Dissertations / Theses: 'HIV infections – Treatment – Botswana'

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Seleke, Rachel. "A comparison of treatment response in two cohorts of once daily HAART and twice daily HAART in a sample population in Gaborone, Botswana." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/80462.

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Thesis (MFamMed) -- Stellenbosch University, 2012.
ENGLISH ABSTRACT: Background Sub-Saharan Africa has been hard hit by the HIV/AIDS epidemic with an estimated 22.9 million adults infected in 2010. The advent of antiretroviral therapy (ART) has seen significant reduction in mortality from AIDS related illnesses. With the reduction of mortality and the indisputable positive results seen from the use of Anti-retroviral Treatment (ART), the demand both from people living with HIV and health care providers to phase in less toxic ARVs while maintaining simplified fixed-dose combinations has increased considerably. Botswana like most low-resource countries has adapted the WHO recommendation of daily ART as opposed to the previous twice daily HAART. No evidence from resource limited settings has been found that clearly indicates the superiority of regimens based on AZT, d4T or TDF. Aim The primary aim was to compare treatment response between two cohorts. The secondary aim was to compare any association of regimen to age or gender. Objectives To comparatively determine treatment response at 3 months based on immunological response (shown by an increase in CD4 above pre-therapy levels) and viral load response. Methods The study is a retrospective comparative cohort study. Three ART sites were selected from a total of 6 sites. A sample size of 263 was required to achieve a 90% effect power. An equal number of patient records were reviewed per site and each arm had an equal number of reviewed records. A total of 286 patient record files which fit the inclusion criteria were retrospectively analysed and data entered in Excel before being analysed using Statistica Version 10. A p <0.05 represents statistical significance whilst a 95% confidence interval was used for estimation of unknown variables. Results n=263. The overall sample was predominantly male (75.19%). An overwhelming majority (95.88%) of patients in both arms had undetectable viral loads (VL<400). A significant association was found between the regimen and viral load (p=0.0315-Pearson Chi Test). The difference in CD4 between the two arms was not statistically significant (p=0.655890-ANOVA). A positive association was found between the regimen and gender (p=0.03190-Pearson Chi Test). This was possibly owing to the high numbers of males and no statistical adjustment to gender made. No association was found in the difference in CD4 cell counts for regimen and gender (p=0.612191-Anova). Conclusion Treatment response at 3 months post initiation between once daily and twice daily HAART in Gaborone Botswana by use of virologic and immunologic response has been shown to be comparable. The use of one regimen over the other as first line as recommended by WHO and the subsequent adoption of the current first line regimen by the Botswana Ministry of Health may be justified. This study has therefore reinforced the applicability of previous findings in other settings of this recommendation. As part of the targeted audience and indeed as a partner in the care and management of HIV, the responsibility to ensure applicability of the recommendations set out for resource limited areas has been achieved through this study. However, bigger randomized trials in resource limited settings are needed to justify and accredit these findings as well as add to the evidence obtained in developed countries.

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Tau, Nontobeko Sylvia. "An analysis of TalkBack, an interactive HIV and AIDS education programme on Botswana Television." Thesis, Nelson Mandela Metropolitan University, 2015. http://hdl.handle.net/10948/5043.

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The Republic of Botswana (2011a) recognises behaviour change as the only long term solution to the HIV and AIDS epidemic that has become a leading health and development challenge for the country. The study aimed to examine how Talk Back, an interactive HIV and AIDS educational programme on Botswana television, capacitates the school community to deal with challenges brought about by the HIV and AIDS epidemic. The study was based on recordings of 2014 Term One theme— ‘Paediatric care and support: challenges and implications in the teaching and learning environment. The study conducted a content analysis of Talk Back to determine behaviour change communication categories employed in producing the programme. All aspects of the Talk Back programme were also analysed to establish communication strategies employed in the presentation of content. Talk Back employed communication approaches such as panel discussions of matters related to HIV and AIDS by various specialists, video clips to present content, and viewers phoning in to interact with the panellists. A number of the callers identified challenges; the most common identified challenge was that parents tended not to disclose their children’s HIV status to the children due to the negative social stigma attached to HIV and AIDS. Although Talk Back provides a forum for interactive behaviour change communication, some listeners questioned the use of technical language.

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Motswaledi, Modisa Sekhamo. "The role of blood groups in preventing or enhancing HIV infection in Botswana." Thesis, Cape Peninsula University of Technology, 2019. http://hdl.handle.net/20.500.11838/2813.

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Thesis (DPhil (Biomedical Science))--Cape Peninsula University of Technology, 2019.
Knowledge of population vulnerabilities to infectious diseases is key in managing many public health problems and for mapping appropriate strategies for prevention or intervention. A number of genes associated with resistance to HIV infection, such as the double deletion of 32 base pairs in the CCR5 gene , have been described and potentially account for lower HIV infections in some populations. The magnitude of the HIV pandemic in Sub-Saharan Africa warrants an investigation of the peculiar genetic factors that may have exacerbated its spread. An understanding of the genetic factors that are involved may aid in the development of specific strategies for prevention such as vaccine development, genetic counselling as well as gene therapy. The aim of this project was therefore to study the relationship between blood groups and HIV-infection in Botswana. HIV infection in Africa has not been linked to particular blood groups. The project was undertaken in two phases from December 2012 to December 2017. In the first phase, 346 subjects of known HIV status (negative or positive) were phenotyped for 23 erythrocyte antigens via standard scientific procedures. A Chi-square analysis was used to determine those antigens associated with increased or reduced risk of HIV infection. In the second phase, 120 samples were phenotyped for the protective blood group (RhC) and the risk-associated groups (Lub and P1). The samples were also characterized according to their laboratory results for viral load, lymphocyte sub-populations, complete blood count and blood chemistry, including total cholesterol. Some of the samples were also assessed for erythrocyte-associated viral RNA. Generally, the prevalence of the blood groups in the general population in Botswana did not differ with the known prevalence for Africans broadly. Three novel findings were established. First, the blood group Rh(C) was associated with a 40% risk reduction for HIV infection. Immunologically, carriage of the C antigen was associated with a more robust cell-mediated immunity as evidenced by enhanced cytotoxic T cell counts. Moreover, this antigen occurred with a frequency lower than 30% in all countries where HIV prevalence was high. There was therefore an inverse relationship between Rh(C) frequency and HIV prevalence. An examination of reports from previous studies revealed that the pattern was consistent in Africa, Europe, Asia, South America and Caribbean countries. It appears that the population frequency of this antigen explains, at least in part, a genetic factor that puts some African populations at higher risk for HIV infection. These results are novel in that Rh antigens have not been previously associated with immunity in any reports. Novel findings regarding the P1 blood group was its association with a double risk for HIV infection. While the plasma viral load did not differ between P1-positive and P1-negative subjects, P1-positive erythrocyte lysate yielded more viral RNA than P1-negative cells, implying more intracellular HIV RNA. Intra-erythrocytic viral RNA was detected even in patients with an undetectable plasma viral load. Glycosphingolipids, of which P1 is an example, have been documented to promote viral fusion to cells independent of CD4 receptors or other ligands. In at least one report, the presence of sphingolipids in lipid rafts was considered to be sufficient for viral fusion. The presence of viral RNA even in erythrocyte lysates corroborates this phenomenon and potentially explains the double risk of HIV infection observed. The occurrence of HIV RNA in erythrocyte lysate is a novel finding that suggests a new viral reservoir. Apparently, P1 has a high frequency among Africans and low in other races.

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Mothuba, Bamby G. Amara Soonthorndhada. "Relationship between partners age and HIV status of young women in Botswana /." Abstract, 2007. http://mulinet3.li.mahidol.ac.th/thesis/2550/cd404/4938530.pdf.

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Weinberger, Beverley Slome Kloss Jacqueline D. "Posttraumatic stress in adolescents with HIV and its relationship with treatment adherence : the role of health beliefs /." Philadelphia, Pa. : Drexel University, 2010. http://hdl.handle.net/1860/3221.

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Petoumenos, Kathy Public Health &amp Community Medicine Faculty of Medicine UNSW. "Treatment experience and HIV disease progression: findings from the Australian HIV observational database." Awarded by:University of New South Wales. School of Public Health and Community Medicine, 2006. http://handle.unsw.edu.au/1959.4/24937.

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The Australian HIV Observational Database (AHOD) is a collaboration of hospitals, sexual health clinics and specialist general practices throughout Australia, established in April 1999. Core data variables collected include demographic data, immunological and virological markers, AIDS diagnosis, antiretroviral and prophylactic treatment and cause of death. The first electronic data transfer occurred in September 1999 followed by six monthly data transfers thereafter. All analyses included in this thesis are based on patients recruited to AHOD by March 2004. By March 2004, 2329 patients had been recruited to AHOD from 27 sites throughout Australia. Of these, 352 (15%) patients were recruited from non-metropolitan clinics. The majority of patients were male (94%), and infected with HIV through male homosexual contact (73%). Almost 90% of AHOD patients are antiretroviral treatment experience, and the majority of patients are receiving triple therapy as mandated by standard of care guidelines in Australia. Antiretroviral treatment use has changed in Australia reflecting changes in the availability of new treatment strategies and agents. The crude mortality rate was 1.58 per 100 person years, and of the 105 deaths, more than half died from HIV-unrelated deaths. The prevalence of HBV and HCV in AHOD was 4.8% and 10.9%, respectively. HIV disease progression in the era of highly active antiretroviral treatment (HAART) among AHOD patients is consistent with what has been reported in developed countries. Common factors associated with HIV disease progression were low CD4 cell count, high viral load and prior treatment with mono or double therapy at the time of commencing HAART. This was demonstrated in AHOD in terms of long-term CD4 cell response, the rate of changing combination antiretroviral therapy and factors predicting death. HBV and HCV coinfection is also relatively common in AHOD, similar to other developed country cohorts. Coinfection does not appear to be serious impediments to the treatment of HIV infected patients. However, HIV disease outcome following HAART does appear to be adversely affected by HIV/HCV coinfection but not in terms of HIV/HBV coinfection. Patients attending non-metropolitan sites were found to be similar to those attending metropolitan sites in terms of both immunological response and survival.

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Masokwane, Patrick Maburu Dintle. "Prevalence of non-AIDS defining conditions and their associations with virologic treatment failure among adult patients on anti-retroviral treatment in Botswana." University of the Western Cape, 2016. http://hdl.handle.net/11394/5247.

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Magister Public Health - MPH
Background: The recognition of HIV/AIDS as a chronic life-long condition globally in recent years has demanded a different perception and an alignment to its association with other chronic diseases. Both HIV and other chronic non-communicable diseases are significant causes of morbidity and mortality. Their combined DALY contributions for Botswana would be significant if research and strategies in controlling these conditions are not put in place. Natural aging and specific HIV-related accelerated aging of patients who are on antiretroviral treatment means that age-related diseases will adversely affect this population. Princess Marina Hospital Infectious Diseases Care Clinic has been in operation since 2002. The clinic has initiated over 16 000 patients on anti-retroviral treatment (ART) since 2002. The current study estimated the prevalence of non-AIDS defining conditions (NADCs) in the attendees of the clinic in 2013. The majority of patients that attended the clinic had been on treatment for over three years with some patients more than ten years. These ART experienced patients were more likely to be susceptible to chronic non-communicable diseases, including non-AIDS defining conditions. The nomenclature used in classification of NADCs in the current study was appropriate for resource-limited settings; because the study setting offered HIV treatment under resources constraints. Aim: The current study characterised non-AIDS defining conditions, and determined their associations with virologic treatment failure in a cohort of patients that were enrolled at Princess Marina Hospital antiretroviral clinic in Gaborone, Botswana. Methods: A retrospective cross sectional study of records of patients who attended the Princess Marina Infectious Diseases Care Clinic in 2013. Stratified random sampling of a total of 228 patients’ records was achieved from a total population of 5,781 records. Data was transcribed into a Microsoft Excel Spreadsheet and then exported to Epi-Info statistical software for analysis. Results: Eighty (35%) cases of NADCs were reported/diagnosed in the study sample; with 27% (n=62) of the patients having at least one condition, 6.7% (n=17) two conditions, and 0.4% (n=1) three conditions. The top prevalent conditions were hypertension (n= 40), hyperlipidaemia (n=7) and lipodystrophy (n=7). The prevalence of NADCs on the various categories of patients compared with the total sample population was as follows: active patients (prevalence ratio= 0.70), transferred out patients (prevalence ratio = 1.24), patients who died (prevalence ratio=2.04) and patients who were lost to follow-up (prevalence ratio =2.86). The prevalence of NADCs was significantly associated with increasing age (p<0.001); having social problems (p=0.028); having been on treatment for over three years (p=0.007); an outcome of death (p = 0.03) and being lost to follow-up (p=0.007). The study showed that being controlled on second line or salvage regimen (p=0.014) and the presence of adherence problems in the past was associated with virologic failure (p=0.008). There was no association of presence of NADCs to virologic failure. Conclusions: There was significant morbidity of non-AIDS defining conditions in the Princess Marina Infectious Diseases Care Clinic shown by a prevalence of NADCs in the clinic of 35% in 2013.The significant associations of the presence of NADCs and virologic failure with outcomes of death and loss to follow-up illustrate the adverse effects that NADCs are having, and calls for strategies to address multi-morbidities in HIV patients on antiretroviral treatment.

