In South Africa, co-infection with HIV and intestinal parasites is a major challenge in disadvantaged communities who live in densely populated under-serviced urban informal settlements. This pilot cross sectional study evaluates the immunological effects of co-infection with Ascaris lumbricoides and Trichuris trichura on the immune response to HIV. The work was a substudy of a prospective double blind, placebo-controlled investigation to test whether regular deworming changes the immune profile of HIV positive individuals with concurrent helminth infection. The substudy has a cross sectional design and presents pilot data that defines immune profiles of HIV-1 positive individuals with and without gastrointestinal helminth (Ascaris lumbricoides and Trichuris trichura) infection. The hypothesis was that concurrent helminth infection adversely affects immune responses against HIV. It was conducted in an area of high helminth endemnicity and limited infrastructural resources. Individuals with known HIV infection were recruited from an HIV Support Group and HIV negative individuals residing in the same area (for demographic matching) were used for comparison. The substudy was to provide pilot data for future larger scale and possible interventional studies. The current work is limited by the cross sectional design, moderate sample size and practical challenges. The profile of lymphocyte phenotypes, viral loads, eosinophils, activation markers, expression of the nuclear proliferation antigen-Ki67 and activation regulator antigen CTLA-4 were analysed using flow cytometry in HIV positive and negative subgroups with or without helminth infection. The type-1, type-2 and inflammatory cytokines were analysed using multiplex cytokine array technology. These were correlated with immune responses to HIV. Non parametric statistics were used to describe differences in the variables between the subgroups. A major finding of the study was the result of the supplementary use of the serological marker, Ascaris lumbricoides-specific IgE in addition to the presence (or absence) of helminth eggs in stools to classify intestinal helminth infection status. Two significant outcomes of this measure were the enhancement of diagnosis of current or recent helminth infection and, more importantly, the distinction of different phenotypes of individuals who displayed different immunological responses to co-infection with HIV and helminths. The different helminth infection phenotypes are defined by stool egg positivity (egg⁺) or negativity (egg⁻) with either high or low Ascaris-specific IgE (IgEhi or IgElo) respectively. The four subgroups, egg⁺IgEhi, egg⁺IgElo, egg⁻IgEhi and egg⁻IgElo showed different interactions with regards to immune response to HIV. It should be noted that no Trichuris specific IgE tests are commercially available but that there is significant antigenic cross-reactivity with Ascaris antigen. The presence of helminth stool eggs and high Ascaris IgE (egg⁺IgEhi) was associated with the following characteristics: reduction in numbers of all lymphocyte populations, frequent eosinophilia, highly activated immune profiles, antigen specific proliferative hyporesponsiveness, impaired type 1 cytokine responses in unstimulated and antigen stimulated cells and increased TNFα levels. In HIV infected individuals, the egg⁺IgEhi helminth infection status was associated with lower but not significant CD4⁺ counts and higher viral loads. A strong negative correlation was observed between viral loads, CD4⁺ and CD8⁺ cells in this subgroup. Subgroups with high IgE (egg⁺IgEhi and egg⁻IgEhi) had elevated Th2 markers with lower CD4⁺ counts and higher viral loads in the HIV⁺ group. The inverse correlation between viral load and CD4⁺ counts found in all the HIV⁺ participants was strongest in these two subgroups. Individuals with parasite eggs in stool and low Ascaris IgE (egg⁺/IgElo) presented a modified Th2 profile. This subgroup had high absolute numbers of all lymphocyte subsets in both HIV⁻ and HIV⁺ groups with higher CD4⁺ counts in the HIV⁻ and lower viral load in the HIV⁺ groups as well as higher interferon gamma, lower IL-4 and higher IL-10. In conclusion, the results suggest that helminth infections may be associated with deleterious effects on the immune responses to HIV in certain groups of susceptible individuals. The underlying reasons for the different stool egg/Ascaris IgE combinations in settings with high exposure to helminthes is currently not clear but genetic predisposition and environmental factors could play a role. Future studies of helminth- HIV co-infection have to ensure adequate definition of helminth infection status by the use of both stool examination and measurement of helminth-specific IgE as the infection phenotype is associated with differential effects on HIV associated immune responses. This may also apply to co-infection with other pathogens, including tuberculosis. The long-term effect of helminth co-infection in HIV positive people was not assessed in this study but requires further studies. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2009.

