Rozprawy doktorskie: „Antiretroviral agents”

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陳惠結 i Wai-kit Chan. "The most effective method to improve antiretroviral drug adherence". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40720329.

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Chan, Wai-kit. "The most effective method to improve antiretroviral drug adherence". Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40720329.

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Terblanche, Lauren Muriel. "The knowledge about HIV/AIDS and antiretroviral treatment of patients receiving antiretroviral therapy". Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20131.

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Thesis (MCur)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Many HIV positive patients are on antiretroviral therapy (ART) to assist in decreasing the replication of the HIV virus within the body. Adherence to this medication is important, as non- adherence can have serious repercussions. Therefore, the patients’ knowledge of ART and their disease is crucial in ensuring good adherence. A range of barriers to patient education were suspected by the researcher in this community of Delft. The high influx of patients into the clinic everyday minimized consultation time and thereby diminished the opportunity for effective patient education. Consequently, adherence to medication which is closely related to the knowledge and understanding of patients about the disease may be affected. The following research question was therefore explored: What is the knowledge of infected HIV/AIDS patients who are receiving antiretroviral treatment about HIV/AIDS and ART? The objectives set were to evaluate the patient’s knowledge of HIV/AIDS, evaluate the knowledge of ART and to determine whether there are statistical differences between the dependant and independent variables within the study. A quantitative descriptive correlational research design was applied and a convenience sample of n= 200 (8.5%) patients was selected from a population of N= 2349 at the Delft Community Health Centre. A multiple choice questionnaire comprising of mainly closed ended questions with multiple responses was used in individual interviews conducted by either the researcher or fieldworker. Reliability and validity was ensured through the consultation of experts in the fields of research methodology, statistics, HIV/AIDS and the Health Research Ethics Committee of Stellenbosch University. Permission to conduct this study was granted by the Health Research Ethics Committee of Stellenbosch University, the Provincial Regional Head for Primary Health Care Services, as well as the head of the Delft Community Health Centre. Data revealed that the participants were mainly female (n=145/72.5%), and the mean age was 37.5 years. Participants were mostly Xhosa speaking and literate, and the majority (n=112/56%), of the participants had a highest education level between grade 9 and grade 12. Many (n=73/36.5%) of the participants had been living with HIV for more than 5 years, but had been on ART for between 1 to 3 years. Knowledge was assessed by asking questions about various aspects of HIV and ART throughout the study. Scores for the 14 critical questions revealed that (n=0/0%) of the participants had good knowledge, (n=40/20%) of the participants had average knowledge and (n=160/80%) of the participants had poor knowledge. The average score for all participants for all 20 knowledge testing questions was (12.6/63%). The findings showed that the overall knowledge (n=160/80%) is poor. Basic terms and principles of HIV/AIDS and ART were not understood and serious misconceptions regarding the disease were revealed.
AFRIKAANSE OPSOMMING: Baie MIV positiewe pasiënte is op antiretrovirale terapie (ART) om te help met die vermindering van die replisering van die HIV virus in die liggaam. Gebruik van hierdie medikasie is belangrik omdat versuiming van inname ernstige gevolge kan hê. Dus, is die pasiënte se kennis van ART en hul siekte van deurslaggewende belang om volgehoue inname te verseker. ’n Reeks van hindernisse om pasiënte te onderrig, is deur die navorser in die Delftgemeenskap vermoed. Die hoë toestroming van pasiënte na die kliniek elke dag het die konsultasietyd tot die minimum beperk en daardeur die geleentheid vir effektiewe pasiëntonderrig laat verminder. Gevolglik, kan die nakoming om die medikasie te neem wat ’n noue verband toon met die kennis en begrip wat pasiënte het oor die siekte, geaffekteer word. Die volgende navorsingsvraag is gevolglik ondersoek: Wat is die kennis van geïnfekteerde HIV/VIGS pasiënte wat antiretrovirale behandeling ontvang oor HIV/VIGS en ART? Die doelwitte wat gestel is, is om die pasiënt se kennis van HIV/VIGS te evalueer, die kennis van ART te evalueer en te bepaal of daar ’n statistiese verwantskap tussen onafhanklike en afhanklike veranderlikes binne die studie is. ’n Kwantitatiewe beskrywende korrelerende navorsingsontwerp is toegepas en ’n gerieflikheidsmonster van n= 200 (8.5%) pasiënte is geselekteer uit ’n bevolking van N = 2349 by die Delftgemeenskap Gesondheidssentrum. ’n Veelkeusige vraelys wat hoofsaaklik uit geslote vrae met veelkeusige response bestaan het, is gebruik in individuele onderhoude wat deur of die navorser of veldwerker gevoer is. Betroubaarheid en geldigheid is verseker deur oorlegpleging met spesialiste op die gebied van navorsingsmetodologie, statistiek, HIV/VIGS en die Gesondheidsnavorsing se Etiese Komitee van die Universiteit van Stellenbosch. Toestemming om die navorsing te doen, is gegee deur die Gesondheidsnavorsing se Etiese Komitee van Stellenbosch Universiteit, die Provinsiale Streekshoof vir Primêre Gesondheidsdienste, asook die hoof van die Delftgemeenskap Gesondheidssentrum. Data het bewys dat die deelnemers hoofsaaklik vroulik is (n=145/72.5%) en die gemiddelde ouderdom 37.5 jaar. Deelnemers is meestal Xhosasprekend en geletterd en die meerderheid (n=112/56%) van die deelnemers se hoogste opleidingsvlak is tussen graad 9 en graad 12. Baie (n=73/36.5%) van die deelnemers het met HIV geleef vir 5 jaar, maar was op ART vir tussen 1 tot 3 jaar. Kennis is geassesseer deur vrae te stel oor verskeie aspekte van HIV en ART dwarsdeur die ondersoek. Puntetelling vir die 14 kritiese vrae het aan die lig gebring dat (n=0/0%) van die deelnemers goeie kennis het, (n=40/20%) van die deelnemers beskik oor gemiddelde kennis en (n=160/80%) van die deelnemers se kennis is gering. Die gemiddelde puntetelling vir al die deelnemers van al 20 kennisvrae wat getoets is, is (12.6/63%). Die bevindinge bewys dat die algehele kennis (n= 160/80%) gering is. Basiese terminologie en beginsels van HIV/VIGS en ART word nie begryp nie en ernstige wanopvattinge aangaande die siekte is geopenbaar.

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Maseko, Batlile Paulos. "Antiretroviral treatment programme outcomes scenarios in South Africa in the next two decades". Thesis, University of Limpopo (Medunsa Campus), 2012. http://hdl.handle.net/10386/1094.

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Gaula, M. D. "Drug adverse effects in HIV-infected patients receiving antiretroviral therapy-a pharmacovigilence approach". Thesis, University of Limpopo ( Medunsa Campus), 2011. http://hdl.handle.net/10386/396.

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Thesis (M Med Pharmacy)--University of Limpopo, 2011
Most pharmaceutical agents can result in side effects and toxicities that in some instances may be life threatening, especially if there is delay in their recognition. For various reasons it is therefore imperative to study adverse events associated with antiretroviral agents (ARVs). The aim of this study was to study the adverse events in adult HIV-infected patients receiving antiretroviral therapy at a public health treatment site, and to quantify the frequency of adverse events in different population subgroups. A retrospective cohort study was conducted in a sample of 99 patients (i.e. 70% females and 30% males) from a public health clinic providing antiretroviral drugs to more than 1500 patients. The reported adverse events were neurological disorders (33%), rash (17%), gastrointestinal toxicity (16%), lactic acidosis (14%), hepatitis (7%), lipodystrophy (7%), pancreatitis (5%), IRIS (3%), anaemia (1%), and gynaecomastia (1%). Based on the analysis of the presented data in this report, age, weight, gender, and pCD4 count are not the predictors for the development of lactic acidosis, pancreatitis, and peripheral neuropathy. The duration of treatment was found to be the predictor for the development of lactic acidosis, pancreatitis, and peripheral neuropathy in this study sample. More frequent and closer monitoring of the reported adverse events will be necessary for patients treated longer on ART. Information bias is possible as case data for all reported adverse effects were collected retrospectively from hand-written patient records which were not consistent and standardised.

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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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Nikisi, Joseph. "Access to antiretroviral treatment in the public sector, in Zambia /". Access to E-Thesis, 2005. http://upetd.up.ac.za/thesis/available/etd-04282009-163207/.

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Togami, Hiroaki. "Comprehensive in vitro susceptibility analysis of simian retrovirus type 4 to antiretroviral agents". Kyoto University, 2013. http://hdl.handle.net/2433/179351.

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Casey, Ryan Edward. "Mouse strain-specific splicing of Apobec3". Digital WPI, 2006. https://digitalcommons.wpi.edu/etd-theses/950.

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"Host resolution of viral infection is dependent upon components of the innate and acquired immune system. The mammalian protein Apobec3 plays an important role as part of the immune systemâ€™s innate defenses through its modification of reverse transcribed viral DNA. Recently, Apobec3 was found to directly inhibit HIV-1 and HBV replication through deaminating newly transcribed deoxycytidine residues to deoxyuridine. The ability of mouse and simian Apobec3 variants to inhibit human retroviruses and vice versa highlights the utility of analyzing cross-species homologues. To better understand this editing enzyme, differentially pathogen-susceptible inbred mice were used as an experimental model. The purpose of this project is to examine the effects of murine Apobec3 (muA3) alternative splicing on its DNA-editing characteristics. Three distinct Apobec3 isoforms were isolated from pathogen-susceptible BALB/cByJ (â€œCâ€) inbred mice, and two Apobec3 isoforms came from pathogen-resistant C57BL/6ByJ (â€œYâ€) mice. The five muA3 isoforms were cloned, sequenced, and expressed from a constitutive promoter in a haploid Saccharomyces cerevisia strain. MuA3 DNA-editing activity was measured via the CAN1 forward mutation assay. The five isoforms studied in this project were discovered to be strain-specific. One isoform from each mouse strain mutated the yeast CAN1 locus significantly. Additionally, both muA3 isoform mRNAs derived from the pathogen-resistant Y mice were found to persist at a higher level (2.7 -12.4 fold) than any of the C mouse isoforms. This suggests that the absence of exon 5 or some other signal in the Y mice may influence transcript stability. Evidence also suggests that the murine Apobec3 start codon is actually 33bp upstream of its reference start, with implications for previous research performed using muA3. Sequencing analysis of genomic DNA revealed the presence of a 4bp insertion in a region of BALB/cByJ muA3 which may have disrupted an intronic splicing enhancer signal. Furthermore, a novel BALB/cByJ Apobec3 isoform was characterized. This is the first report of strain-specific processing with regard to muA3."

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Esposito, Francesca. "Impact of highly active antiretroviral therapy (HAART) on body composition and other anthropometric measures of HIV-infected women in a primary healthcare setting in KwaZulu-Natal : a pilot study". Thesis, Link to the online version, 2008. http://hdl.handle.net/10019/1886.

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Kubashe, Nomachina Theopatra. "Disclosure of HIV status and adherence to antiretroviral therapy". Thesis, Nelson Mandela Metropolitan University, 2009. http://hdl.handle.net/10948/1174.