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Taylor, Debra Lynn. "Investigation of different antiviral strategies for the treatment of HIV infections." Thesis, Queen Mary, University of London, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260877.

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Awotedu, Kofoworola Olajire. "Functional changes of the vasculature in HIV/AIDS patients on Haart and Haart Naïve HIV participants." Thesis, Walter Sisulu University, 2013. http://hdl.handle.net/11260/185.

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

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Cassidy, Rebecca Jane. "Changing understandings of HIV and AIDS through treatment interactions." Thesis, University of Sussex, 2011. http://sro.sussex.ac.uk/id/eprint/7603/.

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The problem of HIV internationally has many wide ranging impacts on people, communities and countries' development. In the last decade antiretroviral (ARV) treatment has emerged as the major scientific-technical solution, albeit a costly one. Access to ARV treatment is of vital importance across Africa and around the world. Resources for HIV treatment, care and support are transferred globally on a massive scale. However, how such programmes operate ‘on the ground' in different contexts is still unclear. This research contributes to understanding the experience of the people who access such treatment programmes in different contexts. This research focuses on this gap, exploring how treatment programmes are experienced, how the availability of treatment impacts both on people's experience of being HIV+ and how the availability of treatment may also change perceptions of what it means to be HIV+, both individually and at a societal level. This research focuses on the lives and experiences, particularly the treatment experiences, of people living with HIV in peri-urban Gambia. Low prevalence countries such as The Gambia can provide a compelling example of the ways in which meanings and understandings of HIV are created. Here, entering a field of health pluralism and fluid knowledge creation around HIV-infection, came large scale actors providing a high-profile ARV treatment programme through clinic-based medicine, and an effective de-pluralisation of the medical field in relation to HIV, inviting scrutiny of how such knowledge relations and differences are experienced. Although not anticipated at the outset of the research, in parallel the Gambia has become the locus of a major, politically-backed, ‘alternative' AIDS treatment programme. This has thrown the personal and societal meanings of HIV into a new and sensitive context, compelling research attention into how knowledge, status and meanings around HIV are negotiated, and how people make choices amongst different treatment options.

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Mallon, Patrick William Gerard School of Medicine UNSW. "Clinical and molecular aspects of HIV-associated lipodystrophy." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/33048.

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HIV-associated lipodystrophy (HIVLD) syndrome is a condition comprising abnormalities in distribution of body fat and metabolism of lipids and glucose that arises in HIV-infected patients on long-term antiretroviral therapy. This thesis describes clinical research into aspects of the natural history and treatment of HIVLD, as well as molecular research into its pathogenesis centred on subcutaneous adipose tissue. Results demonstrate HIVLD to be a treatment-induced syndrome characterised by initial gains in body fat followed by selective, progressive loss of limb fat. Exposure to thymidineanalogue nucleoside reverse transcriptase inhibitors (tNRTI) induces lipoatrophy through mitochondrial dysfunction of which inhibition of mitochondrial RNA expression, rather than mitochondrial DNA depletion, is an early feature. Mitochondrial dysfunction is associated with decreases in expression of peroxisome proliferatoractivated receptor gamma (PPAR??), an adipocyte transcription factor, which helps explain how tNRTI exposure leads to the loss of adipocyte function. Once established, lipoatrophy is characterised by mitochondrial DNA depletion, although this depletion occurs throughout the mitochondrial genome, suggesting an underlying cause other than inhibition of DNA polymerase gamma. HIVLD is a difficult syndrome to treat. Lipoatrophy is resistant to treatment with rosiglitazone, an agonist of PPAR??, which is ineffective in the setting of ongoing tNRTI therapy and mitochondrial dysfunction. Dyslipidaemia is also difficult to treat as use of pravastatin in the setting of ongoing exposure to protease inhibitors results in only modest declines in fasting cholesterol concentrations. Gains in central fat, such as that seen in patients with buffalo hump, are associated with insulin resistance and diabetes, but only occur in a relatively small percentage of treated patients, suggesting a role for genetic factors in its development. Use of strategies such as avoidance of tNRTI in firstline ART, genetic screening to identify those at risk of toxicities and targeted selection of interventions in subgroups of affected patients, may help prevent this syndrome occurring and better treat those patients in which it has already occurred.

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Hutchinson, Angela Blair. "A health technology assessment of HIV counseling and testing technologies." Diss., Georgia Institute of Technology, 2004. http://hdl.handle.net/1853/8077.

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Moyle, Graeme John. "Treatment of HIV infection with didanosive and foscarnet /." Title page, contents and abstract only, 1995. http://web4.library.adelaide.edu.au/theses/09MD/09mdm938.pdf.

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Cederfjäll, Claes. "Aspects of care among HIV infected patients : needs, adherence to treatment and health related quality of life /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-288-4.

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Phalafala, Mathatho Samuel. "The effects of HIV status disclosure on antiretroviral treatment adherence." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96973.

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Thesis (MSc)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: Successful antiretroviral therapy (ART) depends on appropriate use of antiretroviral agents; which ultimately prevents replication of Human Immunodeficiency Virus (HIV) thus delaying clinical progression of the disease. This study explored how HIV status disclosure affects adherence to antiretroviral therapy at Mamelodi Hospital, using a convenience sampling method with a sample size of 50 adults above 18 years who were on treatment for a minimum of two years prior to the study. An interview protocol was used to uncover patients’ demographics, sexual orientation, and HIV status disclosure, adherence to antiretroviral drugs, drug side effects, how often they missed their doses and how HIV status disclosure / non-disclosure affected their adherence to treatment. Patients’ medical records were assessed to validate and correlate the information obtained from the interviews. The scientific test results used were the CD4count and Viral loads which are used to monitor the HIV/AIDS disease progression. All partakers involved in the study made their HIV status known and reported taking their medicines regularly. The patients’ CD4 count and VL were verified, the CD4 count has shown an upward trend while the VL load showed a downward trend in keeping with patients who are adhering to ART. The majority of participants (54% or 27 patients) reported they had never skipped taking their medication. The participants also reported they had taken their medicine in front of other people and they constituted 74% (37) of the group. Of this 74%, 78.38% (29 patients) said it was because they had disclosed their status. This observation supports the fact that if you have disclosed your HIV status, you have better chances of adhering to prescribed medication. Findings from the study at Mamelodi Hospital revealed that for as long as one has disclosed their HIV status, the outcome of treatment adherence will be better. The only shortfall noted was lack of partakers who did not divulge their HIV status thus a comparison could not be done. It was acknowledged that some participants in the study might have reported disclosure of their HIV status to be in good favour of the researcher to create an impression that they are adhering to their medication. The study has confirmed the existence of a relationship between HIV status disclosure and adherence to ART.
AFRIKAANSE OPSOMMING: Suksessvolle antiretrovirale terapie (ART) hang af van die toepaslike gebruik van antiretrovirale middels, wat replikase van die MI-virus verhoed, en dus die kliniese vordering van die siekte vertraag. Hierdie studie het ondersoek hoe die bekendmaking van MIV-status die gehoorsaamheid tot ART beïnvloed het by die Mamelodi Hospitaal. ‘n Gerieflikheid-streekproef met ‘n groote van 50 volwassenes bo 18 jaar is gebruik en die deelnememers moes ten minste vir twee jaar voor die studie reeds op behandeling gewees het. Data is deur middel van onderhoude ingesamel, met die doel om pasiënte se demografiese inligting, seksuele orientasie, MIV-status, gehoorsaamheid tot ART en newe-effekte van ART in te samel. Pasiënte se mediese rekords is nagegaan om die inligting wat uit die onderhoude verkry is te bevestig. Die wetenskaplike toetse wat gebruik is, was die CD4-telling en virale lading wat gebruik word om MIV/Vigs te monitor. Al die deelnemers het hul MIV-status bekend gemaak en aangedui dat hul hul medikasie gereeld gebruik. Die pasiënte se CD4-tellings en virale lading is bevestig, die CD4-tellings het ‘n opwaartse neiging getoon terwyl die virale lading ‘n afwaartse neighing getoon het. Die meerderheid van die deelnemers (54%) het aangedui dat hul nog nooit hul medikasie oorgeslaan het nie. 74% van die deelnemers het aagedui dat hul hul medikasie voor ander mense neem - hul noem dat dit as gevolg van die feit is dat hul hul status bekend gemaak het. Dit ondersteun die feit dat mense wie hul status bekend maak beter kanse het om gehoorsaam hul medikasie te gebruik. Die studie by die Mamelodi Hospitaal toon dat solank mense hul MIV-status bekend maak, hul meer gehoorsaam is teenoor die gebruik van hul medikasie. Die studie bevestig dus die verband tussen bekendmaking van MIV-status en gehoorsaamheid tot ART.

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Arias, Mayra S. "Determinants of self-efficacy to seek care for tuberculosis and complete tuberculosis treatment among HIV-positive individuals attending HIV/AIDS clinics in Honduras." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2010. https://www.mhsl.uab.edu/dt/2010p/arias.pdf.

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Liang, Jianguo, and 梁建国. "HIV-1 early diagnosis of men having sex with men in Hong Kong and discovery of novel agents for HIV-1 treatment from traditional Chinese herbal medicine." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196459.

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Over the 30 years since it was first identified, the HIV/AIDS epidemic has had historically unprecedented severity and impact. There are approximately 33.4 million people living with HIV-1/AIDS which urges to seek novel approaches for HIV-1 diagnosis and HIV-1 therapy. Men who have sex with men (MSM) are severely affected by HIV-1 and constitute a large proportion of HIV-infected individuals. In Hong Kong, the transmission route of homosexual and bisexual contacts accounted for nearly 50% of incidence in 2012. To investigate HIV-1 prevalence among MSM in Hong Kong, the combination of fast antibody test (FAT) and real-time dried-blood-spot-based quantitative polymerase chain reaction (DBS-qPCR) was employed for 474 participants chosen randomly from community testing sites of MSM within a one-year period which showed a 4.01% (19/474) rate of HIV-1 prevalence among MSM in Hong Kong with three cases at the acute phase among the newly infected participants. The new survey demonstrated that the risk factors of MSM are mostly correlated with the receptive role during anal sex and syphilis infection. In this study, two traditional Chinese herbal medicines (TCHM), Sanguisorba officinalis (SO) and Spatholobus suberectus (SS), inhibited the infection of model cell lines expressing HIV-1 targets by HIV-1 pseudoviruses, while the anti-HIV-1 properties of SO were demonstrated for the first time. Both SO and SS were able to block not only infection by pseudoviral HIV-1 CCR5-tropic and CXCR4-tropic strains, but also RT and PI drug-resistant strains. Mechanistic studies revealed that SO and SS interact with the viral envelope to prevent the infection of target cells by HIV-1. Two compounds derived from SO and SS, named Gallic acid (GA) and Jiazhi (JZ), retained anti-HIV-1 properties and blocked HIV-1 infection by acting on the viral envelope. Small molecules derived from TCHM were also investigated for their capacity to activate HIV-1 from latency. A small molecule derived from SS, Daidzein (DDZ), demonstrated the potentials to trigger HIV-1 reactivation in latently infected cell lines. DDZ enhanced gene expression from HIV-1 LTR in which the Sp1 binding site plays an important role. The Akt pathway is also involved in the initiation of DDZ-induced activation. Phosflow analysis revealed that DDZ activated the Akt pathway in various subpopulations of T cells, including memory CD4+ T cells which are considered to be a major reservoir for HIV-1. The structure-activity relationships (SARs) study demonstrated the 4'-hydroxyisoflavone as bio-functional core structure. Addition of a hydroxyl group on C-5 position significantly decreases its biological function of HIV-1 latency activation. In summary, this study investigates HIV prevalence and incidence using an assay for early HIV-1 diagnosis and performs an analysis of risk factors of behavior which contributes to the effective control of HIV transmission in Hong Kong and its neighbors in Asia. It also demonstrates a drug research sourced from traditional Chinese herbal medicines that which sheds lights on drug discovery from traditional herbal medicines and facilitates mechanistic drug design for HIV-1 eradication.
published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy

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Jusayo, Nomonde. "Factors affecting the utilisation of a workplace voluntary counselling and testing programme in the Eastern Cape." Thesis, Nelson Mandela Metropolitan University, 2013. http://hdl.handle.net/10948/d1010273.

