Currently, HIV/AIDS is one of the greatest threats to child survival in South Africa. It is estimated that approximately 6000 newborn babies become infected with the HIV virus monthly i.e. approximately 200 babies per day. During a 24 month period (October 1999 &ndash / October 2001), a descriptive prevalence study of the oro-facial manifestations affecting HIV-positive children was conducted in the Cape Peninsula, South Africa. The study population consisted of 268 vertically infected HIV-positive children. The study was motivated by the lack of data regarding oral mucosal lesions in children with vertically acquired HIV-infection.<br /> <br /> The study design was descriptive, and the population included consecutive, vertically infected HIV-positive patients sourced from out-patient clinics, hospital wards and special child-care facilities. The children were examined once consent was obtained from caregivers. The findings were documented using data capturing sheets. The data was captured on the Microsoft Excel program and analysed using the Epi 2000 program. The results indicated that a large proportion of HIV-infected children presented with orofacial manifestations at some stage during the course of HIV-infection. Oro-facial manifestations were observed in 70.1% of the study population. The prevalence of the most commonly observed manifestations were: oral candidiasis, 38.8% / parotid gland enlargement, 10.8% / oral ulceration, 5.6% / molluscum contagiosum, 7.8% / periodontal conditions, 3.4% / and herpes simplex infection, 0.7%.It can be concluded that in this sample of HIV-infected children, the prevalence of orofacial manifestations is higher than, and comparable with the findings of similar studies conducted in other regions of the world.

Indiana University-Purdue University Indianapolis (IUPUI) / Pneumocystis pneumonia (PCP) is the leading opportunistic disease in immunocompromised individuals, particularly in AIDS patients. The alveolar macrophage (AM) is the major type of cell responsible for the clearance of Pneumocystis organisms; however, they undergo a high rate of apoptosis during PCP due to increased intracellular polyamine levels. This study examined the mechanism of this polyamine mediated apoptosis and investigated an alternative therapy for PCP by targeting this mechanism. The elevated polyamine levels were determined to be caused by increased polyamine synthesis and uptake. Increased polyamine uptake was found to be AM-specific, and recruited inflammatory cells including monocytes, B cells, and CD8+ T cells were found to be a potential source of polyamines. The expression of the antizyme inhibitor (AZI), which regulates both polyamine synthesis and uptake, was found to be greatly up-regulated in AMs during PCP. AZI overexpression was confirmed to be the cause of increased polyamine synthesis and uptake and apoptosis of AMs during PCP by gene knockdown assays. Pneumocystis organisms and zymosan were found to induce AZI overexpression in AMs, suggesting that the β-glucan of the Pneumocystis cell wall is responsible for this AZI up-regulation. In addition, levels of mRNA, protein, and activity of polyamine oxidase (PAO) were also found to be increased in AMs during PCP, and its substrates N1-acetylspermidine and N1-acetylspermine were found to induce its up-regulation. These results indicate that the H2O2 generated during PAO-mediated polyamine catabolism caused AMs to undergo apoptosis. Since increased polyamine uptake was demonstrated to be a pathogenic mechanism of PCP in this study, the potential therapeutic activity of five putative polyamine transport inhibitors against PCP was tested. Results showed that compound 44-Ant-44 significantly decreased pulmonary inflammation, organism burden, and macrophage apoptosis, and prolonged the survival of rats with PCP. In summary, this study demonstrated that Pneumocystis organisms induce AZI overexpression, leading to increased polyamine synthesis, uptake, and apoptosis rate in AMs and that targeting polyamine transport is a viable therapeutic approach against PCP.

No description available.

Thesis (MPH.) --Univesity of Limpopo, 2014 / Background: The main goal of HAART is to achieve maximal viral suppression. However, with poor adherence to therapy the chances of achieving and maintaining successful viral suppression are decreased, leading to virological failure. And virological failure has been recognized by WHO as one of the early warning signs of drug resistance. This operational research sought to explore virological failure as a treatment outcome to evaluate program performance at a facility level. Methods: Purposive sampling as per inclusion and exclusion criteria was used to retrospectively review clinical records of the first 700 adult HIV positive patients (350 males and 350 females) who initiated antiretroviral treatment between April 2004 and December 2007 at this adult HIV clinic, were followed up for at least 3 years and treated according to the South African government’s National Department of Health 2004 HIV treatment guidelines for adults and adolescents. Major Results: 268 clinical records, 97 (27.71%) male and 171 (58.86%) female records were eligible for inclusion in the study. The proportion of females was higher (63.8%) than males (32.8%) with an average age of 38.95 years. 24 (8.9%) patients in the study sample experienced virological failure during the study period; 11 (11.3%) males and 13 (7.6%) females. Two-thirds (66.6%) of patients who failed to suppress at their first viral load measurement proceeded to develop virological failure. Overall, there was no association of statistical significance between age, sex, baseline CD4 cell count and baseline regimen, and virological failure at various intervals, p> 0.05. Conclusion: It was a challenge to keep patients in care but those that remained in care had good treatment outcomes with only 8.9% developing virological failure. Failure to suppress at first viral load preceded virological failure in the majority of patients.

