This study utilised secondary data from a larger study that looked at individuals that are already infected by HIV which is entitled Implicative personal dilemmas and cognitive conflicts in health decision making in HIV positive adults and adults with AIDS. The primary aim of the larger study was to examine the cognitive construction of the individual and how they utilised their individual resources to construct who they are and how they perceived the difficulties and challenges that they face and the decisions they make regarding their health. HIV and AIDS is a debilitating disease and it affects millions worldwide. South Africa, presently, has the largest burden of this disease with those between the ages of 15 – 49 years of age being most affected. As previously mentioned the decisions that individuals make can impact on their health. Decisions to take necessary precautions such as protected sex during sexual intercourse can decrease the progression of the disease. Decisions made regarding abstinence of risky behaviour as well as being committed to taking medication could also positively impact health. People living with HIV and AIDS find it difficult to adjust to the challenges that this disease presents. Depression is often experienced due to the changes in self image and perception. Studies show that females are twice more likely to experience depression than men. There has however been no conclusive evidence showing the reason for this, however, the perception of stress based on gender could shed some light on this matter and how these perceptions can increase the likelihood of women being more vulnerable to depression. Due to the limitation of this study, it will only look at depression as it relates to HIV and AIDS. Psychological problems such as depression can hamper the adjustment process and the effect of depression is evident in that it can lower the CD 4 + cells. Not only are those living with HIV and AIDS affected by depression, but they also have a lifetime prevalence to depression. It is important to have an effective screening tool for depression so that the detection of this disease can be made and effective treatment can be implemented to enhance health. The sample consisted of 113 adult participants that have already been diagnosed with HIV and AIDS. The primary aim of this study was to compare the Beck’s Depression Inventory II (BDI II) and the Hospital Anxiety and Depression Scale –(the Depression component) (HADS-D) as a screening tool for depression.Exploratory Factor Analysis revealed a 5 factor structure which accounted for 60.14 % of the total variance. The HADS yielded one factor accounting for 14.33% of total variance. The BDI II has proven to be more a reliable measure of depression with 0.89 according to the Cronbach’s Alpha co efficient opposed to 0.375 as per the HADS-D. The secondary aim was to establish the sociodemographic and disease profiles of the participants under study. / Magister Psychologiae - MPsych

There is a global rise in the use of herbal products in combination with allopathic medicines, while most patients do not inform their health care providers of the use of these natural products. Both pharmacodynamic and pharmacokinetic interactions between herbal products and conventional drugs must be avoided for the wellbeing of the patient. Increasing evidence from in vitro and in vivo studies indicate that changed drug pharmacokinetics by co-administered herbs may be attributed to modulation of efflux drug transporters such as P-glycoprotein (P-gp). Garlic (Allium sativum), lemon (Citrus limonum) and beetroot (Beta vulgaris) are widely used by human immunodeficiency virus (HIV) patients, especially following the pronouncement by a former President of South Africa and the Ministers of Health at that time who promoted the use of these botanicals in HIV patients. The aim of this study was to measure the bi-directional in vitro transport of indinavir, a protease inhibitor, in the presence of crude extracts and pure phytoconstituents of A. sativum (L-alliin and diallyl disulphide), C. limonum (hesperidin and eriocitrin) and B. vulgaris (betaine monohydrate and ß-carotene) across excised porcine intestinal tissue in Sweetana-Grass diffusion chambers. In the negative control group, the transport of indinavir alone (200 M) was determined with no modulator added. In the positive control group, the transport of indinavir was determined in the presence of verapamil (100 M), a known P-gp related efflux inhibitor. The control experiments were used to indicate that the effects of the test compounds were caused by their action and not by chance