HIV-1 is the most prevalent and notorious sexually transmitted pathogen locally, and constantly challenges our foundation of knowledge regarding the classical STIs. The ultimate objective of the syndromic management strategy was to reduce the load of sexually transmitted infections, and hence HIV transmission. This strategy is multifaceted and not only includes the recognition of symptoms by the patient and an effective treatment regime that comprehensively covers the possible aetiological agents for a defined syndrome, but also appropriate health seeking behaviour of infected individuals, recognition of syndromes by the health care worker, partner management (notification and treatment), behavioural counselling and condom promotion. Understanding the complexity of sexual networking and transmission dynamics is part of such a strategy. So, although the rationale and design of syndromic case management appears simplistic, it is by no means easy to implement / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2002.

Introduction Nearly half of all new HIV infections worldwide occur in young people aged 15-24 years. Risky sexual behaviours may lead to the development of lifelong negative habits like having multiple partners, thereby placing young people at risk of a broad range of health problems, including HIV/AIDS. Prevention is therefore critical and includes changing behaviours that are risky, such as the early age of sexual initiation, having many sexual partners and non-use of condoms. The study aimed to evaluate whether a theory based HIV/AIDS intervention, 'Be A Responsible Teenager' (B.A.R.T.), could produce behaviour change among high school learners in South Africa. Methods A pre-test /multiple post-test intervention study was undertaken. All Grade 10 learners (n = 805) from all three public high schools in Wentworth were included in the study. Eleven teachers were interviewed from these schools. Learners completed a questionnaire at baseline (Tl), immediately post intervention 1 (T2), post intervention 2 (T3) and after a period of seven months (T4). The B.A.R.T.intervention was implemented in the intervention schools while the control group did not receive any intervention. Qualitative data was analyzed according to themes, while quantitative data was analyzed cross sectionally and longitudinally. Results Teachers reported many obstacles in implementing the HIV/AIDS Life Skills' curriculum, including the poor quality of training and inadequate resources in schools. Further, learners practised high-risk sexual behaviours. Gender differences in sexual behaviour were reported with males predominately practising higher risk behaviours than females.The B.A.R.T. intervention did show changes in behaviour for alcohol use at last sex and for the determinants knowledge, attitudes, beliefs, self-efficacy and intentions to practise safer sex respectively, over time. However, the intervention didnot positively impact abstinence behaviours, condom use and the reduction in partners. Further, subjective norms did not change. Conclusion The major obstacles to AIDS prevention include the current practices of risky sexual behaviours including age mixing, early sexual initiation, multiple partners, forced sex and receiving money or gifts for sex among others. Social norms as potrayed by parents, peers and religious groups play a pivotal role in promoting protective sexual behaviours. The role of gender and the gaps in LHAP (Life Skills' HIV/AIDS programme) also require urgent attention. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2008.

