging from 0.79 to 0.94 in the six domains of the instrument. The study iv also showed that the quality of life varied by socio-demographic characteristics such as ethnic group, sex, marital status, number of children, employment status and membership of HIV/AIDS support groups. The observed difference reflects poor financial capacity and activity tolerance across the various categories of the participants and at different times. While significant changes in the quality of life was noted between the baseline data and the six and twelve months data respectively, little or no improvements were seen between the six and twelve months data. The participants were actually more likely to have a better quality of life at six months when compared to their quality of life at twelve months. In the same manner, the median CD4 cell count and viral load were very similar at six and twelve months but differed significantly with the baseline reports. Over time and across cultural groups, the participants reported lower quality of life in the level of dependence domain and financial support subscale. There were little or no associations between the biomedical markers and HRQOL indicators. In addition, the quality of life tended to increase with increase in CD4 cell count. The validation of the WHOQOL-HIV using the MOS-HIV through a correlation of similar domains and their limits of agreement largely suggests that the WHOQOL-HIV is valid but both instruments are not exact replicas in their measurements. The multidimensional nature hypothesized by the original WHOQOL-HIV instrument study was also demonstrated by the factor analysis component matrix. Attempts to shorten the WHOQOL-HIV proved to be impossible as the items with highest item-total correlation varied with the participants’ duration on treatment. In conclusion, this study suggested the needs and factors that contribute to the quality of life of PLWH in Limpopo and how those factors can be harnessed through a set of modifying factors. With this, an individual’s quality of life is determined by the delicate balance between intervening and modifying factors. The linkages between the observed determinants of quality of life suggest a vicious circle where one determinant may exacerbate the effect of another determinant. The study also showed that the WHOQOL-HIV instrument is valid and reliable in measuring the quality of life of PLWH in the province. The observed poor to no associations between the health related quality of life indicators and the biomedical makers show that they cannot be direct proxies of each other. Finally, the study discourages any further shortening of v the WHOQOL-HIV instrument on the basis that HIV-infected people are not a homogenous group as their bio-psychosocial needs vary with time and their position along the trajectory of the disease.

Objectives: To determine the impact of human immunodeficiency (HIV) infection on rheumatoid arthritis (RA) disease activity. Patients & Methods: Retrospective record review of RA patients who HIV sero-converted, compared to a HIV negative RA control group. DAS28-ESR and -CRP scores were collected at the initial presentation (T0), time when HIV diagnosis made (TH) and the last clinic visit (TL). Results: Forty three HIV positive RA patients were included. At TL disease activity was similar between the groups, despite methotrexate (MTX) being continued in only 11.6% of the HIV group (vs. 83.7% in the control group, p=0.0002). In the HIV group, all clinical parameters improved except the ESR, which accounted for the significantly higher DAS28-ESR compared to the DAS28-CRP at TL (p=0.004). At TL only 13.9% HIV patients had ongoing moderate to high disease activity. Conclusion: Overall disease activity improved with HIV seroconversion in spite of stopping MTX in the majority of patients. The DAS28-ESR overestimated disease activity compared to DAS28-CRP following HIV seroconversion.