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The Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) is one of the leading chronic diseases affecting people in South Africa and throughout the world. This study aimed to investigate the effect disclosure of HIV status had on antiretroviral therapy (ART) adherence. A convenience sample of 65 HIV positive adult patients currently taking ART at a public Primary Health Care (PHC) clinic in the Nelson Mandela Metropole was selected. Participation was voluntary and confidentiality was maintained at all times. Data was collected using three tools/techniques: (1) a Patient Questionnaire (PQ) to extract information on patient's demographics, HIV disclosure status, regimen the patient was on and self-reported adherence to ART; (2) an audit of a Patient Medical Record (PMR) for information on the regimen the patient was on, the period during which the patient had been on ART medication, the adherence to ART care and the level of the patient‟s biological markers; and (3) Pill Counts (PC) performed on the patient's medical supply to validate the self-reported adherence to ART. There was no significant relationship between the disclosure of HIV status and adherence to ART (p= 0.59; Chi²). However, the relationship between the adherence to ART and increase in the CD4 count levels of patients on ART in this population was significant (p=0.03; Chi²). It can be concluded that no direct relationship was found between the disclosure of HIV status and adherence to ART in this population. However, several factors affected the reasons and decisions of individuals to disclose their HIV status and this influenced their daily taking of medication.

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Vermeulen, Jacomina Hendrina. "Identifying structural barriers to antiretroviral therapy adherence". Thesis, Stellenbosch : University of Stellenbosch, 2011. http://hdl.handle.net/10019.1/6539.

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Thesis (MA)--University of Stellenbosch, 2011.
ENGLISH ABSTRACT: The topic of antiretroviral adherence remains a subject of continued importance, as it is associated with positive health outcomes amongst patients attending public healthcare facilities. Available literature on adherence behaviour mainly focuses on the psychological and behavioural barriers, while overlooking the multitude of structural barriers within the patient’s environment affecting the patient’s adherence to antiretroviral treatment and care. The present study provides a unique perspective on adherence behaviour amongst persons living with HIV and receiving antiretroviral treatment, as it identifies important structural barriers to clinical attendance and pill-taking. The sample for this study were selected from patients attending an infectious diseases clinic at a major peri-urban secondary hospital and receiving antiretroviral therapy, nurses and doctors providing health services to patients, and patient advocates providing psychosocial support to patients under the auspices of a local non-governmental organisation. The participants included in this study were selected by means of convenience sampling to participate either in semi structured interviews or focus group discussions. Participants were assured of the confidentiality of the process and their anonymity in both cases. Both semi structured interviews and focus groups were digitally recorded and transcribed after which transcriptions were entered into Atlas.ti for textual analysis. Transcriptions were thematically analysed according to the perceptions of various participants. The main themes that emerged from the present study included individual barriers, poverty-related barriers, institutionrelated barriers, and social and community-related barriers. The results of the present study were triangulated by considering the concurrences and discrepancies between the patients, clinicians and patient advocates on the main, and subthemes. These themes were then discussed according to Bronfenbrenner’s (1972) Ecological Systems Theory, which divided the main themes identified according to the different systems operating within the patient’s environment, i.e. the micro-, exo-, and macrosystem. The microsystem included both individual psychological and behavioural barriers and poverty-related barriers. Institutional barriers were considered within the exosystem of the patient’s ecological environment. And the social and community-related barriers were considered within the macrosystem of the patient’s ecological environment. The significance of this study lies in the identification of adherence behaviour as the product of the patient’s environment through the examination of triangulated data. Future research may include effective ways in which patients can be assisted in developing the necessary skills to cope with their environment and to enhance social support. The development of strategies to support newly-enrolled patients also still needs investigation.
AFRIKAANSE OPSOMMING: Volgehoue antiretrovirale behandeling bly ‘n onderwerp van voortdurende belang omdat dit geassosieer word met positiewe gesondheidsuitkomste onder pasiënte wat van openbare gesondheidsfasiliteite gebruik maak. Beskikbare literatuur oor volhoudings gedrag fokus grootliks op sielkundige en gedragshindernisse, terwyl veelvuldige strukturelehindernisse binne die pasiënt se omgewing steeds misgekyk word. Dié studie bied ‘n unieke perspektief op volhoudingsgedrag onder MIV-positiewe pasiënte wat tans antiretrovirale terapie ontvang, aangesien dit belangrike strukturele hindernisse tot kliniek bywoning en die neem van medikasie identifiseer. Dié steekproef sluit pasiënte in wat tans antiretrovirale terapie by ‘n aansteeklike siektes-kliniek by ‘n peri-stedelike sekondêre hospitaal ontvang. Dit sluit ook dokters en verpleegsters in wat gesondheidsdienste aan dié pasiënte verskaf, en pasiënt- advokate wat psigo-sosiale ondersteuning aan pasiënte verskaf onder die vaandel van ‘n plaaslike nieregerings organisasie. Dié deelnemers is deur middel van gerieflikheidssteekproef geselekteer om aan semi-gestruktureerde onderhoude of fokusgroepbesprekings deel te neem. Deelnemers van albei groepe is van hul anonimiteit en die vertroulikheid van die proses verseker. Beide die semi-gestruktureerde onderhoude en die fokusgroepbesprekings is digitaal opgeneem en transkripsies is daarvan gemaak, waarna die transkripsies in Atlas.ti gelaai is vir tekstuele analise. Transkripsies is tematies geanaliseer volgens die persepsies van die verskeie deelnemers. Die hooftemas wat na vore gekom het, sluit in individuele hindernisse, armoedeverwante hindernisse, institusieverwante hindernisse asook sosiale en gemeenskapsverwante hindernisse. Resultate van dié studie is getrianguleer deur die verskille en ooreenkomste te vind tussen pasiënte, klinici en pasiënt-advokate oor die hoof- en subtemas. Die hooftemas is toe volgens Bronfenbrenner (1972) se Ekologiese Sistemeteorie verdeel in die verskillende sisteme teenwoording in die pasiënt se omgewing, naamlik die mikro-, ekso-, en makrosisteem. Die mikrosisteem het individuele sielkundige en gedragshindernisse asook die armoedeverwante hindernisse ingesluit. Institusieverwante hindernisse is binne die eksosisteem van die pasiënt se ekologiese omgewing beskou en sosiale en gemeenskapsverwante hindernisse is beskou binne die makrosisteem van die pasiënt se ekologiese omgewing. Die belang van dié studie lê in die identifisering van volhoudingsgedrag as produk van die pasiënt se omgewing, soos beskou deur die Ekologiese Sistemeteorie. Toekomstige navorsing kan fokus op effektiewe maniere waarop pasiënte bygestaan kan word om die nodige vaardighede te ontwikkel om hul omgewing beter te kan hanteer en beskikbare sosiale ondersteuning te kan verbeter. Die ontwikkeling van strategieë om nuwe pasiënte by te staan, benodig ook verdere navorsing.

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Nqabeni, Luxolo. "Development of an antiretroviral solid dosage form using multivariate analysis". Thesis, Nelson Mandela Metropolitan University, 2007. http://hdl.handle.net/10948/705.

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The aim of pharmaceutical development is to design a quality product and the manufacturing process to deliver the product in a reproducible manner. The development of a new and generic formulation is based on a large number of experiments. Statistics provides many tools for studying the conditions of formulations and processes and enables us to optimize the same while being able to minimize our experimentation. The purpose of this study was to apply experimental design methodology (DOE) and multivariate analysis to the development and optimization of tablet formulations containing 150 mg lamivudine manufactured by direct compression.

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Moitra, Ethan Herbert James D. "Acceptance-based intervention to promote HIV medication adherence /". Philadelphia, Pa. : Drexel University, 2009. http://hdl.handle.net/1860/3035.

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Nyakwezi, Kamugasha Sheila. "The use of anthropometric indices as an alternative guide to initiating antiretroviral therapy (ART) in children at the Mildmay Centre in Uganda /". Link to the online version, 2008. http://hdl.handle.net/10019/1502.

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Saal, Wylene Leandri. "The applicability of the theory of planned behaviour in predicting adherence to antiretroviral therapy (ART) among a South African sample". Thesis, Stellenbosch : University of Stellenbosch, 2011. http://hdl.handle.net/10019.1/6821.

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Thesis (MSc)--University of Stellenbosch, 2011.
ENGLISH ABSTRACT: The primary aim of the study was to determine the applicability of the theory of planned behaviour (TPB) in predicting adherence to ART among South African patients attending public health clinics. The second aim was to determine the relationship between self-reported adherence and viral load. The results from the hierarchical multiple regression analyses revealed that the linear combination of the variables of the TPB significantly explained 12% of the variance in intentions to adhere to ART. Perceived behavioural control was the only variable that significantly predicted intentions to adhere to ART. The inclusion of perceived stigma was not a useful addition to the model. The results also reflect the relationship between intentions to adhere to treatment and self-reported adherence, which was not significant. The TPB was unable to significantly account for variance in self-reported treatment adherence. When perceived stigma was added to the TPB, the model was still unable to significantly explain variance in self-reported adherence. Nonetheless, attitudes towards treatment were the only variable that significantly accounted for variance in self-reported treatment. It was concluded that interventions aimed at improving adherence among South African patients attending public health clinics, should aim to encourage positive attitudes towards treatment, should aim to increase perceived subjective norms, should increase the patients’ perceptibility that they are able to be adherent and should aim to decrease perceived stigma. Improving adherence to ART can result in increasing the quality of life of patients living with HIV/AIDS.
AFRIKAANSE OPSOMMING: Die primêre doel van die studie was om vas te stel of die teorie van beplande gedrag (TPB soos voorgestel in die studie) antiretrovirale terapie (ART) nakoming onder Suid-Afrikaanse pasiёnte by publieke gesondheidsklinieke kan voorspel. Die sekondêre doel was om die verhouding tussen self-gerapporteerde volgehoue behandeling en virale lading te bereken. Die uitslae van die hiёrargiese veelvuldige regressie analise het getoon dat die linêere kombinasie van die veranderlikes van TPB 12% van die verandering in ART voornemens akkuraat kon voorspel. Waargenome gedragsbeheer was die enigste veranderlike wat ART voornemens akkuraat kon verklaar het. Die insluiting van waargenome stigma was nie beduidend ten opsigte van die model nie. Geen beduidende verband tussen voorneme om met behandeling vol te hou en self-gerapporteerde volgehoue-behandelingsgedrag word uitgebeeld. Waargenome gedragsbeheer kon wel ‘n bydrae lewer om verandering in die voorneme om met behandeling vol te hou verklaar. Die TPB kon egter nie ‘n verduideliking bied vir die verandering in self-gerapporteerde volgehouebehandelingsgedrag nie. Toe waargenome stigma by die TPB gevoeg is, was die model steeds nie daartoe instaat om die verandering in self-gerapporteerde volgehouebehandelingsgedrag te verklaar nie. Nietemin, houdings teenoor behandeling was die enigste veranderlike wat verandering in self-gerapporteerde gedrag verklaar. Daar is tot die gevolgtrekking gekom dat intervensies gerig op die verbetering van volhoubare gedrag onder Suid-Afrikaanse pasiёnte wat openbare gesondheidsklinieke bywoon,positiewe houding teenoor behandeling moet aanmoedig, subjektiewe norme verhoog, die pasiёnte se persepsie dat hulle instaat is om volhoubare gedrag kan toon moet verhoog en ook waargenome stigma moet verminder. Beter ART nakoming kan lei tot ‘n toename in die MIV/VIGS pasiёnt se kwaliteit van lewe.

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Aung, Kay Tu Jittima Dhitavat. "Pulmonary tuberculosis treatment outcomes in HIV infected patients on antiretroviral therapy /". Abstract, 2006. http://mulinet3.li.mahidol.ac.th/thesis/2549/cd388/4838793.pdf.

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Cantrell, Ronald Alexander. "Diagnosing antiretroviral treatment failure in resource-limited settings". Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/cantrell.pdf.

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Rojas, Liévano Jhon Fredy. "Nuevas estrategias para mejorar la tolerabilidad del tratamiento antirretroviral y disminuir su impacto sobre las comorbilidades". Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668145.