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The world has entered the third decade of the HIV and AIDS epidemic under different times in which the epidemic is treatable. The International Labour Organisation (ILO) (2005) declares HIV and AIDS a developmental crisis destroying developmental gains over generations. Since HIV and AIDS affect the most productive segment of the labour force, it is therefore not only a threat to development but also to the world of work without which development will be sacrificed (ILO, 2001). Collaborative response efforts that seek to mitigate the HIV pandemic by government, business and higher education institutions have been fraught with challenges. The main challenge that beset these efforts is that, in the absence of an HIV vaccine, voluntary counselling and testing remains the gateway to access treatment and care. Regrettably, participation in VCT has been confronted by challenges of low utilisation. This precedes the objectives of this study, which were to explore and describe factors that serve as barriers and facilitators of workplace VCT programmes with the objective to improve participation in these programmes. The current study was a product of a qualitative and exploratory-descriptive research design. A nonprobability convenience sampling method was used to sample participants for this study. The targeted population in this study were the non-academic employees of an academic institution in the Eastern Cape. Data was collected by means of focus group discussions and by using semi-structured interviews. The focus group samples comprised of an equal number of men and women with an overall participation of fifty-six participants. Data obtained was transcribed, thematically analysed and coded using Henning, Van Rensburg, and Smit's (2004) qualitative analysis and interpretation method. Findings of this research revealed that factors that facilitate and inhibit voluntary counselling and testing are psychosocial and cultural by nature. At psychosocial level, participants reported factors that facilitate voluntary counselling and testing to include psychological readiness to go for HIV testing, reassurances of confidentiality of HIV test results and normalising HIV testing (making the process more like that for screening and diagnostic testing). Cultural factors included cultural practices and beliefs such as "intonjane" and traditional circumcision - positive cultural nurturers that could facilitate VCT participation. Results of this study showed a lack of basic knowledge about VCT and fear of knowing one's status, fear of breach of confidentiality, fear of being stigmatised and a lack of trust towards health professional as the major psychosocial factors that serve as barriers to VCT participation. The cultural barriers to VCT pointed to hegemonic masculinity as a socially constructed gender identity that encourages gender inequalities and undermines efforts to improve HIV testing. The study suggested that strategies to increase VCT participation should consider leadership support of VCT programmes, incentivisation of VCT programmes, institutionalisation of HIV and AIDS education and the establishment of integrated wellness services for employees.

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Fialho, Renata. "Neuropsychiatric manifestations of hepatitis C treatment in HIV/HCV co-infection." Thesis, University of Sussex, 2017. http://sro.sussex.ac.uk/id/eprint/71260/.

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Hepatitis C (HCV) infection is associated with high rates of mortality and morbidity. Interferon alpha based treatment for HCV offers a good rate of viral clearance, however the associated neuropsychiatric side effects increase the risk of treatment interruption and disease progression. The HIV/HCV coinfection is of particular interest due to association with higher rates of HCV treatment side effects and earlier treatment discontinuation when compared with HCV mono-infection. Therefore, the aim of the thesis was to further explore the effect of coinfection on mood and cognition and how HCV interferon based treatment influences neuropsychiatric side effects in mono and co-infected samples. Firstly a meta-analysis was performed to explore cognitive impairment and depression in HIV HCV co-infection. The results suggested that there was consistent literature indicating that the coinfected group were more cognitively impaired and more likely to be depressed than the HCV and HIV monoinfected groups. Secondly empirical studies were conducted to analyse the profile of depression during interferon-based treatment, and explore potential risk factors, such as gender and immune profile. Co-infected patients appeared less vulnerable to the emergence of depressive symptoms during HCV treatment than HCV mono-infected patients. Additionally, neither female gender nor immune response were associated with increased vulnerability to depression. Finally, a longitudinal study investigating cognitive performance during interferon-based treatment was conducted. A significant effect of treatment on information processing speed level of executive function was observed. Overall the research reported in this thesis further clarifies the nature of interferon induced depression and cognitive effects differences between mono and coinfected groups. Having identified a neurovegetative symptom profile and speed of processing impairment of executive function during HCV treatment, the discussion considers the potential of targeted interventions via psychotropic medication and cognitive interventions to minimise the impact of these treatment effects and optimise outcomes in this clinical group.

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Matengu, Barbara. "The importance of STI treatment in HIV prevention: knowledge and behaviours of secondary school students in Tsumeb, Namibia." Thesis, University of the Western Cape, 2005. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_8923_1182746437.

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Curricula should be strengthened by teaching the curability of STIs and the importance of STI treatment to prevent HIV transmission. This study focused on the control of sexually transmitted infections as a key HIV prevention strategy. Sexually transmitted infections act as a strong cofactor in the sexual transmission of HIV. Effective STI management can limit the spread of HIV.

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Vu, Phuong Thao. "Transmitted and acquired HIV drug resistence in Vietnam." Thesis, University of Oxford, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711876.

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Gordon, Gregory Ernest Robert. "A chemo-enzymatic process for the production of beta-thymidine, a key intermediate in antiretrovirol manufacture." Thesis, Nelson Mandela Metropolitan University, 2010. http://hdl.handle.net/10948/d1016217.

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The socio-economic impact of HIV/AIDS on South Africa has resulted in lower gross domestic product, loss of skills in key sectors such as education, and increased health-care costs in providing access to treatment. Currently active pharmaceutical ingredients (API’s) such as stavudine (d4T) and azidothymidine (AZT) are imported from India and China, while formulation is conducted locally. A strategy was initiated between CSIR Biosciences and LIFElab under the auspices of Arvir Technologies to investigate the feasibility of local antiretroviral manufacture (d4T and AZT) or the manufacture of a key intermediate such as β- thymidine (dT). Several advantages associated with successful implementation of this strategy include ensuring a local supply of API’s, thus reducing reliance on procurement from foreign sources and reducing the effect of foreign exchange rate fluctuations on providing cost effective access to treatment. A local supply source would also reduce the imports and thus aid the balance of payments deficit, and in addition to this, provide stimulus in the local pharmaceutical manufacturing industry (which has been in decline for several decades), resulting in increased skills and employment opportunities. This thesis describes the development of a superior chemo-enzymatic process for the production of β-thymidine (72 percent yield, prior to isolation), a key intermediate in the preparation of anti-retrovirals. Alternative processes based purely on chemical or bioprocess transformations to prepare either 5-methyluridine (5-MU) or dT suffer from several disadvantages: lengthy transformations due to protection/deprotection strategies, low selectivties and product yields (30 percent in the chemical process) and isolation of the product from dilute process streams requiring the use of large uneconomical reactors (bioprocesss). This contributes significantly to the cost of d4T and AZT manufacture. Our novel chemoenzymatic process comprises of a biocatalytic reaction for the production of 5-MU, with subsequent chemical transformation into dT (3 steps) negating and circumventing the limitations of the chemical or bioprocess routes. During the course of this project development, the β-thymidine selling price declined from 175 $/kg (2005) to 100 $/kg (2008). However, the process described in this work is still competitive based on the current β- thymidine selling price of 100 $/kg. The process economics show that with further optimization and increasing the isolated dT yield from 70 percent to 90 percent, the variable cost decreases from 136 $/kg to 110 $/kg. The increase in isolated yield is highly probable, based on solubility data of β-thymidine. The decrease in β-thymidine selling price and technological improvement in dT manufacture should translate into lower API manufacture costs and more cost effective access to treatment. Our novel biocatalytic process producing 5-MU uses a coupled enzyme system employing PNP, Purine Nucleoside Phosphorylase and PyNP, Pyrimidine Nucleoside Phosphorylase. The overall transglycosylation reaction may be decoupled into the phosphorolysis reaction (PNP) and synthesis reaction (PyNP). During the phosphorolysis reaction, guanosine is converted into guanine and ribose-1-phosphate (R-1-P) in the presence of PNP enzyme. The reaction intermediate R-1-P is then coupled to thymine in the presence of PyNP enzyme during the synthesis reaction, producing 5-MU. The process was scaled up from lab-scale to bench-scale (10 - 20 L) and demonstrated to be robust and reproducible. This is evident from the average guanosine conversion (94.7 percent ± 2.03) and 5-MU yield (88.2 percent ± 6.21) and mole balance (104 percent ± 7.61) which were obtained at bench-scale (3 replicates, 10 L). The reaction was carried out at reactor productivities of between 7 – 11 g.L-1.h-1. The integration of the biocatalytic process and chemical processes was successfully carried out, showing that 5-MU produced using our novel biocatalytic process behaved similarly to commercially available 5- MU (ex. Dayang Chemicals, China). A PCT patent application (Ref. No. P44422PC01) on this chemo-enzymatic process has been filed and currently public private partnerships are being explored through Arvir Technologies to evaluate and validate this technology at one ton scale.

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Srasuebkul, Preeyaporn Public Health &amp Community Medicine Faculty of Medicine UNSW. "Evaluating monitoring strategies, short-term disease progression and rate of treatment change in HIV-infected patients commencing antiretroviral therapy in the Asia-Pacific region." Publisher:University of New South Wales. Public Health & Community Medicine, 2008. http://handle.unsw.edu.au/1959.4/41673.

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This thesis assesses factors associated with a number of short and long-term outcomes in HIV-infected patients receiving antiretroviral treatment in Asia. Analyses in this thesis were based on two cohorts of HIV-infected patients; The Treat Asia HIV Observational Database (TAHOD), a multi-centre prospective observational cohort from countries in Asia-Pacific region, and the HIV Netherlands Australia Thailand (HIV-NAT) collaboration cohort, a cohort of patients treated with antiretroviral treatments at HIV-NAT in Bangkok, Thailand. We examined factors associated with time to immunological failure endpoints, such as CD4≤ 200 cells/??L, CD4≤ 100 cells/ ??L, and CD4 return to baseline, and with the virological failure endpoint, detectable viral load defined as a value greater than 500 copies/mL. Multivariate Cox proportional hazard models were used. Results showed that CD4 count at baseline and changes in CD4 strongly predicted immunological failure. For virological failure, detectable viral load at baseline was the strongest predictor. As a step to developing simplified monitoring strategies, in which patients with a low risk of failure could have their monitoring CD4 count and viral load tests deferred, we developed predictive models for each immunological and virological failure endpoint. Models were developed on the HIV-NAT cohort, and validated on the independent TAHOD cohort. For predictive models, the complementary log-log transformation for each endpoint was fitted appropriate to the interval censored nature of the data. To assess goodness-of-fit, cut-offs were defined for the predicted risks that separated patients from low risk to high risk. Overall, the observed versus expected failures from HIV-NAT data agreed quite well across all endpoints, probably reflecting that the HIV-NAT database was the data we built the models upon. Not only did these models fit the HIV-NAT database well, they also discriminated patients from low to high risk groups. When we validated models with TAHOD data, the observed and expected failures agreed well only in the model for CD4 count return to baseline. For most of the endpoints, the predictive models overestimated the number of failures, with predicted values larger than observed. However, the proportions of failures were lowest in the low risk group and highest in the high risk group, indicating that our models did discriminate between patients at high and low risk, and that the predictive models might still be of use for the purpose of simplified monitoring strategies. With CD4 count and viral load monitoring tests now comprising a large component of the cost of HIV treatment in resource limited settings, we developed and assessed a simplified monitoring strategy that aimed to reduce the numbers of monitoring tests performed. The predictive models developed earlier were used to calculate the probabilities of failure in TAHOD patients. We assumed that patients would have their CD4 and viral load assessments annually, at baseline and at one year, predicted risk of failure at ensuing clinical visits, week 12, 24 and 36. For patients at low predicted risk of failure at ensuing clinical visits, we assessed the effect of deferring monitoring tests, both in terms of blood tests avoided, and in terms of delaying detection of failure in some patients. A number of levels for the predicted risk of failure that lead to deferral of testing were evaluated. The results suggested that predicted probabilities of failure of 10% - 20% gave the best results across all failure endpoints. These cut-offs could save a median of 598 (51.6%) (range 37 (2.6%)_-1,218 (81.9%) ) blood tests over the first year of treatment, but would fail to detect 29 (18%) (range 10 (7.4%) - 128 (39.3%) ) failures. The median time from failure to detection in those patients who did fail and had deferred monitoring tests was 28 weeks. Rates of antiretroviral treatment change in TAHOD were examined. We identified patterns and factors associated with the rate of treatment change. Median time to the first treatment change was 3.2 years. Factors predicting rate of treatment change in TAHOD were treatment combination, being on second or third combination, number of drugs available in each site and being an injecting drug user. The overall rate of treatment change in TAHOD was 29 per 1OO-person-year. Around 30% of patients stopped their treatment due to adverse events. These rates of treatment change are lower than have been seen in patients in western countries. This may be due to patients in developing countries having access to fewer antiretroviral drugs than patients in developed countries.

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Rose, Penelope Cathryn. "Tuberculosis treatment delay in adults and household transmission to children: a community-based study in a setting with high burden of tuberculosis and HIV." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/16726.