A Research Submitted to the Faculty of Health Sciences (School of Public Health), University of the Witwatersrand, in Partial Fulfilment of the Requirements for the Degree of Masters in Public Health in the field of Social Behaviour Change and Communication 27 May 2014 / Introduction: HIV/AIDS services are now given freely at public health facility level. They have been decentralized to the formal primary health facilities in the rural areas. Despite the efforts by the South African government, the utilization of those services remains a challenge. There are gender disparities in utilisation of HIV/AIDS services as females utilize the services in greater numbers compared to their male counterparts. The newly diagnosed seropositive men tend to disappear soon after HIV testing, only to appear in a formal health system when their immune system is seriously suppressed and at a more advanced WHO stage of disease. Therefore, the overall aim of this study was to explore the underlying perceptions and beliefs that influence utilization of HIV/AIDS services by newly diagnosed HIV positive men in Mbashe Sub-District of the Eastern Cape between January 2010 and March 2011 Methods: The study was conducted in the rural Mbashe Sub-District of the Eastern Cape Province and utilized a qualitative methodology. This qualitative approach relied on semi-structured in-depth interviews with newly diagnosed HIV positive men of 18-49 years of age who were either accessing or not accessing the HIV/AIDS services during January 2010 and March 2011.The participants were recruited through purposive sampling and 18 interviews were conducted in 6 different facilities at three different service levels. Interviews were audio-recorded and transcripts were subjected to thematic content analysis based on the Health Belief Model. Results: The results show that both groups of men reacted negatively to HIV positive status. The experiences during HIV Counselling and Testing were not linked to whether men could access services. The barriers to utilizing the available HIV/AIDS services included fear of stigma and discrimination, need for an alternative quick cure which delayed utilization of the services, the clinic as gendered space, compromised Provider-Initiated Counselling and Testing (PICT) model implementation, shortage of food, physical fitness and alcoholism. The facilitators for access included the need for survival, disclosure and social support, and cues to action like witnessing a relative dying due to HIV/AIDS related illness. However, the HBM model could not squarely explain the trends in accessing HIV service since few constructs were found to be relevant and also some issues that are outside the HBM model emerged. Conclusions: The study demonstrates that newly diagnosed men‟s utilization of the subsequent free HIV/AIDS services at the primary health care level is influenced by many factors . There are those factors that trigger men to utilize the services and those that deter them from accessing necessary HIV/AIDS services. The factors that influence their access to services are mainly within the multilevel framework which ranges from individual, family, community and societal factors. Therefore, the targeted interventions to address the issue should focus on addressing stigma and discrimination, policy change on training, recruitment and deployment of male nurses, integration of traditional/spiritual interventions within the mainstream of health services, correct implementation of the PICT model and encouraging couple counselling and testing. The Health Belief Model constructs, especially perceived severity, were not strongly linked to whether men accessed services or not.

Degree of Doctor of Philosophy in Medicine by research only A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the Degree of Doctor of Philosophy in Medicine. Johannesburg, 2014 / Introduction Patients with HIV infection frequently encounter oral candidiasis, caused by Candida species. However, factors responsible for Candida colonisation and development of oral candidiasis in these patients are controversial. This study investigated the effect of social and clinical factors on oral Candida colonisation in HIV positive women. In addition, virulence of these organisms during clinical infection, the role of non-albicans Candida and reinfections with C. albicans were investigated.

Introduction: Migrant and mobile seasonal farm workers face multiple challenges in preventing sexual transmission of HIV. They also fall beyond direct reach of district health promotion services and national HIV prevention communication interventions. HIV prevalence rates in rural farming communities are significantly higher than provincial averages. An integrated health promotion intervention was initiated in 2005 on commercial farms in Hoedspruit, Limpopo province, through the International Organization for Migration. In terms of HIV prevention the Hlokomela project’s key innovation was to employ a local process of participatory communication, with and within the farm worker community, in order to create a local context enabling of health promotion and within which efforts to prevent HIV could be more effective. The research sought to explore the social processes and actions related to the on-going process of dialogue at the core of the participatory communication process. The objective was to describe and analyse the role of dialogue during regular purposive face to face interactions with farm worker change agents, in promoting health and addressing vulnerability to HIV. Method: The study population comprised