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La infección por el virus de la inmunodeficiencia humana (VIH) continúa siendo un problema importante de salud pública mundial. En 2017 aproximadamente 36,9 millones de personas eran portadoras del VIH (incluidos 1,8 millones de niños), con una prevalencia global del virus del 0,8% entre los adultos. A pesar de que el tratamiento antirretroviral (TAR) es cada vez mejor tolerado y más simple, hasta el 70% de discontinuaciones se debe a intolerancia/toxicidad o conveniencia (datos de la Cohorte ICONA) y en el contexto del envejecimiento de la población las interferencias/interacciones del TAR con las comorbilidades/polifarmacia respectivamente serán cada vez más frecuentes. Ante estas limitaciones, observamos la necesidad de crear estrategias de optimización del TAR tanto en pacientes naive como suprimidos; en este sentido diseñamos una serie de estudios organizados apartir de 3 grandes hipótesis: Primera. Es posible diseñar nuevas estrategias de TAR que disminuyan o mejoren la toxicidad: - En lo relacionado con la lipodistrofia: -Estudio LIPOKAL: Estudio piloto, aleatorizado, abierto, multicéntrico, fase IV a 96 semanas. Observamos que en pacientes infectados por el VIH con lipoatrofia y no tratados actualmente con análogos de timidina el cambio de efavirenz a lopinavir/ritonavir mejoró la grasa de las extremidades. Segunda. Es posible diseñar nuevas estrategias de TAR que tengan un mejor impacto sobre las comorbilidades: -En lo relativo al impacto del TDF: -Estudio KiRilNa: Estudio observacional, retrospectivo y multicéntrico realizado en ocho hospitales universitarios españoles. Observamos que en pacientes infectados con VIH-1 que no habían recibido tratamiento previo abacavir/lamivudina+rilpivirina fue una opción efectiva y segura. - Estudio KIVI: Estudio de cohorte observacional, retrospectivo y multicéntrico. Observamos que en pacientes infectados con VIH-1 que no habían recibido tratamiento previo abacavir/lamivudina+nevirapina fue un régimen efectivo, con buen perfil lipídico y una toxicidad temprana limitada. - Estudio ZEST: Estudio aleatorizado, abierto, multicéntrico, fase IV a 24 meses. Observamos que en pacientes VIH tratados con una pauta que contiene tenofovir disoproxil fumarato con carga viral suprimida y densidad mineral ósea (DMO) baja, la estrategia de tratamiento con ácido zoledrónico fue más eficaz que el cambio de tenofovir para mejorar la DMO. Tercera. Es posible diseñar nuevas estrategias de TAR que disminuyan la carga del TAR: - Estudio Dolutegravir en monoterapia: Estudio retrospectivo, no intervencional, unicéntrico. Observamos que la monoterapia con dolutegravir se asocia a un riesgo potencial de fracaso virológico acompañado de desarrollo de mutaciones de resistencia a los inhibidores de integrasa. - Estudio DOLAM: Ensayo clínico multicéntrico, paralelo, abierto, aleatorizado y controlado con tratamiento activo. Observamos que la simplificación del TAR triple estándar a la terapia dual dolutegravir más lamivudina es una opción viable, pero no así la monoterapia con dolutegravir que mostró un riesgo inaceptable de fracaso virológico con desarrollo de mutaciones de resistencia cruzada a los inhibidores de la integrasa. - Estudio de tolerabilidad de los inhibidores de la integrasa en la vida real: Estudio retrospectivo, no intervencional, unicéntrico. Observamos que los efectos neuropsiquiátricos y osteomusculares fueron la principal causa de interrupción del TAR con cualquiera de los tres inhibidores de la integrasa actualmente disponibles, aunque los efectos adversos neuropsiquiátricos fueron significativamente más frecuentes con dolutegravir. El aumento de la edad fue el único factor independiente identificado que se asoció a un mayor riesgo de discontinuación debido a efectos adversos. - Estudio A-TRI-WEEK: Estudio piloto, aleatorizado, abierto, prospectivo, unicéntrico, fase IV. Observamos en un estudio piloto que la simplificación del TAR en pastilla única efavirenz/lamivudina/tenofovir isoproxil fumarato (Atripla®) de una vez al día a 3 días por semana mostró no ser inferior virologicamente y redujo la toxicidad subclínica.
Even though antiretroviral treatment (ART) is increasingly better tolerated and simpler, it has limitations. We designed new ART strategies based on three major hypotheses: First. It is possible to design new ART strategies that decrease or improve toxicity: -LIPOKAL Study: We observed that in HIV-infected patients with lipoatrophy and not currently treated with thymidine analogues the change from efavirenz to lopinavir/ritonavir improved limb fat. Second. It is possible to design new ART strategies that have a better impact on comorbidities: -KiRilNa Study: We observed that in naive HIV-infected patients, abacavir/lamivudine+rilpivirine was an effective and safe option. -KIVI Study: We observed that in naive HIV-infected patients, abacavir/lamivudine+nevirapina, was an effective regimen, with good lipid profile and limited early toxicity. -ZeST Study: We observed that in HIV-infected patients treated with a regimen containing tenofovir disoproxil fumarate with suppressed viral load and low bone mineral density (BMD), the zoledronic acid treatment strategy was more effective than changing tenofovir to improve BMD. Third. It is possible to design new ART strategies that reduce the burden of ART: -Dolutegravir monotherapy study: We observed that dolutegravir monotherapy is associated with a potential risk of virologic failure accompanied by development of resistance mutations to integrase inhibitors. -DOLAM Study: We observed that simplification from standard triple ART to dual dolutegravir plus lamivudine therapy is a viable option, but not dolutegravir monotherapy which showed an unacceptable risk of virologic failure with development of cross-resistance mutations to integrase inhibitors. - Tolerability study of integrase inhibitors in real life: We observed that neuropsychiatric and musculoskeletal effects were the main cause of ART discontinuation with any of the three integrase inhibitors currently available, although neuropsychiatric adverse effects were significantly more common with dolutegravir. Increasing age was the only independent factor identified that was associated with an increased risk of discontinuation due to adverse effects. -A-TRI-WEEK Study: We observed in a pilot study that the simplification of single pill ART efavirenz/lamivudine/tenofovir disoproxil fumarate (Atripla®) from once daily to 3 days per week showed not to be inferior virologically and reduced subclinical toxicity.

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Ren, Yuan. "The Plasma, Whole Blood and Intracellular Concentrations of Antiretroviral Agents in South African Children Receiving Combination Antiretroviral Therapy with and without Concomitant Antitubercular Treatment". Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3297.

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Background: Tuberculosis (TB) is the most common opportunistic infection in children with human immunodeficiency virus (HIV) infection in developing countries, and co-treatment for HIV infection and TB is frequently indicated. Efavirenz and lopinavir/ritonavir (ratio 1:1) as part of antiretroviral therapy are used in combination with rifampicin-based antitubercular treatment in South African TB/HIV co-infected children. Adult studies show that concomitant rifampicin significantly reduces efavirenz and lopinavir plasma concentrations. However, the pharmacokinetics (PK) of efavirenz and lopinavir/ritonavir are poorly characterized in children, especially African children and no study has evaluated the effect of rifampicin-based antitubercular treatment on efavirenz and lopinavir/ritonavir plasma concentrations in children. Although therapeutic drug monitoring (TDM) is recommended in selected patients (including young children and patients receiving concomitant antitubercular treatment), TDM is seldom available in resource-constrained countries. There is an urgent need to develop a field friendly method which requires small volumes of blood, and inexpensive processing and storage conditions. Furthermore, because HIV replicates in the cells, efavirenz and lopinavir need to penetrate into these infected cells to inhibit viral replication. Therefore, directly measurement of intracellular concentrations of these drugs in HIV-infected children could provide better understanding of drug exposure at the action site. It is also important to evaluate the effects of frequently co-administered drugs on intracellular accumulation of efavirenz and lopinavir. Objectives: 1) To evaluate efavirenz and lopinavir/ritonavir plasma concentrations and determine the effects of rifampicin on efavirenz and lopinavir/ritonavir PK in HIV-infected African children with and without rifampicin-based antitubercular treatment. 2) To develop and validate the dried blood spot (DBS) method as an alternative to conventional plasma methods of drug concentration measurement in TDM. 3) To evaluate in vivo intracellular concentrations of efavirenz and lopinavir/ritonavir in HIV-infected children with and without concomitant antitubercular treatment. 4) To determine the in vitro modulation effects on the intracellular accumulation of efavirenz IV and lopinavir in human peripheral blood mononuclear cells (PBMCs) by drug efflux protein inhibitors, as well as frequently co-administered rifampicin and ritonavir (at low dose; as pharmacoenhancer). Methods: 1) Plasma efavirenz and lopinavir/ritonavir concentrations were measured by validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method in TB/HIV co-infected children during and after rifampicin-based antitubercular treatment as well as in a group of controls (HIV-infected children without TB). Children in the efavirenz study (n= 30) were receiving standard doses of efavirenz as part of antiretroviral treatment. Trough concentrations (Cmin) of efavirenz were estimated by extrapolation of the log-linear concentration-time line to 24 hours after the previous dose. Children in the lopinavir/ritonavir study were receiving additional ritonavir (lopinavir: ritonavir ratio 1:1) during antitubercular treatment (n= 15), and standard doses of lopinavir/ritonavir (LPV/r; ratio 4:1) after antitubercular treatment, and in controls (n= 15). The PK of lopinavir and ritonavir were characterized from concentration-time curves using WinNonlin version 4.1 by non-compartmental analysis. 2) Aliquots of 50 Î¼ L of whole blood from the efavirenz and lopinavir/ritonavir studies were dried onto filter paper. The drug concentrations were analyzed using validated LC/MS/MS method. The effects of high temperature and direct sunlight on the stabilities of these antiretroviral drugs in DBS samples were tested. 3) Intracellular concentrations of efavirenz, lopinavir and ritonavir were measured in trough concentrations of 11 TB/HIV co-infected children using a validated LC/MS/MS method. Six children were receiving double dose of LPV/r (4:1) with concomitant rifampicin; 5 children were receiving standard doses of efavirenz with rifampicin-based antitubercular treatment, 3 of them had intracellular concentrations measured again after completing rifampicin-based antitubercular treatment. 4) in vitro intracellular accumulation of efavirenz and lopinavir were measured in human PBMCs in the absence and presence of P-glycoprotein inhibitors (verapamil at 50 Î¼ M, V furosemide at 50 Î¼ M and cyclosporine A at 20 Î¼ M) and frequently co-administered drugs at levels representing the average concentrations found in patients (ritonavir at 5 mg/L and rifampicin at 4 mg/L). The concentrations of efavirenz and lopinavir in PBMCs were determined by LC/MS/MS. Results and Conclusions: 1) The co-administration of rifampicin did not significantly reduce efavirenz estimated Cmin concentrations. A high proportion of children with and without concomitant antitubercular treatment had sub-therapeutic efavirenz concentrations despite being correctly dosed according to the manufacturer's instructions, raising concerns about the adequacy of current efavirenz dosing recommendations in children. The lopinavir key PK parameter, Cmin, was not significantly different in same group of children during and after rifampicin-based antitubercular treatment or compared to HIV-infected children without tuberculosis. The recommended minimum therapeutic concentration was achieved in 87% of children during antitubercular treatment and in 92% without concomitant antitubercular treatment. Therefore, in the context of limited options, LPV/r with additional ritonavir (ratio 1:1) is an acceptable approach to treat young children receiving concomitant rifampicin-based antitubercular treatment, although safety remains a concern and hepatic alanine transaminase levels should be monitored regularly. 2) Plasma and DBS concentrations of efavirenz, lopinavir and ritonavir were strongly correlated. The median (interquartile range, IQR) DBS/plasma concentration ratios for efavirenz, lopinavir and ritonavir were 0.93 (IQR 0.83, 1.08), 0.73 (IQR 0.61, 0.90) and 1.05 (IQR 0.74, 1.21), respectively. PK parameters of efavirenz and ritonavir were closely similar between DBS and plasma; whereas lopinavir pre-dose and Cmin (at 12 hours after lopinavir intake) concentrations were 16% lower in DBS samples. The 3 antiretroviral drugs in DBS samples were stable at 37 deg C for 7 days and with exposure to direct sunlight for 2 hours. DBS can be used as an alternative field-friendly method for efavirenz, lopinavir and ritonavir concentration monitoring. However, pre-dose and Cmin concentrations of lopinavir in DBS samples need to be increased by 16% when used to predict plasma concentrations. VI 3) In vivo median intracellular/plasma concentration ratios for efavirenz, lopinavir and ritonavir amongst 11 TB/HIV co-infected children during antitubercular treatment were 0.91 (IQR 0.54, 1.19), 0.22 (IQR 0.09, 0.31) and 4.17 (IQR 1.30, 7.33), respectively. Two children had efavirenz intracellular/plasma concentration ratios during vs. after antitubercular treatment: 1.00 vs. 0.61 and 0.27 vs. 0.79. 4) Furosemide significantly increased efavirenz and lopinavir accumulation in healthy human PBMC samples by 1.2- 1.5 fold. Whereas, neither verapamil nor cyclosporin A had significant effects on efavirenz or lopinavir intracellular accumulation. Despite being an inducer of P-glycoprotein, rifampicin increased the accumulation of both efavirenz and lopinavir to different extents in all 3 PBMC samples. The low-dose ritonavir (at the concentration found in HIV-infected patients) had no effect on intracellular accumulation of efavirenz and lopinavir at therapeutic concentrations.

