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1
Russell, Rodney S. "The influence of HIV-1 proviral burden on disease progression and response to antiretroviral therapy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0015/MQ55539.pdf.
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Hejdeman, Bo. "Studies on medical and immunological interventions in HIV-1 infection /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-019-2/.
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Fernandez, Sonia. "CD4⁺ T-cell deficiency and dysfunction in HIV patients receiving combination antiretroviral therapy /." Connect to this title, 2006. http://theses.library.uwa.edu.au/adt-WU2007.0120.
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De, Milito Angelo. "Immune activation during HIV-1 infection : implication for B cell dysfunctions and therapy monitoring /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-170-5.
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Srasuebkul, Preeyaporn Public Health & 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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Behbahani, Homira. "Immune dysregulation in HIV-1 infected lymphoid tissue /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-193-4.
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Fernandez, Sonia. "CD4? T-cell deficiency and dysfunction in HIV patients receiving combination antiretroviral therapy." University of Western Australia. School of Surgery and Pathology, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0120.
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[Truncated abstract] Failure to fully reconstitute the immune system is a common clinical problem in HIV patients who were severely immunodeficient before responding to combination antiretroviral therapy (CART). This can manifest as a deficiency in the number or function of CD4+ T-cells and occurs most often in patients who had a nadir CD4+ T-cell count below 100/μl when CART was commenced. Observational studies of large cohorts of HIV patients, such as the D:A:D study, have demonstrated that patients with low CD4+ T-cell counts have increased rates of death compared with patients who have normal CD4+ T-cell counts. Furthermore, individual case studies suggest that impaired recovery of pathogen-specific immune responses during CART is associated with opportunistic infections or disease progression. This thesis addresses possible causes of deficiencies in CD4+ T-cell number or function in HIV patients who were very immunodeficient prior to treatment and are responding (virologically) to CART. Firstly, the role of the thymus in producing naive CD4+ T-cells and the effects of persistent immune activation on the recovery of CD4+ T-cell numbers were assessed in patients with either low or high CD4+ T-cell counts after long-term CART. ... Proportions of antigen presenting cell (APC) subpopulations were examined in HIV patients with low or high CMV-specific CD4+ T-cell responses after long-term CART. HIV patients had significantly lower proportions of plasmacytoid dendritic cells (pDC) than HIV-negative controls. Furthermore, the proportions of pDC were positively correlated with CMV-specific CD4+ T-cell responses in HIV patients. Proportions of myeloid dendritic cells (mDC) were significantly higher in HIV patients than controls, and were also increased in patients with low CMV-specific CD4+ T-cell responses. Proportions of M-DC8+ dendritic cells or CD14+ monocytes did not differ between patients and controls, nor were they associated with CMV-specific CD4+ T-cell responses. Quantitation of cytokine (interferon-α, tumour necrosis factor-α, interleukin (IL) -12, IL-23, IL-15, IL-18 and IL-10) mRNA in unstimulated, purified populations of the APC described above revealed few significant differences between patients with low or high CD4+ T-cell IFN-γ responses to CMV. The only notable difference was the slight elevation of IL-15 mRNA levels in patients compared to controls. Since patients in the high responder group had the highest levels of IL-15 mRNA, this association may reflect the anti-apoptotic properties of IL-15. These studies provide valuable insights into the causes of persistent CD4+ T-cell deficiency and dysfunction in HIV patients on CART and may lead to better monitoring and treatments.
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Parathyras, John Burns. "Molecular genetic analysis of human immunodeficiency virus antiretroviral therapy response in South Africa : a pharmacogenetics study." Thesis, Link to the online version, 2007. http://hdl.handle.net/10019/453.
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Lindström, Anna. "Resistance to antiviral drugs in HIV and HBV /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-239-X/.
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Atlas, Ann. "Immunological and virological response to antiretroviral treatment (art) in patients infected with different HIV-1genetic subtypes /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-645-X/.
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Megazzini, Karen M. "Provision of rapid HIV testing and nevirapine administration in Zambian labor wards to improve population antiretroviral coverage of HIV-infected women and their HIV-exposed infants." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2009r/megazzini.pdf.
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Bernstein, Molly. "Intimate partner violence among HIV-infected pregnant women initiating antiretroviral therapy in South Africa." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15601.
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Background: Intimate Partner Violence (IPV) is recognized globally as a major public health concern linked to numerous adverse physical, mental, sexual and reproductive health outcomes. IPV is associated with both pregnancy and HIV-infection independently, but there are few data on IPV in populations of HIV-infected pregnant women. We examined the prevalence and predicators of IPV among pregnant women initiating lifelong antiretroviral therapy (ART) in a large primary care clinic in Cape Town, South Africa. Methods: Consecutive pregnant women seeking antenatal care in Gugulethu, Cape Town were recruited into the MCH-ART study examining service models for postpartum ART care. IPV, depression, alcohol and drug use, and emotional distress were assessed using the 13-item WHO Violence Against Women questionnaire, the Edinburgh Postnatal Depression Scale (EPDS), alcohol and drug use disorders identification test (AUDIT/DUDIT) and the Kessler-10 (K-10) scale, respectively. Questionnaires were administered privately by trained interviewers. Women identified with specific IPV or mental health concerns were referred to appropriate services. Logistic regression was used to examine factors independently associated with experiences of IPV after adjusting for age and socioeconomic status. Results: From April 2013-May 2014, 623 women were enrolled (median age, 28 years):97% reported being in a relationship, 38% were married and/or cohabiting and 70% reported not having discussed or agreed on pregnancy intentions prior to conception . Overall, 21%(n=132) reported experiencing ≥ 1 act of IPV in the past 12 months, including emotional violence(15%), physical violence(15%) and sexual violence(2%). Of those reporting any IPV, 48% reported experiencing multiple types. Emotional and physical violence were most prevalent among women 18-24 years old, while sexual violence was most commonly reported among women 25-29 years old. Women who reported not discussing or disagreeing on pregnancy intentions with their partners prior to conception were significantly more likely to experience violence(p=0.030), and women who experienced IPV reported higher levels of substance abuse, depression and emotional distress(p<0.001 for all associations). Discussion: These data demonstrate high levels of IPV in this population. While the potential impact of HIV-infection, pregnancy and pregnancy intention on the risk of IPV and related factors require further research, IPV-related screening and support services should be considered as part of the package of care for ART in pregnancy.
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O'Sullivan, Briana Jean. "Adherence in HIV-positive women entering antenatal care on antiretroviral therapy: A cross-sectional study." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/16701.
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Includes bibliographical referencesProper implementation of and adherence to antiretroviral therapy (ART) is significantly associated with better health and longer life in HIV-positive individuals. Consistent, adequate adherence has been shown to lead to a suppressed viral load. A low viral load delays the virus's progression and leads to better health outcomes for the individual. Adequate adherence is especially important among HIV-positive pregnant women. How well a woman adheres to her ART can not only improve her health during pregnancy but can protect the infant from HIV by preventing in utero transmission of the virus. Continuing ART protects against transmission via breastmilk later in the infant's life. While the benefits of good adherence are undeniable, the definition of adequate adherence varies widely in the literature. Taking 80 to 100% of pills as prescribed is commonly used as the threshold for adequate adherence levels. Various methods exist for measuring ART adherence, and while some are more reliable than others, there is no gold standard. This ambiguity in ART research extends to pregnant women, with even less known about HIV infected women established already on ART who then become pregnant. Changes in treatment protocols in the Western Cape and improvement of ART delivery throughout South Africa have resulted in this group of long-term users growing in size. Without more research into the barriers of ART adherence in these women, efforts to scale up treatment programs and to end mother to child transmission of HIV will ultimately fail. This dissertation is an exploration of these ideas. It begins to fill the gap in current knowledge related to ART compliance in pregnant women, and gives new insights into how specific barriers to adherence can adversely affect this specific group of established ART users.
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Wong, Mei-wan Farah, and 黃美雲. "Financial burden for HIV/AIDS patients to access antiretroviral therapy in Asian developing countries." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193826.
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Background: Since the beginning of 21st century, several Asian countries started implementing their national free antiretroviral therapy (ART) programs to tackle one of the most striking public health issues in Asia – HIV/AIDS. Despite the efforts being made, the treatment coverage remains as low as 44% in 2010. Previous studies have identified financial constraint is a major barrier in accessing ART and an important reason of poor ART adherence in Asia. The purpose of this literature review is to explore the extent of financial burden experienced by people living with HIV (PLHIV) where free ART policy is implemented, and to provide valuable information for policy-making in reducing financial barriers and improve uptake of ART.
Methods: Literature search was performed by entering keywords in PubMed and Medline. Articles were screened and selected for in-depth review according to the inclusion and exclusion criteria. A process on data synthesis was performed on the final eligible papers.
Results: Five studies from four Asian countries describing the out-of-pocket health expenditure incurred by PLHIV during the delivery of ART were included in this review.
Findings: Out of all direct medical costs, the cost of drug was most important in contributing to the total costs for patients without health insurance, while the cost of transportation was more important for patients covered by health insurance. Direct medical costs increased with advancing stage of disease. Rural patients would have spent up to 1,173% of their monthly income per capita, or more than 100% of their total household expenditure even when ART was provided free-of-charge. Patients have also highlighted free ARV drugs were sometimes not available in the health facility and they had to turn to the private market. Hence, the extent of financial burden in this review might be underestimated.
Conclusion: Based on the data available, we concluded that increased accessibility of free ART should be accompanied with sustained ARV drugs supply and increased financial support for PLHIV.published_or_final_version
Community Medicine
Master
Master of Public Health
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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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Kambale, Herve Nzereka. "Factors that affect adherence to antiretroviral therapy among adolescent patients at selected Palapye clinics." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79965.
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Thesis (MPhil)--Stellenbosch University, 2013.ENGLISH ABSTRACT: This study, which was conducted from 1 to 31 October 2012, was aimed at describing the main factors that influence adolescent adherence to antiretroviral treatment in three selected health facilities of Palapye Health District. During the one-month data collection period, 30 adolescents were interviewed using semi-structured interview tools. Different factors influencing adolescent adherence to antiretroviral treatment were highlighted and adherence to such treatment was measured using the method of calculating the percentage of returned pills. The mean adherence level for the entire sample was 76.96%, with common factors contributing to poor adherence among adolescents being found to be the poor processing of disclosure, stigma, the accessibility of health facilities, due distance and waiting time, the nature of social support, and feelings toward taking antiretroviral. Thus, by addressing adolescent adherence to antiretroviral treatment, adolescent-adherence counselling before and during treatment is to be shaped, insisting on the preparation of young patient caregivers for the process of disclosure; the reinforcement of positive messages during consultations; insistence on the importance of disclosing HIV status to others; the implementation of the antiretroviral dispensing outreach at health posts; and exerting effort to reduce the waiting time at health facilities prioritising young patients and adolescents.
AFRIKAANSE OPSOMMING: Hierdie studie, wat vanaf 1 tot 31 Oktober 2012 onderneem is, het ten doel gehad om die hooffaktore te beskryf wat adolessente se getrouheid met antiretrovirale behandeling in drie gekose gesondheidsfasiliteite in die Palapye-gesondheidsdistrik beïnvloed. Semigestruktureerde onderhoude is gedurende die maand lange datainsamelingstydperk met 30 adolessente gevoer. Die studie dui op verskillende faktore wat adolessente se getrouheid met antiretrovirale behandeling beïnvloed, welke getrouheid gemeet is aan die hand van die persentasie teruggestuurde pille. Die gemiddelde getrouheidsvlak vir die algehele steekproef was 76,96%. Algemene faktore wat oënskynlik tot swak behandelingsgetrouheid onder adolessente bydra, is die swak verwerking van MIV-statusonthulling, stigma, die toeganklikheid van gesondheidsfasiliteite, reisafstand en wagtyd, die aard van maatskaplike steun, en gevoelens oor die gebruik van antiretrovirale middels. Hierdie ondersoek na adolessente se getrouheid met antiretrovirale behandeling behoort adolessentberading oor behandelingsgetrouheid voor én gedurende behandeling te rig. Die klem moet in die besonder val op die voorbereiding van die versorgers van jong pasiënte om die onthullingsproses beter te hanteer; die versterking van positiewe boodskappe gedurende konsultasies; die belang van MIV-statusonthulling aan ander; die inwerkingstelling van uitreikaksies om voorskrifte vir antiretrovirale middels by sogenaamde ‘gesondheidstasies’ te resepteer, en daadwerklike pogings om die wagtyd by gesondheidsfasiliteite te verkort, met voorrang aan jong pasiënte en adolessente.
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Veerasami, Sowbagium. "A retrospective study of the clinical management and treatment outcomes of patients established on antiretroviral therapy who are newly diagnosed with tuberculosis in the public sector, KwaZulu-Natal." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/80334.