interferences or external factors. Samples collected at pre-determined time intervals were analysed by means of a validated high performance liquid chromatography (HPLC) method and the transport was expressed as the apparent permeability coefficient (Papp) and the transepithelial flux (J) from which the efflux ratio (ER) and the net flux (Jnet) values were calculated. Statistical analysis was used to compare the results of the test compounds with the control groups in order to indicate significant differences. The mean ER value for indinavir in the negative control group was 1.41 ± 0.170 and in the positive control group it was 0.56 ± 0.0426. Statistically significant (p < 0.05) inhibition of indinavir efflux as indicated by reduced ER values was obtained for L-alliin (ER = 0.280 ± 0.030), diallyl disulphide (ER = 0.505 ± 0.034) and ß-carotene (ER = 0.664 ± 0.075). Inhibition of indinavir efflux will lead to increased transport and therefore a potentially higher bioavailability. Statistically significant (p < 0.05) promotion of indinavir efflux as indicated by increased ER values was obtained for C. limonum crude extract (ER = 5.551 ± 0.575) and hesperidin (ER = 3.385 ± 0.477), which potentially may lead to lower bioavalability. B. vulgaris crude extract (p = 0.8452), betaine monohydrate (p = 0.9982), A. sativum crude extract (p = 0.7161) and eriocitrin (p = 0.4431) displayed no statistically significant effect compared to the negative control group on indinavir transport across excised porcine intestinal tissue. The results from this study demonstrate that L-alliin, diallyl disulphide and ß-carotene have an inhibitory effect on indinavir efflux, which may significantly increase indinavir plasma levels after oral administration. C. limonum crude extract and hesperidin promote indinavir efflux, which may significantly reduce indinavir plasma levels. These pharmacokinetic interactions between certain drugs and plant extracts may negatively affect the anti-retroviral treatment of HIV patients, but deliberate and controlled inclusion of L-alliin, diallyl disulphide and ß-carotene in dosage forms may possibly cause more effective delivery of protease inhibitors after oral administration resulting in less frequent dosing intervals. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

There is a global rise in the use of herbal products in combination with allopathic medicines, while most patients do not inform their health care providers of the use of these natural products. Both pharmacodynamic and pharmacokinetic interactions between herbal products and conventional drugs must be avoided for the wellbeing of the patient. Increasing evidence from in vitro and in vivo studies indicate that changed drug pharmacokinetics by co-administered herbs may be attributed to modulation of efflux drug transporters such as P-glycoprotein (P-gp). Garlic (Allium sativum), lemon (Citrus limonum) and beetroot (Beta vulgaris) are widely used by human immunodeficiency virus (HIV) patients, especially following the pronouncement by a former President of South Africa and the Ministers of Health at that time who promoted the use of these botanicals in HIV patients. The aim of this study was to measure the bi-directional in vitro transport of indinavir, a protease inhibitor, in the presence of crude extracts and pure phytoconstituents of A. sativum (L-alliin and diallyl disulphide), C. limonum (hesperidin and eriocitrin) and B. vulgaris (betaine monohydrate and ß-carotene) across excised porcine intestinal tissue in Sweetana-Grass diffusion chambers. In the negative control group, the transport of indinavir alone (200 M) was determined with no modulator added. In the positive control group, the transport of indinavir was determined in the presence of verapamil (100 M), a known P-gp related efflux inhibitor. The control experiments were used to indicate that the effects of the test compounds were caused by their action and not by chance interferences or external factors. Samples collected at pre-determined time intervals were analysed by means of a validated high performance liquid chromatography (HPLC) method and the transport was expressed as the apparent permeability coefficient (Papp) and the transepithelial flux (J) from which the efflux ratio (ER) and the net flux (Jnet) values were calculated. Statistical analysis was used to compare the results of the test compounds with the control groups in order to indicate significant differences. The mean ER value for indinavir in the negative control group was 1.41 ± 0.170 and in the positive control group it was 0.56 ± 0.0426. Statistically significant (p < 0.05) inhibition of indinavir efflux as indicated by reduced ER values was obtained for L-alliin (ER = 0.280 ± 0.030), diallyl disulphide (ER = 0.505 ± 0.034) and ß-carotene (ER = 0.664 ± 0.075). Inhibition of indinavir efflux will lead to increased transport and therefore a potentially higher bioavailability. Statistically significant (p < 0.05) promotion of indinavir efflux as indicated by increased ER values was obtained for C. limonum crude extract (ER = 5.551 ± 0.575) and hesperidin (ER = 3.385 ± 0.477), which potentially may lead to lower bioavalability. B. vulgaris crude extract (p = 0.8452), betaine monohydrate (p = 0.9982), A. sativum crude extract (p = 0.7161) and eriocitrin (p = 0.4431) displayed no statistically significant effect compared to the negative control group on indinavir transport across excised porcine intestinal tissue. The results from this study demonstrate that L-alliin, diallyl disulphide and ß-carotene have an inhibitory effect on indinavir efflux, which may significantly increase indinavir plasma levels after oral administration. C. limonum crude extract and hesperidin promote indinavir efflux, which may significantly reduce indinavir plasma levels. These pharmacokinetic interactions between certain drugs and plant extracts may negatively affect the anti-retroviral treatment of HIV patients, but deliberate and controlled inclusion of L-alliin, diallyl disulphide and ß-carotene in dosage forms may possibly cause more effective delivery of protease inhibitors after oral administration resulting in less frequent dosing intervals. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Registered nurses are exposed to the risk of Human Immunodeficiency Virus (HIV) infection and contracting the Acquired Immunodeficiency Syndrome (AIDS). Qualitative phenomenological research was conducted to explore registered nurses' experiences of working in such a high-risk environment and how their experiences influence the therapeutic relationship. A sample of registered nurses who care for HIV-infected persons or persons who suffer from AIDS was purposefully selected. Focus group interviews were conducted. Qualitative data analysis was performed. Frankl's theory of meaning of life served as a theoretical foundation for interpreting the research findings. The research results revealed that registered nurses experience existential frustration due to the intentional and unintentional risks that they are exposed to. This negatively impacts upon their ability to maintain a healthy therapeutic relationship with patients. However, evidence was obtained indicating that some factors support their quest for finding meaning in life in the workplace. / Health Studies / M.A. (Health Studies)

The treatment of human immunodeficiency virus (HIV-1) infection faces the challenge of drug resistance. The high mutation rate of HIV-1 allows it to develop resistance against all available drugs. New mechanisms of intervention that do not succumb to failure through resistance are thus being explored. Mutagens that increase the viral mutation rate are a promising class of drugs. They can drive HIV-1 past a critical mutation rate, called the error threshold, and induce a catastrophic loss of genetic information. The treatment duration for a mutagen to drive HIV-1 beyond this error threshold is not yet estimated. We devise a detailed stochastic simulation of HIV-1 infection to estimate this duration. The simulations predict that the required duration is inversely proportional to the difference between the mutation rate induced by a mutagen and the error threshold. This scaling is robust to changes in simulation parameters. Using this scaling, we estimate the required duration of treatment with mutagens to be many years. Unfortunately, all available drugs, including mutagens, fail to clear the infection because HIV-1 establishes a reservoir of latently infected cells harbouring silent HIV-1 integrated genomes. A new \shock and kill" strategy that aims to activate latent cells and render them susceptible to immune killing or viral cytopathicity and thus to eradicate the HIV-1 latent reservoir has been suggested. Several latency reversal agents (LRAs) have been developed. Individual LRAs fail to show any decline in the HIV-1 latent reservoir in clinical trials. Combinations of LRAs have been tested in a few in-vitro and ex-vivo experiments. It has been found that in combination LRAs act synergistically. Finding the drug concentrations that yield the maximum synergy may be helpful in achieving a sterilizing cure. Here, we develop an intracellular model to estimate these drug concentrations. We