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Bergin, Hild. "Cardiovascular side effects of the antiretroviral agents rilpivirine, efavirenz, etravirine and abacavir : possible underlying mechanisms". Thesis, University of Brighton, 2014. https://research.brighton.ac.uk/en/studentTheses/59df6711-f1e9-4190-97ea-31953c1b3661.

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The introduction of highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of HIV infected individuals. With the increased lifespan, complications associated with HAART are becoming more evident. Together with HIV itself and a higher prevalence of traditional risk factors, the antiretroviral agents are linked to an increase in cardiovascular diseases in the HIV population. In the present in vitro study the direct cardiac effects of a nucleoside reverse transcriptase inhibitor (NRTI) abacavir in combination with palmitic acid or cobalt chloride mimicking a diet high in saturated fatty acids or hypoxia respectively, were studied. Exposure to abacavir has been associated with an increased risk of myocardial infarction in clinical studies, but the damaging molecular mechanism remains elusive. Furthermore the in vitro cardiovascular effects of three non-nucleoside reverse transcriptase inhibitors (NNRTIs) were investigated; first generation NNRTI efavirenz and the second generation NNRTIs rilpivirine and etravirine.

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Peplinski, Kyle P. "The effects of antiretroviral access on the creation and maintenance of HIV-seropositive identity". unrestricted, 2008. http://etd.gsu.edu/theses/available/etd-07122008-133945/.

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Thesis (M.A.)--Georgia State University, 2008.
Title from file title page. Cassandra White, committee chair; Kathryn A. Kozaitis, Susan McCombie, committee members. Electronic text (95 p.) : digital, PDF file. Description based on contents viewed Sept. 29, 2008. Includes bibliographical references (p. 90-94).

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Waltje, Andrea H. "Predictors of nonadherence to antiretroviral therapies in HIV-infected older adults". Ohio : Ohio University, 2003. http://www.ohiolink.edu/etd/view.cgi?ohiou1067542971.

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Tiraboschi, Juan Manuel. "Penetration and antiviral activity of antiretroviral drugs in the Central Nervous System". Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/396308.

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INTRODUCTION: With successful treatment and near-normal life expectancy of people living with HIV, the focus of care has shifted towards minimizing toxicity from long term exposure to antiretrovirals (ARVs) and preventing co-morbidities. The prevalence of neurocognitive abnormalities has been reported to remain high, including in patients treated with cART. A low level viral replication in the central nervous system (CNS) may persist even in patients presenting with HIV-1 suppression in plasma, leading to local inflammation, neuronal damage and a poorer neuropsychological performance. A poor penetration of ARV drugs into the CNS may allow local HIV replication and may be associated with asymptomatic and even symptomatic HIV-related neurocognitive impairment or neurologic symptoms, which may be severe and present as HIV encephalitis in some occasions. For this reason we consider it extremely important to conduct research in order to improve the knowledge of the newer antiretroviral drugs penetration into the CNS and so to carry out a pilot study based on these results. HYPOTHESIS: 1. Maraviroc may reach pharmacological concentrations above the IC50 range in the CSF. 2. Maraviroc in combination with other antiretroviral drugs may help to maintain HIV viral suppression in the CSF. 3. Etravirine concentrations in CSF may be low but higher than the IC50. 4. Etravirine in combination with other antiretroviral drugs may help to maintain HIV viral suppression in the CSF. 5. Amprenavir concentrations in CSF may be above the IC50. 6. Fosamprenavir/ritonavir monotherapy may be sufficient to maintain HIV viral suppression in CSF. 7. A treatment switch from tenofovir, emtricitabine and efavirenz to abacavir, lamivudine and maravicoc in patients with neurocognitive impairment may be associated with a reduction on CSF inflammatory markers, CSF HIV RNA and an improvement in their neurocognitive performance. CONCLUSIONS: 1. Maraviroc concentrations in CSF in HIV-infected patients. -In all except 1 CSF sample, MVC concentrations exceeded the median serum- adjusted IC90. -Our data suggest that MVC may contribute to inhibit HIV-1 replication in CNS. -Maraviroc in combination with nucleoside-sparing regimens, including new ARV drugs, seems to be locally active. 2. Etravirine concentrations in CSF in HIV-infected patients -In all samples Etravirine concentrations exceeded the IC50 range. -Our data suggest that Etravirine may contribute to inhibiting HIV-1 replication in the CNS and that combined nucleoside sparing regimens, including new antiretroviral drugs, seem to be locally active. 3. Viral response in stable patients switching to fosamprenavir/ritonavir monotherapy. -Although the high percentage of viral failure with FPV/r monotherapy found in our study, this study is a proof of concept that boosted PI monotherapy could be enough to suppress HIV viral replication in CSF. 4. Viral and inflammatory markers in cerebrospinal fluid of patients with HIV-1-associated neurocognitive impairment during antiretroviral treatment switch. -There was a non-statistically significant reduction on the CSF HIV viral load after six months. -A significant reduction on TNF-α would suggest a reduction on local inflammatory reaction following treatment switch. This could be related to a reduction in CSF viral load, the anti-inflammatory effect of Maraviroc or both. -A trend towards an improvement in neurocognitive performance could be related to the above mentioned effects. - A switch to a regimen with a higher CPE score containing MVC was associated with a trend towards an improvement in neuropsychological performance and a reduction in TNF-α. In CSF. GENERAL CONCLUSION. The study of the concentrations and antiviral activity in CSF of the antiretroviral drugs will make possible the design for more effective combinations to be implemented in patients with NCI. A treatment switch can contribute to clinical and virological improvement as well as a reduction in the inflammatory markers.
INTRODUCCIÓN: En los últimos años diversos estudios han puesto en evidencia la persistencia de trastornos neurocognitivos (TNC) asociados al VIH, siendo en su mayoría formas asintomáticas o leves y moderadas. Si bien son múltiples los factores que favorecen la presencia de TNC en individuos infectados por el VIH (hepatopatía crónica, enfermedad cardiovascular, alcoholismo, uso de drogas, psicofármacos, etc), el virus –que ingresa en el SNC desde los primeros días de la infección- parece jugar un papel importante y ser causa de TNC incluso severos y/o enfermedad neurológica en forma de encefalitis aguda que puede llevar al coma y la muerte. En este contexto, la diferente penetración de los fármacos ARV podría jugar un papel en la prevención, y tratamiento de estas alteraciones. OBJETIVO GENERAL: Generar conocimiento sobre la penetración y actividad de diferentes fármacos antirretrovirales. Utilizar dicha información para poner en práctica una intervención destinada a mejorar la eficacia de una combinación antirretroviral en SNC. HIPÓTESIS: 1. Maraviroc alcanzaría niveles farmacológicos en LCR superiores a la CI50. 2. Maraviroc en combinación con otros fármacos antirretrovirales ayudaría a mantener la supresión viral en LCR. 3. Las concentraciones de Etravirina en LCR serían bajas aunque superiores a la CI50. 4. Etravirina en combinación con otros fármacos antirretrovirales contribuiría a mantener la supresión viral en LCR. 5. Las concentraciones de Amprenavir en LCR serían superiores a la CI50. 6. Fosamprenavir/ritonavir en monoterapia sería suficiente para mantener la supresión viral en LCR. 7. En pacientes que reciben una pauta de emtricitabina/tenofovir/ efavirenz y presentan deterioro neurocognitivo, el cambio a abacavir/lamivudina/maraviroc se asociaría a una disminución de marcadores inflamatorios, carga viral en LCR y a una mejoría en los TNC. CONCLUSIÓN: El estudio de las concentraciones de fármacos antirretrovirales y su actividad en LCR permitirá diseñar con mayor eficacia las pautas a utilizar en pacientes con TNC. Aunque hacen falta estudios más amplios, nuestros datos sugieren un posible beneficio clínico, virológico y de parámetros inflamatorios en pacientes con TNC que cambian a un TAR con mayor penetrabilidad en SNC.

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Wahba, Alexander. "Modified nucleotides and nucleic acids for the discovery of antiretroviral agents targeting HIV-1 reverse transcriptase". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=94986.

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The reverse transcriptase (RT) of the human immunodeficiency virus (HIV) has both polymerase and ribonuclease H (RNase H) activity, and is a key enzyme in the HIV life cycle as it converts the viral RNA genome into double-stranded DNA. A series of studies built around the theme of chemically modified nucleic acids are described in order to: (1) better understand the biochemical processes of reverse transcription in HIV-1, (2) synthesize antiretroviral agents directed to novel targets on HIV-1 (RT), and (3) develop screening methods incorporating fluorescent nucleobase analogues to uncover new drug candidates. We demonstrated how chemically modified nucleic acid hairpins inhibited the RNase H activity of HIV-1 RT. For example, substituting natural RNA for 2'-deoxy-2'-fluoro-ribonucleotides, 2'-deoxy-2'-fluoro-arabinonucleotides, locked nucleic acids or conjugation of cholesterol at the 5'-terminus modulated the potency of hairpins for RNase H activity. Biochemical methods indicated that the substrate for HIV-1 RT, a short primer-long template, may be bound at the polymerase domain with its trajectory diverted away from the RNase H domain by the presence of the synthetic hairpins. Furthermore, the binding of hairpins to HIV-1 RT had no adverse affects on the potency of chain terminators such as 3'-azido-3'-deoxythymidine (AZT), a widely used antiviral agent. This discovery supports a model where the RNase H activity can be an antiretroviral target independent of the rest of RT. We synthesized 6-phenylpyrroloribocytidine (PhpC), a novel fluorescent cytidine analogue incorporated into RNA. The PhpC-containing RNA formed native-like duplex structures with complementary strands and fluorometrically reported upon binding to complementary RNA and DNA strands. PhpC was shown to rank among the brightest fluorescent cytidine analogues based on quantum yields. RNA containing PhpC was cleaved by HIV-1 RT RNase H with a 14-fold increase in fluorescence intensity. In contrast
La transcriptase inverse (RT) du virus de l'immunodéficience humaine de type 1 (VIH-1) possède deux activités: polymérase et ribonucléase H (RNase H), en faisant l'enzyme clé pour le cycle de vie du VIH puisqu'elle convertit l'ARN viral génome en ADN à double brins. Des études portant sur des acides nucléiques modifiés chimiquement sont ici décris afin de: (1) mieux comprendre les procédés biochimiques sous-tendant la transcription inverse du VIH-1, (2) synthétiser des agents antirétroviraux dirigés contre de nouvelles cibles de la RT, et (3) développer des méthodes de criblage incorporant des analogues de nucléobase fluorescente afin de découvrir de nouveaux candidats thérapeutiques. Nous avons ainsi démontré comment de petits acides nucléiques modifiés (épingles) inhibent l'activité RNase H de la RT VIH-1. La substitution de l'ARN naturel par des acids nucléiques modifiés chimiquement ont modulé la puissance de l'épingle face à l'activité de la RNase H. Des méthodes biochimiques ont démontré que le substrat de la RT VIH-1 peut être lié au domaine polymérase lorsque sa trajectoire est déviée du domaine RNase H par la présence d'épingles. Cette découverte supporte le modèle selon lequel l'activité de RNase H représente une cible antirétrovirale indépendante du reste de la RT. Nous avons synthétisé la 6-phénylpyrroloribocytidine (PhpC), un nouvel analogue fluorescent de la cytidine incorporé dans l'ARN. Cet ARN contenant de la PhpC a formé des structures ressemblant à des brins doubles natifs ayant des branches complémentaires et est reconnu par fluorométrie après liaison à une branche d'ARN ou d'ADN complémentaire. Se basant sur son rendement quantique, la PhpC se révéla un des analogues fluorescents de la cytidine les plus lumineux. Mais encore, l'ARN contenant de la PhpC fût coupé par la RNase H de la RT VIH-1, augmentant quatorze fois l'intensité de la fluorescence. Contrairement aux mêmes ol

