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Relationship between adherence to antiretroviral therapy and the cost-effectiveness of antiretroviral therapy and the patterns of antiretroviral regimen switchesHabib, Mohdhar Jeilan, 1971- 28 August 2008 (has links)
Not available / text
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Causes of non-adherence to antiretroviral therapy in Wellness Clinic, Tshepong Hospital, KlerksdorpDas, C. R. 12 1900 (has links)
ENGLISH ABSTRACT: HIV/AIDS is the leading cause of death in Sub-Saharan Africa. According to 2001 estimates, there are 28.5 million people living with HIV in Africa, comprising more than 70% of the world’s HIV-infected population. HIV/AIDS remains one of the most important social and public health threats in Sub-Saharan Africa. UNAIDS 2006 estimates that 5.5 million people are living with HIV, and almost 1,000 AIDS deaths occur every day in South Africa. South Africa is currently one of the most severely affected countries in the world. Antiretroviral therapy (ART) is currently the only treatment available for HIV. It does not cure HIV infection, but reduces HIV related mortality and morbidity. / AFRIKAANS ABSTRACT: No abstract available
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African traditional medicine-antiretroviral interactions : effects of Sutherlandia frutescens on the pharmacokinetics of AtazanavirMüller, Adrienne Carmel 28 March 2011 (has links)
In response to the urgent call for investigations into antiretroviral (ARV)-African traditional medicine (ATM) interactions, this research was undertaken to ascertain whether chronic administration of the ATM, Sutherlandia frutescens (SF) may alter the bioavailability of the protease inhibitor (PI), atazanavir (ATV), which may impact on the safety or efficacy of the ARV. Prior to investigating a potential interaction between ATV and SF in vitro and in vivo, a high performance liquid chromatography method with ultraviolet detection (HPLC-UV) was developed and validated for the bioanalysis of ATV in human plasma and liver microsomes. An improved and efficient analytical method with minimal use of solvents and short run time was achieved in comparison to methods published in the literature. In addition, the method was selective, linear, accurate and precise for quantitative analysis of ATV in these studies. Molecular docking studies were conducted to compare the binding modes and affinities of ATV and two major SF constituents, Sutherlandioside B and Sutherlandin C, with the efflux transporter, P-glycoprotein (P-gp) and the CYP450 isoenzyme, CYP3A4 to determine the potential for these phytochemicals to competitively inhibit the binding of ATV to these two proteins, which are mediators of absorption and metabolism. These studies revealed that modulation of P-gp transport of ATV by Sutherlandioside B and Sutherlandin C was not likely to occur via competitive inhibition. The results further indicated that weak competitive inhibition of CYP3A4 may possibly occur in the presence of either of these two SF constituents. The Caco-2 cell line was used as an in vitro model of human intestinal absorption. Accumulation studies in these cells were conducted to ascertain whether extracts and constituents of SF have the ability to alter the absorption of ATV. The results showed that the aqueous extract of SF significantly reduced ATV accumulation, suggesting decreased ATV absorption, whilst a triterpenoid glycoside fraction isolated from SF exhibited an opposing effect. Analogous responses were elicited by the aqueous extract and a triterpenoid glycoside fraction in similar accumulation studies in P-gp overexpressing Madin–Darby Canine Kidney Strain II cells (MDCKII-MDR1), which signified that the effects of this extract and component on ATV transport in the Caco-2 cells were P-gp-mediated. The quantitative analysis of ATV in human liver microsomes after co-incubation with extracts and components of SF was conducted to determine the effects of SF on the metabolism of ATV. The aqueous and methanolic extracts of SF inhibited ATV metabolism, whilst the triterpenoid glycoside fraction had a converse effect. Analogous effects by the extracts were demonstrated in experiments conducted in CYP3A4-transfected microsomes, suggesting that the inhibition of ATV metabolism in the liver microsomes by these SF extracts was CYP3A4-mediated. A combination of Sutherlandiosides C and D also inhibited CYP3A4-mediated ATV metabolism, which was in contrast to the response elicited by the triterpenoid fraction in the liver microsomes, where other unidentified compounds, shown to be present therein, may have contributed to the activation of ATV metabolism. The in vitro studies revealed the potential for SF to alter the bioavailability of ATV, therefore a clinical study in which the effect of a multiple dose regimen of SF on the pharmacokinetics (PK) of a single dose of ATV was conducted in healthy male volunteers. The statistical analysis showed that the 90 % confidence intervals around the geometric mean ratios (ATV + SF/ATV alone) for both Cmax and AUC0-24 hours, fell well below the lower limit of the "no-effect" boundary of 0.8 – 1.25, implying that the bioavailability of ATV was significantly reduced in this cohort of subjects. It may thus be concluded that if the reduction in bioavailability observed in this clinical study is found to be clinically relevant, co-administration of SF commercial dosage forms and ATV in HIV/AIDS patients may potentially result in subtherapeutic ATV levels, which may in turn contribute to ATV resistance and/or treatment failure. This research has therefore highlighted the potential risk for toxicity or lack of efficacy of ARV regimens which may result when ATMs and PIs are used concurrently and that patients and health care practitioners alike should be aware of these perils.