choose drugs from two different classes of LRAs and show that our model captures quantitatively recent in-vitro experiments of their activity individually and in combination. With this model, we estimate the concentrations of the drugs required to obtain the maximum synergy. Strong CD8+ T cell responses against viruses have been associated with low levels of viremia. Elite controllers of HIV-1, who are known to have low or undetectable viremia, mount a cross-reactive CD8+ T cell response against the pathogen which controls viral mutation-driven escape from immune activity. These cross-reactive responses are against specific epitopes of HIV-1. Our goal was to examine whether such epitopes could be identified systematically so that a cross-reactive immune response could be induced by using these epitopes as immunogens. Immune recognition of an epitope involves two parts: presentation of the epitope, or peptide, by the major histocompatibility complex (MHC) molecules in the host and high a finity binding of the peptide-MHC complex with a T cell receptor (TCR). Immune escape could occur at either of these steps. Here, we examined the first step. We devise the following procedure to identify peptides that sustain HLA binding despite mutations. First, from the full length HIV-1 (HCV) proteome, we identify viral peptides that bind tightly with MHC molecules using the software NetMHCpan2.8. Next, we pick the peptides and their complementary MHC molecules that yield tight binding and mutate the peptides bit by bit to examine whether binding was compromised. We identify several viral peptide-MHC pairs that display tight binding despite all possible single mutations of the peptides both with HIV-1 and HCV. These peptides present candidates which can be tested for their TCR binding and cross-reactive immunogenic potential.

Le développement de médicaments efficaces contre le virus de l'immunodéficience humaine (VIH) est l'une des plus grandes réussites dans l'histoire médicale récente: lorsque la thérapie combinée est devenu la norme des soins en 1996, une maladie mortelle a été progressivement transformée en une maladie chronique gérable. Les décennies suivantes ont été consacrées à l'élaboration des schémas thérapeutiques consolidés pour les adultes et les enfants, à la prévention de la transmission mère-enfant et à élargir l'accès à la thérapie antirétrovirale dans les pays en développement. La réussite d'un traitement antiviral de l'infection par le VIH est devenue un modèle pour l'élaboration de stratégies de traitement efficaces pour d'autres maladies virales, telles que les hépatites, les infections à herpesviridae, enteroviridae, et la grippe A et B. Cette thèse vise à tracer une ligne continue depuis : (1) de nouveaux modèles in vitro pour simuler un traitement combiné contre un VIH-1 multirésistant afin de promouvoir la sélection du régime le plus/ durable chez les patients en sauvetage thérapeutique, à (2) la meilleure approche e11 termes de coût-bénéfice pour la surveillance de la pharmacorésistance dans les cohortes de patients traités dans des milieux à faibles ressources, et enfin jusqu'à (3) une approche translationnelle vers la gestion du traitement de la grippe et la prédiction du développement- de virus résistants aux médicaments chez les enfants. Elle vise à fournir une synthèse des leçons apprises dans l'optimisation de stratégies de traitements antiviraux et de la prévention des résistances contre le VIH et le virus de fa grippe chez les adultes et les enfants. / The development or efficacious drugs against the human immunodeficiency virus is one of the greatest success stories in the recent medical history: when combination therapy became standard of care after the Vancouver Conference in 1996, a deadly disease was gradually turned into a manageable chronic condition. The following decades have been dedicated to developing consolidated treatment regimens for both adults and children, to the prevention of mother-to-child transmission and to expanding access to antiretroviral therapy (AR1) in developing countries. Subsequently, the success story of antiviral treatment of Hl V infection has become a model for tl1e development of successful treatment strategies for other viral diseases, such as hepatitis and infections with herpesviridae, enteroviridae and influenza A and B. This thesis aims to draw a continuous line from: (1) new in vitro models to simulate comhination therapy against multidrug-resistant HIV-1 promoting the selection of the most sustainable regimen in salvage patients, to (2) a cost-effective approach to monitoring drug resistance in treatment cohorts in low-resource settings, and finally to (3) a translational approach to managing influenza therapy and predicting the development of drug resistant influenza in children. The work presented herein aims to provide a comprehensive view of the lessons learned in optimizing antiviral treatment strategies against HIV and influenza virus in adults and children