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Thesis (MCurr)--Stellenbosch University, 2013.ENGLISH ABSTRACT: Taking into consideration the long duration of standard treatment for Mycobacterium tuberculosis (TB), the high prevalence of HIV co-infection and the growing prevalence of drug-resistant TB, there is an urgent need for improved treatment approaches for TB and HIV. However, there is inadequate information regarding the burden being placed on the Department of Health (DOH) systems by the current treatment of patients established on Antiretroviral Therapy (ART) who are newly diagnosed with TB, and by their clinical management. The aim of the study was to determine what proportion of patients established on ART were newly diagnosed with TB, and what their clinical and treatment outcomes were in different public sector settings in the eThekwini Region, KwaZulu-Natal (KZN). Approval for the study was obtained from the Human Research Committee of Stellenbosch University and from the Biomedical Research Committee, KZN. The study used a retrospective, quantitative, cohort technique at both TB and ART clinics at three sites in the eThekwini region, KZN. These sites were DOH clinics and were selected as they all had a TB clinic and a DOH-registered ART clinic. The study focused on a period of one year prior to a patient established on ART developed TB. The study population comprised all TB patients who attended the selected DOH clinics. A data collection tool was developed and pilot-tested. A small sample of patient files (n=15, representing 2% of the study population) was randomly selected; five from each site. The files and data were excluded from the main study. A total of 1824 files (579 from the TB clinics and 1245 from the ART clinics) were reviewed. The data were captured into an electronic database (EpiData Version 3.3) and analyzed using STATA (Version 11.0) with the assistance of a statistician. The findings show that of the study sample from the TB clinics (N=579), 78% (454/579) were newly diagnosed with TB. Of the new TB cases, 90% (409/454) had pulmonary TB and 71% (413/579) were HIV-positive. Nearly 50% (68/137) of the patients had commenced ART prior to TB diagnosis and treatment, and 14% (19/137) had commenced ART after TB. Of those who commenced ART prior to TB diagnosis and treatment, 29% (20/68) had commenced ART more than three months prior to acquiring TB. The findings from the ART clinics show that of the files (N=1245) reviewed, 40% (501/1245) had TB, and of these 8% (42/501) developed TB after three months or more of ART. Missing data in the patient medical files was a major challenge. The lack of recorded data about ART in the TB clinics and about TB in the ART clinics suggests suboptimal clinical management and poor integration of HIV and TB services. It was therefore not possible to derive a combined HIV-TB outcome measure. Recommendations to promote and implement the integration of TB and HIV services included policy changes and implementation, management and practice suggestions, education and training to integrate TB/HIV services and increase research to identify gaps in clinical management and to improve integration of services.
AFRIKAANSE OPSOMMING: Met inagneming van die lang duur van die standaard behandeling vir Mycobacterium tuberkulose (TB), hoë voorkoms van MIV-infeksie en die groeiende voorkoms van dwelmweerstandige TB, is daar ’n dringende behoefte aan verbeterde behandelingbenaderings vir TB en MIV. Daar is egter ’n gebrek aan inligting oor die las geplaas op die Departement van Gesondheid (DvG) se stelsels deur die huidige behandeling van pasiënte op antiretrovirale terapie (ART) wat gediagnoseer is met TB en deur hul kliniese bestuur. Die doel van die studie was om vas te stel watter persentasie van pasiënte wat op ART gevestig is, wel met TB gediagnoseer is, en wat hul kliniese en behandeling-uitkomste was in verskillende openbare-sektorinstellings in die eThekwini-streek, KwaZulu-Natal (KZN). Goedkeuring vir die studie is verkry van die Menslike Navorsingskomitee van die Universiteit van Stellenbosch en van die Biomediese Navorsingskomitee, KZN. Die studie het gebruik gemaak van ’n retrospektiewe, kwantitatiewe ‘cohort’-tegniek by beide TB en ARB-klinieke op drie plekke in die eThekwini-streek, KZN. Hierdie terreine was DvG-klinieke en is gekies omdat hulle almal oor ’n TB-kliniek en 'n DvGgeregistreerde ART-kliniek beskik. Die studie het gefokus op ’n tydperk van een jaar voor ’n pasiënt wat op ART is, TB ontwikkel het. Die studiepopulasie bestaan uit alle TBpasiënte wat die geselekteerde DvG-klinieke bygewoon het. ’n Data-insamelinginstrument is ontwikkel en getoets. ’n Klein voorbeeld van die pasiëntlêers (n = 15, 2% van die studie bevolking verteenwoordig) is ewekansig gekies: vyf uit elke plek, en die data is vervat in ’n elektroniese databasis (EpiData Version 3,3). ’n Totaal van 1824 lêers (579 in die TB-klinieke en 1245 lêers in die ART-klinieke) is ondersoek. Die data is ontleed deur gebruik te maak van Stata (weergawe 11,0) met die hulp van ’n statistikus. Die bevindinge toon dat van die studiemonster in die TB-klinieke (N = 579), 78% (454/579) met TB gediagnoseer is. Van die nuwe TB-gevalle, het 90% (409/454) pulmonêre TB gehad en was 71% (413/579) MIV-positief. Byna 50% (68/137) van die pasiënte het ART begin vóór hulle TB-diagnose en -behandeling, en 14% (19/137) ART ná TB. Van dié wat ART voor TB-diagnose en -behandeling begin het, het 29% (20/68) meer as drie maande voor die opdoen van TB met ART begin. Die bevindinge van die ART-klinieke toon dat van die lêers (N = 1245) wat bestudeer is, 40% (501/1245) TB het, en hiervan het 8% (42/501) TB na drie of meer maande van ART ontwikkel. Ontbrekende data in die pasiënt se mediese lêers was ’n groot uitdaging. Die gebrek aan aangetekende data oor ART in die TB-klinieke en oor TB in die ART-klinieke dui op suboptimale kliniese bestuur en swak integrasie van MIV- en TB-dienste. Dit was dus nie moontlik om ’n gesamentlike MIV-TB uitkomsmaatreël af te lei nie. Aanbevelings om die integrasie van TB- en MIV-dienste te bevorder en te implementer, het beleidveranderinge en -implementering ingesluit, asook bestuur- en praktykvoorstelle, onderwys en opleiding om TB-/MIV-dienste by DvG-vlak te integreer en meer navorsing om gapings in die kliniese bestuur te identifiseer en die integrasie van dienste te verbeter.
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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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Okoli, Emmanuel Ikechukwu. "Psychosocial characteristics of AIDS patients with unsuppressed viral load after six months of antiretroviral therapy." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79983.
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Thesis (MPhil)--Stellenbosch University, 2013.ENGLISH ABSTRACT: STUDY AIM The aim of the study is to explore the psychosocial characteristics of HIV positive clients who are yet to achieve viral load suppression after six months of commencing ARV at Sundumbili CHC in order to plan positive intervention strategies. RESEARCH DESIGN Non-experimental quantitative design was used in carrying out the study. The data was collected through retrieval of information from clinic records and completion of questionnaires to clients on ARV who met the inclusion criteria and consented to participating in the study. A total of 51 adults aged more than 18 years that were initiated in 2010/2011 and still access their treatment at Sundumbili CHC were enrolled into the study. They were selected through convenience sampling. FINDINGS Psychosocial challenges still exist among research participants whose viral load results were not suppressed after six months on ARV. This affected the adherence of some of them to their antiretroviral treatment. CONCLUSION Given the rural nature of Sundumbili and surroundings where the bulk of the patients reside, there are several psychosocial challenges affecting the patients. No known previous study has been undertaken to ascertain the psychosocial characteristics of this group of patients and the impact they may have on viral load suppression after six months of treatment. The study is therefore significant as the findings have provided more insight into the plight of the patients. It is envisaged that the recommendations from the study will assist the relevant management staff in the department in planning and subsequently implementing more positive intervention strategies. The strategies should be targeted at improving the quality of care of the HIV positive clients and attending to their psychosocial needs.
AFRIKAANSE OPSOMMING: STUDIEDOELWIT Die doel van die studie was om ondersoek in te stel na die psigososiale kenmerke van MIV-positiewe kliënte wie se virustellings ná ses maande van antiretrovirale (ARV) behandeling by die gemeenskapsgesondheidsentrum op Sundumbili steeds nie onder beheer was nie, ten einde positiewe intervensiestrategieë te beplan. NAVORSINGSONTWERP ’n Nie-eksperimentele kwantitatiewe ontwerp is gebruik om die studie te onderneem. Die data is ingesamel deur die herwinning van inligting uit klinieklêers sowel as die afneem van vraelyste onder kliënte op ARV’s wat aan die insluitingsmaatstawwe voldoen en tot deelname aan die studie toegestem het. Altesaam 51 volwassenes bo die ouderdom van 18 wat in 2010/2011 met ARV behandeling begin het en dit steeds by Sundumbili-gemeenskapsgesondheidsentrum ontvang, is in die studie opgeneem. Dié groep is deur middel van geriefsteekproefneming gekies. BEVINDINGE Psigososiale uitdagings was steeds te bespeur by navorsingsdeelnemers wie se virustellings nog nie ná ses maande op ARV’s onder beheer was nie. Dit het sommige se behandelingsgetrouheid beïnvloed. GEVOLGTREKKING In die lig van die landelike aard van Sundumbili en omgewing, waar die meeste van die pasiënte woon, kom pasiënte voor verskeie psigososiale uitdagings te staan. Daar is klaarblyklik nog nooit vantevore ’n studie onderneem om die psigososiale kenmerke van hierdie groep pasiënte, en die moontlike impak daarvan op die onderdrukking van virustellings ná ses maande van behandeling, te bepaal nie. Hierdie studie is dus waardevol, aangesien die bevindinge groter insig in die lot van die pasiënte bied. Daar word beoog dat die aanbevelings uit die studie tersaaklike bestuurspersoneel in die Departement van Gesondheid sal help om meer positiewe intervensiestrategieë te beplan en gevolglik in werking te stel. Die strategieë behoort daarop afgestem te wees om die gehalte van sorglewering aan MIV-positiewe kliënte te verbeter en in hul psigososiale behoeftes te voorsien.
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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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Maie, Aramaki Udomsak Silachamroon. "Immune reconstitution inflammatory syndrome during highly active antiretroviral therapy in advanced HIV-infected patients /." Abstract, 2007. http://mulinet3.li.mahidol.ac.th/thesis/2550/cd400/4938550.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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Mwingira, Betty. "Development and assessment of medicines information for antiretroviral therapy in Sub-Saharan Africa." Thesis, Rhodes University, 2005. http://hdl.handle.net/10962/d1003257.
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Labeodan, Moremi Morire OreOluwapo. "Stochastic analysis of AIDS epidemiology." Thesis, Pretoria : [s.l.], 2009. http://upetd.up.ac.za/thesis/available/etd-10172009-112824.
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Singh, Vikesh. "Implementation of the dual therapy prevention of mother-to-child transmission protocol." Thesis, Nelson Mandela Metropolitan University, 2010. http://hdl.handle.net/10948/1374.
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Antiretroviral drugs taken during pregnancy, reduce the rates of mother-to-child transmission from 35 percent to as low as 1 to 2 percent (UNAIDS, 2009). In 2002, the Prevention of Mother-to-Child Transmission (PMTCT) programme was implemented in South Africa. Studies on the implementation of the PMTCT programme have shown that understaffed and under-developed health care facilities were key barriers to the provision of PMTCT services (Health Systems Trust, 2002: 6; Skinner et al., 2003). The aim of this study was to assess the challenges experienced by health care workers working in public sector facilities in the Nelson Mandela Metropole after implementation of the dual therapy PMTCT programme. Four areas were investigated: Infrastructure; Drug Supply Management; Clinic Procedures and Staffing. A quantitative descriptive study was conducted in August 2009 at nine public health care facilities in the Nelson Mandela Metropole, South Africa. Questionnaires were issued to 81 nurses and 41 pharmacy personnel (pharmacists and pharmacist assistants). Checklist audit forms were issued to the Facility Manager of each facility and completed with the researcher. The key findings for Infrastructure were lack of space at patient waiting rooms (9; 100 percent n=9), counselling area (5; 55.5 percent; n=9), nurse consultation rooms (6; 66.6 percent; n=9), storage areas (5; 55.5 percent; n=9) and filing areas (7; 77.7 percent; n=9). The key findings for Drug Supply Management were none of the dispensaries (0 percent; n=10) were fully compliant with Good Pharmacy Practice, pharmacy personnel indicated that there were no stock cards for medication (13; 31.7 percent; n=41); there was less than two weeks supply of buffer stock kept for zidovudine and nevirapine (13; 35.1percent; n=37) and medication orders were placed without any reference to minimum and maximum levels of medication (15; 36.5 percent; n=41) . The key findings for Clinic Procedures were only two facilities followed up on patients that had missed appointments (22.2 percent; n=9) and four facilities (44.4 percent; n=9) had a tracking system for patients that had defaulted. Of the nine facilities only three (33.3 percent; n=9) updated patient demographic details regularly. The key findings for Staffing were a shortage of doctors, nurses, counsellors and pharmacists at the facilities. One of the major challenges identified was the lack of training offered on new PMTCT protocols with 56.2 percent (45; n=80) of the nurses stating that no training was provided on the dual PMTCT protocol. Only 54.3 percent (44; n=81) of nurses stated that they knew the criteria to start the mother on dual PMTCT therapy. In conclusion there is an urgent need for barriers such as lack of staff, lack of space, lack of training on PMTCT and standard procedures for follow up of patients to be addressed in order to ensure the successful scaling up of PMTCT.