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Pharmaceutical analysis and drug interaction studies : African potato (Hypoxis hemerocallidea)Purushothaman Nair, Vipin Devi Prasad January 2006 (has links)
In order for a medicinal product to produce a consistent and reliable therapeutic response, it is essential that the final composition of the product is invariable and that the active ingredient/s is/are present in appropriate, non-toxic amounts. However, due to the complexity involved in the standardization of natural products, quality control (QC) criteria and procedures for the registration and market approval of such products are conspicuously absent in most countries around the world. African Potato (AP) is of great medical interest and this particular plant has gained tremendous popularity following the endorsement by the South African Minister of Health as a remedy for HIV/ AIDS patients. Very little information has appeared in the literature to describe methods for the quantitative analysis of hypoxoside, an important component in AP. It has also been claimed that sterols and sterolins present in AP are responsible for its medicinal property but is yet to be proven scientifically. To-date, no QC methods have been reported for the simultaneous quantitative analysis of the combination, β- sitosterol (BSS)/ stigmasterol (STG)/ stigmastanol (STN), purported to be present in preparations containing AP. The effect of concomitant administration of AP and other herbal medicines on the safety and efficacy of conventional medicines has not yet been fully determined. Amongst the objectives of this study was to develop and validate quantitative analytical methods that are suitable for the assay and quality control of plant material, extracts and commercial formulations containing AP. Hypoxoside was isolated from AP and characterized for use as a reference standard for the quality control of AP products and a stability-indicating HPLC/ UV assay method for the quantitative determination of hypoxoside was developed. In addition, a quantitative capillary zone electrophoretic (CZE) method was developed to determine hypoxoside, specifically for its advantages over HPLC. A HPLC method was also developed and validated for the quantitative analysis of BSS, STG and STN in commercially available oral dosage forms containing AP material or extracts thereof. The antioxidant activity of an aqueous extract of lyophilized corms of AP along with hypoxoside and rooperol were investigated. In comparison with the AP extracts and also with hypoxoside, rooperol showed significant antioxidant activity. The capacity of AP, (extracts, formulations, hypoxoside and rooperol as well as sterols to inhibit in vitro metabolism of drug substrates by human cytochrome P450 (CYP) enzymes such as CYP 3A4, 3A5 and CYP19 were investigated. Samples were also assessed for their effect on drug transport proteins such as P-glycoprotein (P-gp). Various extracts of AP, AP formulations, stigmasterol and the norlignans, in particular the aglycone rooperol, exhibited inhibitory effects on CYP 3A4, 3A5 and CYP19 mediated metabolism.These results suggest that concurrent therapy with AP and other medicines, in particular antiretroviral drugs, can have important implications for safety and efficacy. Large discrepancies in marker content between AP products were found. Dissolution testing of AP products was investigated as a QC tool and the results also revealed inconsistencies between different AP products.
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A strategy for the management of HIV/AIDS in the health sector of the City of JohannesburgBarnard, Antonia Wilhelmina 22 November 2010 (has links)
M.Cur. / The HIV/AIDS pandemic is posing major challenges to all sectors in South Africa, including the Health sector of the City of Johannesburg. The Health sector of the City of Johannesburg, as a result of the pandemic, is faced with increasing demands on its scarce resources at a time of major reform at local government level including transformation of the health sector. The inhabitants of the City of Johannesburg are particularly vulnerable to high levels of HIV/AIDS infection because of job prospects in the city, a good transport infrastructure, high levels of mobility of the community, the existence of single sex-hostels, marginalised communities living in informal settlements, poverty income inequality. An increase in the prevalence of HIV/AIDS is inevitable, unless a concerted effort is established to curtail the spread of the disease. An impact analysis conducted, revealed that already in the year 2000 an estimated 168 921 HIV infected persons were living in the city (City of Johannesburg, 2001 :21). In high-risk groups, such as attenders to services for the treatment of Sexually Transmitted Infections (STls), prevalence rates as high as 53% among females, and 35.8% among male persons were recorded (SAIMR, 2000:1). The City of Johannesburg, a local government structure, has not formally adopted a strategic plan to address the pandemic. The national and proVincial governments have responded to the pandemic and their 3-5 year strategic plans are known and pUblished. In spite of the absence of an official strategic plan to address the pandemic in the City of Johannesburg, the political will and strategic intentions to address the pandemic have been declared by management. Although all sectors of the City are affected, it is generally assumed that the Health sector would assume the leading role in addressing the pandemic. The objective of this study has thus been to explore and describe a strategy for the management of HIV/AIDS by the Health sector of the City of Johannesburg. The question presented for research was formulated as follows: " What strategy should be adopted by the Health sector of the City of Johannesburg to manage the HIV/AIDS pandemic in future?" An exploratory, descriptive and quantitative research design was utilised. The strategy for the management of HIV/AIDS was formulated according to the UNAIDS "Guide to the strategic planning process for a national response to HIV/AIDS" (1998), and the content validity was determined according to Lynn (1986) "Determination and quantification of Content Validity".