Magister Public Health - MPH / Kangaroo mother care (KMC) was first initiated in Colombia due to shortages of incubators and the incidence of severe hospital infections of new-born infants during hospital stay (Feldman, 2004). Currently it is identified by UNICEF as a universally available and biologically sound method of care for all new-borns, particularly for low birth weight infants (Department of Reproductive Health and Research, 2003) in both developed and developing countries. The Western Cape Provincial Government implemented a policy on KMC as part of their strategy to decrease the morbidity and mortality of premature infants in 2003 (Kangaroo Mother Care Provincial task team, 2003). Essential components of KMC are: skin-to-skin contact for 24 hours per day (or as great a part of the day as possible), exclusive breastfeeding and support to the motherinfant dyad. Successful implementation of KMC requires relevant education of nurses, education of mothers on KMC by nursing staff, monitoring of the implementation of KMC by nurses, planning for a staff mix with varying levels of skill and experience with KMC, the identification of institution specific barriers to the implementation of KMC, and the implementation of institution specific strategies to overcome these barriers (Wallin,et al., 2005; Bergman & Jurisco, 1994; Cattaneo, et al., 1998). This study aims to determine the knowledge of and attitude towards kangaroo mother care, of nursing staff and kangaroo mothers in the Eastern sub-district of Cape Town. / South Africa

Magister Psychologiae - MPsych / The aim of the study was to establish what the perceptions and attitudes are of employees at different levels of the organisation with regard to HIV/AIDS testing. A further aim was to identify possible reasons for the poor employee response to voluntary HIV/AIDS testing. It was thus important for this research to gauge employee knowledge, attitude and behaviour toward HIV/AIDS in order for organisations to develop strategies for effective HIV/AIDS counselling and testing programmes.

Magister Artium (Social Work) - MA(SW) / The burden of HIV disease is concentrated in sub-Saharan Africa and South Africa (SA) is particularly affected. Whilst there have been many studies conducted on the biomedical and socio-psychological aspects of HIV and AIDS, insufficient attention has been paid to the quality of life of those infected with the virus. The primary purpose of this study was to determine the predictors of quality of life enjoyment and satisfaction (Q-LES) of individuals living with HIV and or AIDS and those on anti-retroviral treatment or being prepared for it. Further, the study determined the relationship between psychological distress and Q-LES of HIV positive individuals because psychological distress is reported to contribute substantially to the burden of the disease in sub-Saharan Africa, including SA. This quantitative study used a battery of questionnaires administered to 121 participants in an out-patient clinic setting. The main hypothesis tested in this study is: psychological distress is a strong predictor of Q-LES. The Hospital Anxiety and Depression Scale (HADS) was used to screen for psychological distress and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) to assess the various components of QoL. A purposive sampling strategy was used to recruit participants into the study. Data analysis included descriptive and inferential statistics using SPSS to test the hypothesis. Of the total sample (N=121), 74% were females. The study found that a large proportion (49.5%) of the sample within the age group 25-49 years old had significant presence of psychological distress. Those not on ART yet were significantly affected (66%). The relationship between Q-LES subscales and psychological distress was significant (p< 0.01). The results show that psychological distress was significantly prevalent among HIV positive individuals and it was the strongest predictor of Q-LES among the study participants. Modifying the current psychological intervention programmes, in the public health clinics, for individuals vi infected with the HI virus will assist in improving the current health outcomes and also help to achieve better Quality of Life outcomes.