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Includes bibliographical references
Background: Tuberculosis (TB) control depends on interrupting transmission through rapid diagnosis and treatment initiation of infectious TB cases. With increasing delay in the diagnosis and treatment of pulmonary TB, disease is likely to progress, leading to progressive lung cavitation and increased sputum bacillary load, likely increasing TB transmission. This study investigated the effect of treatment delay in adult TB patients on the risk of TB infection and disease in child household contacts. Methodology: Secondary analysis was performed using data from a community-based household contact investigation study. Cross-sectional analysis was conducted of baseline data collected at enrolment. Children aged three months to fifteen years with documented household exposure to an adult with TB were enrolled between December 2007 and June 2012. These children were screened for TB infection (Mantoux tuberculin skin test [TST] and two interferon-gamma release assays [IGRA]) and disease. Total treatment delay was measured in adult TB source cases as the time from cough onset until treatment initiation, with those reporting no cough serving as the reference category. Logistic regression models were used to evaluate the effect of total treatment delay in adults on the risk of TB infection in child household contacts, with TB disease evaluated as a secondary endpoint. Results In total 671 children were enrolled as household contacts of 290 adult TB source cases. In multivariate analysis, the odds of TST positivity increased with cough duration ≥4 weeks prior to TB treatment initiation (odds ratio (OR) = 1.77 [95% CI 1.02-3.09] for cough <4 weeks; OR = 2.74 [95% confidence interval ( CI ) = 1.39-5.40] for cough 4-12 weeks; OR = 2.39 [95% CI = 1.19-4.82] for cough >12 weeks, compared to non-coughing adult TB patients), child's age ≥5 years (OR = 4.51, [95% CI = 2.60-7.83]), sharing the same bedroom (OR = 2.17, [95% CI = 1.43-3.31]), more than one household TB contact (OR = 2.70, [95% CI = 1.35- 2 5.42]) and with household tobacco smoke exposure (OR = 2.10, [95% CI = 1.22-3.61]). Adult TB source case HIV status did not modify the association between cough duration and risk of infection in children. Results of analyses of TB infection indicated by IGRA positivity were consistent with TST results. Prevalent TB disease in child contacts was associated with source case sputum smear and culture positivity, additional household TB contacts and decreasing age of the child. Conclusions: Delays of longer than four weeks from cough onset until TB treatment initiation were associated with increased risk of TB infection in child household contacts. These findings confirm the importance of reducing delays in TB diagnosis and treatment in adults to reduce transmission, ideally to less than four weeks. Although HIV co -infected TB patients are often considered less infectious, delayed treatment initiation remained associated with TB transmission, even amongst HIV co-infected adults with TB. In addition to the traditional risk factors for developing TB disease after infection, source case exposure factors also increased the risk of exposed children developing TB disease.

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Pace, Craig Stuart. "The influence of APOBEC3G and deoxythymidylate kinase genetic diversity on HIV-1 hypermutation and response to treatment." Pace, Craig Stuart (2006) The influence of APOBEC3G and deoxythymidylate kinase genetic diversity on HIV-1 hypermutation and response to treatment. PhD thesis, Murdoch University, 2006. http://researchrepository.murdoch.edu.au/242/.

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This thesis addresses two important topics in HIV-1 medicine; (i) the clinical relevance of pre-treatment G-A hypermutation and the contribution of host and viral genetics to its development and; (ii) the influence of genetic variation in host enzymes responsible for antiretroviral drug metabolism on response to therapy. These themes are outlined below. HIV-1 Hypermutation At present, limited data exists regarding the relative roles of host encoded cytidine deaminases APOBEC3G and APOBEC3F in promoting G-A hypermutation of HIV-1 proviral DNA in vivo, nor the clinical relevance of hypermutation or the influence of genetic diversity of the APOBEC3G locus and of the viral encoded vif protein that counteracts the action of APOBEC3G. The analyses contained within this thesis demonstrate that within the WA HIV cohort, clinically relevant hypermutation is restricted to a minority of individuals and is mediated predominantly by APOBEC3G. In this study, the presence of HIV-1 hypermutation had a substantially greater effect on plasma viremia than other known host antiviral factors such as CCR5D32 or specific HLA-B alleles. Furthermore, the considerable genetic diversity of the vif gene is likely to make a greater contribution to the development of hypermutation than the limited genetic diversity of the APOBEC3G gene in Caucasians. These data indicate that G-A hypermutation is a clinically relevant phenomenon and may provide a fresh perspective to the area of HIV/AIDS therapies. Genetic Determinant of HIV-1 Treatment Response Thymidine kinase 2 (TK2) and thymidylate kinase (dTMPK) are rate limiting enzymes for the metabolism of the antiretrovirals d4T and AZT, respectively, and are thus central to the antiviral efficacy and toxicity of these agents. However, the genetic diversity of TK2 and dTMPK and their influence on toxicities associated with their use is largely unknown. The results discussed in this thesis indicate that in contrast to the highly conserved TK2 locus, the dTMPK locus of Caucasian individuals, including regulatory regions potentially influencing transcription and translation, is considerably polymorphic and organised into five common haplotypes. The results regarding the contribution of dTMPK genetic variation to toxicities associated with AZT therapy are encouraging. A common dTMPK haplotype had significant, albeit modest, effect on haematological parameters (haemoglobin and mean corpuscular volume) in HIV-infected patients, although no AZT-specific treatment effect was observed in this relatively haematologically stable cohort. In addition, another common dTMPK haplotype provided significant protection against AZT-induced adipocyte mtDNA depletion in a pilot study of AZT- and d4T-treated individuals. The dTMPK haplotypes characterised in this thesis should facilitate further studies regarding dTMPK genetic variation in HIV-1 infection and response to treatment, which are warranted from the clinical results presented herein.

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Mohaleni, Mamabolo Promise. "Pre-and post-HIV diagnosis help-seeking behaviour by patients receiving antiretroviral treatment at Witbank Hospital in Mpumalanga Province." Thesis, University of Limpopo (Turfloop Campus), 2013. http://hdl.handle.net/10386/1049.

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Thesis (M.A. (Clinical Psychology)) --University of Limpopo, 2013
Studies have indicated that help-seeking behaviour of people living with HIV is not predictable and linear and may entail the utilization of western medicine, traditional medicine and/or complementary medicine. The aim of this study was to explore pre- and post- HIV diagnosis help-seeking behaviour by patients receiving antiretroviral treatment at Witbank Hospital in Mpumalanga Province (South Africa).A qualitative, descriptive phenomenological approach was utilized in the study. Ten participants (male = 5; female = 5, and aged between 30 and 50 years)diagnosed with HIV and who came to the hospital to collect their treatment and for medical review were interviewed using semi-structured interviews. Interpretive analysis method was used to analyse the data. The results suggest the preference for western medicine pre-and post-HIV diagnosis. The results further suggest that help-seeking behaviour is a dynamic process embedded mainly in the conceptualization of the health problem, perception of its severity, the treatment given, and social support experienced.

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Ali, Ali Salim. "Male circumcision managers' attitudes toward safe male circumcision program implementation and scale up in Botswana." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79949.

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Thesis (MPhil)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Background: Safe Male circumcision (SMC) divides people for or against it, depending upon their attitudes. The Ministry of health (MOH) has built capacity in the country for rapid scale up of the program since 2009. However, despite the efforts, the number of men circumcised is lagging behind set targets. We do not know to what extent attitudes of the managers at national and district levels do influence this underperformance? The effectiveness of the managers at workplace at large will depend on their attitudes towards SMC. Managers with positive attitudes bring at workplace energy, creativity and momentum to fulfill the work objectives and goals. Objectives: The objectives of the study were to; 1) establish the current situation of SMC implementation in Botswana, 2) establish the required attitudes for managers towards SMC program, 3) establish the attitudes of SMC managers at all levels toward SMC program, 4) determine the gap between the required attitudes and SMC managers’ current attitudes toward SMC, and 5) Provide recommendation for reinforcing positive attitudes toward SMC program. Methods: The study used an explorative qualitative design. It was carried out at the Ministry of health headquarters and in ten districts in Botswana. A total of 26 SMC program managers were interviewed using a semi-structured interview guide. Results: The study found that the managers were confirming to positive attitudes toward the program as prescribed by the MOH’s standards. Data revealed a positive trend in scaling up of the program albeit lagging behind set targets. Conclusion: This study looked at the desired attitudes of SMC managers should posses and the level of attitudes currently have towards the program. It was not easy to link attitude and performance of individuals. High turnover rate of SMC officers was a worrisome finding that calls for further study.
AFRIKAANSE OPSOMMING: Agtergrond: Na gelang van hul houdings, is die meeste mense hetsy sterk ten gunste van of heftig gekant teen veilige manlike besnydenis (VMB). Die Ministerie van Gesondheid is reeds sedert 2009 besig met vermoëbou-inisiatie we om die VMB-program vinnig uit te brei. Ondanks hierdie pogings, is die aantal mans wat ingevolge dié program besny word egter veel minder as die vasgestelde teikens. Dit is nie bekend in watter mate die houdings van VMB-programbestuurders op nasionale en distriksvlak hierdie onderprestasie beïnvloed nie. Die algehele doeltreffendheid waarmee dié bestuurders die program in werking stel, sal immers grootliks afhang van hul houdings jeens VMB. Bestuurders met ’n positiewe houding sal energie, kreatiwiteit en stukrag aan die werkplek verleen ten einde die programoogmerke en -doelwitte te verwesenlik. Oogmerke: Die oogmerke van die studie was: 1) om die huidige stand van VMB-inwerkingstelling in Botswana te bepaal; 2) om te bepaal watter houdings bestuurders behóórt te hê jeens die VMB-program; 3) om te bepaal watter houdings bestuurders op alle vlakke wél het jeens die VMB-program; 4) om vas te stel in watter mate bestuurders se vereiste houdings en huidige houdings jeens VMB verskil; en 5) om aanbevelings te doen vir die versterking van positiewe houdings jeens die VMB-program. Metode: Die studie het van ’n verkennende kwalitatiewe ontwerp gebruik gemaak. Dit is by die hoofkantoor van die Ministerie van Gesondheid sowel as in tien gesondheidsdistrikte in Botswana onderneem. Onderhoude aan die hand van ’n semigestruktureerde onderhoudsgids is met altesaam 26 VMB-programbestuurders gevoer. Resultate: Die studie bevind dat die bestuurders wél positiewe houdings jeens die program toon soos wat die standaarde van die Ministerie van Gesondheid vereis. Data dui op ’n positiewe tendens in die uitbreiding van die program, al word die vasgestelde teikens nie bereik nie.

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Kang, Yuanxi, and 康元曦. "Mechanism study of novel CCR5 antagonists and their potential as anti-HIV-1 microbicides." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47849393.

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R5-tropic HIV-1 is predominantly transmitted during unprotected sexual contacts, rendering CCR5 antagonist as an attractive agent not only for antiretroviral therapy but also for prevention. Here, we report two 1,3,3,4-tetrasubstituted pyrrolidine embodied compounds, TD-0232 and TD-0680, as novel small molecule CCR5 antagonists and investigate their specificities, potencies and underlying mechanisms. We found that both TD-0232 and TD-0680 inhibited a diverse group of R5-tropic HIV-1 and SIV strains in both single-cycle infectivity assays and live viral PBMC assays. When compared to other CCR5 antagonists, such as TAK-779 and the only FDA-approved Maraviroc, TD-0680 displayed the highest potency with EC50 values at the subnanomolar levels (range 0.09nM-2.29nM). TD-0232 and TD-0680, but not Tenofovir, a nucleoside reverse transcriptase inhibitor, completely blocked envelope-mediated cell-cell fusion and subsequent viral transmission. Critically, TD-0680 was potent at inhibiting the replication of a TAK-779/Maraviroc-resistant HIV-1 variant in PBMCs at a subnanomolar concentration. Interestingly, despite binding to a similar transmembrane pocket of CCR5, TD-0232 and TD-0680 functioned differently as revealed by site-directed mutagenesis and drug combination assays. Based on the sequence homology, we constructed a CCR5 molecule model using the crystallized CXCR4 as a template. By docking of CCR5 antagonists with CCR5, we identified a unique binding mode of TD-0680, which has not been described previously. TD-0680, with an exo-configuration, extended its interaction with the ECL-2 region of CCR5 in a protruding manner, thereby interrupting the interaction between the virus and its co-receptor more effectively. In an antibody recognition assay, we confirmed that TD-0680 had an enhanced inhibitory activity against the anti-ECL2 monoclonal antibodies binding. Furthermore, we investigated the antiviral activities of TD-0232 and TD-0680 that were formulated into a thermo-reversible acidic microbicide gel. Both drugs were stable in the acidic gels and could be released rapidly for long lasting and potent antiviral activities. Although human semen could enhance the infection of HIV-1, it did not seem to affect the potencies of the TD-0232 and TD-0680 gels. In summary, our findings suggest that TD-0232 and TD-0680 can be further developed not only as anti-HIV-1 agents for therapeutic purposes but also as potent microbicides for the prevention of sexual transmission of R5-tropic HIV-1.
published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy

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Makhubele, Jabulani Calvin. "The impact of culture on the prevention and treatment of HIV/AIDS amongst people in low-resourced areas :a social work perspective." Thesis, University of Limpopo, 2004. http://hdl.handle.net/10386/2027.

