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Thesis (MSc Virology)--University of Limpopo, 2010. / OBJECTIVES: To date there is no effective and safe vaccine to stop the spread of human immunodeficiency virus (HIV) and provide cross protection among different subtypes. HIV accessory genes were overlooked for many years and recently they are becoming candidates for development of new anti-HIV drugs and vaccines. This is supported by their ability to elicit cytotoxic T lymphocyte response. To date, there are limited studies on accessory genes (nef, vif, vpr and vpu) on South African HIV strains. This study sought to amplify and analyse the sequences of HIV-1 subtype C accessory genes (vif, vpr and vpu) to assess the genetic diversity as well as the motifs and residues associated with key biological functions of these genes. This study further sought to compare the degree of genetic diversity between the accessory and structural genes. METHODS: The study was an exploratory study using stored (-70ºC) HIV positive plasma samples. The study population comprised of 25 HIV positive plasma samples which were already sequenced in the gag and env genes in another study. The samples were drawn from the neighbouring townships of Pretoria: Ga-Rankuwa, Soshanguve, Mamelodi, Laudium, Kalafong, Jubilee and Mabopane. For the purpose of this study, the same samples were amplified, sequenced and characterised in the pol and accessory (vif, vpr and vpu) genes in order to obtain near full length sequences of the HIV isolates from Pretoria region. Six samples were cloned for accessory genes. Five clones from each sample were selected. Sequence analysis was performed for all the PCR amplicons and clones. Base calling for the sequences generated was performed on Chromas Pro program. Computing of phylogenetic tree was performed with MEGA 4 program. ClustalW software was used for sequence alignment and translation of nucleotides to amino acids was performed with BioEdit. The amino acid alignments were analysed on graphic view. RESULTS: All 25 samples were successfully amplified for accessory genes (vif, vpr and vpu) and pol gene. All the 25 pol PCR amplicons were successfully sequenced, while all but one accessory PCR amplicons were successfully sequenced. A number of conserved motifs and residues were observed in all the four genes (vif, vpr, vpu and pol). Vif and vpr showed to harbour most of these conserved motifs and residues; 144-SLQYLA-149 and H71 respectively. In addition, the R77Q mutation associated with long term non-progressors was observed in the vpr gene of 15 sequences. Drug resistant mutations were evaluated in both protease and RT regions. Nine samples had one or two drug resistant mutations i.e T74S, L10I, V179D, E138A/D, Y318F,Y181C and K108N. Phylogenetic analysis confirmed the 25 HIV positive samples to be HIV-1 subtype C in both structural and accessory genes. The genetic diversity of HIV-1 subtype C was compared between accessory (vif, vpr and vpu) and structural (pol, gag and env) genes. The gag and env sequences were available from a previous project (Musyoki, 2009). The gag and vif gene sequences were highly conserved (89% to 96% and 88% to 96%, respectively), as compared to vpr gene (84% to 94%), the pol gene (79% to 95%), the env gene (83% to 93%) and finally the vpu gene (73% to 92%). CONCLUSION: This study found that amplification of clones was more sensitive as compared to direct samples and analysis of clone sequences was more clear than analysis of direct PCR products. Functional motifs and residues observed in all accessory genes were highly conserved. Vif was more conserved, followed by vpr and vpu, respectively. Genetic analysis of pol gene revealed that there were drug resistant strains in circulation. This indicates that the patients were infected with drug resistant viruses; this cannot be verified from the study population. And that most of the strains in this study had mutations associated with long term non-progressors (LTNP’s). However, it is not known whether these patients were indeed LTNP’s. Comparison of genetic diversity between structural and accessory genes demonstrated that, gag, vif and vpr were more conserved than pol, env and vpu.