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Nikisi, Joseph. "Access to antiretroviral treatment in the public sector, in Zambia". Diss., Pretoria : [s.n.], 2006. http://upetd.up.ac.za/thesis/available/etd-04282009-163207.

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Berbaum, Jennifer Bentz Joe. "Investigating the role of nuclear receptors in HIV/HAART-associated dyslipidemic lipodystrophy /". Philadelphia, Pa. : Drexel University, 2007. http://hdl.handle.net/1860/1759.

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Wu, Lucy Mimi. "Antiretroviral prophylaxis for prevention of mother to child transmission of HIV through breastfeeding: asystematic review and meta-analysis of infant treatment regimens". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48426581.

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A systematic review and meta-analysis was conducted to evaluate the efficacy of different infant antiretroviral (ARV) prophylaxis regimens for prevention of mother to child transmission (MTCT) of human immunodeficiency virus (HIV) infection in breastfeeding infants who were born to HIV positive mothers but were HIV uninfected at birth. The systematic review of the literature published during January 2000 to April 2012 resulted in ten randomized and controlled clinical studies which met the study inclusion criteria. Two datasets were identified from the ten selected clinical trials. One dataset contains six studies evaluating short-course ARV prophylaxis regimens, and the second dataset contains four studies evaluating short-course versus extended ARV prophylaxis regimens. The odds ratio was used as the effect size to measure the efficacy between two comparative infant ARV prophylaxis regimens. Meta-analyses were conducted to assess the overall (pooled) treatment effect of the two comparative infant ARV prophylaxis regimens of the two datasets. The pooled ARV treatment effect was calculated as a weighted average of the effect estimated in the individual studies. If no heterogeneity was identified, a fixed-effect meta-analysis by the Mantel-Haenszel method was used. The random-effects method was used when there was heterogeneity in the meta-analysis. The inverse-variance method was used in the random-effects method of meta-analysis. Heterogeneity in the meta-analysis was accessed by the Chi-squared (χ2) test and I2 test. The combined sample size of all ten clinical trials was a total of 10,316 breastfeeding infants, and the overall postnatal HIV transmission rate regardless of ARV regimens and the timing of HIV infection status was approximately 8.7%. The overall HIV transmission rates of the short-course ARV prophylaxis regimen groups were 10.3% at 4-8 weeks and 9.0% at 6-9 months, respectively. The overall late postnatal HIV transmission rate (at 6-9 months after birth) was 5.5% in the extended ARV prophylaxis regimen group. The first dataset contains six randomized and controlled studies to evaluate the efficacy outcome (defined as the unadjusted HIV infection status at 4-8 weeks after birth) of two short-course infant ARV prophylaxis regimens, the nevirapine (NVP) regimen and the zidovudine (ZDV) with or without combination of lamivudine (3TC) or NVP regimen. Due to the existence of substantial heterogeneity, a random-effects method was used to test for the overall treatment effect. The results show that there was no significant difference between the two short-course infant ARV prophylaxis regimens (odds ratio:1.07; 95% CI: 0.69-1.66; Z=0.31, p=0.76). The results of the meta-analysis of five comparative short-course versus extended infant ARV prophylaxis regimens from four randomized and controlled clinical trials, demonstrate a favorable efficacy outcome (defined as the unadjusted HIV infection status at 6-9 months after birth), of the extended ARV regimens. There was no heterogeneity found in this dataset. There was a highly significant difference in the overall effect between the two ARV prophylaxis regimens by a fixed-effect model (odds ratio: 1.72; 95% CI:1.45-2.04; Z=0.68, p<0.00001). In summary, there was no significant difference in the overall treatment effect in reducing the early postnatal MTCT of HIV infection by infant short-course regimens of ARV prophylaxis, which include NVP, ZDV and their combination regimens. In comparison with the short-course ARV regimens, the extended ARV prophylaxis further reduced the risk of the late postnatal MTCT of HIV infection in breastfeeding infants.
published_or_final_version
Public Health
Master
Master of Public Health

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Wu, Charlotte Audris. "Qualitative Assessment of Adherence to Antiretroviral Therapy among Chinese Intravenous Drug Users". Yale University, 2008. http://ymtdl.med.yale.edu/theses/available/etd-08282007-153749/.

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Injection drug users (IDUs) account for an estimated 44% of people living with HIV/AIDS in China and are the major driving force behind the expanding epidemic. Developing effective antiretroviral therapy (ART) adherence interventions in the Chinese IDU population is a major challenge. In conjunction with ART scale-up in Yunnan province, our goal was to gather patient perspectives on ART and ideas for feasible adherence support. Between December 2005 and March 2006, eight focus groups with a total of 55 HIV positive IDUs were conducted at three sites in Yunnan to ascertain ART knowledge, barriers to adherence, and acceptable adherence support methods. Focus groups included ART experienced and naïve participants, and HIV positive IDUs in methadone maintenance clinics. Discussions were audiotaped, notes were transcribed and coded for analyses. All participants were former or current IDUs and 31 were from the rural countryside (59.6%), and 19 (36.5%) resided in a small city. ART was viewed positively but the principal barriers for urban IDUs were stigma and discrimination, while geography was the main problem for rural IDUs. Major themes were stratified between four components: knowledge, motivation, cues to action, and access to care. Adherence tools that were spontaneously endorsed included watches, pill boxes, and diaries. Directly observed therapy (DOT) within methadone programs was acceptable but community-based DOT would need to address stigma issues in urban areas. Two separate HIV epidemics exist within IDUs in China, stratified between small-city urban and rural populations. No single model for adherence will work and interventions must be broad-based. This study provides an expanded conceptual framework for ART adherence in the HIV positive IDU population, which includes the unique barriers posed by the ecological context surrounding this doubly-discriminated population.

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Innes, Steven Eugene Vere. "Lipoatrophy in HIV-infected children on antiretroviral therapy". Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79864.

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Thesis (PhD)--Stellenbosch University, 2013.
Bibliography
ENGLISH ABSTRACT: Introduction: Lipoatrophy is a common adverse effect of stavudine and this effect is strongly dose-dependent. Stavudine remains the most commonly used paediatric antiretroviral drug in sub-Saharan Africa, yet when the current study began in 2009, the prevalence and severity of lipoatrophy in children on antiretroviral therapy in sub-Saharan Africa had never been studied. The development of lipoatrophy may have serious and far-reaching consequences for patients and their families. The off-label stavudine dosing method, prescribed to children whose caregivers do not have access to a refrigerator, in which the contents of an adult capsule is mixed into tap water, has potential for over-dosing or under-dosing. In addition, children on stavudine continue to be exposed to a disproportionately high dose out of line with the reduced adult dose. Aims: 1. a) To investigate the prevalence and risk factors for lipoatrophy in HIV-infected children in Southern Africa b) To identify a simple anthropometric screening tool to detect early lipoatrophy in children 2. To validate the off-label stavudine dosing method prescribed to children whose caregivers do not have access to a refrigerator, with a view to reducing the recommended dose and thereby the side-effects. Methods: 1. a) We recruited pre-pubertal children on antiretroviral therapy from a family HIV clinic in our facility. Lipoatrophy was identified by two experienced paediatric HIV clinicians using a standardized grading scale. A dietician performed dietary assessment and anthropometric measurements. Previous antiretroviral exposures were recorded. A subset of recruits received Dual-Energy X-ray Absorbtiometry scanning. b) Anthropometric measurements in children with and without lipoatrophy were compared using multivariate linear regression adjusting for age and gender. The most discerning anthropometric variables underwent Receiver Operating Characteristic curve analysis to identify the most appropriate diagnostic cut-off. 2. a) Accuracy of the standard off-label stavudine dosing method was investigated using high-performance liquid chromatography to recover active drug from solutions made up using the prescribed method. This was compared to the stated drug content of the capsules. b) Bioavailability was investigated by performing a randomized crossover pharmacokinetic study wherein healthy HIV-seronegative adult volunteers received one of two generic stavudine capsule formulations, either intact or mixed in water using the prescribed method. Plasma stavudine concentrations were assayed by liquid chromatography tandem mass spectrometry. Results: 1. a) Prevalence of lipoatrophy was 36%, and incidence was 12% per person-year. Adjusted odds ratio for developing lipoatrophy was 1.9 (CI: 1.3–2.9) for each additional year of accumulated exposure to standard-dose stavudine. b) Baseline biceps skin-fold thickness correlated well with maximum lipoatrophy grading score at any site, giving a partial correlation coefficient of 0.33 (p=0.0006), and a receiver operating characteristic area-under-curve value of 0.75 (CI: 0.64 – 0.84). Biceps skin-fold thickness <5mm at baseline had a sensitivity of 89% (CI: 67–100%) and a negative predictive value of 97% (CI: 91–100%) for predicting which children would go on to develop lipoatrophy by 15 month follow-up. Specificity was 60% (CI: 46–75%) and positive predictive value was 32% (CI: 14–50%). 2. a) Recovery of active drug from solution was 97.1%, 97.4% and 93.8% for the proprietary and two generic formulations respectively. b) Pharmacokinetic parameters of the off-label dosing method were well within the target range of intact capsule dosing for both generics. Conclusions: 1. a) The prevalence and incidence of lipoatrophy in pre-pubertal children on antiretroviral therapy in South Africa is high. Cumulative exposure to standard-dose stavudine was the greatest risk factor for lipoatrophy. b) Biceps skin-fold thickness provided reasonable sensitivity and specificity to detect and predict lipoatrophy in pre-pubertal children on antiretroviral therapy. 2. The off-label dosing method for stavudine prescribed to children whose caregivers do not have access to a refrigerator is reasonably accurate and is bioequivalent to intact capsule administration.
AFRIKAANSE OPSOMMING: Inleiding: Lipoatrofie is 'n algemene nadelige uitwerking van stavudien en hierdie effek is sterk dosis-afhanklike. Stavudien bly die mees algemeen gebruikte paediatriese antiretrovirale medikasie in sub-Sahara Afrika, maar toe ons studie begin het, was lipoatrofie in kinders op antiretrovirale terapie in sub-Sahara Afrika nog nooit voorheen bestudeer nie. Die ontwikkeling van lipoatrofie kan ernstige en verreikende gevolge vir die pasiënt en hul familie hê. Die af-etiket stavudien dosering metode voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie het 'n aansienlike potensiäal vir oor-dosering of onder-dosering. Daarbenewens, is kinders op stavudien blootgestel aan 'n disproporsionele hoë dosis uit-pas met die verminderde volwasse dosis. Doelwitte: 1. a) Om ondersoek in te stel na die voorkoms en risiko faktore vir lipoatrofie in MIV-geïnfekteerde kinders in Suid Afrika b) Om 'n eenvoudige antropometriese instrument te identifiseer om vroeë lipoatrofie op te spoor in kinders op antiretrovirale medikasie 2. Om die af-etiket stavudien dosering metode wat voorgeskryf is aan kinders wie se versorgers nie toegang tot 'n yskas het nie te valideer, met 'n oog op die vermindering van die aanbevole dosis Metodes: 1. a) Ons het 'n groep van onder-puberteitsjarige kinders op antiretrovirale terapie gewerf uit 'n familie MIV kliniek in ons fasiliteit. Lipoatrofie is geïdentifiseer deur twee ervare MIV pediaters deur gebruik van 'n gestandaardiseerde gradering skaal. 'n Diëetkundige het diëet assessering en antropometriese metings uitgevoer. Vorige antiretrovirale blootstellings is aangeteken. In 'n subset was Dual-energie X-straal Absorbtiometry (DXA) skandering uitgevoer. b) Antropometriese metings in kinders met en sonder lipoatrofie is vergelyk met behulp van meerveranderlike lineêre regressie aangepas vir ouderdom en geslag. Die mees kieskeurige antropometriese veranderlikes het Receiver Operating Curve analise ondergaan om die mees geskikte diagnostiese afgesnypunt te identifiseer. 2. a) Akkuraatheid is ondersoek deur gebruik te maak van hoë werkverrigting vloeistofchromatografie om aktiewe medikasie vanuit oplossings te herstel, wat gemeng is soos aangedui deur die voorgeskrewe af-etiket dosering metode. b) Biobeskikbaarheid is ondersoek deur die uitvoering van 'n ewekansige oorgesteekde farmakokinetiese studie waarin gesonde MIV- negatiewe volwasse vrywilligers een van twee generiese stavudien kapsule formulerings ontvang het, óf heel of in water gemeng soos aangedui deur die voorgeskrewe af-etiket dosering metode. Plasma stavudien konsentrasies is gemeet deur vloeistofchromatografie tandem massaspektrometrie. Uitslae: 1. a) Voorkoms van lipoatrofie was 36%, en insidensie was 12% per persoon-jaar. Aangepaste Odds ratio vir die ontwikkeling van lipoatrofie was 1,9 (CI: 1,3-2,9) vir elke addisionele jaar van opgehoopte blootstelling aan standaard dosis stavudien. b) Biceps vel-vou dikte <5mm het 'n sensitiwiteit van 89% (CI: 83-96%) en 'n negatiewe voorspellende waarde van 90% (CI: 84-96%) vir die opsporing en voorspelling van lipoatrofie. 2. a) Herwinning van aktiewe medikasie uit oplossings was 97,1%, 97,4% en 93,8% vir die oorspronklike en twee generiese formulerings onderskeidelik. b) Farmakokinetiese parameters van die af-etiket dosering metode was wel binne die teikenband van ongeskonde kapsule dosering vir beide generiese formulerings. Gevolgtrekkings: 1. a) Die voorkoms van lipoatrofie in onder-puberteitsjarige kinders op antiretrovirale terapie in Suid-Afrika is hoog. Die bedrag stavudien waaraan kinders blootgestel is moet hersien word. Die standaard stavudien dosis vir kinders moet herge-evalueer word. b) Biceps vel-vou dikte het redelike goeie sensitiwiteit en spesifisiteit om lipoatrofie op te spoor en te voorspel. 2. Die af-etiket dosering metode vir stavudien voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie is redelik akkuraat en is bio-ekwivalent aan ongeskonde kapsule administrasie.