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Bayliss-Hillman adducts as scaffolds for the construction of novel compounds with medicinal potentialIdahosa, Kenudi Christiana January 2012 (has links)
This project has focused on exploring the application of Baylis-Hillman (BH) {a.k.a. Morita-Baylis-Hillman (MBH)} scaffolds in the construction of various compounds with medicinal potential. A series of 2-nitrobenzaldehydes has been treated under BH conditions, with two different activated alkenes, viz., (MVK) and methyl acrylate, using (DABCO) or (3-HQ) as catalyst. While most of the BH reactions were carried out at room temperature, some reactions were conducted using microwave irradiation. The resulting BH adducts have been subjected to dehydration, conjugate addition and allylic substitution to obtain appropriate intermediates, which have been used in turn, to synthesize possible lead compounds, viz., cinnamate esters as HIV-1 integrase inhibitors, 3-(aminomethyl)quinolines and quinolones as anti-malarials and cinnamate ester-AZT conjugates as dual-action HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. Conjugate addition reactions of methyl acrylate-derived BH β-hydroxy esters with the amines, piperidine, propargylamine and 2-amino-5-(diethylamino)pentane, has afforded a range of products as diastereomeric mixtures in moderate to excellent yields. Catalytic hydrogenation of the aminomethy β-hydroxy esters derivatives, using a palladium-oncarbon (Pd-C) catalyst, has afforded the corresponding, novel 3-aminomethyl-2- quinolone derivatives in moderate yields. Effective allylic substitution reactions of the MVK-derived BH β-hydroxy ketones (via a conjugate addition-elimination pathway) using in situ-generated HCl has afforded the corresponding α-chloromethyl derivatives, which have been reacted with various amines, including piperidine, piperazine, propargylamine and 2-amino-5-(diethylamino)pentane, to yield α-aminomethyl derivatives. Catalytic hydrogenation of selected α-aminomethyl derivatives, using a Pd-C catalyst, has afforded the corresponding, novel 3- (aminomethyl)-2-methylquinoline derivatives in low to moderate yields. A bioassay, conducted on a 6-hydroxy-2-methyl-3-[(piperidin-1-yl)methyl]quinoline isolated early in the study indicated anti-malarial activity and prompted further efforts in the synthesis of analogous compounds. Reaction of the methyl acrylate-derived BH adducts with POCl3 has provided access to α-(chloromethyl)cinnamate ester derivatives, which have been aminated to afford α- (aminomethyl)cinnamate ester derivatives as potential HIV-1 integrase inhibitors. The α- (propargylaminomethyl)cinnamates were used, in turn, as substrates for the “click chemistry” reaction with 3'-azido-3'-deoxythymidine (AZT– an azide and an established reverse transcriptase HIV-1 inhibitor) to afford cinnamate ester-AZT conjugates as potential dual-action HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. Computer modelling and docking studies of a cinnamate ester-AZT conjugate into the HIV-1 integrase and reverse transcriptase active-sites revealed potential hydrogen-bonding interactions with amino acid residues within the receptor cavities. The isolated products have been appropriately characterized using IR, 1- and 2-D NMR and HRMS techniques, while elucidation of the stereochemistry of the double bond in the BH-derived halomethyl derivatives has been assigned on the basis of NOE, computer modelling and X-ray crystallographic data.
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Studies towards the synthesis of novel, coumarin-based HIV-1 protease inhibitorsRashamuse, Thompho Jason January 2008 (has links)
A series of the Baylis-Hillman adducts have been obtained by reacting protected O-benzylated and unprotected substituted salicylaldehydes with methyl acrylate or tertbutyl acrylate, respectively, using DABCO as catalyst. Treatment of the Baylis-Hillman adducts with HCl in a mixture of acetic acid and acetic anhydride afforded the corresponding 3-(chloromethyl)coumarin derivatives with yields of up to 94%. Similar use of HI afforded the corresponding 3-(iodomethyl)coumarins but, depending on the reaction time, the reduced 3-methyl analogues could also be obtained. Arbuzov reactions of the 3-(halomethyl)coumarin derivatives have been undertaken to afford 4-phosphorylated and 1’-phosphorylated derivatives, regioselectivity being dependent on the halide-leaving group. The 3-(chloromethyl)coumarin derivatives have been subjected to nucleophilic (SN) attack by benzylamine to give the corresponding 3- [(benzylamino)methyl]coumarin derivatives in yields of up to 74%. Further treatment of the 3-[(benzylamino)methyl]coumarin derivatives with chloroacetyl chloride afforded the chloroacetamide derivatives, which exhibit hindered rotation about the amine C(O)-N bond. The acetamide derivatives have also been subjected to Arbuzov reaction conditions to afford the phosphorylated derivatives in yields of up to 86%. In a preliminary modelling study, hydrolysed analogues of the synthesized phosphorylated derivatives have been docked into the active site of the HIV-1 protease enzyme using the Cerius-2 Ligandfit software module to provide an insight into potential receptor-ligand hydrogen bonding interactions.
