Dissertation (PhD)--University of Stellenbosch, 2005. / Bibliography. Also available via the Internet.

The present study sought to explore the functional changes that occur in the vasculature of HIV positive participants of African origin in Mthatha district of South africa which might lead to increased risk in their cardiovascular system. Available literature shows that arterial stiffness plays an important role in cardiovascular events such as stroke, vasculitis and myocardial infarction. Measurement of (aortic pulse wave velocity; PWV) provides some of the strongest evidence concerning the prognostic significance of large artery stiffening. This study was aimed at investigating the relationship between anthropometry, age, E-Selectin level, cytokine levels, haemodynamic variables, blood counts and blood lipid profile with pulse wave velocity. Some traditional cardiovascular risk factors such as alcohol, and smoking were also taken into account. This was a cross-sectional study comprising of 169 participants (62 males and 107 females). 63 were HIV negative (group A), 54 HIV positive on treatment (group B), and 52 were HIV positive not on treatment (group C). Pulse wave velocity (PWV) was assessed using the Sphygmocor Vx. Statistically, ANOVA was used for variables with normal distribution and non parametric tests were used for variables with skewed distribution. Notable significant differences were seen in the means of the following variables across all the 3 groups. Conclusion: This study showed that HIV infected patients with or without antiretroviral therapy have increase arterial stiffness which is associated with an increased cardiovascular risk. The sphygmocor is an accurate, non invassive and useful tool in the evaluation of arterial stiffness and its use in clinical practice should be encouraged. PWV and the augmentation index (AIx) are the two major non- iv invasive methods of assessing arterial stiffness. Life style modification should be incorporated into the management of HIV patients so as the continuous monitoring of their haematological and lipid profile.

The overall objective of the study was to investigate the relationship between male circumcision status and HIV infection in men from Salima district in Malawi. A cross-sectional survey-based study of men aged 15 years or more was conducted at three sites in Salima district, each of which targeted 90 participants, half of whom were circumcised and the other half uncircumcised. These participants had already decided on their own to visit HIV Testing and Counseling centres at these sites to know their HIV serostatus. Consenting men were drawn into the study using quota sampling, interviewed through a structured questionnaire in local language and tested for HIV during January and March 2011. Measures of association were performed using analysis of contingency tables and Pearson’s chi-square tests or Fisher’s exact tests for comparison of proportions in STATA version 11.0 and PASW Statistics 18.0 software. Unadjusted odds ratios were used to approximate the direction and strength of association. Further, a multivariable logistic regression model was fit to determine which other variables were significantly associated with HIV infection. The study was approved by University of Fort Hare Interim Research Ethics Committee and National Health Sciences Research Committee in Malawi. The overall prevalence of HIV infection was 11.5 percent. However, it was less than half in circumcised males (7.4 percent) compared with uncircumcised counterparts (15.6 vi percent). While Fisher’s exact test revealed a borderline statistically significant association between male circumcision status and HIV infection (p 0.055), Pearson’s chi-square test showed a stronger significant association between the two variables ( p 0.036). The strength of the association was manifested by the odds of HIV infection being roughly 0.43 times lower for circumcised males than their uncircumcised counterparts with a 95 percent confidence interval of (0.20 0.96). Although the association was maintained after controlling for some variables, it lost statistical significance when adjusted for other variables. A multivariable logistic regression revealed that three other variables had significant associations with HIV infection and these were: falling in the age group of 25 years or more (OR 4.69; p 0.020), having had sex with an HIV positive partner (OR 12.15; p 0.000) and having contracted a sexually transmitted infection (OR 3.25; p 0.032). Male circumcision status is significantly related to HIV infection. Although the study involved a small sample size and undertaken in one district in Malawi, the finding is consistent with existing clinic-based findings in literature that indicate a lower risk of HIV infection in circumcised males than in uncircumcised males. Consequently, male circumcision could be considered if it can prove to be a public health intervention in the Malawi context aimed at reducing the risk of uncircumcised males becoming infected by HIV.