Hlokomela coordinators, farm worker change agents (Nompilos and Gingirikani) and key farm stakeholders from the 59 partner farms. Research was conducted in Hoedspruit, at the Hlokomela Wellness Centre and on a partner farm. A grounded theory approach was used for sampling: participants were selected through purposive sampling for the initial study sample, and theoretical sampling for the balance. Data was gathered monthly, in three stages between August and November 2010, through: 10 semi-structured in-depth individual interviews; 5 focus group discussions, and observation of 2 monthly meetings and a special event organised by the change agents. Data was analysed using a grounded theory approach. Findings: Farm workers perceive and experience the process of on-going dialogue in face to face interactions as being intertwined with other aspects of the intervention, in particular identification and action to enable access to health services. Hlokomela Coordinators guide and support the process as a means to empower a corps of primary farm worker Change Agents (Nompilos). Nompilos, in turn, apply the system to benefit and empower a wider group of farm worker as second level change agents (Gingirikani). Through this system farm workers have found ways to negotiate HIV-related stigma and cultural taboos on speaking about sex, and to address interpersonal tensions and violence, often gender related, on farms. They have come to consider themselves leaders and role models. Individuals have been enabled to define for themselves appropriate HIV-protective behaviours, and new HIV protective social norms which enable protective behaviours, have gained local currency. These norms include placing value on the opportunity and ability to communicate, to learn from each other, to develop different views, and to attain or protect family, physical and spiritual wellness. Discussion: The process of engagement and regular dialogue, nested in processes related to the other elements of the projects, has positively altered the material, experiential and symbolic context on partner farms. It constitutes effective communication for social change, and has enabled health promotion, as described by the Ottawa Charter, to be realised. This demonstrates that an on-going, participatory process of local communication can create an enabling environment for health promotion. A community of communication practice has been developed in the farming community; this constitutes a reservoir of social capital and capacity to communicate and addresses the need for innovative communication in rural settings. A discursive space and public of discourse around wellness and HIV has been created, and new leaders and alternative narratives, which constitute self and collectively defined “AIDS competency” in a marginalised setting, are becoming visible, suggesting pathways for future interventions to enable equivalent responses in similar settings. Conclusion: An opportunity exists to make more effective use of the power of face to face communication in defined local settings, in order to enable disempowered individuals to claim their human and health rights, to protect themselves from HIV, and to help activate and realise synergies in health and development objectives such as the Millennium Development Goals.

Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science in Medicine. Johannesburg, 2012 / Introduction: Most new HIV-1 infections world-wide are caused by subtype C viruses. The C3V4 region, including the alpha2-helix and V4 loop, has been identified as a major target for autologous neutralising antibodies in subtype C infections. Factors associated with the immunogenicity of this region, and the mechanisms of escape from anti-C3V4 responses have not been described, although charge changes in the alpha2-helix have been proposed to mediate neutralisation escape. Methods: Seventeen HIV-1 subtype C infected individuals were classified as C3V4 responders or nonresponders using chimeric viruses in env-pseudotyped neutralisation assays. Longitudinal sequences obtained from C3V4 responders were used to identify putative neutralisation escape mutations. The role of these mutations in mediating escape was investigated using site-directed mutagenesis. Results: The C3V4 region was confirmed as a major target in HIV-1 subtype C infections. The development of an anti-C3V4 response was associated with shorter V4 loops and fewer potential N-linked glycans (PNGs) in the C3V4 region. Anti-C3V4 responses were associated with higher autologous neutralising titres. Neutralisation escape from an anti-C3V4 response was rarely mediated by charge changes in the alpha2-helix and generally occurred through mutations in other structurally proximal regions of the envelope. This study confirmed the use of glycan shuffling as a predominant escape pathway. In three individuals multiple mechanisms of escape were identified and in two other cases escape mutations within the C3V4 and structurally proximal regions clustered at opposite termini of the alpha2-helix, inconsistent with the surface area of a single epitope. Conclusion: A more exposed and accessible C3V4 region was more likely to elicit an anti-C3V4 response. The highly immunogenic nature of this region may contribute to the higher overall neutralisation titres in subtype C infections. Distinct clusters of mutations may suggest the existence of two “sub-epitopes” within the C3V4 domain that warrant further investigation. These findings emphasise the adaptability and plasticity of the C3V4 region in the context of viral evasion of host defences.