The HIV/AIDS pandemic has had a seriously negative impact on the South African workplace, with industries experiencing the many adverse effects of the disease such as the problem of absenteeism. Other effects of HIV/AIDS at the workplace include loss of productivity and profitability, especially if the disease is not managed properly. The aim of this study was to investigate the effects of HIV/AIDS within the private medical practice industry in Umlazi Township, in the Province of KwaZulu Natal. The research methodology used was quantitative. There are only 40 private medical practices in Umlazi Township. The entire population of private medical practices is included in the sample because of the manageable population size. No sampling method was therefore used. Close-ended questionnaires ware hand delivered to all the doctors in all the private medical practices in Umlazi. The questionnaires were collected once the doctor indicated that s/he completed it. The salient finding of this study were that HIV/AIDS induced absenteeism is a major challenge for private medical practitioners. A good HIV/AIDS policy is necessary for the medical doctors to effectively manage HIV/AIDS at their private medical practices. While the respondents acknowledged the effectiveness of an HIV/AIDS policy if implemented, they understood that it would be difficult to implement it. Because of its effect on business sustainability, HIV/AIDS can result in serious problems for private medical practices, including bankruptcy. The recommendations of the study are for private medical practices to implement their own HIV/AIDS policy – which must encompasses education, training and treatment of those that are infected and/or affected by HIV/AIDS. The study highly recommends and encourages staff to undergo VCT (Voluntary Counselling and Testing) so that the disease can be identified early – which makes management of it timely, and more effective. / Thesis (MBA)-University of KwaZulu-Natal, Durban, 2012.

HIV drug resistance (HIVDR) has emerged as a major clinical and public health challenge in many resource poor countries especially in Africa. HIVDR testing has become increasingly important and is of significant value in the management of HIV. The use of low cost technologies and procedures in testing HIVDR is being recommended. HIVDR computer interpretation algorithms make use of artificial intelligence and other computer technologies to predict HIVDR, and are recommended for use in resource poor countries. However, there is little known about the knowledge, attitude and perception of HIVDR computer algorithms by doctors in developing countries who are supposed to use computer algorithms. This study aimed to determine the knowledge, attitude and perception regarding computer interpretation algorithms of the 4th and 5th year medical students at Nelson R. Mandela School of Medicine, University of KwaZulu Natal in South Africa. Primary data collection was done using a questionnaire administered to a convenience sample of 216 4th and 5th year medical students. The study revealed that 90% of the respondents were aware of HIV drug resistance testing in South Africa but only 4% had knowledge of the computer interpretation algorithms. The study revealed that although the UKZN medical students are not aware of computer interpretation algorithms, majority are willing to use them in the future. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2013.