The AIDS epidemic in Africa has reached dramatic proportions. Of the 42 million people infected with HIV worldwide, 30 million are in Africa. Current available therapies have begun to transform this fatal disease into a chronic condition but there are still major obstacles that have resulted in a great demand for new and better drugs. The aim of this study was to synthesize novel and effective HIV protease inhibitors. This work describes the first account of pentacycloundecane (PCU)-peptide and peptoid based protease inhibitors. These inhibitors are proposed to bind the wild type C-South African HIV protease (C-SA) catalytic site via the norstatine or dihydroxylethelene type functional group of the PCU. The desired compounds were synthesized by the coupling of the peptides and peptoids to the PCU cage which resulted in a series of promising and structurally diverse HIV-1 protease inhibitors. The inhibitors were characterized by Nuclear Magnetic Resonance (NMR) and evaluated against the wild type C-SA enzyme for its ability to inhibit 50 % of the enzyme’s activity (IC50). Two of the compounds reported herein, inhibited the enzyme activity at concentrations less than 80 nM. NMR investigations indicated that the activity was related to the chirality of the PCU moiety and its ability to induce conformations of the coupled peptide side chain. Employing the new Efficient Adiabatic Symmetrized Rotating Overhauser Effect Spectroscopy (EASY-ROESY) technique enabled us to obtain vital information about the 3D structure of these small linear peptides and peptoids in solution. This technique is the first example describing the successful through space correlations of such small peptides. Furthermore, docking and a combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics MD simulation at the AM1 semi empirical level mirrored the observed NMR results and the experimental IC50 activity profile of the considered inhibitors. The combination of these experimental and theoretical methods provided a powerful insight into the interaction mode of these cage peptide and peptoid inhibitors with the enzyme. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2011.

The intentions of this research were to determine the general knowledge, transmission knowledge and prevention knowledge of AIDS prior to commencing an AIDS awareness-training programme; establish the general knowledge, transmission knowledge and prevention knowledge of AIDS after completing an AIDS awarenesstraining programme; to determine whether there is a significant difference in the subject's general knowledge, transmission knowledge and prevention knowledge of AIDS after completing an AIDS awareness-training programme and to establish whether there is a significant difference between the pre-test and retest scores in terms of general knowledge, transmission knowledge and prevention knowledge of AIDS, among the respective biographical variables. The results of the study established that all participants had some General Knowledge, Transmission Knowledge and Prevention Knowledge on AIDS. Employees who participated in the programme had improved their knowledge on AIDS after attending the training programme. The results of the study had found no significant difference between pre-test and retest score for age groups, race groups, religious groups, marital status groups and language groups. The results did however indicate some variation in pre-test scores and retest scores between the gender groups. The literature review examined AIDS from a biological perspective, a global and South African perspective and an Industrial relations perspective. The workplace issues pertaining to AIDS were discussed and responses to the AIDS crisis were highlighted. AIDS policies, training programmes and employee's assistance programmes were analysed, as options for organisations, in their fight against AIDS. A questionnaire was used to establish the general knowledge, transmission knowledge and prevention knowledge of AIDS of the 307 employees that participated in the programme. The findings in this study support the perception by companies that providing awareness training programmes will assist by increasing the knowledge of what is AIDS, how is it transmitted and how it can be prevented. This study revealed that after a training programme, employees were more knowledgeable on AIDS than before the training programme. / Thesis (MBA)-University of KwaZulu-Natal, 2008.

Background Several case reports and studies have alluded to an increased prevalence of venous thrombosis in human immunodeficiency virus positive (HIV-positive) patients. Although a relationship between HIV infection and thrombotic disease has been suggested, the mechanisms predisposing to thrombosis have not been fully elucidated. Aim A prospective study, to determine possible coagulation factor abnormalities that could explain the predisposition to thrombosis in HIV-infected African (Black) patients, was undertaken. Method African (Black) patients, with acute upper segment deep vein thrombosis (DVT) confirmed by duplex ultrasound, were enrolled. Patients who had recognisable risk factors such as recent surgery, pregnancy or malignancy, were excluded. After informed consent, blood samples were taken for baseline tests as well as a thrombophilia screen. The control group comprised known HIV-positive African (Black) patients without DVT. Patients with DVT who were found to be HIV-negative were also analysed. Analysis was done in 2 parts: HIV-positive patients with and without thrombosis and HIV-positive and negative patients with thrombosis were compared. Results Part A: HIV-positive patients with and without thrombosis Of the 77 patients with DVT, 50 patients tested HIV-positive. These 50 patients (HIV-positive DVT-arm), as well as 56 controls (HIV-positive, no DVT), were enrolled into the study. The groups were well matched with regard to age, sex and cluster designation 4 (CD4) count. On univariate analysis, significant findings in the DVT-arm were a history of active tuberculosis on treatment, low protein C levels and a positive qualitative D-dimer, whereas on multivariate analysis, only tuberculosis and an elevated D-dimer proved to be significant. Part B: HIV-positive and negative patients with thrombosis There were 20 HIV-negative patients with DVT who met our inclusion criteria Limited assessment was done on this group owing to unavailability of some data. The mean age of the HIV positive DVT group was significantly lower than the HIV-negative group with DVT (31.78 vs. 41.45 years; p=0.005). There was no significant difference in the prevalence of tuberculosis between the HIV-positive and HIV-negative patients with thrombosis (p = 0.269). Mean protein C levels were reduced in the HIV-positive group and normal in the HIV-negative group. They were significantly lower in the HIV-positive patients compared to the negative group (p=0.02). Conclusion The findings of the study suggest a relationship between HIV, its complications and DVT. Although this study confirms HIV infection as a risk factor for thrombosis, clear pathogenetic mechanisms remain to be elucidated. In our population, tuberculosis appears to be an important risk factor predisposing patients to the development of DVT, both in the HIVpositive and negative population. Further studies will need to be done to confirm this hypothesis. / Thesis (MMed)-University of KwaZulu-Natal, Durban, 2006.