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Thesis (M. A. (Social Work)) -- University of Limpopo, 2004.
The aim of this study was to explore the impact of culture on the prevention and reatment of HIV/AIDS amongst people in low-resourced areas like Malamulele. he study focused on the lifestyles, beliefs, attitudes and perceptions around ultural elements and practices, which might impact negatively on the prevention nd treatment of the HIV/AIDS epidemic. There were three groups of research espondents namely: learners from three high schools in Malamulele, some arents of the learners and the traditional/cultural leaders. The researcher ollected both qualitative and quantitative data. The data was gathered through he use of an interview schedule (questionnaire), focus group discussions and ound-table discussion sessions. The data was presented, analysed and nterpreted by means of tables and charts. t was found that people in low-resourced (rural) areas have little knowledge about HIV/AIDS, causes, symptoms and how the disease is transmitted. Despite the fact that awareness and educational campaigns and programmes are being rendered, people in low-resourced (rural) areas have little knowledge and needed skills about prevention and treatment of the pandemic. Polygamy and extra-marital relations by men is still highly valued and viewed at high esteem. Religious structures seem to be detached to the issue of HIV/AIDS as they mentioned that talking about HIV/AIDS is immoral and against their principles. The study also tried to explore the extent to which people in low-resourced areas view and use condoms as a protective means.

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Nxumalo, Vusie Alvitt. "Cell-Life: a needs assessment study for an HIV/AIDS management tool." Master's thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/15415.

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This research presents a proposal for the assessment of technology to manage antiretroviral treatment. The system called Cell-Life has been successfully tested at a pilot site in Gugulethu, Cape Town from September 2002 till date and offers a cost-effective solution for adherence monitoring, side effect management, effective home based care and reducing pill count dependence at the clinic. With the aid of the Cell-Life SIM card menu (please see Appendix A, page 63) on a cell-phone the therapeutic counsellor is equipped with a live-link to the clinic or doctor while visiting patients. The menu allows entering data about the patient's drug adherence, side effects and symptoms, scheduling visits to the clinic and alert messages. The data is sent using short message service (SMS) and stored in a database, which can be accessed via the Internet by a doctor who will receive a complete report on the patient's status quo. The main benefits of the system lie in creating a communication link between the clinic/doctor and the therapeutic counsellor at minimal cost. Another benefit is the collection of reliable data relating to drug adherence and the minimising of human error through preset menu options on the phone. The pilot study has shown that management of anti-retroviral therapy is possible in resource-constraint urban settings. But for a provincial or national rollout of the Cell-Life system, the challenge is the lack of the required infrastructure, technology, personnel and logistics for effective operation of the Cell-Life systems specifically in the rural areas of South Africa. This research investigated the availability of the Cell-Life requirements in the Western Cape. The findings showed that the Cell-Life systems could be implemented in the health regions investigated across the Western Cape. It was also shown that an in depth needs assessment study is required before implementing the Cell-Life system in any community.

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Komanyane, Lorato. "Factors influencing the utilization of voluntary counselling and testing services amongst employees of the Lobatse Town Council in Botswana." Thesis, Nelson Mandela Metropolitan University, 2007. http://hdl.handle.net/10948/535.

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In this study both qualitative and quantitative methods were used to find out to what extent the Lobatse Town Council employees used Voluntary Counseling and Testing (VCT) HIV and AIDS services, the reasons for using or not using the services, the preferred service providers reasons for choosing a service provider. Lastly recommendations were made on how the uptake HIV and AIDS VCT services could increased amongst the employees. A sample of 200 respondents was selected from the employees of the Lobatse Town Council, and it was established that 65.5 percent of the respondents had used VCT. Females had a higher testing participation rates than males, white collar respondents had a higher testing participation than the blue collar respondents. There was a higher rate amongst the married than the single respondents and the older ages of 30 and above than the young ages of 29 years and under. In the study it was also established that the majority of the respondents considered voluntary counselling and testing for HIV and AIDS as being important. However there were some groups that were more positive than others regarding the importance of testing. More females than males were positive regarding the importance of testing, and also amongst the employment categories the white collar respondents were more positive than the blue collar respondents regarding the importance of HIV and AIDS testing. Furthermore it was established that the most important reason for testing amongst the employees that did test for HIV and AIDS was that they felt that they needed to undergo testing before they tested. The respondents that did not test for HIV and AIDS indicated that the most important reason for not testing was that they were scared the results could not be kept confidential. The research also showed that the most preferred service provider was Tebelopele. Tebelopele was the most used and preferred service provider amongst both gender and age groups, all marital groups and the blue collar group in the employment categories. However, for the white collar group the most preferred service provider was the private practitioners. The most common reason for choosing a service provider was confidentiality and privacy. Lastly, the research makes recommendations on what needs to be done to increase the uptake of VCT HIV and AIDS testing amongst the Lobatse Town Council employees. One of the recommendations is that there was a need to educate the employees of the Lobatse Town Council and that the education should be specific for each group. For example from the group discussion the participants felt that the reason to why males did not want to utilise HIV and AIDS VCT was because they lacked knowledge on the importance of testing. Also the respondents indicated that there was a need to remove stigma and discrimination through removing confidentiality attached to HIV and AIDS. It was also, recommended that the Lobatse Town Council formulate and implements a workplace policy on HIV and AIDS

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Mberengo, Sarah. "The relationship between socio-economic status and the practice of HIV self-protective/preventive behaviours among the residents of Maruapula, Gaborone." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79948.

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Thesis (MPhil--Stellenbosch University, 2013.
ENGLISH ABSTRACT: The incidence of HIV/AIDS in Botswana is one of the largest in the world taking its toll on many lives and posing developmental challenges to the nation. Nearly 25% of the population is living with HIV and 14% are newly infected; AIDS is acknowledged as the major cause of death. Most HIV and AIDS studies have been dominated by surveillance, biomedical and ethical methodologies. These approaches failed to stem the tide of HIV infection because they did not follow-up with the tracking of risky behaviours and the underlying causes of the behaviours. This research scrutinized socio-economic factors in relation to the spread of the epidemic. Available literature showed that little or no attention has been paid to the socio-economic backgrounds in which individuals exist in connection with understanding HIV and AIDS. This study used an economic model of risky sexual behaviour to explore the link between socio-economic status and the practice of HIV self-protective/preventive behaviours in Maruapula, Gaborone, Botswana. The research is vital as it goes beyond surveillance in an effort to establish why the community of the study is susceptible to HIV infection. This research l used both collected data and that from BAIS II.
AFRIKAANSE OPSOMMING: Die navorsing is oor die verhouding tussen sosio-ekonomiese status en die praktyk van MIV self-protective/preventive gedrag binne Maruapula distrik. Die doel van die studie is om vas te stel of daar 'n verband tussen sosio-ekonomiese status en die praktyk van MIV-voorkomende gedrag onder die inwoners, van Maruapula, Gaborone, Botswana. Data is ingesamel deur die gebruik van vraelyste en die ontleding van die statistiek het getoon dat die is geen verwantskap tussen sosio-ekonomiese status en die praktyk van MIV self-protective/preventive gedrag onder die inwoners. Aanbevelings gebaseer op die bevindinge is gemaak met betrekking tot MIV-voorkoming in die woongebied in die besonder en in die land in die algemeen.

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Lunat, Imran. "Traditional, complementary and alternative medicine use in HIV-positive patients." Thesis, Nelson Mandela Metropolitan University, 2011. http://hdl.handle.net/10948/1388.

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The standard anti-retroviral drugs (ARVs) used for the treatment of HIV/AIDS have significant side effects resulting in a lack of adherence and the emergence of multidrug resistant viral strains. These drugs are also expensive, making it essential to investigate all alternatives to classical HIV/AIDS treatment. A wide variety of nonconventional medicines are used by patients for the treatment HIV and for symptoms associated with HIV. So long as they are safe and effective, traditional, complementary and alternative medicines (TCAMs) may be considered more advantageous for developing countries as they are relatively cheap, more accessible and widely accepted by local populations. The aim of this study was to determine the prevalence of TCAM use in HIV-positive patients, prior to, and during ARV therapy. The study was exploratory, cross sectional and observational in nature. Participants were selected via convenience sampling from the Nelson Mandela Bay Municipality, and included 244 HIV-positive patients, 29 health care professionals (HCPs) and 30 traditional, complementary and alternative practitioners (TCAMPs). A wide variety of TCAMs were used by the sample population. These medicines were more commonly used by non-ARV patients (36 percent) compared with ARV patients (22 percent). A significant statistical difference in TCAM use between the ARV and non- ARV population was found in relation to education, employment, period of status awareness, patient opinion of personal health and the reasons for TCAM use. Amongst the HCPs, 24 percent recommended TCAM use prior to ARVs, and 55 percent were aware of patients self-prescribing before and during ARV treatment. Amongst the TCAMPs, 90 percent provided a wide range of TCAMs for HIV, with some giving consideration to conventional management. TCAMs are commonly used by HIV-positive patients on ARVs, as well as by those not on ARVs. These medicines are also the preferred form of treatment for those not seeking conventional treatment. TCAMs are widely available and recommended by TCAMPs as well as some HCPs. Due to public health concerns, clinical trials of the widely used TCAMs are crucial in order to establish the safety and efficacy of these medicines in HIV.

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Wong, Mei-wan Farah, and 黃美雲. "Financial burden for HIV/AIDS patients to access antiretroviral therapy in Asian developing countries." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193826.

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Background: Since the beginning of 21st century, several Asian countries started implementing their national free antiretroviral therapy (ART) programs to tackle one of the most striking public health issues in Asia – HIV/AIDS. Despite the efforts being made, the treatment coverage remains as low as 44% in 2010. Previous studies have identified financial constraint is a major barrier in accessing ART and an important reason of poor ART adherence in Asia. The purpose of this literature review is to explore the extent of financial burden experienced by people living with HIV (PLHIV) where free ART policy is implemented, and to provide valuable information for policy-making in reducing financial barriers and improve uptake of ART. Methods: Literature search was performed by entering keywords in PubMed and Medline. Articles were screened and selected for in-depth review according to the inclusion and exclusion criteria. A process on data synthesis was performed on the final eligible papers. Results: Five studies from four Asian countries describing the out-of-pocket health expenditure incurred by PLHIV during the delivery of ART were included in this review. Findings: Out of all direct medical costs, the cost of drug was most important in contributing to the total costs for patients without health insurance, while the cost of transportation was more important for patients covered by health insurance. Direct medical costs increased with advancing stage of disease. Rural patients would have spent up to 1,173% of their monthly income per capita, or more than 100% of their total household expenditure even when ART was provided free-of-charge. Patients have also highlighted free ARV drugs were sometimes not available in the health facility and they had to turn to the private market. Hence, the extent of financial burden in this review might be underestimated. Conclusion: Based on the data available, we concluded that increased accessibility of free ART should be accompanied with sustained ARV drugs supply and increased financial support for PLHIV.
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Community Medicine
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Master of Public Health

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Lu, Hang. "The synthesis and structure-activity relationship study of azo dye related HIV replication inhibitors : Part 2: Plant isolation of signalling pathways inhibitors as anti-cancer agents." Diss., Georgia Institute of Technology, 1994. http://hdl.handle.net/1853/27436.

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Lufuluabo, Ngeleka Albert. "Role of contraception in HIV prevention." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79936.