Thesis (MSc)--Stellenbosch University, 2002. / ENGLISH ABSTRACT: The aim of this study at the Brooklyn Chest Hospital (BCH) was to assess the change in the oral carriage of Candida species in twenty-nine patients co-infected with the Human Immunodeficiency Virus (HIV) and Tuberculosis (TB), before and after anti-fungal treatment. Each patient accepted onto the study underwent a comprehensive oral and peri-oral examination where the presence, site and clinical features of all oral and peri-oral lesions were recorded. The purpose of the examination was to provide a clinical diagnosis of oral candidasis. Each patient was also asked to provide a sample of oral fluid for laboratory analysis. This was collected using an oral rinse. The results of a variety of laboratory investigations were used to identify the species of Candida obtained from the oral rinse. Both the oral and peri-oral examination and the oral rinse procedure were repeated after one month and at three months. A sample from each oral rinse was inoculated on CHROMagar Candida chromogenic medium (CHROMagar Candida, France, Paris). CHROMagar is used for the isolation and presumptive identification of Candida sp. from other yeasts on the basis of strongly contrasted colony colours, which are produced by the reactions of species-specific enzymes with a proprietary chromogenic substrate. After forty-eight hours the CHROMagar plate was examined for growth, when a record of colony morphology and colour was made. A single sample from each different colour-coded colony was taken and streaked onto a Sabouraud plate (Oxoid, Basingstake, England) and then incubated for forty eight hours at thirty-seven degrees centigrade. A variety of laboratory investigations were subsequently carried out on a single colony taken from the Sabouraud agar plate (Oxoid). The results of these tests were used to identify the individual species of Candida isolated from each oral rinse. Oral candidasis was the most prevalent oral lesion observed on admission and at three months. Six different species of Candida were identified during this study, namely Candida albicans, Candida dubliniensis, Candida krusei, Candida glabrata, Candida parapsilosis, and Candida tropicalis. C.albicans was the most commonly identified species in study population. Candida dubliniensis was isolated and identified for the first time in a South African HIV population. Each specimen of Candida sp. identified by laboratory analysis was tested for sensitivity to Nystatin, Amphotericin B and Fluconazole anti-fungal agents. An additional sensitivity test was performed using Ajoene and Allicin (extracts of garlic) to assess the comparative antifungal properties of these compounds. / AFRIKAANSE OPSOMMING: Die doelwit van hierdie studie by die Brooklyn Borshospitaal (BCH) was om die verandering in orale draerstatus van die Kandida spesies in nege-en-twintig HIVfTB koïnfekteerde pasiënte vas te stel, voor- en na antifungale behandeling. Elke pasiënt in die studie het 'n volledige intra- en ekstra-orale ondersoek ondergaan. Die teenwoordigheid, area en kliniese voorkoms van alle letsels is noteer. Die doel van die ondersoek was om 'n kliniese diagnose van orale kandidiase te verkry. 'n Monster orale vloeistof is geneem van elke pasiënt vir laboratorium analise. Die monster is in die vorm van 'n mondspoel geneem. Verskeie toetse is gedoen om die verskillende Kandida spesies in elke monster te identifiseer. Die orale- en ekstra-orale ondersoek sowel as die mondspoelmonster is na 1 en 3 maande herhaal. Elke mondspoelmonster is op CHROMagar Kandida chromogene medium (CHROMagar Candida, France) inokuleer. CHROMagar word gebruik vir die vermoedelike identifikasie en isolasie van Kandida spesies teenoor ander swamme. Dit word gedoen op die basis van kontrasterende koloniekleure, wat teweeggebring word deur spesie-spesifieke ensiemreaksies op 'n chromogene substraat. Die CHROMagar plate is na 48 uur ondersoek vir groei en die kolonie-morfologie en - kleur is noteer. 'n Enkel monster. is geneem van elke verskillende kolonie (geskei op kleur) en is uitgestreep op 'n Saboraud plaat (Oxoid, Basingstoke, England). Dit is dan vir 48 uur inkubeer teen 37°C. Verskeie laboratorium ondersoeke is daarna uitgevoer op 'n enkel kolonie geneem vanaf die Saboraud agar plaat (oxoid). Die resultate van die ondersoeke is gebruik om individuele spesies van Kandida te identifiseer. Orale Kandidiase was die mees algemene orale letsel geïdentifiseer by toelating en 3 maande ondersoeke. Ses verskillende spesies Kandida is identifiseer tydens die studie, naamlik: Kandida albicans, K.dubliniensis, K.Krusei, K.glabrata, K.parapsilosis en K.tropicalis. K.albicans was die mees algemeen identifiseerde spesie in die studiepopulasie. K.dubliniensis is vir die eerste keer in Suid-Afrika in 'n HIV<+lpopulasie isoleer en geïdentifiseer. Elke monster van identifiseerde Kandida spesies is getoets vir sensitiwiteit teenoor Nistatien, Amfotensien B en Flukonasool. Addisioneel is ook getoets vir sensitiwiteit teenoor Ajoene en Allicin (knoffelekstrakte).