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Vazi, Thulani. "The quality of life of adolescents living with early childhood HIV-Infection on highly active antiretroviral therapy in Port Elizabeth." Thesis, Nelson Mandela Metropolitan University, 2014. http://hdl.handle.net/10948/d1021043.
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This study aimed to explore and describe the quality of life of adolescents living with early childhood HIV infection on Highly Active Antiretroviral Therapy (HAART) in Port Elizabeth. The advent of HAART has resulted in HIV being managed as a chronic illness, instead of the fatal disease that it once was. Children born with HIV can now live longer lives, progressing to adolescence and beyond. Chronic illness is known to impact one’s quality of life, so does adolescent development. A convenient sample of 31 adolescents was used in this study, with an exploratorydescriptive research design. The data was gathered using a cross cultural structured questionnaire developed by the World Health Organization, as well as through individual interviews. The data was then analysed by means of descriptive statistics and thematic content analysis. The results identified and presented the quality of life issues that are specific to this population. The results indicate that HIV as a chronic illness does impact the quality of life of adolescents. The adolescents living with early childhood HIV-infection on HAART in this study were very satisfied with their perceptions of their overall quality of life and general health perceptions. They were least satisfied in the Spirituality/Religion/Personal Beliefs and Social Relationships domains; and were most satisfied in the Level of Independence and the Psychological domains. There is a need for the development of (medical and psychosocial) services that can focus on adolescents as a special population with specific developmental needs in order to improve their treatment outcomes and quality of life.
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Ngandu, Jean Pierre Kabue. "Coreceptor expression and T lymphocyte subset distribution in HIV-infected and TB co-infected South African patients on anti-retroviral therapy." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/2219.
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Thesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2009.ENGLISH ABSTRACT: In 2007, AIDS caused an estimated 2.1 millions deaths worldwide; about 70% in sub-Saharan Africa. HIV preferentially targets activated CD4 T cells, expressing the major HIV receptor CD4, as well as the major chemokine coreceptors CCR5 and CXCR4. These coreceptors play a prominent role during HIV cell entrance phase, HIV transmission and also disease progression. They have been found to be differentially expressed by CD4 T cell subsets. Tuberculosis coinfection may enhance immune activation in vivo thus accelerating HIV disease progression and has become a major challenge in the control of TB in Africa. Introduction of HAART has reduced disease progression to AIDS, as well as risk of further morbidity and mortality. HAART results in a rapid decline of viral load and an initial increase of peripheral CD4 count, however little is known on the effect of HAART in regulation of coreceptor expression, immune activation status and CD4 T cell subset distribution in HIV infection and HIV/TB coinfection. This study is a cross-sectional analysis of coreceptor expression, immune activation status and CD4 T cell subpopulation distribution in South African HIV and HIV/TB coinfected patients before and after ARV. A total of 137 South African individuals were investigated, comprising 15 healthy normal donors (healthy subgroup), 10 patients with active pulmonary tuberculosis (PTB subgroup), 33 HIV-1 positive patients without active PTB (HIV subgroup), 23 positive patients with active PTB (HIV/PTB subgroup), 36 HIV-1 positive patients on ARV (HIV on ARV subgroup) and 20 HIV-1 positive patients with active PTB on ARV (HIV/PTB on ARV subgroup). CD4 absolute count and plasma viral load were determined for all donors. Freshly isolated PBMC were classified by flow cytometry into the following CD4+ T lymphocyte subsets: naïve (CD45+, CD27+), effector memory (CD45-, CD27-), central memory (CD45-, CD27+), and effector (CD45+, CD27-). Coreceptor expression and activation status was assessed by CCR5, CXCR4 and CD38 expression on CD4 T cell subsets. HIV, TB and HIV/TB coinfection was associated with a decrease in percentage CCR5+ T cells as compared to healthy controls, with the HIV/TB group showing the most extensive decrease. In treatment naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 as determined by mean fluorescence intensity in HIV/TB co-infection compared to HIV infection alone. The percentage of antigen-experienced cells was higher in the HIV/TB co-infected group compared to the HIV group. The percentage of naïve T cells was decreased in both the HIV infected and the HIV/TB co-infected groups compared to healthy controls. HIV patients with more than 6 months of ARV showed decreased CCR5 and CD38 surface level expression in the HIV and the HIV/ TB co-infected subgroups. An increased percentage of naïve T cells was observed in the HIV infected subgroup, but not in the HIV/TB subgroup, similarly, a decreased percentage of antigen-experienced cells was observed in the HIV subgroup, but not in the HIV/TB co-infected subgroup. A positive correlation was found between CCR5 and CD38 expression, and CXCR4 and CD38 expression (Spearman coefficient of correlation respectively: r=0.59, p<0.001 and r=0.55, p<0.001). Furthermore we found plasma viral load positively associated with CD38 expression (r=0.31, p<0.001) and percentage activated CCR5+ expressing CD4 T cells positively related to viral load (r=0.31, p<0.001). Percentage naïve CD4 T cells was positively associated with CD4 count (r=0.60, p<0.001) and negatively correlated to viral load (r=-0.42, p<0.001). These results indicate that TB coinfection exacerbates certain aspects of dysregulation of CD4 T cell homeostasis and activation caused by HIV infection. In addition, ARV-associated decrease in coreceptor expression, immune activation status and a normalisation of CD4 T cell subset distribution was observed in HIV infected individuals, but not in HIV/TB coinfection. Despite viral suppression after ARV treatment, the decline in the immune activation marker CD38 and coreceptor CCR5 expression, increase in percentage naïve CD4 T cells and decrease of antigen-experienced cells did not reach the levels displayed in the healthy control group. This may indicate that ongoing (albeit reduced) T cell immune activation may occur in the presence of ARV. Further longitudinal studies are needed to closely monitor immune activation during ARV treatment. This study highlighted an association of TB disease with immune activation in HIV infection, the importance of T-cell activation in HIV pathogenesis and its impact on ARV treatment. Further studies are needed to identify causative factors that may lead to a persistent immune activation status during ARV treatment, and how TB coinfection confounds normal responses to ARV.
AFRIKAANSE OPSOMMING: In 2007 was ongeveer 2.1 miljoen sterftes wêreldwyd veroorsaak deur VIGS; ongeveer 70% in Sub-Sahara Afrika. CD4 T selle is die hoof teiken van MIV, aangesien dit die primêre CD4 reseptor, sowel as een of beide van die vernaamste chemokien koreseptore CCR5 en CXCR4 vrystel. Hierdie koreseptore speel ‘n prominente rol wanneer die MIV die sel binnedring, asook tydens MIV oordrag en verloop van die siekte. Dit word ook deur verskillende fraksies van CD4 T selle vrygestel. Gelyktydige TB infeksie mag immuunaktivering in vivo verhoog en dus die siekeproses versnel. MIV het ‘n groot uitdaging geword in die beheer van TB in Afrika. Bekendstelling van HAART het die ontwikkeling van VIGS vertraag, asook die risiko van verdere morbiditeit en mortaliteit. HAART veroorsaak ‘n vinnige afname in virale lading ‘n toename in CD4 telling, hoewel die spesifieke invloed van HAART op die regulering van koreseptor vrystelling, immuunaktivering en verspreiding van CD4 fraksies in MIV en MIV/TB infeksies nog onduidelik is. Hierdie studie het gepoog om koreseptor vrystelling, immuunaktiveringstatus en die verspreiding van CD4 subpopulasies in pasiënte met MIV en MIV/TB voor en na ARV behandeling te ondersoek. ‘n Totaal van 137 Suid-Afrikaanse individue is ondersoek en die studiegroep het bestaan uit 15 normale persone (gesonde subgroep), 10 pasiënte met aktiewe pulmonale TB (PTB subgroup), 33 MIV positiewe pasiënte sonder PTB (MIV subgroep), 23 MIV positiewe pasiënte met aktiewe PTB (MIV/PTB subgroep), 36 MIV positiewe pasiënte op ARV (MIV op ARV subgroep) en 20 MIV positiewe pasiënte met aktiewe PTB op ARV (MIV/PTB op ARV subgroep). Absolute CD4 telling en virale ladings was bepaal vir alle deelnemers. Vars geïsoleerde perifere bloed mononukleêre selle is geklassifiseer deur middel van vloeisitometrie as die volgende CD4 T limfosiet subgroepe: naïewe selle (CD45+, CD27+), effektor geheueselle (CD45-, CD27-), sentrale geheueselle (CD45-, CD27+), en effektor selle (CD45+, CD27-). Koreseptor vrystelling en aktivering was beoordeel volgens CCR5, CXCR4 en CD38 vrystelling op CD4 T sel subgroepe. HIV, TB en MIV/TB ko-infeksie is geassosieer met ‘n afname in die persentasie CCR5+ T selle, vergeleke met gesonde kontroles, waar die MIV/TB subgroep die grootste afname getoon het. In onbehandelde pasiënte het die CD4 T selle verhoogde vrystelling van CCR5 en CD38 op die oppervlakte getoon en dit is bevestig deur die gemiddelde fluoresserende vii intensiteit in die MIV/TB subgroep vergeleke met die subgroep met slegs MIV. Die MIV/TB subgroep het verder ook ‘n verhoogde persentasie totale geheue T selle getoon vergeleke met die MIV subgroep. Die persentasie naïewe T selle was egter verlaag in beide die MIV en MIV/TB subgroepe vergeleke met normale kontroles. MIV pasiënte wat langer as 6 maande op ARV behandeling was in beide die MIV en MIV/TB subgroepe, het ‘n verlaagde vrystelling van CCR5 en CD38 op die oppervlakte van die CD4 selle getoon. ‘n Verhoogde persentasie naïewe T selle het in die MIV subgroep voorgekom, maar nie in die MIV/TB subgroup nie. ‘n Soortgelyke tendens is gevind waar die persentasie totale geheueselle verlaag was in die MIV subgroep, maar nie in die MIV/TB subgroep nie. ‘n Positiewe korrelasie is gevind tussen CCR5 en CD38 vrystelling, asook CXCR4 en CD38 vrystelling (Spearman korrelasie koëffisiënt: r=0.59, p<0.001 en r=0.55, p<0.001 onderskeidelik). Verder het die plasma virale lading ‘n positiewe assosiasie getoon met CD38 vrystelling (r=0.31, p<0.001) en die persentasie geaktiveerde CCR5+ vrystellende CD4 T selle met virale lading (r=0.31, p<0.001). Die persentasie naïewe CD4 T selle het ‘n positiewe assosiasie getoon met CD4 telling (r=0.60, p<0.001) en ‘n negatiewe korrelasie met virale lading (r=-0.42, p<0.001). Volgens hierdie resultate vererger TB ko-infeksie sekere aspekte van die disregulasie van CD4 T selhomeostase en aktivering as gevolg van MIV infeksie. Verder kon ‘n ARVgeassosieerde afname in koreseptor vrystelling, immuunaktivering en normalisering van CD4 T sel fraksies bespeur word in die MIV subgroep, maar nie in die MIV/TB subgroep nie. Ten spyte van virale onderdrukking veroorsaak deur ARV behandeling, het die afname in die immuunmerker CD38 en koreseptor CCR5, toename in die persentasie naïewe CD4 selle en afname in totale geheue CD4 T selle nie die vlakke van die normale kontrolegroep bereik nie. Dit is moontlik dat volgehoue verlaagde T sel immuunaktivering nog steeds mag plaasvind in die teenwoordigheid van ARV. Verdere longitudinale studies is nodig om immuunaktivering tydens ARV behandeling te monitor. Hierdie studie het die belangrikheid van T sel aktivering in MIV patogenese en dit impak daarvan op ARV behandeling beklemtoon. Verdere studies is nodig om moontlike oorsake of bydraende faktore te identifiseer wat tot volgehoue immuunaktivering tydens ARV behandeling kan lei, asook tot mate waartoe TB ko-infeksie kan inmeng met die normale werking van ARV behandeling.
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Ajudua, Febisola Ibilola. "Adherence to antiretroviral therapy at the Dora Nginza Hospital adult wellness clinic, Port Elizabeth, South Africa." Thesis, Stellenbosch : University of Stellenbosch, 2015. http://hdl.handle.net/10019.1/97197.
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Thesis (MFamMed)--Stellenbosch University, 2015.ENGLISH SUMMARY: Background: Sub Saharan Africa is home to approximately two thirds of the world’s population of HIV positive individuals. In view of the socioeconomic challenges of the region governments have provided antiretroviral therapy free to improve chances of survival among patients. However, adherence to antiretroviral therapy is recognised as more important in predicting patient survival. Aim: The study aimed to describe the prevailing factors that influence adherence to antiretroviral therapy. Methods: The study design was carried out using three methods of data collection. Focus group discussions, semi structured interviews and a questionnaire format. Setting: This study has been conducted among adult patients attending the Dora Nginza Hospital Adult wellness clinic. Results: The methods highlighted factors that influence antiretroviral therapy revealing psychosocial factors – lack of family support, not wanting to take medicines in front of people outside the home; patient factors – co morbidities that disturb patient adherence to therapy, a lack of trust in the patient-care giver relationship, fear of the drug side effects; socioeconomic factors – patients’ inability to afford food or transport costs to clinic appointments. In the semi structured interviews, 25% of patients self reported on poor adherence while in the questionnaire 5% of patients reported poor adherence. In assessing the effect of adherence to therapy on CD4 count and viral load there was a general increase in CD 4 count and a drop in viral load indicating clinical improvement in patients on therapy. Recommendation: There is a need for clinicians developing a health relationship with patients to facilitate adherence. The interventions designed to help patients in adherence to therapy should involve the patients in question in the designing of these interventions. Conclusion: Adherence monitoring is an important aspect of managing patients on antiretroviral therapy. The factors highlighted are similar to findings of other studies in similar contexts i.e. resource poor settings.