Thesis M. Med.(Family Medicine))--University of Limpopo (Medunsa Campus), 2010. / Background The use of HAART in HIV/AIDS patients has been recognised worldwide to improve the quality of life and survival prospects. Neverthess, factors such as WHO clinical stage III-IV, CD4< 200, VL> 100,000, anaemia, blood transfusion, malnutrition, male gender, intravenous drug use, drug toxicity, HAART experienced by patients, hospitalization, older age and depression have been reported to be associated with negative outcomes whereas, in contrast, white ethnicity, adherence > 90%, antiretroviral naïve subjects, longer period of viral suppression, younger age, and female gender have been reported to be associated with positive clinical outcomes. Methods The researcher conducted a descriptive retrospective study of 78 systematically selected patients who initiated HAART during the period of 5 June 2007 to 5 December 2008. Data regarding demographics, nutritional status, patients’ opportunistic infections, patients’ use of ARV drugs and HAART regimens, side effects and adverse events, baseline and follow up measurements of CD4 cell count, VL, ALT and Hb were collected at initiation, 6 and 12 months of HAART and analysed, utilizing descriptive statistics. Results Of the 78 patients recruited for the study, 60 (77%) were females and 18 (23%) males, 77 (98.8%) black and 1 (1.2%) coloured. The majority of patients belonged to the two age-groups 26-35 years (35.9%), and 36-45 (37.2%). The majority of patients [73/78 (93.4%)] were unemployed and residents of Vryburg town. Nutritionally, 17/78 (21.8%) patients were underweight. Clinically, 79.4% were classified as WHO clinical stage III - IV. The mean weight improved in both sex at 6 and 12 months of HAART respectively, from 57.5kg (SD 8.0) to 63.0kg (SD 13.0) and 65.2kg (SD 4.5) for males. 12 Conclusion The administration of HAART to patients attending ARV clinic at Vryburg District Hospital was followed by better clinical outcomes in terms of weight gain, correction of anaemia, increase in CD4 and achievement of virological suppression. Female gender, VL > 100,000 copies/ml, Younger age (< 46 years) and good adherence were found to have positive influence on clinical outcomes.

Thesis (M. Med.(Family Medicine))--University of Limpopo (Medunsa Campus), 2010. / A study on Factors associated with non-disclosure of HIV positive status to sexual partners by adult patients attending the VCT clinic at Nhlangano health centre, Swaziland. Aim: To describe the factors associated with non-disclosure of known HIV sero-positive status to sexual partners by adult patients attending the VCT clinic at Nhlangano health center, Swaziland. Design:- Cross-sectional study using questionnaire administered by a trained research assistant. Setting:- Nhlangano health center VCT clinic, Nhlangano town in the Shiselweni region, Southern Swaziland. Study population:- All adult patients above the age of 18 years who had undergone HIV testing, who knew their positive HIV status and had follow up visits at the VCT clinic of Nhlangano health centre, from November 2005 (when the centre started rendering VCT service) till the beginning of the data collection, in September, 2008. Results:-The vast majority (89.1%) disclosed their positive HIV status to their sexual partners and 94.6% believed that letting their sexual partner/s know about their HIV status was very important. In terms of knowing the HIV status of their partners, 55.4% knew the HIV status of all of their sexual partners and 44.6% knew only the status of the regular partner/s. With regard to condom use, 96.7% believed that using condoms helps them to prevent transmission of HIV and 91.3% expected that letting their partners know about their HIV status would help them use condom IV more frequently. Only 53.3% said they would insist on condom use even if their partner is not willing to use. Conclusion:-  The rate of positive HIV status disclosure to sexual partner found in this study compared to many studies done in other settings is considerably high. This is encouraging especially considering the existing very high prevalence of HIV infection in the country. Despite this though, knowing partner's HIV status was relatively lower. Therefore, people are more likely to share their HIV status with a partner than insist that the partner does the same.  Even though the study was done only amongst patients attending VCT, it is important to note that the majority of the patients had positive attitudes about HIV status disclosure to a partner, and believed in the importance of letting their sexual partner/s know about their HIV status. Patients understood the unethical nature of engaging into sexual intercourse without disclosing their positive HIV status to their partner. It is possible to conclude that factors which contributed to these positive results should be implemented at a larger scale, namely creating awareness, health education, good counseling and follow up of treatment.  Awareness of the importance of condom use in preventing HIV transmission (including the fact that disclosure of HIV status to a partner enhances its better use) was impressively high amongst almost all participants. But it is worrisome that only half of the participants said they would insist on condom use irrespective of their partners’ willingness to use it or not. V  The variables that were found to be independently associated with disclosure to a partner comparing those who disclosed with those who did not were gender, age, marital status, education, number of sexual partners, and stage of the HIV condition.