No description available.

As manifestações bucais da AIDS têm sido relacionadas a diversas características clínicas da infecção pelo HIV como decréscimo de células T CD4+, aumento de carga viral e falha terapêutica, entre outras. Os avanços recentes da medicina mostram que a falha terapêutica, nesses pacientes, está diretamente vinculada a mutações na transcriptase reversa (TR) e na protease (PR). O objetivo deste estudo foi descrever, em pacientes HIV+ apresentando falha terapêutica, o perfil de mutações do vírus e o perfil de resistência a antirretrovirais, e correlacioná-los as manifestações bucais da imunodeficiência. Foram acessados prontuários, laudos de genotipagem e informações de bancos de dados digitais de pacientes com AIDS, que se submeteram a genotipagem no Centro de Referência e Treinamento em Doenças Sexualmente Transmissíveis e AIDS (CRT-DST/AIDS), entre 2003 e 2010. Os dados foram transferidos para o Epiinfo, onde foi construído um banco de dados informatizado para posterior análise estatística. O evento lesões orais foi escolhido como variável dependente. Calculou-se o odds ratio para cada variável independente, utilizando intervalo de confiança de 95%. Foram cruzados dados sobre mutações encontradas no vírus e resistência às medicações com a presença e tipo de manifestações bucais. O teste de Bartlett foi utilizado para testar a normalidade dos dados. Para variáveis sem distribuição normal foram aplicados os testes de Mann-Whitney ou Kruskal-Wallis. Para comparação entre frequências e proporções, foi utilizado o Teste de Exato de Fisher ou o Qui quadrado. O nível de significância foi estabelecido como 0,05 ou 5%. A análise de características sociocomportamentais e clínico laboratoriais permitiu verificar que a presença de lesões orais pode ser relacionada estatisticamente a baixas taxas de CD4 (p<0,05), faixa de carga viral (p=0,048) e ao uso prévio de mais de cinco esquemas antirretrovirais diferentes (p=0,021). Verificou-se maior prevalência de lesões virais (75%) e bacterianas (66,7%) do que de lesões fúngicas (37,3%) apenas em pacientes que apresentavam resistência a inibidores de protease (IP) (p=0,02). Foram encontradas 146 mutações diferentes nos pacientes que apresentavam lesões orais, dentre essas, quatro (101E, 20T, 188L, 93L) apresentaram correlação negativa com a presença de lesões orais (respectivamente, p=0,01, p=0,01, p=0,03, p=0,03) e oito (215Y, 118I, 20R, 44D, 71I, 82I E 84V) apresentaram correlação positiva (respectivamente p=0,04, p=0,05, p=0,03, p=0,01, p=0,01, p=0,04, p=0,0004). Subsequentemente, as mutações que apresentaram correlação positiva com a presença de lesões orais foram avaliadas para verificar se sua presença estaria realmente associada a resistência aos ARVs (aos quais seriam supostamente resistentes). Foram excluídas dessa avaliação as mutações 71I e 82I, por apresentarem uma quantidade extremamente pequena de ocorrências. Todas as mutações apresentaram correlação estatística positiva para a resistência aos respectivos antirretrovirais (p<0,05). Em pacientes HIV+, que apresentavam falha terapêutica e manifestações bucais, foram identificadas as mutações 84V e 20R na PR e as mutações 215Y, 44D e 118I na TR e a presença dessas mutações foi associada a resistência a inibidores de protease e inibidores de transcriptase reversa nucleosídeos, respectivamente. / Oral manifestation of AIDS have been associated with several clinical characteristics of HIV infection such as reduction in T CD4+ cells, increase in viral load and treatment failure, among others. Recent advances have shown that treatment failure in these patients is directly linked to mutations in reverse transcriptases (RT) and in proteases (PR). The objective of the present study was to describe the profile of virus mutations and of resistance to antiretroviral drugs in HIV+ patients in treatment failure, and to correlate mutations to the oral manifestations of the immunodeficiency. Patient charts, genotyping results and information from digital databases of AIDS patients, who underwent genotyping at the