AFRIKAANSE OPSOMMING: Opsomming nie beskikbaar.
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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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Chilufya, Patrick Mukuka. "Impact of antiretroviral therapy on risky sexual behaviour in people living with HIV and AIDS (PLWHA) in Lusaka District of Zambia." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97951.
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Thesis (MPhil)--Stellenbosch University, 2015.ENGLISH ABSTRACT: The aim of the study was to investigate to what extent the availability of antiretroviral treatment has influenced sexual risk behavior practices in people living with HIV and AIDS (PLWHA) in order to provide suggestions to improve HIV prevention messages. The study was conducted among adult HIV patients on ART aged 18 and above and affiliated to the Network of Zambian People Living with HIV/AIDS (NZP+) in Lusaka District. A purposive sampling method was used to select study units and a sample of 40 was selected. Data was collected from participants using a self-administered questionnaire. SPSS version 20 software computer package was used to analyze data. Chi- square was used to measure associations between dependent variables (risky sexual behavior and initiation of ART) and the independent variable (duration of time on ART). With the confidence interval set at 95%, the P value was used to ascertain the degree of significance by using the decision rule which rejects the null hypothesis if P value is equal or less than 0.05. The findings revealed that the participant's mean age was 2.8 ± 1.3 SD. More than half (68%, n=27) of the participants had adequate knowledge on HIV prevention while 90% (n=36) of participants had a good (positive) attitude towards ART. 82.5% (n=33) of the participants on ART had sexual intercourse in the last 6 month, and 21.2% (n=7) of these did not use a condom for secondary prevention. There was no significant correlation between being on ART and having sexual intercourse, condom usage or number of sexual partners OR (P value of 0.45 and 0.85), (P values 0.37 and 0.5) and (P value 0.34 and 0.57) respectively. In multivariable analysis, the majority of the respondents (35.5%, n=11) indicated that continued sensitization would improve HIV prevention messages to support communities affected. Few (29%, n=9) stated that: "promoting abstinence among the youths or use of a condom for those that are sexually active and intensifying VCT campaign would reduce HIV transmission" and 7% (n=2) of the respondents suggested that; "involving the families and communities affected, civic, religious, and traditional leaders to educate both the young and adult citizens in schools, colleges and churches to support PLWH and fight against HIV-related stigma and discrimination. Stellenbosch University https://scholar.sun.ac.za iii A significant association was not found between an increase in risky sexual behavior or an upsurge in the occurrence of unprotected sex, initiation of ART and duration of being on ART. The majority (83%, n=15) of the respondents on ART for less than sixty months had protected sexual intercourse and 73% (n=11) on ART for sixty months and above also used protection. This association was statistically not significant (Chi-square value 2.95. P value > 0.05). However; other studies need to explore these subjective interpretations further.
AFRIKAANSE OPSOMMING: Nie beskikbaar
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Ramela, Thato. "An illustrated information leaflet for low-literate HIV/AIDS patients on antiretroviral therapy : design, development and evaluation." Thesis, Rhodes University, 2009. http://hdl.handle.net/10962/d1007563.
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South Africa's HIV prevalence rate is estimated to be 5.7 million and at the end of2007 a total of 45845 HIV/AIDS adult patients were taking antiretroviral therapy (ART). The global incidence of HIV/AIDS has been slowly decreasing over the years but is still widespread. This disease is still more prevalent in sub-Saharan Africa than in other parts of the world, with more than 60% people living with HIV/AIDS. Highly active antiretroviral therapy (HAART), the treatment of choice, slows the progression of the human immunovirus but demands a high adherence rate in excess of 95%. Patients who are poorly informed about antiretrovirals (ARVs) and misunderstand medicine-taking instructions or experience unexpected side effects may interrupt therapy, predisposing them to the development of resistance. Such patients need information but, given the poor literacy skills prevalent in South Africa, written information is often not fully comprehended and is often written at too high a reading level. The objectives of this research project were to design, modify and evaluate HIV / AIDS patient education materials for low-literate isiXhosa speaking adults residing in Grahamstown and to examine their impact on the understanding of various aspects of the disease and its treatment. Pictograms illustrating common side effects of ARVs (e.g. stavudine, efavirenz, lamivudine), as well as various sources 'for purchasing nonprescription medicines, storage and medicine-taking instructions were designed and evaluated both qualitatively, using group discussions, and quantitatively through individual interviews where interpretation of the pictograms was assessed. These pictograms were incorporated in a patient information leaflet (PIL) which had been specifically designed for people with limited reading skills and was a simple document containing the minimum of essential text. A previously developed PIL was modified in collaboration with the target population and two versions were produced, one incorporating pictograms illustrating side effects, the other with none. Pictograms were used in both to illustrate other medicine-taking instructions. The PILs were tested objectively to assess the readability, format, content, and general design. They were translated into isiXhosa prior to being qualitatively and quantitatively evaluated in a low-literate isiXhosa speaking population. Understanding of the PILs was assessed by asking a series of questions about the PIL content. Participant opinion of the readability and appearance of the PIL was recorded. The relationship between PIL understanding and selected demographic variables was investigated. Findings from this study illustrated that well designed pictograms assist in the location of information in written leaflets and they may enhance understanding of the information. It was further demonstrated that education influences total understanding of PIL content thus emphasizing the need for tailor-written information in accordance with the education level of the target population. A desire to receive PILs incorporating pictograms was expressed by the majority of participants. Collaboration with the intended target population is essential to design culturally acceptable, easily interpreted pictograms and to produce user-friendly, easy-to-read, comprehensible patient education materials. The rigorous, iterative design, modification and testing process described in this study is one that should be adopted in producing all health-related education materials.
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Maseko, Phiri Thabiso. "Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71845.
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Thesis (MSc)--Stellenbosch University, 2012.Background: While Selection of reverse transcriptase (RT) mutation has been reported frequently, protease (PR) mutations on antiretroviral therapy (ART) including boosted Protease inhibitor (PI) have not been reported as much in Zambia. Affordable in-house genotyping assays can been used to expand the number of patients receiving drug resistance geno-typing, which can aid in determining prevalence of RT/PI emerging mutations. Methods: A previously published drug resistance genotyping assay was modified and used to genotype RT and PR genes. 19 patients virologically failing first-line regimen and 24 failing second-line regimen were studied to determine resistance patterns. Virological failure was defined as failing to maintain <1000 copies/mL during ART. Only major and minor RT and PR mutations (IAS-USA 2010) were considered for analysis. The in-house assay was validated by comparing sequence data of 7 previously ViroSeq tested samples and 5 randomly selected samples to determine reproducibility. Results: The in-house assay efficiently amplified all 12 validation samples with the lowest sample scoring 99.4% sequence homology. The most common RT mutation was M184V (79% n=19) and (71% n=24) first and second-line respectively. No significant differences were reported in all the other RT mutations between first-line and secondline regimens. Drug resistant PI mutations (I54V, M46I and V82A all present 20.8%) were only found in the second-line regimen and were insignificant, p= 0.0562. Conclusion: The in-house assays can be used as alternatives for commercial kits to genotype HIV-1C in Zambia without compromising test quality. The insignificant PI drug resistant mutations which were found, despite virological failure in patients, could indicate a possibility of other mutations within the HIV-1 genome that could reduce PI susceptibility.
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Buriti, Ana Karina Lima. "HIV/AIDS e suas repercussões na audição em crianças." Universidade Federal da Paraíba, 2012. http://tede.biblioteca.ufpb.br:8080/handle/tede/5083.
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Acquired immunodeficiency syndrome (AIDS), transmitted by Human Immunodeficiency Vírus (HIV) it attacks the immune system, which may cause adverse effects on the general state of health, and in particular, the hearing health. The objective of this study was to evaluate the hearing of children with HIV/AIDS and to assess the association of audiological findings in children with HIV/AIDS, relating them to the viral load, the opportunistic diseases and to antiretroviral treatment (TARV) instituted. We analyzed 23 children with HIV/AIDS that were followed at two specialized care services (SCS). Those responsible for the children responded to a questionnaire that included data on the clinical situation and the hearing health of children, which was subsequently complemented by information contained in medical records. Then, the external acoustic meatus was inspected and where necessary, the children were referred to the ent propitiate the realization of the audiological exams. The audiological evaluation was composed by examination of audiometry and immitanciometry (tympanometry and stapedial reflexes). For descriptive analysis of the data was used to the technique of inferential statistics, using Fisher's exact test, when the conditions for use of the test thur-square has not been verified. They were complied with the guidelines for research involving human beings contained in Resolution CNS N° 196/1996. There was an occurrence of hearing loss by ear in 84.8 % of the children analyzed, prevailing a percentage of 76.9 % of hearing loss discrete and 67.4 % for tympanometry curve type B. The otologic manifestations were observed in 65.2 % of the children, with the ear pain to the highest occurrence (66.7 %), there was no significant association with hearing loss (p=0.001). In relation to the association of hearing loss with the causal factor, there was no statistically significant association with the use of anti-retroviral therapy (p=0.031) and with the otitis (p=0.003), not showing for the variables viral load and the number of opportunistic diseases (p>0.05). The study showed the presence of hearing loss in children with HIV/AIDS, associated with the use of TARV and the otitis, but possibly not related solely to these, suggesting risks of damage to the linguistic development of children. The auditory follow in children with HIV/AIDS is important to diagnose and intervene as soon as possible on the possible causal factors of hearing loss, in order to preserve the hearing and to promote a development appropriate language, thus reducing the difficulties in the process of learning, education and social inclusion.
A Síndrome da Imunodeficiência Adquirida (AIDS) transmitida pelo Human Immunodeficiency Vírus (HIV) ataca o sistema imunológico, podendo causar repercussões sobre o estado geral de saúde e, de modo particular, à saúde auditiva. Objetivou-se avaliar a audição de crianças com HIV/AIDS e analisar a associação dos achados audiológicos em crianças com HIV/AIDS, relacionando-os à carga viral, às doenças oportunistas e ao tratamento antirretroviral (TARV) instituído. Foram analisadas 23 crianças com HIV/AIDS que estavam em acompanhamento em dois serviços de atendimento especializado (SAE). Os responsáveis pelas crianças responderam um questionário que continha dados sobre a situação clínica e a saúde auditiva das crianças, o qual foi posteriormente complementado por informações contidas em prontuário. Em seguida, foi realizada a inspeção do meato acústico externo e, quando necessário, as crianças foram encaminhadas ao otorrinolarigologista para propiciar a realização dos exames audiológicos. A avaliação audiológica foi composta pelo exame de audiometria tonal e imitanciometria (timpanometria e reflexos estapedianos). Para análise descritiva dos dados foi utilizada a técnica de estatística inferencial, através do teste Exato de Fisher, quando as condições para utilização do teste Qui-quadrado não foram verificadas. Foram respeitadas as orientações para pesquisa em seres humanos contidas na Resolução CNE N° 196/1996. Observou-se uma ocorrência de perdas auditivas por orelha em 84,8% das crianças analisadas, prevalecendo um percentual de 76,9% de perdas auditivas discretas e 67,4% para timpanometria de curva tipo B. As manifestações otológicas foram observadas em 65,2% das crianças, sendo a otalgia a de maior ocorrência (66,7%), havendo associação significativa desta com a perda auditiva (p=0,001). Em relação à correlação da perda auditiva ao fator causal, ocorreu associação estatisticamente significativa com o uso da terapia antirretroviral (p=0,031) e com a otite (p=0,003), não apresentando para as variáveis carga viral e o conjunto das doenças oportunistas (p>0,05). O estudo evidenciou a presença de perda auditiva nas crianças com HIV/AIDS, associada ao uso da TARV e da otite, mas possivelmente não relacionados exclusivamente a estes, sugerindo riscos de prejuízos para o desenvolvimento linguístico das crianças. O acompanhamento auditivo em crianças com HIV/AIDS é importante para diagnosticar e intervir o mais cedo possível sobre os possíveis fatores causais de perdas auditivas, a fim de preservar a audição e favorecer um desenvolvimento linguístico adequado, diminuindo as dificuldades no processo de aprendizagem, educação e inclusão social.
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Chinkubala, Lontia. "To investigate the extent to which under-five HIV positive children access Antiretroviral Therapy (ART) : a case of Siavonga District of Southern Province of Zambia." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97087.