HIV-2 is a contemporary human retrovirus with the majority of infections localised to West Africa. Both HIV-1 and HIV-2 are able to cause AIDS; however, in contrast to HIV-1 infection, a common outcome following HIV-2 infection (∼ 37% of patients in this study cohort) is long-term non-progression (LTNP), where patients remain aviraemic and asymptomatic in the absence of treatment, often for decades. HIV-1 and HIV-2 both arose following zoonotic transmission of SIVs from non-human primates at around the beginning of the 20^th century and when patients develop AIDS caused by HIV-2 infection, it is clinically indistinguishable from AIDS following HIV-1 infection. Whilst the estimated number of HIV-2 infections remains small in the context of the global HIV pandemic (HIV-2 ∼ 2 million, HIV-1 group M ∼75 million), the differences in pathogenicity between these two viruses has been a source of great interest, particularly the features of LTNPs that allow control of viral replication in the absence of anti-retroviral treatment. The studies described in this thesis were carried out using samples collected from a well-characterised longitudinal community cohort in Caió, Guinea-Bissau. Chapter 3 of this thesis presents an investigation into the variation and evolution present in the HIV-2 specific accessory gene vpx. The data showed significantly increased signals of positive selection pressure in vpx in viraemic when compared to non-viraemic patients and also allowed the identification of novel variations at high frequencies (up to 22%) in this cohort that were previously un-described. Chapters 4 and 5 present a novel application of shotgun RNA sequencing (RNA- Seq) to HIV ex vitro and ex vivo samples. Chapter 4 demonstrates the divergence seen in a cultured viral isolate at the level of the whole genome, in the absence of many of the biases typically involved in sequencing of RNA viruses. Chapter 5 further extends this method to show the applicability of using RNA-Seq on primary patient HIV samples for the first time. Analysis of diversity estimates over the whole genome in the context of a low bias sequencing method show a high level of diversity in HIV-2 pol and low diversity in vpx. The aim of this work was to combine traditional and novel sequencing methods to facilitate assessment of the variation and evolution acting on vpx and to generate an accurate picture of the genetic diversity over the whole genome of HIV-2.

Second year psychology students (N=176) from Rhodes University were surveyed using an anonymous questionnaire to obtain information on sexual behaviour and knowledge of the acquired immunodeficiency syndrome (AIDS) among young people. The following information was obtained: Knowledge of safe sex practices and HIV transmission was high although a number of misconceptions were noted. Only fifty six percent of students viewed oral sex with a condom as safe and thirty one percent do not consider mutual masturbation with a condom safe. Thirteen percent and twenty five percent respectively identified insects and saliva as being routes of HIV transmission. Magazines (96%), informal discussions with friends (95%), public pamphlets (86%) and public television (79%) were preferred sources of information. The students' knowledge did not appear to significantly affect sexual behaviour. Eighty percent of respondents were intimately involved with another person during the past twelve months, and only fifteen percent always made use of a latex barrier when being sexually intimate. Despite high rates of alcohol and/or drug consumption (80% of students use such substances), and the belief by the majority of respondents that alcohol and/or drugs facilitate higher risk behaviours, no support for the alcohol/risky sex hypothesis was found. Students were found to score highly on proneness to psychological and behavioural risk taking, and no significant relationship between this and unprotected sex was found. It can be concluded that educational programmes need to focus on what constitutes safe sexual practices in order to equip young adults with the knowledge they need to make informed choices regarding the relative risks of various sexual activities.

M.Tech. (Homoeopathy) / Please refer to full text to view abstract

The HIV and AIDS pandemic has resulted in 14 million children being orphaned worldwide. In Lesotho alone, where this study was carried out, there are about 180 000 of these children (UNAIDS, 2007). Teachers, especially in Lesotho‘s primary schools need to be equipped to better deal with the challenges that result from having these children in their classrooms. At the Lesotho College of Education, where I have worked for 12 years as a teacher educator, pre-service and in-service student teachers are not trained to offer care and support to orphans and vulnerable children. They experience problems in the classroom emanating from the needs of these children. This study followed an action research design to find ways to support teachers to better deal with the issues they face as a result of having orphans and vulnerable children in their classes. Using a qualitative approach, educators perceptions, feelings, attitudes and experiences in dealing with orphans and vulnerable children in their schools were identified, and it became apparent that educators were negatively affected on a personal and professional level. It was concluded that the development of resilience in educators would help them to better cope with orphans and vulnerable children in their classes. The chosen intervention Resilient Educators Programme (REds) was implemented and evaluated and findings revealed that it was beneficial in increasing educator resilience. Recommendations, based on the findings of the study, were made for future teacher education in this area.