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The effects of a group-based cognitive behavioural intervention on mood change and interpersonal behaviour in HIV-positive personsMessini, Lambros 14 April 2014 (has links)
M.A. (Psychology) / The Acquired Immunodeficiency Syndrome (AIDS) has become one of the major challenges that the health care system has had to face and will continue to present a significant health challenge well into the 21st century. Up to the present time no effective treatment method has been found as the retroviral agents typically only cause a temporary inhibition of the progression of the Human Immunodeficiency Virus (HlV) and not a permanent cessation of the activity ofthe virus. Psychosocial approaches to the management of HlV have been moderately successful, but more successful then the retroviral agents during the HIV but non Clinical stage. Considering the proportions of the HlV disease, there are few studies in South-Africa, that describe the therapeutic effects of a stress management package consisting of aerobic exercise, group-based cognitive behavioural therapy and relaxation training on mood state changes of asymptomatic and early symptomatic HIV sufferers. Psychological measures, like depression and anxiety have been found to be associated with lowered immune responsivity, thus enhancing the underlying immunodeficiency found in HlV/AIDS sufferers. Past research has also illustrated the benefits that may be derived from aerobic exercise on the physiological mechanisms of the body. The intention of this research, was therefore to further reinforce the positive effects of aerobic exercise by using a biopsychosocial approach in the treatment of HIV, leading to an overall improvement in the immunological status, depression and distress levels of HlV patients, as well as their ability to cope with the disease. The study took place within the context of a wider project, forming a component of the AIDS research conducted by Prof. E.Wolff (Rand Afrikaans University). The study assessed the relevance of this intervention for the South African Setting.
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Antiretroviral drug susceptibility of a hinge region variant of HIV-1 subtype C proteaseZondagh, Jake January 2018 (has links)
A thesis submitted to the Faculty of Science, University of the Witwatersrand,
Johannesburg in fulfilment of the requirements for the degree of Doctor of
Philosophy. Johannesburg, 28 May 2018. / Since their discovery, protease inhibitors continue to be an essential component of
antiretroviral treatment for human immunodeficiency virus type 1 (HIV-1). However, the
development of resistance to protease inhibitors remains one of the most significant challenges
in the fight for sustained viral suppression in those infected with HIV-1. Studies show that
specific mutations arising within the HIV-1 gag and protease genes can lead to the
development of resistance. In this research, a South African HIV-1 subtype C Gag-protease
variant (W1201i) was investigated. This variant was considered due to the presence of a
mutation and insertion (N37T↑V), located within the hinge region of the protease enzyme.
Moreover, the variant displayed the following polymorphisms: Q7K, I13V, G16E, M36T,
D60E, Q61E, I62V and M89L. Genotyping of W1201i Gag revealed a previously unreported
MSQAG insertion between the CA/p2 and p2/NC cleavage sites. Additionally, a mutation and
insertion (I372L↑M), and multiple polymorphisms (S369N, S371N, I373M and G377S) were
discovered within the p2/NC cleavage site. Single-cycle phenotypic assays were performed to
determine the drug susceptibility and replication capacity of the variant. The results show that
the mutations present in the N37T↑V protease conferred a replicative advantage and reduced
susceptibility to lopinavir, atazanavir and darunavir. Interestingly, the mutations in W1201i
Gag were found to modulate both replication capacity and protease inhibitor susceptibility.
In silico studies were performed to understand the physical basis for the observed variations.
Molecular dynamics simulations showed that the N37T↑V protease displayed altered dynamics
around the hinge and flap region and highlighted the amino acids responsible for the observed
fluctuations. Furthermore, induced fit docking experiments showed that the variant bound the
iv
protease inhibitors with fewer favourable chemical interactions than the wild-type protease.
Collectively, these data elucidate the biophysical basis for the selection of hinge region
mutations and insertions by the HI virus and show that protease, as well as Gag, needs to be
evaluated during resistance testing. / EM2018
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Rallying resources : strategies of therapeutic engagement among patients living with HIV in SenegalGilbert, Hannah January 2003 (has links)
No description available.
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