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Thesis (MPhil)--Stellenbosch University, 2015.ENGLISH ABSTRACT: The impact of HIV/AIDS has affected all categories of people in society, including children under the age of five. This segment of the population depends entirely on adults and older children in order for them to survive. This research endeavoured to investigate the extent to which under-five HIV positive children access ART in Siavonga District in the Southern Province of Zambia. The necessity of such information for all cannot be over-emphasised as this category of the population under study is among the most neglected when it comes to issues of HIV/AIDS. Under-five HIV positive children need special attention in order for them to enjoy their right to survival and development. In terms of methodology, the research took an interpretive approach as it employed the qualitative methodology in its endeavours, in order to get an in-depth understanding of people’s views on the topic under research. Different interview schedules were used to collect data from community members, Community Health Workers (CHW), Home-based Care Providers (HBCP), staff of the Ministry of Health and District AIDS Task Force (DATF). The findings of this research addressed all the objectives but one. This research revealed that almost all the community members in Siavonga District had general knowledge about HIV/AIDS and the need for under-five HIV positive children accessing antiretroviral therapy. However, their attitudes and practices varied when it came to the application of this knowledge. According to respondents, the major challenges that under-five HIV positive children were facing when it came to accessing ART were as follows: food insecurity, followed by access to health facilities and social matters. Others included stigma and discrimination, long distances to health facilities, inadequate disposable income at household level and negative attitudes by some people who think that it is a waste of time and resources to give too much attention, including ART to under-five HIV positive children whom according to them will die soon. However, the majority of respondents indicated that there was need to accept these children like any other as they too had the right to live; hence, they needed care and support which included facilitating their access to ART. This research was an eye opener to all duty bearers to recognize and acknowledge the importance of under-five HIV positive children’s access to ART. This will contribute towards enhancing the will to step up efforts for this intervention. From the findings, it is evident that there is need for income generating activities to provide disposable income to people of Siavonga District so that they give appropriate support, particularly to children who are infected or affected by HIV/AIDS. Furthermore, more resources are required from NGOs, government and other stakeholders to enhance not only sensitization on the importance of the target population’s access to ART, but also provision of these ART services. All relevant stakeholders should heed the call to aggregate information for under-five HIV positive children in question so as to specially target interventions accordingly.
AFRIKAANSE OPSOMMING: Die impak van MIV/Vigs raak alle kategoriee van mense in die samelewing, insluitende kinders jonger as vyf jaar oud. Die segment van die bevolking is heeltemal afhanklik van volwassenes en ouer kinders om te oorleef. Hierdie navorsing poog om die omvang van kinders jonger as vyf, wie MIV positief is, se toegang tot antiretrovirale terapie (ART) in die Siavonga Distrik van die suidelike provinsie van Zambia te ondersoek. Die noodsaaklikheid van sodanige inligting vir alle sektore in die samelewing kan nie oorbeklemtoon word nie, aangesien hierdie kategorie van die bevolking een van die mees verwaarloosde is wanneer dit kom by MIV/Vigs verwante kwessies. Kinders jonger as vyf wie MIV positief is, moet spesiale aandag ontvang sodat hulle reg op oorlewing en ontwikkeling kan geskied. In terme van die metodologie het die navorsing ‘n beskrywende benadering gevolg om die kwalitatiewe metode in sy poging, ten einde ‘n in-diepte begrip van mense se standpunte oor die onderwerp onder navorsing te kry. Verskillende onderhoude is gebruik om data in te samel van gemeenskapslede, gesondheidswerkers in die gemenskap, tuisversorgers, personeel van die Ministerie van Gesondheid en Distriks vigs-taakspan. Die bevindinge van hierdie navorsing het al die doelwitte, behalwe een, aangespreek. Die navorsing het getoon dat byna al die gemeenskapslede in Siavonga Distrik algemene kennis het oor MIV/Vigs en die behoefte van kinders jonger as vyf se toegang tot ART. Hul houdings en praktyke verskil egter in die toepassing van hierdie kennis. Volgens die respondente is die grootste uitdagings wat kinders jonger as vyf ondervind wanneer dit kom by toegang tot ART is voedselonsekerheid, gevolg deur toegang tot gesondheidsfasiliteite en sosiale aangeleenthede. Ander sluit in stigma, diskriminasie, lang afstande na gesondheidsfasiliteite, onvoldoende besteebare inkomste op huishoudelike vlak en negatiewe houdings van sommige mense wat dink dat dit ‘n vermorsing van tyd en hulpbronne is om aan kinders jonger as vyf te spandeer, aangesien, die kinders in elk geval (volgens hulle) binnekort sal sterf.Die meerderheid van die respondente het aangedui dat dit nodig is om hierdie kinders soos enige ander kind te aanvaar en dat hulle ook die reg het om te leef: daarom dat hulle sorg en ondersteuning benodig, wat die fasilitering van hul toegang tot ART insluit. Hierdie navorsing het weer die klem geplaas op die belangrikheid van kinders jonger as vyf se toegang tot ART. Dit is duidelik dat daar ‘n behoefte is aan inkomste-genererende aktiwiteite en om besteebare inkomste aan die mense van Siavonga Distrik te voorsien, sodat hulle toepaslike ondersteuning kan bied, veral aan kinders wat deur MIV/Vigs geraak word. Verder is meer hulpbronne nodig van nie-regeringsorganisasies, die regering en ander belanghebbendes, nie net om die belangrikheid van die teikenbevolking se toegang tot ART nie, maar ook vir voorsiening van hierdie ATR dienste.
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Jackson, Dawne Shirley. "The experiences of people living with HIV-AIDS with regard to the comprehensive antiretroviral therapy management received from registered nurses at selected public primary heathcare clinics in Nelson Mandela Bay." Thesis, Nelson Mandela Metropolitan University, 2009. http://hdl.handle.net/10948/1253.
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Currently South Africa has the highest number of persons living with HIV-AIDS (PLWAs) in the world. Focus-group discussions conducted by Moon (2005:3) in the Eastern Cape indicated that people may not want to get tested for HIV or to access antiretroviral therapy (ART) for fear of disclosure of their HIV-positive status and of stigmatization. These findings prompted the researcher to conduct a study in this field. The objectives of this study are to explore and describe the experiences of PLWAs with regard to the comprehensive ART management received from registered nurses at selected public primary healthcare clinics in Nelson Mandela Bay; and to develop guidelines for registered nurses that could facilitate them in rendering appropriate comprehensive ART management. The research study is based on a qualitative, explorative, descriptive, phenomenological and contextual research design. The research population comprised of HIV-positive patients who received treatment at the selected public primary healthcare clinics. Criterion-based, purposive sampling was used to select participants for the interviews. Ten in-depth unstructured interviews were conducted. Data was then transcribed and coded. One central theme identified the fact that PLWAs experienced both positive and negative experiences at the clinics. The main findings of this research included evidence of various forms of stigma experienced by the PLWAs; distrust of the lay health counselors; but also that PLWAs were generally well-treated and satisfied with the service they had received. Broad guidelines for registered nurses was formulated that could facilitate them in rendering appropriate comprehensive ART management. The study concludes with recommendations made with regards to the areas of nursing practice, education and research. Throughout the study the researcher abided by the ethical considerations. The aspects of trustworthiness implemented in this study, included dependability, credibility, transferability and confirmability (Holloway & Wheeler, 2002:354).
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Mulinge, Florence Muthoni. "Identifying, recording and monitoring adverse effects associated with antriretroviral treatment." Thesis, Nelson Mandela Metropolitan University, 2010. http://hdl.handle.net/10948/1491.
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South Africa, with an estimated 5.7 million people living with HIV, continues to have one of the largest epidemics in the world. The introduction of HAART resulted in prolonged and improved quality of life of many infected patients. However, adverse effects caused by these drugs have become a major concern as they affect the adherence of patients and in some cases even result in the death of patients. Although much research has been and is still being conducted in the area of understanding, preventing and management of ARV adverse effects, there is still a need for patients to be actively involved in self-monitoring for adverse effects. This will assist health care professionals in early identification of serious or potentially serious ARV effects. This study aimed at evaluating the usefulness of strategies developed and employed in the identification, recording and monitoring of adverse effects. The study was conducted with patients receiving HAART from a private HIV and AIDS clinic in Uitenhage, Eastern Cape, South Africa. The research project was approved by the Nelson Mandela Metropolitan University Research and Ethics Committee and the research site. This was an experimental, randomized controlled study carried out over a period of three months (August to October 2009), with a sample size of 160 patients divided into four study groups of 40 patients each. Two monitoring strategies, namely an ARV adverse effect monitoring tool and a patient self-monitoring diary were developed and used for the identification and recording of adverse effects. The four study groups included a Control group, a Tool group, a Diary group and a Tool-Diary group. Willing patients, after signing an informed consent form, were randomly assigned to one of the four groups by participating health care workers at the study site. Data was retrieved from the patient files by the researcher. Descriptive statistical analysis of the findings of the study was conducted using SPSS®. One hundred and forty nine patients were included in the final data analysis. Of the 80 diaries handed out to patients, only 33 were returned and due to errors only 31 were suitable for analysis. Monitoring tools were completed and analysed for 36 patients. The tool was found to be more effective in identifying adverse effects of a physical nature (such as peripheral neuropathy and lipodystrophy) than the usual methods of monitoring employed by the clinic, whilst the diary, used alone, was found to be less effective. Use of the tool and diary combined resulted in the most significant identification and recording of central nervous system related adverse effects and physical adverse effects. However due to the low return rate of the diaries and the majority of the monitoring tool not being completed in many instances the results of this study may not be generalisable. The study results did however suggest that combining the tool and the diary methods of adverse effect identification, yielded the most favourable results when compared to each method alone. This may be attributed to the fact that the tool is useful in identifying objective symptoms and the diaries subjective symptoms, particularly in instances where the patients forget to report their symptoms to healthcare professional whilst at the clinic. The diaries were also reported to improve adherence for more than 90 percentage (n=31) of the patients. More research would be needed in order to verify the exact significance of the tool and the diary in identifying and recording adverse effects and symptoms of adverse effects.
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Desmonde, Sophie. "Care of HIV-infected children before and after antiretroviral therapy initiation in West Africa : contribution towards the development of a multi-state model." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22112/document.
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L’accès aux interventions de la prévention de la transmission mère-enfant (PTME) est limité en Afrique de l’Ouest et les mères infectées continuent de transmettre le virus à leurs enfants. D’importantes questions sur le diagnostic et traitement antirétroviral (TAR) précoce pour les enfants dans les pays à ressources-limitées restent sans réponses. La simulation est un outil utile qui permet d’intégrer toutes les données disponibles et de projeter à long terme les retombées cliniques et économiques de l’infection à VIH pédiatrique et informer les politiques de santé. Bien que les modèles de simulation soient mathématiquement sophistiqués, l’utilité des études basées sur la simulation dépend de la qualité des données de départ. L’objectif principal de ce travail était de fournir des données originales et récentes sur la mortalité, morbidité sévère et recours aux soins chez les enfants infectés par le VIH suivis dans des programmes de soins, avant et après initiation du TAR, dans le contexte du passage à l’échelle du TAR depuis 2004 en Afrique de l’Ouest. Nos résultats font ressortir un taux de mortalité comparable à d’autres études, atteignant 5.5% après 18 mois de suivi dans une cohorte d’enfants non traités par TAR, inclus à un âge médian de 5 ans. Les taux de morbidité sévère étaient élevés chez les enfants non traités mais aussi traités. Nous avons rapportés qu’une hospitalisation sur trois était provoquée par une morbidité infectieuse, évitable par une prophylaxie par cotrimoxazole, une intervention simple et efficace qui n’est toujours pas accessible à tous en Afrique de l’Ouest. Nous avons également observé un recours aux soins importants associé à la morbidité sévère. Cependant, parmi les enfants non traités, comme les traités, le recours aux soins était plus faible parmi les enfants les plus immunodéprimés. Le principal obstacle aux recours aux soins était le coût associé pour les familles. Enfin, les enfants qui initiaient un TAR l’initiaient trop tard, à un stade trop avancée de la maladie pour une restitution immunitaire pour âge ; la probabilité de rattraper une immunité normale était encore plus faible chez les enfants âgés > 5 ans comparé aux plus jeunes. Globalement, ce travail met en avant la nécessité de la mise en place de stratégies de diagnostic et traitement précoce. Optimiser le parcours de soins ainsi implique des interventions à de nombreux niveaux du système de soins et aucune approche unique ne pourra être efficace. De plus, les coûts liés à une prise en charge à vie devront être estimés dans un contexte où le VIH devient une maladie chronique engendrant un plus gros recours aux soins. Intégrer ces données dans un modèle de simulation permettra d’informer les politiques de santé et les soignants afin d’identifier les stratégies les plus efficaces et coût-efficaces pour le diagnostic, le traitement et le suivi à long terme de l’enfant infecté par le VIH dans les pays à ressources limitéesAccess to prevention of mother-to-child transmission (PMTCT) interventions is limited in West Africa and mothers continue to transmit HIV disease to their children. Important questions on early HIV diagnosis and early antiretroviral therapy (ART) for children in resource-limited settings remain unanswered. Computer simulation models can provide helpful information to project long-term patient outcomes and inform health policy. Although simulation models are computationally sophisticated, the usefulness of the results of modelling studies depends on the quality and accuracy of the data on which they are based. The main objective of the following work was to provide accurate and up-to-date data on mortality, severe morbidity and healthcare resource utilisation in HIV-infected children enrolled in care, before and after ART initiation in the context of the access to ART roll-out since 2004 in West Africa. Our findings suggest mortality rates comparable to those of other studies, reaching 5.5% by 18 months of follow-up in children enrolled in cohorts at a median age of 5 years who had not yet initiated ART. Severe morbidity rates were high, in both ART-treated and untreated children. We found that one hospitalisation in three was caused by an infectious disease, avoidable by cotrimoxazole prophylaxis, a simple and efficient intervention that is still not accessible to all in West Africa. We also reported substantial rates of healthcare resource utilisations associated with this severe morbidity. However, in both untreated and ART-treated children, healthcare resource utilisation was lower in the sickest, most immunodeficient children. Access to healthcare remains limited and one of the explanations we put forward are the costs borne by the families. Finally, children on ART remain initiated at a too late stage to be able to restore normal immunity for age; this is even less likely in those who initiated ART after 5 years compared to younger children. Overall, this work underlines the need for an effective early HIV diagnosis and treatment. Optimising this requires interventions at multiple levels of the healthcare system and no single approach is likely to be effective. Furthermore, lifetime treatment costs will need to be assessed as HIV becomes a chronic disease leading to greater healthcare resource utilisation. Integrating these data in computer simulation models will assist healthcare providers and policy-makers to identify the most effective and cost-effective strategies for diagnosis, treatment and monitoring of paediatric HIV in low income countries
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Hattam, Michelle, Brenda Louw, and Salome Geertsema. "Communication Characteristics of the Pediatric HIV and AIDS Population in a Regional Hospital in Gauteng." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/1983.