Ph.D. / Background: AIDS is characterized by a number of opportunistic infections and the immune depletion caused by HIV infection is the strongest risk factor for both reactivation of tuberculosis (TB) and progression of Mycobacterium tuberculosis (Mtb) infection to disease. Numerous studies have shown that concurrent infection of the same host cell by HIV,and M.tb stimulates replication of both pathogens. The interaction between the two is lethal. A synergistic relationship exists between Mtb and HIV. While HIV spurs the spread of TB, mycobacterial infection results in acceleration of HIV disease progression. The requirement for iron as a crucial factor for cellular processes has long been demonstrated. Excess iron leads to infections with harmful consequences such as cell death and function impairment. During infection, iron is required by both the host cell and the pathogens. Iron chelation is believed to modulate some of these effects. Objectives: Mtb, HIV and Fe-overload are common in sub-Saharan Africa and iron plays a major role in determining the outcome of several infections. In view of this, we wanted to (1) investigate the effect of excess iron on host cell defences during co-infection with the mentioned microorganisms, (2) evaluate the differences in both host and pathogen responses during acute and chronic infection in the presence of iron overload and (3) Determine the efficacy of iron chelation (with DFO) as a means of counteracting conditions associated with iron overload. Hypotheses: The combination of Fe-overload and co-infection of host cells with HIV and Mtb in an in vitro model should stimulate replication of the pathogens, which would ultimately result in host cell stress manifesting as lower viability or cell death and impaired immune defence functions. Also the detrimental effects of excess iron on host cell viability could be counteracted through the use of iron chelators. Methods: We analyzed the in vitro effect of Mtb in bothchronically and acutely HI V-infected cells (PBMC's and monocytes), exposed to 500 uM FeSO 4 and/or DFO for 4 days. Host cell viability, survival and death were assessed through viability assays (MIT and Alamar Blue) and flow cytometric analyses of apoptosis/necrosis (using Annexin V and propidium iodide). Secretion of IL- 6 and TNF-a and production of total nitrate were monitored as host immune/defence responses using specialized ELISAs. HIV replication was investigated by looking at core protein (p24) contents and reverse transcriptase (RT) activity. Mtb replication and growth was monitored using the microplate Alamar Blue assay (MABA) and quantitative culturing.Results: Co-infection caused a reduction of host cell viability (± 20% and 45% inhibition during chronic and acute infection respectively;, as measured by MTT), increases in the numbers of viral particles (2.3 times and 20% increases for chronic and acute infections respectively) and stimulation of both bacterial viability (36%) and host defence responses (30% increase in TNF-ct secretion). Excess iron further decreased viability with a marked increase in necrosis of cells and was found to enhance pathogen replication and growth (26% for HIV and 47% for Mtb). Chelation of iron with DFO abrogated the enhanced replication of the pathogens with a marginal restoration of host viability. Conclusion: The results obtained demonstrate the deleterious effect of excess iron during concurrent infection with both pathogens as well as its stimulating/enhancing properties on pathogens. On the other hand, DFO inhibited pathogen replication and host viability.

Magister Public Health - MPH / The district health report for Livingstone, Zambia, outlined an increasing prevalence of HIV/AIDS iun the district. In 1998 the prevalence wsas at 29%, in 2000 at 30%, in 2002 at 31.8% and in 2004 at 31%. This was above the national prevalence of 20% according to CBoH statistics of 2004. The district has been implementing the HIV/AIDS prevention in various organizations during the past 3 years. Most of the organizations implementing the HIV/AIDS preventive activities do not work collaboratively with other sectors and this has resulted in un-coordinated activities and wstage of the limited resources. This exploratory qualitative study aimed at undestanding participants' perceptions of factors influencing coordination between different organizations that are involved in the implementation of HIV/AIDS activities, and to note the impact that this had in the implementation of activities in a multisectoral approach to HIV/AIDS prevention. / South Africa

The application of Baylis-Hillman methodology has afforded access to a range of β-hydroxypropionate ester-AZT conjugates as potential dual-action HIV-1 IN/RT inhibitors. Two families comprising a total of nine β-hydroxypropionate ester-AZT conjugates were synthesised. The first family was accessed using O-benzylated salicylaldehydes and methyl acrylate and the second from unprotected salicylaldehydes using tert-butyl acrylate as the activated alkene. Spectroscopic methods were employed to fully characterize the compounds. Propargylation of the respective Baylis-Hillman adducts was achieved via conjugate addition of propargylamine. The resulting products were then employed in Cu(I)-catalysed “click” reactions with azidothymidine (AZT) to yield the desired β-hydroxypropionate ester-AZT conjugates. Exploratory studies were also conducted to access 4-hydroxycoumarins from Baylis-Hillman derived adducts and to construct customized chiral Baylis-Hillman reaction sites. Many 4- hydroxycoumarins are known to exhibit a wide range of biological activities, and extending Baylis-Hillman methodology to access these systems is an important challenge. Two approaches were investigated. The first involved the formation of a 4-phthalimidocoumarin, aromatisation and hydrolysis of which was expected to lead to the 4-hydroxycoumarin target. The second, a variation of the first, involved the use of 4-(chrolomethyl)coumarin intermediates. Unfortunately, while various intermediates were prepared and characterised, neither approach led ultimately to the desired targets. N-substituted borneol-10-sulfonamides were constructed from camphor-10- sulfonyl chloride as chiral Baylis-Hillman reaction sites. In a preliminary study, however, none of the N-substituted borneol-10-sulfonamides exhibited Baylis-Hillman catalytic activity.