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Mokheseng, Mamolise. "The management of antiretroviral drug distribution in the Qwaqwa District". Thesis, Nelson Mandela Metropolitan University, 2013. http://hdl.handle.net/10948/d1016077.

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The supply of Antiretrovirals (ARVs) to HIV/AIDS patients in most of the provinces in South Africa is hindered by various factors such as ineffective and inefficient drug procurement, and drug distribution systems. In the QwaQwa district in the Free State Province, a major barrier to the consistent supply of Highly Active Antiretroviral Treatment was identified to be the lack of an effective and efficient ARV drug distribution system. This resulted in major drug supply shortages in the QwaQwa district. A continuous, uninterrupted supply of ARVs to HIV/AIDS patients is critical to avoid drug resistance and therapy failure. Failure of a patient to respond to treatment results in a deterioration of a patient's health, and ultimately leads to death. The purpose of the study was to determine whether the ARV drug distribution practices at the Manapo Hospital in the QwaQwa district were effective and efficient in the management of ARVs. The distribution practices reviewed were the ordering, transportation, the management of inventory and warehousing, and the distribution of treatment to HIV/AIDS patients. Quantitative exploratory, descriptive and contextual methods were used to determine the relationship between the ARV drug distribution practices and the effective management of the ARVs. The study comprised of a sample size of twenty-one participants. The sample size entailed the Manapo Hospital pharmacists and pharmacist assistants who have been or are currently involved in the distribution of ARVs in the QwaQwa district since the initiation of the ARV rollout programme in 2004. The study revealed that the practices performed in the management of ARVs in the QwaQwa district were neither effective nor efficient in the distribution of ARVs. The recommendations of the study were identified to further ensure the effective and efficient management of the ARV drug distribution system, which will ensure a consistent supply of treatment to HIV/AIDS patients. Guidelines were developed for better circulation, thus meeting the objectives of the research.

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32

Knox, Kirstine A. "Antiretroviral agents and HIV-1 disease : analysis of in vitro phenotypic and functional markers of zidovudine therapy". Thesis, Imperial College London, 1991. http://hdl.handle.net/10044/1/46869.

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Adebanjo, Adefolarin Babafemi. "Factors affecting response to antiretroviral agents at one year in an HIV cohort at Roma Hospital, Lesotho". Diss., University of Pretoria, 2012. http://hdl.handle.net/2263/24507.

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Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence predict response to HAART as measured by CD4 count, weight gain and functional status in a cohort of patients in Roma, the Kingdom of Lesotho. Method: Data were collected from a computerised database of the Antiretroviral Centre of the hospital. A cohort of 300 subjects was identified from hospital records from January 2007. Each of these subjects was followed up over a period of 12 months with data obtained for at least two visits within the 12-month span. Data were obtained on weight and CD4 at baseline, three months and also at six and 12 months, and data for haemoglobin were obtained only at 12 months. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints, as well as for each endpoint separately. Results: Three-hundred patient records were analysed. Approximately 70% of the patients had a CD4 increase of at least 150 cells over baseline values at the end of the review period and in 52.3% of the patients an increase in weight of 10% over baseline measurements was seen. Seventy-nine patients (26.3%) had a haemoglobin level of at least 14g/dL at 12 months, regardless of baseline values or gender. The inclusion of Zidovudine (AZT) in treatment regimens was found in 73% of the patients and in multivariate analysis AZT was associated with not having anaemia at the end of the review period. However there was a slight reduction in haemoglobin level in the first two to three months of therapy in comparison with both Stavudine (d4T) and Tenofovir (TDF) but not significant enough to result in clinical anaemia. Baseline CD4 values were similar for all treatments options but dissimilar in other outcome variables and continued to vary significantly throughout the review period. The outcomes of multivariate analyses suggest that the male gender appears to have better response to HAART as seen in each of the multivariate models. The most important determinant of haemoglobin response was baseline haemoglobin values. In the haemoglobin-associated multivariate model, HAART is associated with an increase in haemoglobin over baseline values. A history of TB prior to HAART was a major factor in weight response and it is thought to be as a result of IRIS, which is the unmasking of latent infections as the immune system reconstitutes. CD4 values have no direct influence on weight however, but an increase in weight was observed in all therapy groups. Conclusion: Clinical and immunological parameters can be used to monitor response to HAART and predict treatment outcomes. These parameters can be organised into monitoring tools that will be useful in resource-limited areas. This study suggests that AZT-containing regimens appear not to result in anaemia and that symptomatic anaemia might need additional investigation. Treatment with TDF appeared to have shown the best possible response pattern more but patients on TDF therapy will have to be included in the study to justify this observation.
Dissertation (MSc)--University of Pretoria, 2012.
Clinical Epidemiology
unrestricted

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Das, C. R. "Causes of non-adherence to antiretroviral therapy in Wellness Clinic, Tshepong Hospital, Klerksdorp". Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/97161.

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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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Darin, Areechokchai Wirach Maek-a.-nantawat. "Adverse effects of antiretroviral drugs during pregnancy : A five-year review at Chonburi Hospital, Thailand /". Abstract, 2007. http://mulinet3.li.mahidol.ac.th/thesis/2550/cd400/4938552.pdf.

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Thematic Paper (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2007.
LICL has E-Thesis 0024 ; please contact computer services. LIRV has E-Thesis 0024 ; please contact circulation services.

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Morén, Núñez Constanza. "Mitochondrial functionalism in HIV-infected children receiving antiretroviral therapy". Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/83490.

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It is widely known that HIV and ARV drugs trigger mitochondrial impairment in adults. However, their effects in perinatally-infected children have been poorly explored. For this reason, the main hypothesis of the present Thesis was to demonstrate that mitochondrial abnormalities are present in HIV-infected pediatric patients treated with ARV. It is expected to find mitochondrial alterations in asymptomatic perinatally HIV-infected children. This mitochondrial lesion, manifested in a depletion of the mitochondrial genome, would lead to a reduction of the mitochondrial protein synthesis or to a mitochondrial dysfunction and, as a last resort, compromising the cellular viability. However, it is also possible that the presence of homeostatic mechanisms in mitochondria entails a proper function of some complexes, even in the presence of mitochondrial genome depletion. Rather than a localized mitochondrial alteration in a specific enzymatic activity, it is possible that HIV and ARV cause a diffuse damage in the organelle which may be observed in a general assessment of the respiratory chain. In case of a mitochondrial alteration, either in asymptomatic or symptomatic patients, it would be expected a more evident presentation of mitochondrial toxicity in case of the latter. If our hypothesis of an evidence of mitochondrial toxicity derived from HIV and ARV in children is confirmed, we believe that, once the detrimental agent is withdrawn, a recover of the mitochondrial affectation is possible. Mitochondrial impairment may change depending on the type of HAART regimen, leading us to use mitochondrial parameters as a biomarker or a trail to find the best therapeutic options in the choice of different HAART schedules. In this context, the intensity of mitochondrial impairment over time would be higher in children receiving first generation NRTI which, in turn, have been demonstrated to present a higher mitochondrial toxicity in vitro, than those under second generation NRTI. In order to study and test our hypothesis, the main objectives of the present Thesis are: A) General Objective To test if HIV and ARV mechanisms of mitochondrial toxicity found in adults are present in perinatally HIV-infected children. B) Specific Objectives - Objective 1: To elucidate whether ARV treatment or HIV infection were exerting a mitochondrial toxic effect in asymptomatic perinatally HIV-infected pediatric patients receiving HAART. - Objective 2: To investigate if hypothetic alterations in the mitochondrial genome of asymptomatic HIV-infected children receiving ARV are downstream reflected at transcriptional, translational and functional levels. In case of mitochondrial dysfunction was present, to test whether MRC alterations are focalized or diffuse. - Objective 3: To determine mitochondrial status in lipodystrophic HIV-children and compare them to a group of asymptomatic children and to a group of uninfected controls. - Objective 4: To evaluate whether a 12-month interruption of ARV is able to improve or revert these hypothetic mitochondrial alterations at molecular and/or clinical level. - Objective 5: To compare mitochondrial toxicity derived from different HAART schedules in a longitudinal 2-year follow-up assessment of immunovirological and mitochondrial status under first or second generation NRTI. To elucidate whether those NRTI demonstrated to present high mitochondrial toxicity in vitro present a major toxicity in vivo as well.