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HIV (Human Immunodeficiency Virus) has been shown to have significant effects on the development of a child. Currently there is limited South African research regarding HIV and specific characteristics of communication development, and the treatment thereof, in the child infected with HIV. The objective of the research was to describe the communication characteristics of a group of children between the ages of 0 – 5 years infected with HIV at a hospital in Gauteng, South Africa. Clinic records of 203 children infected with HIV between the ages of 0-5 years were reviewed by using a pre-designed checklist within the outreach clinic of a large regional hospital. A questionnaire was completed by 4 medical practitioners working with this population within the outreach clinic. A total of 91.62% of the infected children were diagnosed as being either in Stage III or IV of the disease (according to the WHO classification system of 2005), with all infants presenting with a CD4 count of ≤ 60. The majority (75.37% of the total sample) were receiving HAART (Highly Active Antiretroviral Therapy) at the time the data was collected. According to their medical, social, communication and general development, almost all the children qualified for Early Communication Intervention (ECI) but were not recorded as being referred for such services. A large proportion of the target population presented with opportunistic infections and/or HIV associated conditions. The results highlight the developmental characteristics of children living with HIV, and identify the need for medical doctors and allied health professionals to be provided with relevant literature or training regarding the communication development of children infected with HIV. This will facilitate appropriate referrals for ECI services.
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Ateba, ndongo Francis. "Traitement antirétroviral précoce des nourrissons infectés par le VIH-1 : évaluation de la réponse virologique à court et moyen termes dans un pays d’Afrique sub-saharienne (Cameroun) Could caregiver reporting adherence help detect virological failure in Cameroonian early treated HIV-infected infants Virological response to early combined antiretroviral therapy in HIV-infected infants: evaluation after 2 years of treatment in the PEDIACAM study, Cameroon Low Birth Weight in Perinatally HIV-Exposed Uninfected Infants: Observations in Urban Settings in Cameroon Feasibility of Routinely Offering Early Combined Antiretroviral Therapy to HIV-infected Infants in a Resource-limited Country: The ANRS-PediaCAM Study in Cameroon Different factors associated with loss to follow-up of infants born to HIV-infected or uninfected mothers: observations from the ANRS12140-PEDIACAM study in Cameroon Cytomegalovirus infection in HIV-infected versus non-infected infants and HIV disease progression in Cytomegalovirus infected versus non-infected infants early treated with cART in the ANRS 12140—Pediacam study in Cameroon." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS322.
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Introduction : Depuis 2015, l’OMS recommande la mise sous traitement antirétroviral systématique de tous les enfants infectés par le VIH pour réduire la mortalité précoce liée au VIH chez les nourrissons en l’absence de traitement. Cependant, malgré la disponibilité des tests de dépistage et des médicaments antirétroviraux, l’initiation précoce de ces traitements reste un défi majeur dans les pays à ressources limitées. L’étude ANRS 12140-PEDIACAM est mise en place pour évaluer la faisabilité, l’efficacité et la tolérance en routine du traitement précoce des enfants infectés par le VIH au Cameroun. Objectifs : Les objectifs de cette thèse visaient à étudier la mortalité et la réponse virologique à deux et quatre ans après l’initiation précoce d’un traitement antirétroviral chez les nourrissons infectés par le VIH, et à identifier les facteurs associés à l’obtention et au maintien d’un succès virologique.Méthodes : Les analyses ont porté sur les 190 enfants infectés par le VIH traités avant l’âge de 1 an (médiane=4 mois), inclus dans les trois sites cliniques du Cameroun participant à la cohorte prospective ANRS PEDIACAM initiée en 2007. La première étude a évalué les performances d’un critère basé sur le nombre de doses manquées de traitement rapporté dans un questionnaire d’observance pour dépister un échec virologique chez les nourrissons. La seconde étude portait sur l’estimation de la fréquence et des facteurs associés à l’obtention d’un succès virologique et à la mortalité à deux ans du traitement, utilisant un modèle de survie à risque compétitif. La troisième concernait l’évolution de la réponse virologique entre 2 et 4 ans du traitement selon le statut virologique obtenu à deux ans.Résultats : Les performances du questionnaire d’observance administré à l’accompagnant du nourrisson s’avèrent limitées, avec une valeur prédictive positive trop faible pour dépister un échec virologique en l’absence de charge virale disponible. La mortalité reste élevée à un an du traitement précoce (18,0% [IC95% : 13,0 - 24,0]). Elle est de 3,3% [IC95% : 0,4 - 6,2] entre 2 et 4 ans de traitement. La probabilité d’atteindre au moins un succès virologique avant 2 ans de traitement est de 80% environ, mais celle d’obtenir une suppression virologique maintenue sur au moins 6 mois n’est que de 67% au seuil de 1000 copies/mL, et de 60% au seuil de 400 copies/mL. A 4 ans du traitement initial, la proportion de charge virale contrôlée (<400 copies/mL) est de 75,2% [68,3-82,1]) chez les 144 enfants toujours vivants et suivis, mais pour 12% la charge virale n’a pas été mesurée. Le seul facteur associé significativement au succès virologique dans les 2 ans du traitement initial est la bonne observance rapportée par l’accompagnant. Et seuls un succès virologique obtenu à 2 ans et l’initiation plus récente du traitement antirétroviral sont associés à un charge virale contrôlée à 4 ans.Conclusion : Même si l’intérêt du traitement précoce des nourrissons infectés par le VIH est démontré, le succès virologique à moyen et long terme passe par des stratégies favorisant l’administration quotidienne soutenue des médicaments et une surveillance régulière de la réponse virologique. L’évaluation de l’observance par questionnaire présente une trop faible performance pour dépister précocement un échec virologique. Il est urgent de donner un accès large à la mesure de la charge virale en routine dans les pays à ressources limitées pour dépister rapidement les échecs virologiques chez les enfants recevant un traitement antirétroviralIntroduction: Since 2015, the WHO recommends to start antiretroviral treatment promptly in all HIV-infected children in order to reduce HIV related mortality. Despite increasing availability of screening tests and antiretroviral drugs, early initiation of antiretroviral treatment (ART) remains challenging in resource-limited countries. The ANRS 12140-Pediacam study assesses feasibility, effectiveness and tolerability in routine practice of early treatment of HIV-infected children in Cameroon. Objectives: The objectives of this thesis are to study mortality and virologic response at 2 and 4 years of early initiation of ART in HIV-infected infants and identify factors associated with virologic success. Methods: The analysis concerned the 190 HIV-infected infants who have initiated ART no later than 1 year (median=4 months) and were enrolled in the 3 Cameroon clinical sites involved in the PEDIACAM prospective cohort study since 2007. The first study evaluated adherence criterium based on the number of missed doses as reported through an adherence questionnaire in oerder to detect virologic failure in infants. The second study concerned the evaluation of the frequency and the factors associated with virologic success and mortality at 2 years of ART initiation, using competing risk regression. The third study concerned the evolution of virologic response between 2 and 4 years of QRT initiation depending on virologic status achieved at 2 years of ART initiation. Results: The performances of adherence questionnaire administered to the infant's caregiver are limited; the positive predictive value is low for detecting virologic failure in the absence of viral load exam. The mortality is high at 1 year after early ART initiation (18.0% [95% CI: 13.0 – 24.0]). The mortality is 3.3% [95%CI: 0.4 – 6.2] between 2 and 4 years of ART initiation. The probability of achieving at least once virologic success within the first 2 years of ART is around 80.0% but the probability of maintaining virologic success for at least 6 months was 67% for threshold=1000 copies/mL and 60% for threshold=400 copies/mL. At 4 years of ART initiation, the proportion of virologic success (viral load<400 copies/mL) is 75.2% [68.3-82.1]) in the 144 children still alive among whom viral load exam was not performed. The only factor associated with virologic success at 2 years of ART initiation is good adherence as reported by the caregiver. Et seuls un succès virologique obtenu à 2 ans et l’initiation plus récente du traitement antirétroviral sont associés à un charge virale contrôlée à 4 ans.Conclusion: Although the interest of early ART in HIV-infected infants is demonstrated, the mid and long term virologic success pass through strategies enhancing supporting steady and daily administration of drugs and regular monitoring of virologic response. The steady evaluation of adherence as reported by questionnaire has a very low performance for early detecting virologic failure. It is urgent to widely get access to routine viral load exam in resource-limited countries for quickly detecting virologic failures in children receiving antiretroviral treatment
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Schiesari, Júnior Arlindo. "Infecções oportunistas em portadores de HIV/AIDS da Rede Pública de Catanduva, Estado de São Paulo, Brasil." Faculdade de Medicina de São José do Rio Preto, 2010. http://bdtd.famerp.br/handle/tede/140.
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Previous issue date: 2010-11-25Hereby we present the epidemiological and clinical profile of the HIV-infected group before and during the HAART era from a tertiary care hospital catering to a large population from the Southeastern Brazilian region. A retrospective, cross-sectional and descriptive study was carried out, which involved the analysis of the medical records of patients diagnosed with HIV-1/AIDS admitted to Hospital Escola Emílio Carlos, located in the municipality of Catanduva, State of São Paulo, Brazil. In both pre-HAART and HAART periods, HIV-1 infection was more prevalent in men. Heterosexuality and secondary education were the risk facts for acquisition of the disease in the HAART period. Statistically significant association was only observed for co-infection with HIV-1/Hepatitis C in the pre-HAART era and the number of patients with opportunistic illness (OI) was lower in the HAART period. Among all these OI it is worth mentioning pulmonary pneumocystosis, since despite being frequent in the two periods, its occurrence was considerably greater in the pre-HAART era. Concerning the distribution of OI according to the HIV-1 viral load and serial count of T CD4+ lymphocytes, a significant association was observed. The association between the number of deaths by OI and the survival rate of less than 1 year in the HAART period was significant. The clinical and epidemiological picture of a specialized HIV-1/AIDS Center in a municipality in the southeastern region of Brazil is consistent with the current epidemiology of AIDS in the country. In conclusion, our results indicate that the OI are still important causes of morbi-mortality among HIV-1/AIDS infected patients in the municipality of Catanduva, particularly pulmonary pneumocystosis, tuberculosis and cryptococcal meningoencephalitis. We are aware that retrospective studies such as ours, which involve the review of patients medical records, may present some limitations arising from the scarcity or even absence of information.
Nós apresentamos o perfil clínico e epidemiológico de indivíduos portadores do HIV-1 antes e durante a era da terapia antirretroviral altamente ativa (HAART) de um hospital terciário que atende uma grande população da região Sudeste do Brasil. Estudo retrospectivo, transversal e descritivo que envolveu a análise de prontuários dos pacientes diagnosticados com HIV-1/AIDS atendidos no Hospital Escola Emílio Carlos, localizado no município de Catanduva, Estado de São Paulo, Brasil. Em ambos os períodos pré-HAART e HAART, a infecção por HIV-1 foi mais prevalente em homens. Heterossexualidade e nível de escolaridade do ensino médio foram os fatores de risco para aquisição da doença no período HAART. Associação estatisticamente significante foi observada somente para a coinfecção HIV-1/Hepatite C na era pré-HAART e o número de pacientes com infecções oportunistas (IO) foi menor no período HAART. Entre todas estas IO vale à pena mencionar a pneumocistose pulmonar, pois apesar de ser freqüente nos dois períodos, sua ocorrência foi significativamente maior na era pré-HAART. Quanto à distribuição de IO de acordo com a carga viral do HIV-1 e contagem de linfócitos T CD4 +, uma associação significativa foi observada. A associação entre o número de mortes por IO e a taxa de sobrevivência de menos de um ano na era HAART foi significativa. O quadro clínico e epidemiológico de um centro de atendimento especializado em HIV-1/AIDS em um município na região sudeste do Brasil é compatível com a epidemiologia atual da AIDS no país. Em conclusão, nossos resultados indicam que as IO ainda são importantes causas de morbi-mortalidade entre os pacientes infectados por HIV-1/AIDS no município de Catanduva, particularmente a pneumocistose pulmonar, a tuberculose e a meningoencefalite criptococócica. Estamos cientes de que estudos retrospectivos como o nosso, que envolvem a revisão de prontuários médicos, podem apresentar algumas limitações decorrentes da escassez, ou mesmo da ausência de informações.