Trichomoniasis has been linked to pelvic inflammatory disease, cervical cancer, increased HIV transmission, infertility as well as co-infections with other STIs. In 2002, an association was found with Trichomonas vaginalis and PID in HIV positive women. Therefore, the question arose whether T. vaginalis is able to invade the upper genital tract of HIV infected women. A prerequisite for invasion of the upper genital tract is the capability of the organism to adhere to the cells of the organs involved. This study therefore investigated the interaction between T. vaginalis and vaginal, cervical and endometrial cells. In comparing adhesion and cytotoxicity of T. vaginalis to cells of the upper and lower genital tract at different pH, immortalized vaginal (VK2), cervical (ME 180) and endometrial (KLE) cells were exposed to a standardized inoculum of trichomonads at pH 4.5 to 7.0. Adhesion was measured microscopically after acridine orange staining and cytotoxicity was established by measuring LDH release using a commercial kit. Adhesion of the ME-180 and VK2 cell lines was found to be pH dependent. However, the KLE cell line was not. As the pH increased, adherence to the vaginal and cervical cells decreased. Adhesion to endometrial cells was minimal at neutral pH but marked adhesion was found at lower pH. For the vaginal cell line, cytotoxicity was minimal at pH 4.5 but substantial (30 to 60%) at higher pH. In contrast, cytotoxicity on cervical and endometrial cells was highest at lower pH. The pronounced toxicity of vaginal epithelial cells at pH 5 and pH 5.5 is in keeping with the pH range found in patients with vaginitis. The observations on the cervical epithelium suggest toxic effect on the ecto-cervical epithelium immediate after acquisition of the infection. Adhesion of trichomonads to the endometrial cell line suggests that T. vaginalis is capable of colonization of the upper genital tract. At pH values applicable to the in vivo situation, toxicity was very low. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2010.

The aim of the study was to explore the perceptions of the HIV negative pregnant women, after their hiv negative results, towards preventive sexual behaviour. Methodology: A qualitative approach was used in exploring the perceptions of hiv negative pregnant women and describing their behaviour according to the findings. Fifteen participants were interviewed. Two semi - structured interviews were conducted with each participant, an initial interview and a verifying interview, for the purpose of saturation and verification. Each interview lasted for 20 - 30 minutes. The interviews were recorded and transcribed. Manual data analysis was used to identify categories and themes. Findings: The study revealed that the participants knew what the negative status entailed. They were also aware that there is a chance of hiv negative person being infected by hiv virus if they do not engage in preventive sexual behaviour. Furthermore, they had also disclosed their hiv negative status to their partners and most of the partners refused to go for testing. Though the participants believed that it was necessary to use condoms even if they were hiv negative, most of them had not use condoms during their last sexual intercourse. Reasons for not engaging in preventive sexual behaviour were revealed by the study. Recommendations were suggested for clinical practice, nursing education, management and research. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2005.