Thesis (M Cur)-- University of Limpopo, 2012. / ABSTRACT Background and problem statement The increase in AIDS related deaths of parents leave many children orphaned and some of these children live with HIV. These children are cared for by primary caregivers who are mostly elderly women. The primary caregivers experiences challenges when caring for the children living with HIV. These challenges may be physical, spiritual, psychological and social. The researcher conducted a study in order to explore the experiences of primary caregivers caring for children living with HIV. Aim and objectives The aim of the study was to promote the mental health of primary caregivers who provide care for children living with HIV attending the Wellness Clinic at the Jubilee Hospital in Hammanskraal. The objectives of this study were to: i) describe the biographical data of primary caregivers who provide care for children living with HIV; ii) explore and describe the experiences of primary caregivers who provide care for children living - with HIV; and iii) make recommendations which are based on the findings of this study in order to assist the nursing personnel at the Wellness Clinic in the promotion of the mental health of primary caregivers based on the findings of this study. Research Design and method A qualitative, exploratory, descriptive and contextual design was utilised to enable the primary caregivers to share with the researchers their experiences of caring for children living with HIV. The setting was the Wellness Clinic at the Jubilee hospital, Hammanskraal. Ethical principles were adhered to in order to protect the rights of the primary caregivers. Throughout the process, the methods to ensyre trustworthiness of the study were foll9wed. A purposive sample of eight primary caregivers was chosen for the unstructured interviews. Data were analysed by the researcher and an independent coder using the Tescn method. Research Findings Consensus was reached after consultation with an independent coder,- about the following categories i) primary caregivers' experiences in caring for a child living with HIV related to the self of the caregiver; ii) primary caregivers' experiences related to the decision to disclose the child's HIV status to various role-players were influenced by stigmatisation and discrimination related to HIV and AIDS; iii) primary caregivers' challenges when caring for a child living with HIV; and iv) the mobilisation of resources by primary caregivers to assist them in caring for a child living with HIV. Findings were contexualised by implementing a literature control and recommendations were made to promote their mental health. Conclusions Primary caregivers who cared for children living with HIV in this study were mostly elderly women who were related to the children. They took over the care of the children living with HIV after the children's parents had died. Although they were faced with many challenges, their concern for the children's wellbeing made them to give the children loving care. They found strength and support from prayer, faith and hope in God. The primary caregivers also appreciated the support they received from the health care workers at the Well"ness Clinic. Key words: caring, mental health, HIV, children, primary caregiver

Thesis (MPH) -- University of Limpopo, 2011. / Introduction HIV/AIDS is major cause of child mortality and an increase in the number of sick children presenting to health services worldwide (UNICEF 2008). A significant number of children live with HIV/AIDS in South Africa. Research indicates that in poor resourced countries, there is an increase in the prevalence of hospital admissions and re-admissions among HIV infected children as compared to developed countries. Research data on hospital admissions, treatment and care of HIV positive children South Africa is limited. Objectives This study was therefore initiated to determine the demographic and clinical causes of HIV positive children admitted and readmitted at the paediatric ward of Dr George Mukhari Hospital (DGMH), South Africa in the year 2003. Methods This was mainly a descriptive quantitative study using medical records of HIV infected children admitted and readmitted in the paediatric ward of DGMH from 1st January to 31st December 2003. A full census of all the records of children admitted in the two paediatric wards was carried out. Descriptive and inferential statistics were used to analyze data. Results The study comprised 74 children, 28 (37.8%) female and 48 (62.2%) males. The average mean of initial admission length of hospital stay was 12.3 days and (SD = 12.1) days. The different diagnoses were classified in accordance with World Health Organization (WHO) Clinical Staging of HIV disease for infants and children with established HIV infection. Out of a total of 581 initial admissions, 74 (12.7%) children were readmitted. The mean interval days between the discharge date and readmission date was 9.8 days (SD = 7.0 days) and 94.6% of the readmissions occurred within the first two weeks of discharge date. Second readmission decreased by 75.3% as only 18 patients were readmitted. A further 95.9% decrease in the third readmission was noted with only 3 patients getting readmitted. iv The commonest causes of admission with HIV were broncho-pneumonia, gastro-enteritis, vomitting, oral thrush, immunosuppression with symptoms like fever,cough, respiratory distress. Causes of readmissions were broncho-pneumonia, oral thrush, diarrhoea, vomitting, immunosuppression, pulmonary tuberculosis, wasting and failure to thrive, dehydration associated with symptoms like fever, cough, respiratory distress and upper respiratory distress. Conclusion The rate of readmission was (12.7%) and majority of the readmitted children were in the 0- 2-year age group. The study results show a high prevalence of diseases of the respiratory system with a high frequency of broncho-pneumonia and a high prevalence of diseases of the digestive system with a high frequency of gastro-enteritis. The average mean of the initial hospital admission stay was 12.3 days, which was significantly higher than other studies previously conducted. The probable reason for a long hospital stay could be the high prevalence of co-infections among the children admitted.