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Moh, Desmorys Raoul. "Intérêt du traitement antirétroviral précoce chez l’adulte infecté par le VIH en Afrique sub-Saharienne." Thesis, Bordeaux 2, 2012. http://www.theses.fr/2012BOR21996/document.
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Les pays africains au sud du Sahara ont vu leur nombre de patients sous traitement antirétroviral (ARV) croître de façon rapide depuis 2005. Si l’impact individuel et collectif de cette montée en puissance des traitements est positif dans l’ensemble, les défis demeurent nombreux en termes de dépistage, d’observance, d’adhésion aux soins, de résistance aux ARV, de dépendance vis-à-vis des bailleurs de fonds, et de disponibilité des personnels. Dans ce contexte, la question du moment idéal pour proposer le début du traitement ARV doit être abordée de façon médicale individuelle (quel est le rapport bénéfices/risques individuel à débuter à des seuils différents ?), mais également de façon collective en terme de bénéfices et risques pour la communauté, d’organisation des soins, d’analyse médico-économique, de prioritisation et d’équité. Cette thèse, qui est une thèse de recherche clinique, aborde le premier volet de la question, celui des bénéfices et des risques pour l’individu à débuter un traitement plus tôt. Sur ce sujet, le raisonnement a beaucoup évolué au cours des 15 dernières années. Après l’arrivée des multithérapies ARV à la fin des années 1990, la crainte de la toxicité des médicaments a d’abord incité à une approche prudente, et à recommander le seuil de début à 200 CD4/mm3 chez les personnes asymptomatiques. Cette crainte de la toxicité a conduit au début des années 2000 à essayer de pratiquer des « interruptions programmées » d’ARV, pour tenter d’obtenir le maintien au dessus d’un seuil de 200 CD4/mm3, tout en limitant l’exposition aux médicaments. Nous avons participé à un de ces essais d’interruptions programmées en Côte d’Ivoire, au cours duquel nous avons contribué à affiner les connaissances sur la toxicité des ARV (Moh, Antivir Ther 2005). Les essais d’interruptions programmées ont conduit à constater que : (i) les personnes qui interrompaient entre 350 et 250 CD4/mm3 avaient plus de risque de morbidité sévère que celles qui n’interrompaient pas, (ii) les personnes qui débutaient leur premier traitement avant 350 CD4/mm3 avaient moins de risque de morbidité que celles qui débutaient plus tard (Moh, AIDS 2007), et (iii) dans l’essai d’interruption Trivacan réalisé en Côte d’Ivoire, cette morbidité sévère intermédiaire était plus fréquente que dans l’essai SMART réalisé sur d’autres continents, et avait un spectre différent, dominé par la tuberculose et les maladies bactériennes sévères. Les conclusions de ces essais ont donc été que le traitement ARV devait être débuté beaucoup plus tôt que ce qui était auparavant recommandé, et que ceci était probablement encore plus vrai en Afrique sub-Saharienne que dans le reste du monde. En 2008, nous avons lancé en Côte d’Ivoire l’essai Temprano ANRS 12136, dont l’objectif est d’évaluer les bénéfices et risques d’un traitement ARV précoce avec ou sans 6 mois de prophylaxie par isoniazide (INH) chez des adultes infectés par le VIH-1 ayant entre 250 et 800 CD4/mm3. De Mars 2008 à Juillet 2012, 2076 adultes ont été inclus dans l’essai Temprano, dont le suivi se terminera en décembre 2014. L’état du suivi est bon, et les incidences de morbidité et mortalité actuellement constatées sont conformes aux hypothèses du protocole. La pratique de la prophylaxie par INH s’avère bien tolérée, et la procédure choisie par notre équipe (radiographie de thorax systématique et période tampon d’observation de un mois avant le début de l’INH) apporte une grande sécurité de prescription (Moh, Plos One, manuscrit en révision). Notre équipe a traversé une crise politico-militaire au 1er semestre 2011, qui n’a pas eu de retentissement sur la qualité de l’essai en cours. Cette crise a par contre eu des effets délétères pour les patients sous traitement ARV, puisque les échecs virologiques retardés sont significativement associés au fait d’avoir été sous traitement pendant cette période (Moh, manuscrit soumis).The African countries situated in the South of the Sahara have seen their number of patients under antiretroviral therapy (ART) grow rapidly since 2005. If the individual and collective impact of this rise of the treatments is positive overall, challenges remain in terms of screening, compliance, accession to care, resistance to ARTs, dependence on donors, and availability of the staff. In this context, the question of the ideal time to propose initiation of ART must be addressed in the individually medical way (what is the individual benefit-harm ratio to start at different thresholds?) but also collectively in terms of benefits and risks for the community, organization of care, medico-economic analysis, prioritization and equity. This thesis, which is a clinical research thesis, addresses the first part of the question, the benefits and risks for the individual to start treatment earlier. On this subject, the rationale has changed considerably over the past 15 years. After the arrival of ART multitherapy at the end of the 1990s, the fear of drug toxicity first prompted a cautious approach, and to recommend the threshold from beginning to 200 CD4/mm3 in the asymptomatic people. This fear of toxicity led in the early 2000s to try to practice "scheduled interruptions" of ARTs, to try to get the maintenance above a threshold of 200 CD4/mm3, in limiting exposure to the drug. We have participated in one of these trials of interruptions programmed in Côte d'Ivoire, in which we have helped to refine the knowledge on the toxicity of ARTs (Moh, Antivir Ther 2005). Testing scheduled interruptions led to see that: (i) persons who interrupted between 350 and 250 CD4/mm3 had greater risk of severe diseases than those who didn’t interrupt, (ii) persons who started their first treatment prior to 350 CD4/mm3 had less risk of morbidity than those who started later (Moh, 2007 AIDS), and (iii) in trial interruption Trivacan launched in Côte d'Ivoire, this intermediate severe morbidity was more frequent than in the SMART trial carried out on other continents, and had a different spectrum dominated by tuberculosis and severe bacterial diseases. The findings of these trials were that the ART should be started much earlier than was previously recommended, and that this was probably even truer in sub-Saharan Africa than in the rest of the world. In 2008, we launched in Ivory Coast the clinical trial, Temprano ANRS 12136, whose objective is to assess the benefits and risks of early ART with or without 6 months of prophylactic isoniazid (INH) in HIV-1 infected adults with CD4 250 and 800/mm3. From March 2008 to July 2012, 2076 adults were included in the trial Temprano, which follow-up will be completed by December 2014. The state of the follow-up is good, and the impact of morbidity and mortality currently observed are consistent with the assumptions of the Protocol. The practice of INH prophylaxis is well tolerated, and the procedure chosen by our team (systematic chest x-ray and period buffer observation of one month before the beginning of the INH) brings a prescription safety (Moh, Plos One manuscript in review). Our team went through a crisis politico-military 1St half 2011, which had no impact on the quality of the ongoing trial. This crisis has however had deleterious effects for patients under ART, since delayed virological failure are significantly related to the fact of having been under treatment during this period (Moh, submitted manuscript)
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Mogatle, Seloi. "African traditional medicines-antiretroviral drug interactions: the effect of African potato (Hypoxis hemerocallidea) on the pharmacokinetics of efavirenz in humans." Thesis, Rhodes University, 2009. http://hdl.handle.net/10962/d1003251.
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African Potato (Hypoxis hemerocallidea), (AP) is an African traditional medicine (TM) that is commonly used for various nutritional/medicinal purposes and also by people infected with the human immuno deficiency virus HIV and AIDS patients as an immune booster. The use of AP has also been recommended by the former Minister of Health of South Africa for use by HIV positive people. The main phytochemical component of AP is a norlignan glucoside, hypoxoside, and other relatively minor components have also been reported. A recent in vitro study reported the effects of AP extracts, hypoxoside and rooperol (the metabolite of hypoxoside) on human metabolic enzymes such as the cytochrome P450 (CYP450) group of enzymes and also on the transporter protein, p-glycoprotein (P-gp). This research focussed on investigating the clinical significance of those in vitro effects on the pharmacokinetics of efavirenz (EFV) in humans. EFV was chosen as the substrate drug because it is in first-line regimen of treatment of HIV/AIDS in South Africa, and also has been reported to be a substrate for the specific CYP isozymes, 3A4 and 2B6, in common with APs metabolic involvement with 3A4. A high performance liquid chromatography method with ultra-violet detection (HPLC-UV) for the quantitative determination of EFV in plasma was developed and successfully validated according to international standards with good reproducibility, accuracy, recovery, linear response and requisite sensitivity. The preparation of the plasma samples for analysis was effected by using a simple and rapid precipitation method, and the mobile phase consisted of readily available solvents. EFV in plasma samples was found to be stable under the relevant storage conditions studied. The oral dose of AP, administered as a freshly prepared traditional decoction, was standardised based on the hypoxoside content, and the quality of all the AP decoctions was analysed immediately prior to administration, using a validated HPLC-UV method. A single dose, two-phase sequential study was conducted over a period of 31 days in 10 healthy volunteers. The clinical study was approved by the Rhodes University Ethical Standards Committee, and all the participants agreed to the conditions of the study by giving their informed consent. On day 1 of the study, human subjects were administered a 600 mg EFV tablet and blood samples were collected before dosing and at various intervals over a period of 48 hr post dosing. From day 16, a traditionally prepared AP decoction was administered daily at a standardized dose of 15 mg/kg/day per subject until day 30. On day 29, volunteers were administered a single 600 mg dose of EFV as was done on day 1. Plasma samples were harvested immediately after blood sample collection and frozen at -80 ºC until assayed. Geometric mean ratios of relevant pharmacokinetic parameters, Cmax (maximum plasma concentration achieved following dosing) and AUC0-48 (area under the curve of a plot of drug plasma concentrations versus time representing the extent of absorption) of EFV before and after co-administration of 14 successive daily doses of AP were compared and evaluated to determine whether an interaction had occurred. All subjects completed the study and the geometric mean ratios of Cmax and AUC0-48 were 97.30 and 102.82 with corresponding 90% confidence intervals (CIs) of 78.81-120.14% and 89.04-118.80%, respectively. Whereas the acceptance criteria for the ratios of the AUCs fell within the preset 90% CIs indicating no interaction, the Cmax ratios fell outside the limits. Although the protocol was developed in accordance with the United States of America Food & Drug Administration’s Guidance for Drug Interactions, a priori stating that both criteria need to fall within the acceptance limits to indicate no interaction, an argument is presented to waive the Cmax requirement for the declaration of an interaction. As a result, the pharmacokinetic data generated during this study indicated that the effect of AP on the pharmacokinetics of EFV is not clinically significant. Hence, co-administration of AP is unlikely to affect the clinical use of EFV. In summary the objectives of this project were: 1. To develop and validate a suitable HPLC-UV method for the quantitative determination of EFV in plasma. 2. To perform a mini-validation of the determination of hypoxoside for use as a marker in the quality control and standardisation of AP decoctions. 3. To conduct a clinical interaction study in order to determine whether AP affects the pharmacokinetics of EFV following concurrent administration. 4. To apply the validated HPLC-UV method to determine plasma concentrations of EFV in plasma of human subjects. 5. To use appropriate statistical methods and treatments such as a non-compartmental pharmacokinetic analysis to determine the occurrence of an interaction.
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Myburgh, Hanlie. "Treatment through empowerment? : exploring the dynamics of ‘responsibility’ in antiretroviral therapy (ART) in two clinics in the Cape Winelands." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79969.
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Thesis (MA)--Stellenbosch University, 2013.ENGLISH ABSTRACT: This study investigates how the new technology of treatment, i.e. antiretroviral therapy (ART), is incorporated into public health care institutions. The success of this technology ideally relies on the notion of the ‘responsibilised’ patient as one who, simply put, consistently maintains the level of ARV-adherence necessary to suppress the viral load and to avoid drug resistance. The stringent management and continual monitoring of treatment adherence necessary to achieve these outcomes lie beyond the direct control of the health care institution. Given that the institution sees its patients irregularly, a patient’s divergence from treatment guidelines is established only after the fact. The institution takes on a supporting role while it is the patient who, on a day-to-day, dose-by-dose basis manages and monitors themselves, making ART a seemingly individual endeavour and responsibility. This shift in responsibility is compatible with the ‘new contract’ between provider and client, necessitated by ART. Even so, the institution attempts to manipulate the day-to-day behaviours of the patient to conform to those required in order to achieve treatment outcomes. This thesis examines how these different aspects of ART play out within two clinics in the Cape Winelands, and more specifically, the institutional intricacies of managing a disease which requires treatment that is not directly observed.