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Hansen, Laura Marie. "Mechanical and structural effects of HIV-1 proteins and highly active antiretroviral therapy (HAART) drugs on murine arteries". Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/45791.

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The overall goals of this project were to develop microstructurally based constitutive models to characterize the mechanical behavior of arteries and to investigate the effects of HIV proteins and antiretroviral drugs on the microstructure and mechanical behavior. To this end we created several constitutive models in aim 1 using a rule of mixtures approach, investigated the role of viral proteins in aim 2 through the use a transgenic mouse model, and studied the effects of the antiretroviral drug AZT administered to mice in aim 3. It is well known that the local mechanical environment which cells experience mediates growth and remodeling and that subsequent growth and remodeling can change that mechanical environment. This remodeling includes changes in the content and organization of the constituents of arteries (collagen, elastin, and smooth muscle cells). The first aim thus created models that incorporated the content and organization of these constituents using a rule-of-mixtures approach. The models we developed were able to capture the mechanical behavior of the arteries as well as previously developed phenomenological models while providing more physical meaning to the parameters, some which can be measured experimentally for incorporation into future models. Aims 2 and 3 investigated the mechanical and microstructural changes to murine arteries in response to HIV proteins or the drug AZT. While the development of antiretroviral therapy has greatly increased the life expectancy of patients with HIV, a number of other complications and co-morbidities including cardiovascular disease have become apparent. While clinical data has implicated both the virus and the antiretroviral drugs as playing roles, this work addressed the need of investigating these effects in a controlled manner. Specifically we used mouse models and focused on the two subclinical markers of increased intima-media thickness and arterial stiffening. Aim 2 used a transgenic mouse that expressed most of the human HIV proteins. We observed both intima-media thickening and arterial stiffening in alignment with clinical data. Other changes that also support a proatherogenic phenotype included decreased elastin content and changes in cathepsin activity. Aim 3 administered the antiretroviral drug AZT to healthy mice and we also observed the same subclinical markers of atherosclerosis including intima-media thickening and arterial stiffening as well as the other proatherogenic changes of decreased elastin and changes in cathepsin activity. Several other parameters including axial behavior, opening angles, collagen content, and collagen fiber angles were also quantified. These were important to fully characterize the vessel and may also be incorporated in the future into the constitutive models developed in aim1. In conclusion, in aim 1 we developed a microstructurally based constitutive model of arteries that effectively captures the mechanical behavior and includes parameters that have more physical meaning and some of which are experimentally tractable. Aims 2 and 3 both observed several subclinical markers of atherosclerosis in mice that express HIV proteins or were given AZT, providing a good model for future work and suggesting that both the HIV virus and antiretroviral drugs may play roles in the development of atherosclerosis in HIV.

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Thobias, Anna. "Exploration of factors associated with poor adherence among patients receiving antiretroviral therapy at Katutura State Hospital Communicable Disease Clinic in Khomas region, Namibia /". Online access, 2008. http://etd.uwc.ac.za/usrfiles/modules/etd/docs/etd_gen8Srv25Nme4_2455_1273775841.pdf.

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Chada, Sravanthi. "A new synthetic approach for preparation of efavirenz". Thesis, Nelson Mandela Metropolitan University, 2017. http://hdl.handle.net/10948/15512.

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Efavirenz, a drug that is still inaccessible to millions of people worldwide, is potent non nucleoside reverse transcriptase inhibitor (NNRTI), is one of the preferred agents used in combination therapy for first-line treatment of the human immunodeficiency virus (HIV). NNRTIs attach to and block an HIV enzyme called reverse transcriptase, by blocking reverse transcriptase; NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body. Efavirenz can't cure HIV/AIDS, but taken in combination with other HIV medicines (called an HIV regimen) every day helps people with HIV live longer healthier lives. Efavirenz also reduces the risk of HIV transmission and can be used by children who are suffering from HIV/AIDS. All the above therapeutic uses of efavirenz prompted us to identify the novel and hopefully cost efficient synthetic methodology for the preparation of efavirenz. In this thesis a new synthetic method for asymmetric synthesis of efavirenz is described. This route started from commercially available starting materials and it is first established in traditional batch chemistry and further the parameters transferred to a semi continuous flow protocol for optimization.

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40

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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41

Li, Wai-sum Rachel, i 李蕙琛. "Effects of abacavir on cardiovascular system". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B46330288.

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Adewumi, Olayinka Anthony. "Treatment outcomes in patients infected with multidrug resistant tuberculosis and in patients with multidrug resistant tuberculosis coinfected with human immunodeficiency virus at Brewelskloof Hospital". Thesis, University of the Western Cape, 2012. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_8245_1375971752.

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Many studies have reported low cure rates for multidrug-resistant tuberculosis (MDRTB) patients and MDR-TB patients co-infected with human immunodeficiency virus (HIV). However, little is
known about the effect of HIV infection and antiretroviral therapy on the treatment outcomes of MDR-TB in South Africa. Therefore, the objectives of the study are: to find out whether HIV infection
and interactions between ARVs and second line anti-TB drugs have an impact on the following MDR-TB treatment outcomes: cure rate and treatment failure at Brewelskloof Hospital. MDR-TB
patients were treated for 18-24 months. The study was designed as a case-control retrospective study comparing MDR-TB treatment outcomes between HIV positive (cases) and HIV negative
patients (controls). Patients were included in the study only if they complied with the following criteria: sensitivity to second line anti-TB drugs, MDR-TB infection, co-infection with HIV (for some
of them), male and female patients, completion of treatment between 1 January 2006 and 31 December 2008. Any patients that presented with extreme drug-resistant tuberculosis (XDR-TB)
were excluded from the study. Data were retrospectively collected from each patient&rsquo
s medical records. There were a total of 336 patients of which 242 (72%) were MDR-TB patients and 94
(27.9%) MDRTB co-infected with HIV patients. Out of the 242 MDR-TB patients, 167 (69.2%) were males and 75 (30.7%) were females. Of the 94 patients with MDR-TB co-infected with HIV, 51
(54.2%) males and 43 (45.7%) females. Patients with multidrug-resistant tuberculosis co-infected with HIV who qualify for antiretroviral therapy were treated with stavudine, lamivudine and
efavirenz while all MDR-TB patients were given kanamycin, ethionamide, ofloxacin, cycloserine and pyrazinamide. The cure rate of MDR-TB in HIV (+) patients and in HIV (-) patients is 34.5%
and 30 % respectively. There is no significant difference between both artes (pvalue = 0.80). The MDR-TB cure rate in HIV (+) patients taking antiretroviral drugs and in HIV (+) patients without
antiretroviral therapy is 35% and 33% respectively. The difference between both rates is not statistically significant. The study shows that 65 (28.0%) patients completed MDR-TB treatment but
could not be classified as cured or failure, 29 (12.5%) patients failed, 76 (32.7%) defaulted, 18 (7.7%) were transferred out and 44 (18.9%) died. As far as treatment completed and defaulted is concerned,
there is no significant statistical difference between HIV (+) and HIV (-) The number of patients who failed the MDR-TB treatment and who were transferred out is significantly higher in the HIV (-)
group than in the HIV (+) group. Finally the number of MDR-TB patients who died is significantly higher in the HIV (+) group). The median (range) duration of antiretroviral therapy before starting
anti-tuberculosis drugs is 10.5 (1-60) months. According to this study results, the MDR-TB treatment cure rate at Brewelkloof hospital is similar to the cure rate at the national level. The study also
hows that HIV infection and antiretroviral drugs do not influence any influence on MDR-TB treatment outcomes.

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Müller, Adrienne Carmel. "African traditional medicine-antiretroviral interactions : effects of Sutherlandia frutescens on the pharmacokinetics of Atazanavir". Thesis, Rhodes University, 2011. http://hdl.handle.net/10962/d1013373.

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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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Sued, Omar Gustavo. "Infección aguda/reciente por el VIH-1. Características clínicas, virológicas e inmunológicas y efectos del tratamiento inmunomediado". Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/396267.

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Durante la infección por VIH se denomina infección aguda al periodo entre la infección y la seroconversión completa (aproximadamente 30 días). Aunque la mayoría de los pacientes presentan un síndrome clínico denominado “síndrome retroviral agudo” y que se compone de fiebre, cefalea, odinofagia, faringitis, adenopatías y erupción cutánea, menos del 3% de los pacientes se detecta durante este periodo. Su identificación es importante ya que desde el punto de vista representa la fase de mayor transmisión, facilita los estudios de incidencia y la vigilancia de resistencia primaria, el inicio de tratamiento precoz mejora los síntomas y además, es una oportunidad única para estudiar la fisiopatología de la infección. El diagnóstico requiere la identificación del virus mediante la detección de ARN viral o antígeno p24, ya que las pruebas que detectan anticuerpos pueden ser negativas durante el primer mes de infección. En Barcelona la prevalencia global de resistencia durante el periodo 1997-2012 fue del 9% aunque los valores fueron más altos antes del 2004, y se redujeron paulatinamente. Por otro lado, la prevalencia de subtipos no-B fueron aumentando hasta alcanzar casi el 20%. Los factores asociados a progresión clínica incluyen la presencia de síntomas y los valores altos de carga viral. El tratamiento precoz mejora la recuperación inmune, reconstituye parcialmente la pérdida linfocitaria asociada a la infección, limita el reservorio viral y evita la progresión clínica. El uso de terapias inmunomediadas con ciclos de suspensión estructurada e IL-2 no mejoró las respuestas inmunoespecíficas ni el control espontáneo de la infección. Es importante seguir explorando nuevas combinaciones enfocadas a lograr la cura funcional del VIH.
Acute HIV infection is defined as the period from the date of infection to the appearance of a full antibody response. Most patients present with symptoms such as fever, headache, pharyngitis, lymphadenopathies and rash but less than the 3% of patients are detected during this period. Identifying patients during this period is important due to epidemiological considerations (higher risk of HIV transmission, best time for surveillance transmitted resistance, represent an in vivo model for understanding the immunological mechanisms of HIV persistence, and allow to initiate early treatment). Diagnosis relies in the detection of viral RNA or p24 antigen. The prevalence of resistance in Barcelona during the 1997-2012 period was 9%, with up to 20% of samples showing non-B subtypes. Factors associated to faster clinical progression were symptomatic infection and high viral load at baseline. Early treatment achieves almost complete immunological reconstitution, limits the size of the reservoir, and avoid clinical progression. Intermittent interruptions of treatment plus IL-2 was not associated with spontaneous viral control after antiretroviral suspension. It is important to continue exploring new combinations targeted to achieve functional cure.

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Jegede, Oyebisi. "Identification and Characterization of Novel Antiretroviral Compounds: from Small Molecule Library Screening to Rationally Designed Compounds". [Kent, Ohio] : Kent State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1185563176.

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Thesis (Ph.D.)--Kent State University, 2007.
Title from PDF t.p. (viewed Mar. 11, 2009). Advisor: Miguel Quiñones-Mateu. Keywords: HIV/AIDS, drug discovery, small molecule library screening, characterization of new antiretroviral drugs, highly active antiretroviral therapy. Includes bibliographical references (p. 180-200).

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Cysique, Lucette Adeline Juliette St Vincent's Hospital UNSW. "Aids dementia complex in the era of highly active antiretroviral therapy: a neuropsychological study". Awarded by:University of New South Wales. St. Vincent's Hospital, 2005. http://handle.unsw.edu.au/1959.4/22074.