Indiana University-Purdue University Indianapolis (IUPUI) / With effective antiretroviral therapy (ART), cardiovascular diseases (CVD), are emerging as a major cause of morbidity and death in the aging population with HIV infection. Although this increase in CVD could be partially explained by the toxic effects of combined anti-retroviral therapy (ART), more recently, HIV infection has emerged as an independent risk factor for CVD. However, it is unclear how HIV can contribute to CVD in patients on ART, when viral titers are low or non-detectable. Here, we provide several lines of evidence that HIV-Nef, produced in infected cells even when virus production is halted by ART, can lead to endothelial activation and dysfunction, and thus may be involved in CVD. We demonstrate that HIV-infected T cell-induced endothelial cell activation requires direct contact as well as functional HIV-Nef. Nef protein from either HIV-infected or Nef-transfected T cells rapidly transfers to endothelial cells while inducing nanotube-like conduits connecting T cells to endothelial cells. This transfer or transfection of endothelial cells results in endothelial apoptosis, ROS generation and release of monocyte attractant protein-1 (MCP-1). A Nef SH3 binding site mutant abolishes Nef-induced apoptosis and ROS formation and reduces MCP-1 production in endothelial cells, suggesting that the Nef SH3 binding site is critical for Nef effects on endothelial cells. Nef induces apoptosis of endothelial cells through both NADPH oxidase- and ROS-dependent mechanisms, while Nef-induced MCP-1 production is NF-kB dependent. Importantly, Nef can be found in CD4 positive and bystander circulating blood cells in patients receiving virally suppressive ART, and in the endothelium of chimeric SIV-infected macaques. Together, these data indicate that Nef could exert pro-atherogenic effects on the endothelium even when HIV infection is controlled and that inhibition of Nef-associated pathways may be promising new therapeutic targets for reducing the risk for cardiovascular disease in the HIV-infected population.

Indiana University-Purdue University Indianapolis (IUPUI) / Magnetic resonance (MR) spectroscopy is a neuroimaging technique. It is widely used to quantify the concentration of important metabolites in a brain tissue. Imbalance in concentration of brain metabolites has been found to be associated with development of neurological impairment. There has been increasing trend of using MR spectroscopy as a diagnosis tool for neurological disorders. We established statistical methodology to analyze data obtained from the MR spectroscopy in the context of the HIV associated neurological disorder. First, we have developed novel methodology to study the association of marker of neurological disorder with MR spectrum from brain and how this association evolves with time. The entire problem fits into the framework of scalar-on-function regression model with individual spectrum being the functional predictor. We have extended one of the existing cross-sectional scalar-on-function regression techniques to longitudinal set-up. Advantage of proposed method includes: 1) ability to model flexible time-varying association between response and functional predictor and (2) ability to incorporate prior information. Second part of research attempts to study the influence of the clinical and demographic factors on the progression of brain metabolites over time. In order to understand the influence of these factors in fully non-parametric way, we proposed LongCART algorithm to construct regression tree with longitudinal data. Such a regression tree helps to identify smaller subpopulations (characterized by baseline factors) with differential longitudinal profile and hence helps us to identify influence of baseline factors. Advantage of LongCART algorithm includes: (1) it maintains of type-I error in determining best split, (2) substantially reduces computation time and (2) applicable even observations are taken at subject-specific time-points. Finally, we carried out an in-depth analysis of longitudinal changes in the brain metabolite concentrations in three brain regions, namely, white matter, gray matter and basal ganglia in chronically infected HIV patients enrolled in HIV Neuroimaging Consortium study. We studied the influence of important baseline factors (clinical and demographic) on these longitudinal profiles of brain metabolites using LongCART algorithm in order to identify subgroup of patients at higher risk of neurological impairment. / Partial research support was provided by the National Institutes of Health grants U01-MH083545, R01-CA126205 and U01-CA086368

This study compared the immunogenicity of inactivated SARS-CoV-2 vaccines between people living with HIV (PLWH) and HIV-negative individuals. We recruited 120 PLWH and 53 HIV-negative individuals aged 18-59 years who had received an inactivated SARS-CoV-2 vaccine in two Chinese cities between April and June 2021. Blood samples were tested for immunogenicity of the inactivated SARS-CoV-2 vaccines. The prevalence and severity of adverse events associated with SARS-CoV-2 vaccines were similar between PLWH and HIV-negative individuals. The seropositivity of neutralizing activity against authentic SARS-CoV-2, of the total amount of antibody (total antibody) and of S-IgG were 71.3%, 81.9%, and 92.6%, respectively, among fully vaccinated PLWH. Among all participants, PLWH had lower neutralizing activity, total antibody, S-IgG, and T-cell-specific immune response levels, compared to HIV-negative individuals, after controlling for types of vaccine, time interval between first and second dose, time after receiving the second dose, and sociodemographic factors. PLWH with a longer interval since HIV diagnosis, who received their second dose 15-28 days prior to study commencement, and who had an interval of ≥21 days between first and second dose had higher neutralizing activity levels. The immunogenicity of the inactivated SARS-CoV-2 vaccines was lower among PLWH as compared to HIV-negative individuals. Vaccination guideline specific for PLWH should be developed.