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Thesis (MPhil)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Reproductive health of people living with HIV/AIDS is a significant public health issue because of its associated risks of HIV transmission to both, the baby and the sexual partner. Provision of effective contraceptive to HIV-positive women is a proven prevention strategy, and can help prevent unintended pregnancy and other sexually transmitted infections. Unmet need for contraception in developing world and rates of unintended pregnancies among women living with HIV remain highly prevalent. The objectives of this study were to identify the current knowledge of HIV-positive women on existing contraceptive methods, determine their current contraceptive practices, identify barriers to contraception use, and provide recommendations on how contraception uptake can be improved among these women in Kasane. A cross-sectional study using qualitative technique was used among twenty five (25) participants at Kasane Primary Hospital. In-depth interviews were conducted with the help of research assistants for data collection. Excel Microsoft Office Software was used for socio-demographics data entry and analysis, and qualitative data were analysed manually using descriptive statistics. Main reasons for low uptake of contraception were desire for children, partner refusal, side effects, and socio-cultural and religious factors. Contraception prevalence was 56 % and condom was the most used contraceptive method (36%). whereas the rate of unintended pregnancies was 60% . Knowledge of contraception was high (100%) but limited proportion of participants (12%) had an expended understanding of contraception as a HIV prevention strategy. Most women living with HIV prefer to space, limit or stop childbearing but do not use any contraceptive method and found themselves with unintended pregnancy. Despite the good knowledge about contraception among participants, the uptake remained low. About half (44%) of the women interviewed were not on any contraceptive method. The choice to use contraception interferes with many factors and the desire to fulfil the primary reproductive intention of men and women, including those living with HIV, mostly override this choice. There is need for a strategic integrated approach that conveys HIV prevention messages and discusses the importance of planning a pregnancy. Thus promoting dual protection among women living with HIV.
AFRIKAANSE OPSOMMING: Die voortplantingsgesondheid van mense wat met MIV/vigs leef, is ‘n belangrike openbaregesondheidskwessie, aangesien voortplantingsgesondheid verband hou met die gevaar van MIV-oordrag na babas sowel as seksmaats. Daar is al bewys dat ander seksueel oordraagbare siektes sowel as onbeplande swangerskappe voorkom word as doeltreffende voorbehoedmiddels verskaf word aan vroue wat MIV-positief is. Dit behoefte aan voorbehoeding in ontwikkelende lande bly egter baie dikwels agterweë, en ‘n groot persentasie vroue wat met MIV leef, raak onbepland swanger. Die doel met hierdie ondersoek is om vas te stel wat vroue wat MIV-positief is, tans oor bestaande voorbehoeding weet, watter voorbehoedingsmetodes hulle tans gebruik en watter struikelblokke daar vir die gebruik van voorbehoeding is, en om voorstelle te maak oor hoe ŉ groter persentasie van hierdie vroue in Kasane oortuig kan word om voorbehoedmiddels te gebruik. ‘n Deursnee-studie wat met behulp van kwalitatiewe tegnieke by die Kasane Primêre Hospitaal uitgevoer is, het vyf en twintig (25) deelnemers betrek. Met die hulp van navorsingsassistente is diepte-onderhoude gevoer om inligting in te samel. Microsoft Office se Excel-sagteware is gebruik om sosio-demografiese inligting in te voer en te ontleed, en kwalitatiewe inligting is met verwysing na beskrywende statistiek met die hand ontleed. Die vernaamste redes vir die trae gebruik van voorbehoeding was die begeerte na ‘n kind, die teenstand van seksmaats, die newe-effekte, en sosio-kulturele en godsdienstige oorwegings. Daar is bevind dat 56% van die deelnemers voorbehoeding gebruik, dat kondome die algemeenste voorbehoedmiddel is (36%) en dat 60% van alle swangerskappe ongewens was. Die deelnemers was almal oor voorbehoeding ingelig (100%), maar slegs ‘n klein persentasie (12%) het ook geweet dat voorbehoedmiddels ‘n voorkomingstrategie vir MIV-infeksie is. Die meeste vroue wat met MIV leef, verkies om swangerskappe te versprei, te beperk of te verhoed, maar gebruik geen voorbehoedmiddels nie en het dus onbepland swanger geraak. Hoewel die deelnemers goed ingelig was oor voorbehoeding, het min van hulle dit gebruik. Ongeveer die helfte (44%) van die vroue met wie onderhoude gevoer is, het geen voorbehoeding gebruik nie. Die keuse om ‘n voorbehoedmiddel te gebruik, word beïnvloed talle ander faktore, en mans en vroue se primêre begeerte om voort te plant – ook al leef hulle met MIV – weeg gewoonlik swaarder as hierdie keuse. Daar is ‘n behoefte aan ‘n strategiese, geïntegreerde benadering wat boodskappe oor MIV-voorkoming oordra en wat tuisbring hoe belangrik dit is om swangerskappe te beplan. Sodoende sal vroue wat met MIV leef, tweedoelige beskerming kry.

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Rose, Nathan Rolf. "Synthesis of novel coumarin derivatives as potential inhibitors of HIV-1 protease." Thesis, Rhodes University, 2007. http://hdl.handle.net/10962/d1007220.

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This research has focused on the development of novel coumann derivatives containing peptide-like side chains as potential HIV-1 protease inhibitors. The reaction of various salicylaldehyde derivatives with tert-butyl acrylate In the presence of 1,4- diazabicyclo[2.2.2]octane (DABCO) has afforded a series of Baylis-Hillman adducts in moderate yield. Cyclisation of the adducts in the presence of HCI afforded the corresponding 3-(chloromethyl)coumarin derivatives, which have been reacted with various amine hydrochlorides in the presence of Proton Sponge® to afford a series of novel 3- (aminomethyl)coumarin derivatives, which were fully characterised by NMR and HRMS methods. Various approaches to the introduction of hydroxyl or amino groups at the C-4 position of coumarin and the 3-(chloromethyl)coumarin derivatives have been explored; these have included dihydroxylation of the coumarin double bond, and the synthesis of 4- benzylaminocoumarin derivatives as potential intermediates. The Vilsmeier-Haack and Mannich reactions have also been investigated as possible methods of introducing the desired peptide-like functionality. Computer modelling of selected structures has indicated that some of the novel 3- (aminomethyl)coumarin derivatives may exhibit activity as inhibitors of HIV-1 protease. The planned enzyme inhibition assays were unfortunately precluded by the aqueous insolubility of the selected compounds. Three ¹³C NMR chemical shift algorithms, viz., Modgraph Neural Network, Modgraph HOSE and Chern Window, have been applied to selected compounds prepared in this study. The Modgraph Neural Network algorithm was found, in all cases, to provide the most accurate correlations with the experimentally-determined chemical shifts.
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Uwimana, Jeannine. "Met and unmet palliative care needs for people living with HIV/AIDS in selected areas in Rwanda." Thesis, University of the Western Cape, 2005. http://etd.uwc.ac.za/index.php?module=etd&amp.

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The aim of this study was to investigate met and unmet palliative care needs for people living with HIV/AIDS in selected areas in Rwanda. The achieve this aim, the study, firstly, identified the palliative care needs of people living with HIV/AIDS, secondly, it identified the health care services available to meet these needs, and thirdly, it determined the extent to which palliative care needs were met.

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Olomola, Temitope Oloruntoba. "Synthesis and evaluation of novel HIV-1 enzyme inhibitors." Thesis, Rhodes University, 2011. http://hdl.handle.net/10962/d1005034.

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This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.

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Rashamuse, Thompho Jason. "Studies towards the synthesis of novel, coumarin-based HIV-1 protease inhibitors." Thesis, Rhodes University, 2008. http://eprints.ru.ac.za/1332/.

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Awortwe, Charles. "Pharmacokinetic herb-drug interaction study of selected traditional medicines used as complementary and alternative medicine (CAM) for HIV/AIDS." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96796.

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Thesis (DMed)--Stellenbosch University, 2015
ENGLISH ABSTRACT: Introduction The increasing intake of traditional medicines among HIV/AIDS patients in sub-Saharan Africa needs urgent consideration by clinicians and other healthcare providers since the safety of such medications are unknown. The pharmacokinetic parameters - Absorption, Distribution, Metabolism and Elimination (ADME) play important role in the safety evaluation of drugs, thus implicating drug metabolizing enzymes and transporters as critical indicators for herb-drug interactions. The objective of this study was to evaluate the risk potential of seven herbal medicines commonly consumed by HIV/AIDS patients for drug interactions applying in vitro models. In this study, inhibition and induction effects of the herbal medicines on cytochrome P450s (CYPs) 1A2, 2C9, 2C19, 2D6 and 3A4 as well as P-glycoprotein (P-gp) were investigated. Methods Herbal medicines – Lessertia frutescens, Hypoxis hemerocallidea, Kalanchoe integra and Taraxacum officinale were sourced from Medico Herbs, South Africa were identified by experts from Compton Herbarium, South African National Biodiversity Institute, Cape Town. Moringa oleifera, Echinacea purpurea and Kalanchoe crenata were obtained from the repository of the National Centre for Natural Product Research (NCNPR), University of Mississippi, USA. Reversible inhibitory effect of aqueous and methanol herbal extracts were evaluated in recombinant CYPs applying the fluorescent metabolites at specified excitation/emission wavelengths; CYP1A2 (3-cyano-7-hydroxycoumarin (CHC); 405/460 nm), CYP2C9, CYP2C19 and CYP3A4 (7-hydroxy-4-(trifluoromethyl)-coumarin (HFC); 405/535 nm) and CYP2D6 (7-hydroxy-4-(aminomethyl)-coumarin (HAMC); 390/460 nm). Comparative studies in human liver microsomes (HLM) and recombinant CYPs were conducted to investigate the inhibitory effect of methanol herbal extracts and fractions on 6β testosterone hydroxylation activity. Time dependent inhibitory (TDI) effect of the herbal extracts were evaluated applying the IC50 shift fold, normalized ratio and the NADPH-, time- and concentration-dependent approaches. Influence of herbal extracts on metabolic clearance of testosterone was assessed in both HLM and human hepatocytes. The effects of each herbal extract on expression of CYP1A2, CYP3A4 and MDR1 genes were evaluated in activated human pregnane X receptor (PXR) co-transfected HepG2 cells. Finally, the inhibitory effect of herbal extracts on P-gp was assessed using the calcein-acetoxymethyl ester (calcein-AM) uptake and the digoxin radiolabelled substrates in MDCKII-MDRI cells. Results The aqueous extracts of Moringa oleifera, Kalanchoe integra, Kalanchoe crenata, Echinacea purpurea and Lessertia frutescens demonstrated high risk of in vivo inhibition on CYPs 3A4 and 1A2 with Cmax/Ki >1.0. Methanol extracts of these herbal medicines also indicated potential risk of reversible drug interaction. The methanol extracts of M. oleifera, K. crenata and L. frutescens showed strong TDI effect on CYP3A4 with IC50 shift fold >1.5 and normalised ratio <0.7. Moringa oleifera intermediately reduced intrinsic clearance of testosterone in human hepatocytes (2 ≤ AUC ratio ≤ 5) when scaled up to humans. Methanol extracts of Echinacea purpurea up-regulated the expression of CYP1A2, CYP3A4 and MDR1 genes in activated PXR. Kalanchoe crenata and Echinacea purpurea indicated strong inhibition on P-gp by reducing transport of digoxin across hMDR1-MDCKII cell monolayer from basolateral to apical with IC50 values of 18.24 ± 2.52 μg/mL and 24.47 ± 4.97 μg/mL, respectively. Conclusion The herbal medicines especially M. oleifera, K. integra and E. purpurea have the potential to cause herb-drug interaction in vivo if sufficient hepatic concentration is achieved in humans.
AFRIKAANSE OPSOMMING: Inleiding Die verhoogde inname van tradisionele medisynes onder MIV/VIGS-pasiënte in sub-Sahara-Afrika verg dringend oorweging deur klinici en ander gesondheidsorgverskaffers, aangesien die veiligheid van sodanige medikasies onbekend is. Die farmakokinetiese parameters – Absorpsie, Distribusie, Metabolisme en Eliminasie (ADME) – speel ’n belangrike rol by die veiligheidsevaluering van geneesmiddels, en impliseer gevolglik geneesmiddel-metaboliserende ensieme en vervoerders as kritiese indikators vir krui-geneesmiddel-interaksies (HDI). Die oogmerk van hierdie studie is om die risikopotensiaal van sewe kruiemedisynes wat algemeen deur MIV/VIGS-pasiënte geneem word, vir geneesmiddel-interaksies te evalueer deur in vitro-modelle te gebruik. In hierdie studie is die inhiberings- en induseringsuitwerkings van die kruiemedisynes op sitochroom P450’s (verkort na CYP’s) 1A2, 2C9, 2C19, 2D6 en 3A4, sowel as P-glikoproteïen (P-gp), ondersoek. Metodes Kruiemedisynes – Lessertia frutescens, Hypoxis hemerocallidea, Kalanchoe integra en Taraxacum officinale – is van Medico Herbs, Suid-Afrika, bekom en deur kundiges van die Compton-herbarium, by die Suid-Afrikaanse Nasionale Biodiversiteitsinstituut, Kaapstad, geïdentifiseer. Moringa oleifera, Echinacea purpurea en Kalanchoe crenata is van die bewaarplek van die Nasionale Sentrum vir Natuurlike Produknavorsing (NCNPR) aan die Universiteit van Mississippi in die VSA verkry. Die omkeerbare inhiberende uitwerking van kruie-ekstrakte in water en metanol is in rekombinante CYP’s geëvalueer deur die gebruik van die fluoresserende metaboliete op gespesifiseerde opwekkings-/emissiegolflengtes; CYP1A2 (3-siaan-7-hidroksikumarien (CHC); 405/460 nm), CYP2C9, CYP2C19 en CYP3A4 (7-hidroksi-4-(trifluoormetiel)-kumarien (HFC); 405/535 nm) en CYP2D6 (7-hidroksi-4-(aminometiel)-kumarien (HAMC); 390/460 nm). Vergelykende studies van menslikelewermikrosome (HLM) en rekombinante CYP’s is uitgevoer om die inhiberende uitwerking van metanolkruie-ekstrakte en -fraksies op 6β-testosteroonhidroksileringsaktiwiteit te ondersoek. Die tydafhanklike inhiberende uitwerking (TDI) van die kruie-ekstrakte is geëvalueer deur gebruikmaking van die IC50-verskuiwingsvou-, die genormaliseerdeverhoudings- en die NADPH-, tyd- en konsentrasieafhanklike benaderings. Die invloed van kruie-ekstrakte op metaboliese testosteroonverheldering is in beide HLM en menslike hepatosiete geëvalueer. Die uitwerkings van elke kruie-ekstrak op die uitdrukking van CYP1A2-, CYP3A4- en MDR1-gene is in geaktiveerde menslike pregnaan-X-reseptor(PXR)-, ko-getransfekteerde HepG2-selle geëvalueer. Laastens is die inhiberende uitwerking van kruie-ekstrakte op P-gp geëvalueer, met gebruikmaking van die kalsien-asetoksimetiel-ester (kalsien-AM)-opname en die digoksien- radiogemerkte substrate in MDCKII-MDRI-selle. Resultate Die ekstrakte in water van M. oleifera, K. integra, K. crenata, E. purpurea en L. frutescens het ’n hoë risiko van in vivo-inhibering op CYP’s 3A4 en 1A2 met Cmaks/Ki >1.0 getoon. Ekstrakte van hierdie kruiemedisynes in metanol het verder potensiële risiko van omkeerbare geneesmiddelinteraksie getoon. Die ekstrakte van M. oleifera, K. crenata en L. frutescens in metanol het sterk TDI-uitwerking op CYP3A4 met IC50-verskuiwingsvou >1.5 en genormaliseerde verhouding <0.7 getoon. M. oleifera het intermediêre vermindering van intrinsieke testosteroonverheldering in menslike hepatosiete (2 ≤ AUC verhouding ≤ 5) tot gevolg wanneer die skaal na mense verhoog word. Ekstrakte van E. purpurea in metanol het die uitdrukking van CYP1A2-, CYP3A4- en MDR1-gene in geaktiveerde PXR opgereguleer. K. crenata en E. purpurea het sterk inhibering van P-gp getoon deur die vervoer van digoksien deur die hMDR1-MDCKII-selmonolaag van basolateraal tot apikaal met IC50-waardes van onderskeidelik 18.24 ± 2.52 μg/mL en 24.47 ± 4.97 μg/mL te verminder. Gevolgtrekking Kruiemedisynes, veral M. oleifera, K. integra en E. purpurea, het die potensiaal om HDI in vivo te veroorsaak indien voldoende hepatiese konsentrasie by mense bereik word.