AFRIKAANSE OPSOMMING: Die studie ondersoek hoe die nuwe tegnologie van behandeling, antiretrovirale behandeling (ARB), in publieke gesondheidsorgklinieke geïntegreer word. Die sukses van hierdie tegnologie hang af van die nosie van die ‘verantwoordelike’ pasiënt wat, eenvoudig gestel, die nodige vlak ARV-gebruik handhaaf om die virale lading te onderdruk en weerstand te voorkom. Die streng kontrole oor die toewyding tot behandeling wat nodig is om hierdie uitkomstes te bereik, lê buite die direkte beheer van die gesondheidsorgkliniek. Aangesien die kliniek sy pasiënte slegs periodiek sien, word ʼn pasiënt se afwyking van behandelingsriglyne eers later gemeet. In hierdie opsig neem die kliniek 'n ondersteunende rol in, terwyl dit die pasiënte is wat op 'n daaglikse, dosis-tot-dosis basis hulself moet handhaaf en monitor. Dit maak ARB 'n oënskynlike individuele onderneming en verantwoordelikheid. Hierdie skuif in verantwoordelikheid is in lyn met die nuwe kontrak tussen die gesondheidsorgdiens en die kliënt, wat deur ARB genoodsaak word. In ieder geval probeer die institusie om die daaglikse gedrag van die pasiënt te manipuleer om te pas by die riglyne wat deur die uitkomstes genoodsaak word. Hierdie tesis ondersoek hoe hierdie verskillende aspekte van ARB binne twee klinieke in die Kaapse Wynland uitspeel, en meer spesifiek, die institusionele bestuur van 'n siekte waarvoor behandeling nie direk geobserveer kan word nie.
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Hermankova, Monika. "HIV-1 persistence under antiretroviral therapy." Available to US Hopkins community, 2002. http://wwwlib.umi.com/dissertations/dlnow/3080676.
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Hotchkiss, Graham. "Towards ribozyme-mediated gene therapy of HIV-1 infections /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4007-X/.
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Duwe, Susanne. "Antiretrovirale Therapie und Resistenz von HIV-1." [S.l.] : [s.n.], 2002. http://www.diss.fu-berlin.de/2003/8/index.html.
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Windsor, Ian William. "HIV-1 protease as a target for antiretroviral therapy." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122533.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019Cataloged from PDF version of thesis.
Includes bibliographical references (pages 395-424).
Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). HIV employs three enzymes in its lifecycle, including a protease that enables maturation of polyprotein precursors. Despite decades of progress studying the lifecycle of HIV and elaboration of therapeutics targeting nearly every aspect of the viral life cycle, a cure remains elusive. Breakthroughs in HIV research have occurred alongside foundational advances of molecular biology, biotechnology, and medicinal chemistry, highlighting the importance revisiting old questions with new approaches. The goal of this thesis is to advance our biochemical knowledge of HIV-I protease and develop novel therapeutics targeting this key viral enzyme. In Chapter 1, I introduce HIV and the role that HIV-1 protease plays in life cycle and current treatment strategies.
In Chapter 2, I describe an assay that enables the determination of sub-picomolar inhibition constants for competitive inhibitors of HIV-1 protease. This advance was made possible by a peptide substrate selected by phage display. I report in Chapter 3 the enhanced hydrogen bonding in the recognition of this peptide by HIV-1 protease as revealed by X-ray crystallography. The mechanism of aspartic proteases, including HIV-1 protease, has been the subject of numerous enzymology studies spanning over half a century. In Chapter 4, I reveal unappreciated non-covalent interactions within substrates of aspartic proteases that assist in catalysis. In addition to biochemical studies, this thesis includes chapters that account the development of novel antivirals. In Chapter 5, I describe the rational drug design of a boronic acid analog of the clinical inhibitor darunavir with improved potency.
A limitation of boronic acids is metabolic instability; in Chapter 6, I reveal an intramolecular protecting group that can confer oxidative stability to boronic acids. Finally, in Chapter 7, I describe an engineering approach to inactivate human RNase 1. The inactivation relies on installing a substrate for HIV- I protease, the cleavage of which unmasks cytotoxic activity. Together these chapters describe new ways forward and novel therapeutics targeting HIV-1 protease. My thesis also includes an Appendix, which describes the elaboration of boronic acid-based covalent pharmacological chaperones of human transthyretin.
by Ian William Windsor.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Chemistry
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Chen, Renxiang. "Studies of HIV-1 mutagenesis during drug therapy and the molecular determinants of HIV-1 variation." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1092663963.
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Thesis (Ph. D.)--Ohio State University, 2004.Document formatted into pages. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 Aug. 16.
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McKenzie, Lauren Clara Browning. "The Effects of Adherence to Antiretroviral Therapy for HIV-1 Infection." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42202.
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The emergence of drug resistance is a serious threat to the long-term virologic success and durability of HIV-1 therapy. Adherence has been shown to be a major determinant of drug resistance; however, each pharmacologic class of antiretroviral drugs has a unique adherence–resistance relationship. We develop an immunological model of the HIV-1 infected human immune system that integrates the unique mechanisms of action of reverse transcriptase and protease inhibiting drugs. A system of impulsive differential equations is used to examine the drug kinetics within CD4⁺ T cells. Stability analysis was preformed to determine the long-term dynamics of the model. Using the endpoints of an impulsive periodic orbit in the drug levels, the maximal length of a drug holiday while avoiding drug resistance is theoretically determined; the minimum number of doses that must be subsequently taken to return to pre-interruption drug levels is also established. Heterogeneity in inter-individual differences on drug-holiday length is explored using sensitivity analysis based on Latin Hypercube Sampling and Partial Rank Correlation Coefficient analysis. Extremely short drug holidays are acceptable, as long as they are followed by a period of strict adherence. Numerical simulations demonstrate that if the drug holiday exceeds these recommendations, the cost in virologic rebound is unacceptably high. These theoretical predictions are in line with clinical results and may also help form the basis of future clinical trials.
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Cheney, Kelly Miriam. "Studies on cellular reservoirs of HIV-1 in patients on antiretroviral therapy / Kelly Miriam Cheney." 2005. http://hdl.handle.net/2440/22239.
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Amendments appended.Bibliography: leaves 140-165.
xi, 165 leaves : ill. ; 30 cm.
Title page, contents and abstract only. The complete thesis in print form is available from the University Library.
Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 2005
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Singh, Michelle. "Pharmaco-immunological-virological dynamics in intrapartum HIV-1 transmission (PIVD study)." Thesis, 2009. http://hdl.handle.net/10413/686.
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Background: Multiple factors contribute to mother-to-child transmission (MTCT) of HIV-1, including virological, obstetric and biological factors. Other possible contributory determinants for high MTCT rates include immunological factors such as host genetics and viral genetic variations. Despite several therapeutic, prophylactic and obstetric interventions to reduce the proportion of infants infected during labour and delivery, mechanisms for intrapartum HIV-1 transmission remain elusive and current interventions, could, therefore remain sub-optimal. Much controversy has surrounded the correlation of HIV-1 RNA (viral load) in the systemic and genital compartments of women. The influence of short-term antiretroviral (ARV) drugs on genital tract HIV-1 is also unclear. At the time the present study was initiated, a regimen of maternal intrapartum and neonatal postpartum single-dose Nevirapine (sdNVP) was the standard of care for the prevention of mother-to-child transmission (PMTCT). In most low and middle-income countries, including South Africa, sdNVP has been documented as effective intrapartum HIV-1 prevention based on plasma pharmacokinetic levels, decreased viral loads (HIV-1 RNA) and reduced rates of intrapartum transmission, yet operational studies continue to report high intrapartum transmission rates despite the administration of sdNVP. As a result perinatal HIV-1 transmission remains a significant public health concern in several African countries. Aim: The primary aim of this study was to describe the pharmacological dynamics of Nevirapine in association with virological and immunological risk factors for intrapartum HIV-1 transmission in a South African PMTCT programme where sdNVP was the standard of care. Methods: Following regulatory approval from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (UKZN), one hundred and twenty pregnant HIV-infected women who received the sdNVP regimen for prevention of mother-to-child HIV-1 transmission were enrolled between April-December 2006 at King Edward VIII Hospital (KEH) in Durban. Blood and cervicovaginal lavage (CVL) samples were collected from women at pre-NVP (during pregnancy) and post-NVP dosing (during labour/delivery). In addition to infant blood sampling at birth (post-NVP), postnatal infants were assessed at four and six weeks postnatally. Pharmacological laboratory investigations involved measurement of NVP drug concentration by Tandem Mass spectrophotometry. Virological investigations comprised HIV-1 RNA (viral load) quantitation, HIV-1 drug resistance testing (HIV-1 transmitting women only) and HIV-1 DNA PCR testing (infants only). Immunological investigations were only undertaken in a selected case-control subset of HIV-1 transmitting women and their infants. In this component, laboratory investigations included the determination of CCL3 and CCL3-L1 gene copy numbers, identification of single nucleotide polymorphisms (SNP’s) and haplotype characterisation of the CCL3 gene. All women were also screened for the presence of sexually transmitted infections (STI’s) during pregnancy. Results: One hundred and twenty women were enrolled onto this study. Of these, 110 women delivered 117 live infants (103 singletons and 7 twin pairs). Twelve (10.9%) women transmitted HIV-1 to their infants, while 95 (86.0%) were classified as non-transmitters. As a result of seven twin deliveries, the infant cohort comprised of 117 infants in total. Following two separate DNA PCR tests, HIV-1 infection was identified in 14 (11.9%) of study infants while the remaining 90 (76.9%) were exposed-uninfected. HIV infection status remained unknown for 13 infants due to infant demise (1.7%), lost to follow-up (7.7%) or study withdrawal (1.7%). During active labour (sampling that was best representative of the intrapartum phase) and within 20 hours of dosing, the median NVP concentration of 1070 ng/ml in the maternal systemic compartment was almost 44 times higher than the NVP levels detected in the genital compartment [24.5 ng/ml] (p < 0.001). NVP drug levels were below the 100 ng/ml therapeutic target in seven (13.7%) of 51 plasma and in all 39 CVL samples. While no significant association was found between NVP concentration in the systemic compartment and HIV-1 transmission (p = 0.4), this association was statistically significant in the genital compartment(p = 0.02). The median plasma NVP level detected among infants at birth was 83 times above the IC50 WT (10 ng/ml) and eight times higher than the 100 ng/ml therapeutic target for NVP. More than 71.0% of the infants achieved NVP drug levels above the therapeutic target. In general, higher levels of HIV-1 RNA (viral load) were observed in maternal plasma when compared to CVL. Following intrapartum sdNVP dosing, reduction in HIV-1 RNA levels did occur, however R80.0% of the women experienced no change to their HIV-1 RNA levels in both systemic and genital compartments during active labour. These findings were further supported by the strong correlation observed when comparing pre and post-NVP HIV-1 RNA levels in both maternal systemic [r = 0.81, p < 0.0001] and genital compartments [r = 0.80, p < 0.0001] during active labour. HIV-1 transmitting women had significantly higher viral loads than their non-transmitting counterparts in systemic and genital compartments, before and after intrapartum sdNVP administration. In terms of perinatal transmission this observation was only statistically significant for plasma (p = 0.02) and not CVL (p = 0.7). Maternal viral load was inversely correlated with maternal CD4 cell counts in both systemic and genital compartments. Almost 40.0% of women in this study had at least one type of STI detected during pregnancy. Maternal STI’s were detected in four (66.6%) intrapartum transmitting women and in 38 (38.8%) of non-transmitting women. No significant association was observed between the presence of maternal STI’s and the risk for intrapartum MTCT (p = 0.2,RR: 2.90, 95% CI: 0.60-15.40). The presence of maternal STI’s was associated with higher median viral loads in both systemic and genital compartments of all women, independent of intrapartum HIV-1 transmission. Despite trial-like conditions and optimal sdNVP dosing, the overall MTCT rate in this exclusively formula-fed cohort was 11.9%, of which 50.0% were in utero and 50.0% were intrapartum HIV-1 transmissions. In utero and intrapartum MTCT rates were 5.9% and 5.9% respectively. Discussion/Conclusion: Detectable CVL HIV-1 RNA that correlated well with plasma HIV-1 RNA, in conjunction with sub-optimal NVP drug concentration in maternal CVL during active labour, suggests that intrapartum HIV-1 infected women continue to act as reservoirs for both vertical and horizontal HIV-1 transmission throughout the duration of pregnancy. These findings confirm that the role of sdNVP in PMTCT was primarily one of infant prophylaxis. This was further supported by relatively unchanged maternal HIV-1 RNA (viral load) during active labour, in both systemic and genital compartments. Early identification of women who need highly active antiretroviral therapy (HAART), and initiation of such therapy as early as possible during pregnancy, not only benefits maternal health but remains the best prophylaxis against mother-to-child HIV-1 transmission. Universal access to HAART and improving strategies to optimize coverage of the current dual ARV regimen sdNVP and Zidovudine for PMTCT remain urgent research priorities in several resource-limited settings. Ongoing STI counseling, intensive screening/testing of women and their partners together promotion of condom usage, safer sex practices and aggressive STI treatment are simple interventions with tremendous impact for PMTCT in resource-limited settings.Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2009.