Thesis (MPH) -- University of Limpopo, 2011. / Introduction With the increased availability of the life-saving ARVs in most Sub-Saharan Africa more HIV -infected children are surviving into their adolescent years and beyond hence giving rise to the question of whether the caregiver should disclose or not disclose the child's HIV diagnosis to child. Little is known of the reasons and experiences that motive or hinder caregivers from disclosing the HIV diagnosis to the child. Study Aim and objectives This was aimed at identifying caregivers' reasons for HIV diagnosis disclosure and non-disclosure to HIV-infected children under their care. The study also explores their experience with process of HIV diagnosis disclosure and non-disclosure to the child. Study methodology Using qualitative descriptive research approach, twenty (20) caregivers of HIV¬infected children aged between 6 - 16 years receiving ART at Thamaga Primary Hospital IDee with unknown HIV diagnosis disclo~ure status were ~.ubjected to audio-taped in-depth interviews for data capturing. Thematic content analysis was used for data analysis using, Nvivo8 software and 16 themes with their sub categories were identified. Findings Both caregivers of disclosed and non-disclosed HIV-infected children perceived disclosure as a good thing to do with majority of the caregivers (60%) having disclosed. Reasons for telling the children their HIV diagnosis were that the child had the right to know his/her status; caregiver tired of keeping child HIV diagnosis a secret; the caregiver's believe that disclosure will improve the child's ART adherence and finally some caregivers felt the child had reached the right age or maturity for disclosure. Non-disclosing caregivers felt that health care workers should assist them in doing disclosure and identified the reasons for non-disclosure as the child being too young and not asking questions about their illness; fear that disclosure might hurt the child psychologically; fear that the child might not keep their HIV diagnosis a secret leading to discrimination in the community while some caregivers lack of knowledge on how to disclose. Non-disclosing caregivers managed disclosure by not telling the child the truth about their diagnosis and using threats to coerce them to take their ARV drugs. Conclusions and recommendations The decision to disclosure or not to disclose the HIV diagnosis to a child by a caregiver is influenced by a number of reasons and their experiences. Caregivers of HIV-infected children need to be assisted by a health care provider when disclosing to the child and further assessment should be made in making disclosure part of the holistic management of an HIV -infected child. v

Thesis (M. Med. Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 75-86).

A series of epidemiological studies are presented of cancer risk after kidney transplantation and in human immunodeficiency virus (HIV) infection, based on data linkage between Australian, nationwide, population-based cohorts of kidney transplant recipients, people with HIV, and cancer. Risk factors were studied for the two most commonly registered cancers after kidney transplantation, lip cancer and non-Hodgkin lymphoma (NHL). The importance of established risk factors for lip cancer was confirmed, including exposure to solar ultraviolet radiation (UVR) and tobacco smoking. New evidence was observed of an association with immunosuppressive agents which potentiate UVR-related cellular damage, which may have broader implications for non-melanoma skin cancer risk in this setting. Clinic-based data suggest that NHL arising early and late after transplantation may be aetiologically distinct. Results observed herein support the possibility of two mechanisms of lymphomagenesis: one predominantly of primary Epstein Barr virus infection during intense immunosuppression and another, of dysregulated lymphoid proliferation in the context of prolonged immunosuppression. Importantly, risk of NHL was observed to persist even ten years after transplantation. For both lip cancer and NHL, risk was significantly reduced on transplant failure and reinstitution of dialysis when immunosuppression is usually ceased. The effect on cancer risk of reduction of immunosuppression was investigated for infection-related and other cancers. Risk was significantly reduced for some other infection- and immunodeficiency-related cancers including Kaposi sarcoma (KS) and melanoma, and non-significantly for anogenital cancers. No effect on risk was observed for cancers of the stomach, leukaemia, or the common epithelial cancers. Risk was significantly higher on reinstitution of dialysis for thyroid cancer. Cancer incidence was examined in HIV infection since the introduction of effective antiretroviral therapy and the reduction in the extent of HIV-related immunosuppression. The patterns observed were entirely consistent with those seen in kidney transplant recipients. Rates of KS, NHL and melanoma declined significantly, whereas rates of anal cancer remained stable. Rates of lung cancer and leukaemia were unchanged. Rates of prostate and colorectal cancers were consistently lower than general population rates. These observations highlight the differential role of current immune function and argue against a generalised effect of immunosurveillance in cancer prevention.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.