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Malinowska-Sempruch, Kasia. "Hiv among drug users in poland; the paradoxes of an epidemic." Thesis, Columbia University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3610085.

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Since 1988 when the first HIV positive drug user was identified in Poland, for close to two decades, the predominant route of HIV transmission has been through injecting drug use. In mid 2000s, Polish officials reported that injecting drug use no longer contributed to incrasing HIV incidence. The consequences of such a statement are that many of the structural and personal risks associated with HIV infection go unaddressed, that drug users are neglected by HIV prevention efforts, that HIV treatment is not made available to drug users and that the policy environment does not adequately support effective public health initiatives. This case study is based on documentation, archival records, interviews, participant observation, and physical artifacts shows that these assertions were made, and continue to be repeated, in a highly political context. Poland is a post-socialist state with strong neoliberal leanings, and it is highly invested in successful integration with the European Union. Powerful Catholic Church serves as an important backdrop. While people considered "at risk" now have more freedom to conduct their lives, they also have a set of neoliberal expectations and religious pressures placed on them. Country's geographic location adds to this complexity - situated between "Old Europe" where HIV problem has been successfully contained and the former Soviet Union, where the HIV incidence among drug users is the highest in the world, Poland attempts to align itself with the success of the West. Furthermore, examination of the available data suggests that the assertions made by Polish officials omit numerous variables. My research shows that even though Polish leadership in the area of HIV and drug policy wishes to resemble Western Europe, Poland does not meet international standards for the prevention of HIV transmission. The interviews I conducted, as well as the review of the literature on drug and HIV policies and programs suggest that these services are scattered, often unavailable, and that their number is stagnating, at best, and in some cases, even decreasing. This maybe a direct result of lack of engagement of drug users in their design. Excluded from the discussion of risk, drug users are thus not the focus of prevention efforts. Based on gathered data, there are seven crucial issues that require immediate action if Poland is to manage HIV prevention and care for people who use drugs in a manner consistent with the international standards. The areas requiring action are: a change in the drug policy from the current very punitive approach, expansion of needle and syringe programs and other harm reduction services, improved data collection and an increase in the availability of HIV testing, scaled-up substitution treatment, improved quality of other forms of drug treatment, greater investment in civil society organizations, improved access to HIV treatment, and educational and training efforts that encourage greater attention to HIV related matters across disciplines.

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Ngugi, Pearl. "Response and adherence of HIV positive women to cervical cancer treatment." Thesis, Nelson Mandela Metropolitan University, 2011. http://hdl.handle.net/10948/d1014129.

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It is estimated that 6742 South African women are diagnosed with cervical cancer and 3681 women die from the disease every year. In 1993, The Centers for Disease Control declared cervical cancer an Acquired Immunodeficiency Syndrome defining illness. Apart from persistent human papillomavirus infection, HIV infection is the most common co-factor contributing to cervical cancer in South Africa. Studies have noted that in HIV positive women, there has been an occurrence of faster progression to more advanced stages of cervical cancer with high cases of treatment failure and recurrence. There is limited literature available regarding the prognosis of HIV positive women who suffer from cervical cancer. Women who are HIV positive and have cervical cancer have not been evaluated in detail regarding their response and adherence to cervical cancer treatment. Standard treatment protocols for this set of patients have not been defined. The aim of this study was to assess how HIV positive women who have been diagnosed with cervical cancer responded and adhered to cervical cancer therapy which includes: curative radiotherapy; curative chemotherapy; concurrent chemoradiation or palliative radiotherapy. The study also evaluated the effects of the concurrent use of antiretrovirals and cervical cancer treatment. This was done to determine whether invasive cervical cancer in women who were HIV positive could be managed using the same treatment protocols as patients who were HIV negative. A historical cohort design was employed for the study. The study was conducted at the Oncology Department of a tertiary level hospital located in the Eastern Cape Province, South Africa. The total sample consisted of 196 medical records of women diagnosed with cervical cancer between 2005 and 2008. One hundred women were HIV negative, 83 were HIV positive and the HIV status of 13 women could not be determined. The records were audited over a period of two years from the date of diagnosis. The term „complete response‟ referred to patients who had no recurrence of cervical cancer and no evidence of metastases after undergoing treatment. At one month following treatment there was a significant difference in the incidence of complete response between the HIV positive patients and the HIV negative patients (Chi2 = 16.4, d.f. = 1, p = 0.00005, Cramer‟s V = 0.31). The significant difference in response to treatment between the HIV positive patients and the HIV negative patients was maintained at six months after treatment (Chi2 = 15, d.f. = 1, p = 0.00011, Cramer‟s V = 0.34), 12 months after treatment (Chi2 = 20.5, d.f. = 1, p = 0.00001, Cramer‟s V = 0.37), 18 months after treatment (Chi2 = 9.8, d.f. = 1, p = 0.00173, Cramer‟s V = 0.28) and 24 months after treatment (Chi2 = 5.0, d.f. = 1, p = 0.02571, Cramer‟s V = 0.26). At each of these intervals, cases of treatment failure and metastases were significantly higher in the HIV positive women than in the HIV negative women. Although there was no significant difference in the incidence of adherence between the HIV negative women, the HIV positive women who were on HAART and the HIV positive women who were not on HAART, there was a significant difference in the incidence of the various reasons for non adherence between the various groups. These reasons included: missed scheduled appointments (Chi2 = 2.9, d.f. = 2, p = 0.02385, Cramer‟s V = 0.31); low blood count (Chi2 = 4.0, d.f. = 2, p = 0.01327, Cramer‟s V = 0.15); radiotherapy induced skin breakdown (Chi2 = 0.6, d.f. = 2, p = 0.04581, Cramer‟s V = 0.16) and radiotherapy induced diarrhoea (Chi2 = 6.9, d.f. = 2, p = 0.03118, Cramer‟s V = 0.19). According to the 2004 National Antiretroviral Treatment Guidelines, cervical cancer patients would fall into the WHO stage IV category of HIV disease thus all patients with confirmed diagnosis of invasive cervical cancer should be commenced on antiretrovirals as soon as the cancer diagnosis is made regardless of their CD4 count. However, in the current study, 13 percent (n= 83) of the HIV positive women were not on antiretrovirals. The study concluded that HIV positive women had a higher incidence of both treatment failure and metastases to cervical cancer treatment. Standard radiotherapy and concurrent chemoradiation cervical cancer treatment protocols should be still be used in both HIV negative patients and HIV positive patients so as not to compromise tumour control. Furthermore, in accordance with the antiretroviral treatment guidelines, all HIV positive patients with cervical cancer should receive antiretrovirals irrespective of their CD4 count.

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44

De, Vos Marieta. "Critical factors in NACOSA’s success as a network organisation in the HIV and AIDS sector." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96802.

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Thesis (MPhil)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: NACOSA had an eventful history spanning 22 years. The first phase between 1992 and 2001 is labeled Great Expectations as the composite multi-sectoral structure started a groundbreaking initiative on HIV and AIDS in South Africa and believed that the first AIDS plan drafted by them would be implemented as planned. Expectations came to nothing as government struggled to find its feet through a decade of blunders leading to the demise of the structure by end 2001. The next phase between 2001 and 2010 is labeled Starting Over as the Western Cape branch of NACOSA reinvented itself as a community mobilisation network for the province. Within a period of ten years Western Cape NACOSA developed into a successful national network with a large membership fully involved through its networking, capacity building and promoting dialogue functions. The third phase between 2010 and 2015 is labeled Rapid Growth as NACOSA developed into a large training and grant management agency with strong systems providing funding to its members through sub-granting. Networking continued at a slower pace but is still highly important for the organisation. The network contributes to localised social capital through shared learning and collaboration. NACOSA‟s sustainability has been developed through the ability to raise long-term funds for network activities, capacity building of members and coordinated service delivery on the ground. NACOSA also has a culture of identifying and acting fast on opportunities and adapting to change when it is needed. Strategic factors attributing to the success of NACOSA are a sector based approach promoting diversity in its membership; a consistently focused and shared purpose throughout the years; a community agent approach believing in and advocating for community systems strengthening; obtaining a mandate from network members for main strategy changes; strategic partnerships; a strong capacity building approach focussing on organisational and programmatic competencies; not competing with network members but acting as main weaver; creating specialist networks for specific HIV-related causes; a committed representative executive committee and skilled staff; bringing groups together on a regular basis for discussions and strategising; a variety of social media; and a network mindset intent on a culture of learning and building trust between member organisations.
AFRIKAANSE OPSOMMING: NACOSA het 'n gebeurtenisvolle geskiedenis wat strek oor 'n periode van 22 jaar. Die eerste fase tussen 1992 en 2001 word genoem Groot Verwagtinge, verwysende na die saamgevoegde multi-sektorale struktuur wat ontstaan het as die eerste groot MIV en VIGS inisiatief in Suid-Afrika. Hulle het verwag dat hul eerste VIGS-plan geïmplementeer sou word soos wat hulle dit beplan het. Hul verwagtinge het egter skipbreuk gely as gevolg van die regering wat oor die dekade heen hul voete gesleep en foute gemaak het wat uiteindelik gelei het tot die struktuur se ondergang in 2001. Die volgende fase tussen 2001 en 2010 word genoem Oorbegin verwysende na die Wes-Kaap tak van NACOSA wat hulself herskep het as „n gemeenskapsmobiliseringsnetwerk. Wes-Kaap NACOSA het binne tien jaar weer ontwikkel in 'n suksesvolle nasionale netwerk met 'n groot ledetal wat volledig ingeskakel is by die organisasie se netwerk, kapasiteitsbou en bevordering van dialoogaktiwiteite. Die derde fase tussen 2010 en 2015 word genoem Snelle Groei verwysende na NACOSA se ontwikkeling in 'n groot opleidings- en fondsbestuursagentskap met sterk stelsels wat befondsing aan hul lede verskaf. Netwerkskakeling het voortgeduur teen 'n stadiger pas maar is steeds baie belangrik vir die organisasie. Die netwerk dra by tot die bou van plaaslike sosiale kapitaal deur middel van samewerking en saam leer. NACOSA se volhoubaarheid het ontwikkel deur hul vaardigheid om langtermynfondse in te samel vir netwerkaktiwiteite, kapasiteitsbou en gekoördineerde dienslewering op grondvlak. NACOSA het ook 'n kultuur om geleenthede vinnig te identifiseer en daarop te reageer, asook om aan te pas by veranderinge wanneer nodig. Strategiese faktore wat bygedra het tot NACOSA se sukses sluit in 'n wye sektorbenadering met diverse lidmaatskap; 'n konsekwente gedeelde doelwit oor die jare; die bevordering van sterk gemeenskapstelsels; die verkryging van 'n mandaat by netwerklede vir strategie-veranderinge; strategiese vennootskappe; 'n sterk kapasiteitsboubenadering wat fokus op organisatoriese en programmatiese vaardighede; geen kompetisie met lede-organisasies maar eerder die rol van “hoofwewer”; skep van spesialisnetwerke vir spesifieke MIV-verwante kwessies; 'n toegewyde raad en vaardige personeel; gereelde bymekaarbring van groepe vir dialoog en strategie bou; 'n verskeidenheid van sosiale media; en 'n netwerk denkpatroon gefokus op 'n leerkultuur en die bou van vertroue tussen lede.

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45

Norris, Gerard Benedict. "Counterfeiting of HIV/AIDS medicines : implications for global epidemic : recommendations for workplace programs." Thesis, Stellenbosch : Stellenbosch University, 2005. http://hdl.handle.net/10019.1/50307.