The human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) is a worldwide pandemic that affects the lives of millions of people across all ages. Its devastating effects are far-reaching and affect all aspects of an individual’s daily life. HIV/AIDS is responsible for widespread clinical manifestations involving the head and neck. Disorders of the auditory and vestibular systems are often associated with HIV/AIDS, however the extent and nature of these vestibular manifestations is still largely unknown. The main aim of this research study was to investigate vestibular functioning and pathology in adults with HIV/AIDS. This was achieved through three main research steps: a systematic literature review of the body of peer-reviewed literature on HIV/AIDS related vestibular manifestations and pathology, a description and comparison of vestibular involvement in adults with and without HIV/AIDS and an investigation to determine if HIV/AIDS influence the vestibulocollic reflex (VCR) pathways. For the first study a systematic literature review related to vestibular findings in individuals with HIV infection and AIDS was conducted. A varied search strategy was used across several electronic databases to identify relevant peer-reviewed reports in English. Several databases (Medline, Scopus and PubMed) and search strategies were employed. Where abstracts were not available, the full paper was reviewed, and excluded if not directly relevant to the study’s aims. Articles were reviewed for any HIV/AIDS associated vestibular symptoms and pathologies reported. For the second and third study, a cross-sectional, quasi-experimental comparative research design was employed. A convenience sampling method was used to recruit subjects. The sample consisted of 53 adults (29 male, 24 female, aged 23-49 years, mean = 38.5, SD = 4.4) infected with HIV, compared to a control group of 38 HIV negative adults (18 male, 20 female, aged 20-49 years, mean = 36.9, SD = 8.2). A structured interview probed the subjective perception of vestibular complaints and symptoms. Medical records were reviewed for cluster of differentiation 4+ (CD4+) cell counts and the use of antiretroviral (ARV) medication. An otologic assessment and a comprehensive vestibular assessment (bedside assessments, vestibular evoked myogenic potentials, ocular motor and positional tests and bithermal caloric irrigation) were conducted on all subjects. The systematic literature review identified 442 records, reduced to 210 after excluding duplicates, reviews, editorials, notes, letters and short surveys. These were reviewed for relevance to the scope of the study. There were only 13 reports investigating vestibular functioning and pathology in individuals affected by HIV/AIDS. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance. The second study showed an overall vestibular involvement in 79.2% of subjects with HIV in all categories of disease progression, compared to 18.4% in those without HIV. Vestibular involvement increased from 18.9% in the Centers for Disease Control and Prevention (CDC) category 1 to 30.2% in category 2. Vestibular involvement was 30.1% in category 3. There was vestibular involvement in 35.9% of symptomatic HIV positive subjects and 41.5% in asymptomatic HIV positive subjects. Individuals with HIV were 16.6 times more likely to develop vestibular involvement during their lifetime, than among individuals without this disease. Vestibular involvement may occur despite being asymptomatic. The third study showed that abnormal cervical vestibular evoked myogenic potentials and caloric results were significantly higher in the HIV positive group (p=.001), with an odds ratio of 10.2. Vestibulocollic reflex and vestibulo-ocular reflex involvement increased with progression of the disease. There were more abnormal test results in subjects using ARV therapies (66.7%) compared to those not using ARV therapies (63.6%), but this difference was not statistically significant. Vestibular involvement was significantly more common in subjects with HIV than among those without this disease. This disease and its associated risk profile include direct effects of the virus on the vestibular system as demonstrated by postmortem studies. Opportunistic infections may compromise the functioning of the sensory and neural structures of hearing and the vestibular system indirectly, causing vertigo, dizziness or disequilibrium. Ototoxicity may also be related to vestibular dysfunction, due to the ototoxic nature of certain ARV medications. HIV/AIDS influence not only the vestibulo-ocular reflex, but also the vestibulocollic reflex pathways. Primary health care providers could screen HIV positive patients to ascertain if there are symptoms of vestibular involvement. If there are any, then they may consider further vestibular assessments and subsequent vestibular rehabilitation therapy, to minimize functional limitations of quality of life. / Thesis (DPhil)--University of Pretoria, 2014. / lk2014 / Speech-Language Pathology and Audiology / DPhil / Unrestricted