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The aim of the thesis was to undertake an evaluation of the neuropsychological functioning of non-demented and demented patients with advanced HIV-infection who have been treated with Highly Active Antiretroviral Therapy (HAART) for several years. One hundred and one non-demented HIV-infected individuals and 23 patients with mild or moderate AIDS Dementia Complex (ADC), from the outpatient clinics and Neurology department at St. Vincent's Hospital, Sydney, Australia were randomly selected to participate in a prospective study of the neurological and neuropsychological complications of HIV disease. All had advanced HIV-infection and all had been on HAART for five years on average. Thirty-one seronegative controls were recruited as controls. All participants completed a standard neuropsychological examination assessing nine cognitive domains. Non-demented advanced HIV-infected individuals participated in three follow-up visits. In addition, we report the results of a multi-centre cohort of 78 patients with mild to moderate ADC on HAART (Abacavir ADC trial). The main findings of our research were that the prevalence of neuropsychological impairment in advanced HIV-infected individuals remains equivalent to the era that preceded the introduction of HAART. Moreover, while complex attention / psychomotor speed remained a marker of HIV-related neuropsychological impairment in the HAART era, impairment in learning, memory and aspects of complex attention may be new indicators of HIV-associated neurocognitive impairment. While progression of neuropsychological impairment is associated with past HIV-related history of brain involvement, we demonstrated that deterioration does not occur in a linear fashion and that over a 27 month period neuropsychological performance stabilizes in the majority. Stabilization of performance may be related to relapses in the course of HIV-associated neurocognitive impairment and HAART optimization especially with antiretrovirals that have good brain tissue penetrance. Our research showed that plasma viral load and current CD4 cell count were generally not associated with the neuropsychological performance, but rather that nadir CD4 cell count was associated with neuropsychological performance suggesting a relation between past immune deterioration and current cognitive status. Cerebrospinal markers of immune and virological activity were found to be partly dissociated from current neurological in contrast to what was observed in the pre-HAART era. Future studies will need to evaluate new factors for underlying HIV-associated neurocognitive impairment as well as factors for underlying partial recovery.

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Masokoane, Kgomotso Quentinne. "Adherence and non-adherence to antiretroviral treatment in HIV people in Port Elizabeth". Thesis, Nelson Mandela Metropolitan University, 2009. http://hdl.handle.net/10948/1185.

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The introduction of antiretroviral drugs (ARVs) in 1996 transformed the treatment of HIV and AIDS, improving the quality and greatly prolonging the lives of many infected people. HIV (Human Immunodeficiency Virus) is the virus that is believed to cause AIDS. AIDS (Acquired Immune Deficiency Syndrome) is the collection of illnesses or symptoms that ultimately results in death. Antiretroviral (ARVs) drugs or Highly Active Antiretroviral Therapy (HAART) is the treatment that has been applied to combat the HI virus in a bid to slow down the progression of AIDS and ultimately prolong the life of the infected individual. The study aimed to explore and describe the factors contributing to adherence and non-adherence to ARVs in individuals on treatment. A sample of 81 individuals who have been on ARV and HAART treatment for six months or more was used. The methodology used was exploratory-descriptive and the data obtained was quantitative in nature. A biographical questionnaire and questionnaire with questions aimed at ascertaining the possible factors that contribute to individuals either adhering to or defaulting on their treatment, such as side effects and cost of treatment, was administered. The data obtained was analysed by means of descriptive statistics and frequency counts. The results of the study showed that the sample had a fairly high level of adherence. The factors that could undermine adherence were identified as lack of support, as familial and health provider support acts as a motivator to adhere; substance abuse as it can lead to forgetting to take treatment; unemployment and poverty, as these can lead to an inability to return for follow up clinic visits or failure to have food to take with the pills; and the type of treatment regimen whereby the more complex the treatment is the more likely it is that adherence will be difficult to maintain. Suggestions were made as to future research involving antiretroviral therapy (ART). Finally the limitations as well as the value of the research were outlined.

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Wagner, Sarah Annette. "Perinatal human immunodeficiency screening in Washington State". Online access for everyone, 2006. http://www.dissertations.wsu.edu/Thesis/Spring2006/s%5Fwagner%5F041406.pdf.

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Fisher, Tarryn-Lee. "The effects of HIV Protease Inhibitors (Lopinavir/Ritonavir) on the non-oxidative pathways of glucose metabolism". Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/86469.

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Thesis (MSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: While antiretroviral therapy decreases HIV/AIDS morbidity and mortality, long-term treatment results in insulin resistance and cardiovascular diseases. A possible cause of such adverse effects may be an increase in oxidative stress resulting from protease inhibitor (PI)-induced mitochondrial dysfunction. We therefore hypothesized that PI treatment, specifically Lopinavir/Ritonavir, results in increases in myocardial reactive oxygen species (ROS), leading to downstream outcomes, i.e. elevated apoptosis. Moreover, we proposed that increased ROS levels in this instance might occur as a result of PI-mediated induction of the non-oxidative glucose pathways (NOGPs). In light of this, we also investigated the effect of PI treatment on the NOGPs by employing both in vitro and in vivo samples. For the in vitro work we employed a rat cardiomyoblast cell line, while tissues (heart, liver) were collected from two separate experimental models, i.e. a) Group A exposed to PIs via mini-osmotic pump for a period of eight weeks, and b) Group B administered PIs via a jelly-based method for 16 weeks. We found that PIs increased mitochondrial ROS levels in vitro but that this was not accompanied by a parallel rise in programmed cell death. Moreover, we found no induction of the NOGPs in response to PI exposure (for both in vitro and in vivo models here employed). However, we found that the AGE pathway was significantly down-regulated in the liver of Group A. Investigation into a proposed mechanism for this observation proved inconclusive and further studies are thus required to clarify the significance in terms of metabolic dysfunction found in the Group A model. Our study thus shows that PIs can increase ROS levels (in vitro) but that compensatory antioxidant mechanisms may prevent this in vivo. Subsequently, downstream effects were limited i.e. we did not observe NOGP induction and programmed cell death. An intriguing finding emerged, however, i.e. that PIs can elicit an impact on the AGE pathway. We propose future studies with modifications to the current rat and cell models in order to evaluate the downstream effects of PIs on the NOGPs and programmed cell death.
AFRIKAANSE OPSOMMING: Terwyl antiretrovirale terapie MIV/VIGS morbiditeit en mortaliteit verlaag, veroorsaak langtermyn behandeling insulienweerstandigheid en kardiovaskulêre siekte. 'n Moonltike oorsaak van sulke newe-effekte kan 'n toename in oksidatiewe stres veroorsaak deur die protease inhibeerder (PI)-geïnduseerde mitochondriale wanfunskionering. Ons hipotetiseer dat PI behandeling, spesifiek Lopinavir/Ritonavir, versoorsaak 'n toename in miokardiale reaktiewe suurstofspesies (ROS), wat aanleiding gee tot afstroom uitkomste, i.e. verhoogde apoptose. Verder, stel ons voor dat verhoogde ROS vlakke in hierdie geval onstaan as gevolg van PI-gemedieerde induksie van die nie-oksidatiewe glukose weë (NOGWe). In die lig hiervan het ons ook die effek van PI behandeling op die NOGWe ondersoek deur beide in vitro en in vivo monsters te gebruik. Vir die in vitro werk het ons van 'n rot kardio-mioblastsellyn gebruik gemaak, terwyl weefsels (hart, lewer) versamel is van twee afsonderlike eksperimentele modelle, i.e. a) Groep A blootgestel aan PIs via mini-osmotiese pomp vir 'n periode van agt weke, en b) Groep B PIs is toegedien via 'n jellie gebaseerde metode vir 16 weke. Ons het bevind dat die die PIs mitochondriale ROS vlakke in vitro verhoog maar dat dit nie vergesel is met 'n paralelle toename in apoptose. Verder is geen induksie van die NOGWe in reaksie op PI blootstelling waargeneem (vir beide in vitro en in vivo modelle). Hoewel ons het bevind dat die AGE weg in die lewer van Groep A beduidend afgereguleer is. Ondersoek na 'n moontlike megansime vir hierdie waarneming was onoortuigend en verdere ondersoek is nodig om die betekenis in terme van die metaboliese wanfunskionering in die Groep A model vas te stel. Ons studie toon dus aan dat PIs, ROS vlakke (in vitro) verhoog, maar dat kompensatoriese anti-oksidant meganismes in die hierdie in vivo model verhoed word. Gevolglik is die afstroom effekte beperk i.e. ons het geen NOGWe induksie en aptoptose waargeneem nie. 'n Interesante bevinding het wel uitgestaan, i.e. PIs kan 'n impak hê op die AGE weg. Ons stel dus voor dat toekomstige studies met modifikasies, tot die huidige rot- en sel-modelle gemaak word om die afstroomeffekte van PIs en apoptose te evalueer.

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Oluoch, Okumu Fredrick. "Synthesis and characterization of bimetallic silver and platinum nanoparticles as electrochemical sensor for nevirapine, an anti-HIV drug". Thesis, Cape Peninsula University of Technology, 2016. http://hdl.handle.net/20.500.11838/2319.

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Thesis (DTech (Chemistry))--Cape Peninsula University of Technology, 2016.
Bimetallic silver-platinum (Ag-Pt) nanoparticles (NPs) were synthesized via simultaneous reduction of varying mole fractions of metal precursors H2PtCl6.6H2O and AgNO3 by sodium citrate. Kinetics rates of were as follows; Ag NPs (0.079 s-1), Ag-Pt NPs 1:1 (0.082 s-1) and Pt NPs (0.006 s-1). The UV visible spectrum of Ag NPs exhibited a characteristic absorption band while Pt NPs and Ag-Pt bimetallic NPs exhibited no absorption peaks. Successful formation of both monometallic and bimetallic NPs was confirmed via transmission electron microscopy (TEM); selected area electron diffraction (SAED) and energy dispersive X-ray (EDX) analysis. TEM images depicted core-shell arrangement in the bimetallic (BM) NP ratios (1:1, 1:3 and 3:1) with an average particle size of 21 nm. The particle size trend where monometallic Ag NPs (60 nm) > Pt NPs (2.5 nm) while in the BM ratios Ag-Pt NPs 1:1 (25 nm) > Ag-Pt NPs 1:3 (20.7 nm). X-ray diffraction (XRD) patterns depicted crystallinity in all the synthesized NPs with confirmation of the face centred cubic structure formation. Transducers were fabricated by drop casting the nanoparticless on the glassy carbon electrode (GCE) and their electrochemical properties studied via cyclic voltammetry (CV). High diffusion coefficient (D) and surface coverage reported were Ag NPs (6.70 cm2 s-1, 54.49 mol cm-2 ) and Ag-Pt NPs 1:1 (0.62 cm2 s-11.85 mol cm-2). Electrochemical band gaps ranged from 1.45 to 1.70 eV while the Tauc’s model band gaps of nanoparticles were found in the range of 2.48 to 3.84 eV. These band gaps were found to be inversely proportional to particle size, which was attributed to the quantum confinement effect. Both optical and electrochemical band gap portrayed similar trend as well as an increase in the BM NP relative to monometallics. These nanoparticles band gaps are within semiconductor range for most materials. The electrochemical behaviour and surface characteristics were studied using 0.1 M PBS solution by scan rates variations for the diffusion coefficient determination of modified electrodes which ranged from 0.62 to 6.10 x 10-5 cm2 s-1. Laviron’s approach for parameters such as apparent charge transfer rate constant, ks, and charge transfer coefficient, α, for electron transfer between NPs and GCE were investigated using CV. The values of electron-transfer coefficients ranged from 0.1 to 0.7 while the charge transfer rate constant values ranged from 0.74 to 31.13 s-1.

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