BACKGROUND Sub-Saharan Africa has the highest number of HIV-infected individuals and limited treatment programs. The use of Highly Active Antiretroviral Therapy (HAART) has resulted in a considerable decrease in morbidity and mortality among HIV-infected individuals. Long-term use of HAART has several limitations relating to cost, drug toxicity and adherence. Structured Treatment Interruption (STI) has been proposed as a therapeutic approach which limits the exposure to continuous HAART, but retains the benefits thereof. The role of HIV-specific Tcell responses in the control of viraemia has not been well studied in children and it is not clear when these responses become detectable or whether they are associated with improved viral control. Furthermore, antiretroviral drug resistance is well documented in adults infected with HIV-1 clade B virus but comparable information is lacking for chronic paediatric clade C virus infection. This pilot study focused on a chronic HIV-infected paediatric cohort from Durban, South Africa, to assess the immunologic and virologic responses in perinatal HIVinfected children undergoing STI. METHODS Thirty chronic HIV-infected treatment naïve children were enrolled and randomised into either the treatment interruption or continuous treatment group. Longitudinal measurements of viral loads and CD4 percentages were done at scheduled intervals. Peripheral blood mononuclear cells (PBMCs) were screened for cytotoxic T-lymphocyte (CTL) gamma interferon (IFN-?) enzyme-linked immunospot (ELISpot) assay responses using 410 peptides which spanned the entire HIV-1 clade C proteome. Intracellular cytokine staining (ICS) was done to distinguish between IFN-? Gag-specific T-helper and cytotoxic T cell responses. Pre-HAART drug resistance mutations testing and HLA typing were done for all children. RESULTS There was a significant increase in the median CD4 percentage after HAART was introduced. Six children randomized to the STI arm did not undergo treatment interruption because their viral loads remained detectable at the time of scheduled interruption. Most HIV proteins were targeted in this paediatric cohort. Gag was the most frequently targeted HIV-1 protein (93.1%). In both treatment groups, there were broadening of T-cell responses, however, the magnitude of T-cell responses decreased over time on HAART. Drug-resistant mutations were detectable in 4/29 children before initiation of HAART. CONCLUSION In this pilot study, the HIV-1-specific CD8+ and CD4+ T-cell responses were detected before and during HAART. Although the treatment interruption period was short, there were no adverse outcomes in either the continuous or treatment interruption groups in terms of death or other clinical outcomes. This study suggests that it is important to continue to explore alternative treatment strategies in order to reduce cost and toxicity as well as to enhance adherence. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2010.

Lavendamycin, an aminoquinolinedione antibiotic is similar to streptonigrin, an antibiotic with known antiretroviral activity. Their applicability as drugs is limited due to their high toxicity to mammalian cells. A series of novel analogs of lavendamycin has been recently synthesized. In initial screening, three of the analogs showed significant inhibitory activity toward the reverse transcriptase (RT) of the avian myeloblastosis virus (AMV) and exhibited little or no animal toxicity and relatively low cellular cytotoxicity.In this study, we determined the anti-retroviral activity of nine analogs by assessing their anti-reverse transcriptase(anti-RT) activity in comparison to streptonigrin. Using both the human immunodeficiency virus (HIV) and AMV reverse transcriptase in vitro we found that the analogs exhibited significant anti-RT activity. The inhibitory activity of the analogs was dose dependent, and they had different effects on the two enzymes. At 30 µM seven of the analogs inhibited HIV-RT activity by 50% or more. At this concentration, two of the analogs were significantly more effective than streptonigrin. AMV-RT was more sensitive toward both streptonigrin and several of the analogs than was HIV-RT. Furthermore, combination of azidothymidine (AZT)-triphosphate (TP) and several of analogs showed synergistic inhibitory effects at low doses. / Department of Biology