Sexually Transmissible Diseases and AIDS Training and Reference Center (CRT-DST/AIDS) between 2003 and 2010, were accessed. Data were transferred to the Epiinfo program, in which a computerized database was built for statistical analysis. The event oral lesions was chosen as a dependent variable. Odds ratio for each independent variable was calculated, using a 95% confidence interval. Data found on virus mutations and drug resistance was analyzed to check for correlation with presence and type of oral manifestations. The Bartlett test was used to test normality of data. Mann-Whitney or Kruskal-Wallis tests were used for variables without a normal distribution. The Fisher Exact or Chi-square Tests were used to compare frequencies and proportions. A 0.05 or 5% significance level was established. The analysis of socio-behavioral and clinical-laboratorial characteristics allowed concluding that the presence of oral lesions may be related to statistically low CD4 rates (p<0.05), viral load range (p=0.048) and previous use of more than five different antiretroviral regimens (p=0.021). A higher prevalence of viral (75%) and bacterial (66.7%) lesions in relation to fungal lesions (37.3%) was observed only in patients who were resistant to protease inhibitors (PI) (p=0.02). We found 146 different mutations in patients with oral lesions, among which, four (101E, 20T, 188L, 93L) with a negative correlation with the presence of oral lesions (p=0.01, p=0.01, p=0.03, p=0.03, respectively) and eight (215Y, 118I, 20R, 44D, 71I, 82I E 84V) with a positive correlation (p=0.04, p=0.05, p=0.03, p=0.01, p=0.01, p=0.04, p=0.0004, respectively). Subsequently, mutations with a positive correlation with the presence of oral lesions were assessed to check if their presence would really be associated with resistance to ARVs (to which they supposedly would be resistant to). Mutations 71I and 82I were excluded from this assessment because they had an extremely low frequency. All mutations had a statistically positive correlation for resistance to their respective antiretroviral drugs (p<0.05). Mutations 84V and 20R were identified in PR, and mutations 215Y, 44D and 118I in TR of HIV+ in patients undergoing treatment failure and presenting oral manifestations. Moreover, the presence of these mutations was associated with resistance to protease inhibitors and to nucleoside reverse transcriptase inhibitors, respectively.

Thesis advisor: Kenneth C. Williams / Individuals infected with Human Immunodeficiency Virus (HIV) are susceptible to pathological abnormalities due to the infiltration of virus into different anatomical compartments. Monocytes are a heterogeneous population that undergoes changes in phenotype with HIV infection. It is hypothesized that changes in monocyte subsets observed through the course of infection will correlate with the development of SIV-Encephalitis (SIVE). 14 CD8+ T cell depleted rhesus macaques were infected with SIVmac251 and changes in 3 monocyte subsets, defined by their CD14 and CD16 surface expression as CD14+CD16-, CD14+CD16+, and CD14-CD16+, were tracked through the course of disease. The CD14+CD16- subset increased in the absolute number of cells and decreased in percentage of the total monocyte population. The CD14+CD16+ and CD14-CD16+ subsets increased in both absolute number and percentage. These changes have a biphasic dynamic that occurs during early infection and is pronounced in encephalitic animals. Several markers showed differential expression with infection and between subsets. Mac387, an early monocyte-macrophage marker, demonstrated a considerable decrease in expression. Concomitant with this change, CD68, CD163, CD44v6, CCR2, and CD64 increased expression in the total monocyte population, with the magnitude of these changes occurring in a subset-specific manner. In conclusion, monocyte subsets undergo changes with SIV infection that correspond to the development of encephalitis, highlighting the contribution of monocytes in neuroAIDS. / Thesis (MS) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.