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Thesis (MPhil)--Stellenbosch University, 2005.
ENGLISH ABSTRACT: multiple therapeutic categories of medicines have been increasingly targeted for counterfeiting. According to Van Niekerk [Van Niekerk, Anton. (2001). Moral and social complexities of AIDS in Africa. University of Stellenbosch], “it is commonplace to identify and bewail a plethora of problems in the developing world generally, and in Africa in particular. Poverty, illiteracy, famine, political instability, natural disasters, and many more misfortunes dominate the history of this part of the world over the past 50 years. It was therefore adding uncalled (undeserved?) insult to already overwhelming injury when HIV/AIDS visibly struck the world since mid-1980. In spite of all the other calamities that Africa has to deal with, it nevertheless is no exaggeration to claim that HIV/AIDS nowadays constitutes the most serious health and social crisis and challenge that has ever befallen the continent”. Similar patterns involving HIV/AIDS are now emerging on other continents. One objective of this recent research study was to explore possible relationships between the growing scourges of the worldwide counterfeiting of medicines and parallels with the expanding global HIV/AIDS pandemic - as well as to examine potential relationships and risks associated with other diseases that have been observed to have ‘special associations’ with HIV and AIDS [e.g. sexually transmitted infections (STI’s), Tuberculosis (TB) and Malaria] - and possible impact on the “World of Work”. A second and important objective was to develop Recommendations for Workplace Programs. The information gathered has also been used to propose future studies regarding HIV/AIDS and counterfeiting. In the developing world, antibiotics and anti-parasitic medicines are included among the counterfeiters’ favorite targets. Strong parallels exist between locations where counterfeiting of medicines is taking place/product being distributed/sold and where HIV/AIDS is most prevalent and/or where the epidemic is expanding progressively. Counterfeiting of medicines used for treating HIV/AIDS raises the possibility of additional future complications developing in managing other global diseases such as Malaria and Tuberculosis, not to mention exacerbating the potential for developing resistance and encouraging mutation of the HI virus itself. It is also noteworthy that certain medical devices have also been found to be counterfeit. Global demographics and with particular reference to projected growth rates of populations of the developing world are of specific relevance to this subject of anticounterfeiting and medicines used for the treatment of HIV and AIDS. Indeed, next generations of humanity appear to be at unnecessary risk of being caught up in a confluence of forces whereby the practice of the counterfeiting of medicines could result in significant complications and unforeseen consequences regarding management of the global HIV/AIDS crisis. Following the research, recommendations for workplace programs were developed. The research study concludes with a comprehensive set of references.
AFRIKAANSE OPSOMMING: Die problamatiek aangaande die vervalsing (namaak) van medisyne word nou wereldwyd ervaar en het ‘n impak op beide die geindustrialiseerde en die ontwikkelende wereld. Menige medisyne in terapeutiese kategoriee is tot op hede as vervals geidentifeseer, met die direkte resultaat dat hulle ‘n minemale of geen terapeutiese uitwerking het nie. Wat nog erger is, is dat hierdie middels uiters gevaarlik is om te gebruik en selfs lewensgevaarlik kan wees. Dit is van groot betekenis dat ook medisyne wat bestem is om persone met HIV/VIGS te behandel, as vervals aangetoon is – en soedoende tot nog toe onbekende gevolge vir pasiente, die werkomgewing en ongekende risiko’s vir wereldwye gesondheidsorg en internasionale veiligheid en sekuriteit inhou. In hierdie studie word die onderwerp in taamlike besonderhede bestudeer en daar word afgesluit met aanbevelings oor programme in die werkplek wat ontwerp is om sorg en ondersteuning te bied aan werkers met HIV/VIGS. Verdere studie word ook aanbeveel om die tergende probleme wat volg op die vervalsing van medisyne in die behandling van persone met HIV/VIGS, en die implikasies hiervan, die hoof te bide.

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46

Wang, Aiqin. "Anti-retroviral activity of lavendamycin analogs." Virtual Press, 1996. http://liblink.bsu.edu/uhtbin/catkey/1036177.

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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

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47

Atlas, Ann. "Immunological and virological response to antiretroviral treatment (art) in patients infected with different HIV-1genetic subtypes /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-645-X/.

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48

Fouche, Desire. "Drug-drug interactions between antiretrovirals and fluconazole in HIV-infected patients." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20079.

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Thesis (MScMedSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Background: HIV-positive patients have a significantly weakened immune system which makes them highly susceptible for opportunistic infections, requiring additional treatment. Cryptococcal meningitis and oropharyngeal candidiasis are treated with oral fluconazole. A great potential for drug-drug interactions (DDIs) between fluconazole and antiretrovirals (ARVs), efavirenz, nevirapine, and lopinavir/ritonavir, exists due to interference in common metabolic pathways. The outcome may result in the development of adverse drug reactions or drug resistance and treatment failure. Aim: The primary aim of this thesis was to evaluate the effect of fluconazole on the pharmacokinetics of efavirenz, nevirapine and lopinavir/ritonavir in HIV-infected patients diagnosed with cryptococcal meningitis or oropharyngeal candidiasis. Methods: A prospective study was conducted in 80 HIV-positive, treatment experienced adults (≥18 years old) treated in three different outpatient clinics in the Western Cape region. Patients were subdivided according to ARV regimen and the use of fluconazole. A sparse sampling design was used and corresponding ARV serum concentrations were determined by established HPLC and GC methods. Fluconazole serum concentrations were determined by a newly developed HPLC method. Patient characteristics, concomitant medications, clinical test data and ARV serum concentrations were included in a NONMEM generated, onecompartment, open pharmacometric model with first order elimination to detect any drugdrug interactions between fluconazole and the studied ARVs. The secondary outcome was to establish which patient characteristics influence ARV pharmacokinetics. Results: From 80 outpatients, a total of 276 ARV serum samples (137 efavirenz, 67 nevirapine and 72 lopinavir) were collected for pharmacokinetic evaluation. Efavirenz clearance was correlated with race and concomitant use of rifampicin. No significant covariates were established in the nevirapine model. In the lopinavir model, concomitant use of clotrimazole and the antituberculosis combination isoniazid, pyrazinamide and rifampicin were identified as significant covariates. Discussion: No significant effects of fluconazole on the pharmacokinetics of any of the studied ARVs were observed. Varying efavirenz plasma concentrations in different ethnic populations may be due to differences in gene expression particularly CYP2B6. Coloured patients had significantly lower efavirenz serum concentrations (56.8% decrease in clearance), which has not been previously described in the South African context. Although gender was not a significant covariate in the nevirapine model, female patients tended to have higher nevirapine serum concentrations. TB treatment in all patients receiving lopinavir consisted of a combination of isoniazid, pyrazinamide and rifampicin, each with different effects on CYP isoenzymes. The exact contributing factor of each drug in the ultimate decrease in lopinavir clearance (46.4%) can therefore not be established. Conclusions: Given the limitations of the sample size in the present study, no statistical significant effect of fluconazole on the pharmacokinetics of the investigated ARVs could be demonstrated. A retrospective analysis of the data showed various co-factors that influence the pharmacokinetics of the investigated ARVs. This data needs to be confirmed in a prospective study as the identified covariates are appropriate in the management of HIVinfected patients in the South African context.
AFRIKAANSE OPSOMMING: Agtergrond: HIV-positief pasiënte het ‘n aansienlike verswakte immuunstelsel, wat hul hoogs vatbaar tot opportunistiese infeksies maak, en dus, addisionele behandeling benodig. Cryptococcal meningitis en orofaringeale kandidiase word met orale flukonasool behandel. As gevolg van middeling in algemene metaboliese paaie is daar ‘n groot moontlikheid van middel-middel interaksies tussen flukonasool en die antiretrovirale (ARV) middels, efavirenz, nevirapine, en lopinavir/ritonavir. Die uitkomste hiervan mag tot die ontwikkeling van nadelige middel-middel interaksies of middelweerstandigheid en mislukte behandeling lei. Doel: Die primêre doel van hierdie tesis was om die effek van flukonasool op die farmakokinetika van efavirenz, nevirapine en lopinavir/ritonavir in HIV geïnfekteerde pasiënte met gediagnoseerde cryptococcal meningitis en orofaringeale kandidiase te evalueer. Metodes: Die studie was met 80 HIV-positief, behandeling-ervare volwassenes (≥18 jaar) onderneem. Voorafgenoemde was in drie verskillende buitepasiëntklinieke in die Wes-Kaap behandel. Pasiënte was volgens ARV regimen en die gebruik van flukonasool, of dan nie, verder verdeel. ‘n Beperkte steekproef ontwerp was gebruik, en ooreenstemmende ARV serum konsentrasies is deurgevestigde HPLC en GC metodes vasgestel. Flukonasool serum konsentrasies was deur ‘n nuutontwikkelde HPLC metode vasgestel. Pasiëntkenmerke, gepaardgaande medikasie, kliniesetoets data en ARV serum konsentrasies was by ‘n NONMEM genereerde, een-kompartement, oop farmakometriese model met eerste orde eliminasie ingesluit om enige middel interaksies tussen flukonasool en die bestudeerde ARVs op te tel. Die sekondêre uitkomste was om vas te stel watter pasiënt kenmerke ARV farmakokinetika beïnvloed. Resultate:Uit 80 buitepasïente was ‘n totaal van 276 ARV serum monsters (137 efavirenz, 67 nevirapine en 72 lopinavir) vir farmakokinetiese evaluasie gekollekteer. Efavirenz opruiming was met ras gekorreleer asook gepaardgaande gebruik van rifampisien. Geen betekenisvolle ko-variante was in die nevirapine model vasgestel nie. In die lopinavir model het die gepaardgaande gebruik van clotrimazole en die anti-tuberkulose kombinasie isoniazied, pyrazinamied en rifampisien, lopinavir opruiming verminder. Bespreking: In hierdie studie is geen betekenisvolle effekte van flukanosool op die farmakokinetika van enige van die bestudeerde ARVs waargeneem nie. Afwisselende efavirenz plasma konsentrasies in verskillende etniese populasies mag aan verskille in geenuitdrukking, veral CYP2B6, toegeskryf word. Kleurling pasïente het betekenisvolle verlaagde efavirenz serum konsentrasies getoon (56.8% verlaging in opruiming). Hierdie bevinding is nog nooit voorheen in die Suid-Afrikaanse konteks beskryf nie. Alhoewel geslag nie ‘n beduidende ko-variant in die nevirapine model was nie, het vroulike pasïente geneig om hoer nevirapine serum konsentrasies te hê. TB behandeling, in alle pasïente wat lopinavir ontvang het, het uit die volgende kombinasie bestaan: isoniazied, pyrazinamied en rifampisien, elk met hul eie effekte op CYP isoensieme. Die presiese bydra van elke middel in die uiteindelike verlaging (46.4%) in lopinavir opruiming kan dus nie vasgestel word nie. Gevolgtrekking: Gegewe die beperkings van die steekproef in die huidige studie, kon geen statistiese beduidende effek van flukonazool op die farmakokinetika van die betrokke ARVs gedemonstreer word nie. ‘n Retrospektiewe analise van die data het gewys dat verskeidene ko-faktore die farmakokinetika van die betrokke ARVs beïnvloed. Hierdie data moet in ‘n prospektiewe studie bevestig word omdat die geidentifiseerde covariates die bestuur van MIV-positiewe pasiente in die Suid-Afrikaanse konteks te verbeter.

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He, Xi, and 何溪. "The impact of lopinavir/ritonavir (Kaletra) on blood lipids in HIV/AIDS antivirus treated naïve patients in China." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46936129.

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50

Lee, Yi-Chen. "Studies towards the development of novel HIV-1 integrase inhibitors." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1005022.

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The project has focused on the preparation of several series of compounds designed as potential HIV-1 integrase inhibitors. Various 2-nitrobenzaldehydes have been reacted with two activated alkenes, methyl vinyl ketone (MVK) and methyl acrylate, under Baylis-Hillman conditions to afford α-methylene-β-hydroxylalkyl derivatives in moderate to excellent yields. The reactions were conducted using the tertiary amine catalysts, 1,4-diazabicyclo[2.2.2]octane(DABCO) or 3-hydroxyquinuclidine (3-HQ) with chloroform as solvent, and yields were optimised by varying the catalyst, reagent concentrations and the reaction time. Reductive cyclization of the Baylis-Hillman adducts via catalytic hydrogenation, using 10% palladiumon-carbon catalyst in ethanol, afforded quinoline and quinoline N-oxide derivatives. In some cases “acyclic” reduction products were also isolated. Reaction of the Baylis-Hillman MVK adducts with HCl, has resulted in effective nucleophilic (SN’) displacement of the hydroxyl group to afford allylic chloride derivatives. Direct substitution of these chloro derivatives by secondary or primary amines, followed by catalytic hydrogenation gave quinoline derivatives containing a 3-aminomethyl substituent. The Baylis-Hillman ester adducts obtained from reaction with methyl acrylate were treated directly with various amines to give diastereomeric conjugate addition products. Reactions with piperazine gave N,N’-disubstituted piperazine products. The piperidine derivatives have been dehydrated to give cinnamate esters in moderate yields. The products, which have all been satisfactorily characterised by elemental (HRMS) and spectroscopic (1- and 2-D NMR) analysis, constitute a “library” of compounds for in silico and in vitro studies as potential HIV integrase inhibitors.

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Dissertations / Theses on the topic 'HIV infections – Treatment – Botswana'

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