Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Thematic Paper (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2006. / LICL has E-Thesis 0011 ; please contact computer services. LIRV has E-Thesis 0011 ; please contact circulation services.

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.

Thesis (D.P.H.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed on June 25, 2009). Includes bibliographical references.

Thesis (M.S.)--Ohio University, August, 2003. / Title from PDF t.p. Includes bibliographical references (leaves 93-114)

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

Thesis (MSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Efavirenz is an antiretroviral drug used in the treatment of HIV-positive patients as part of first line triple-highly active antiretroviral therapy. Treatment response varies among individuals and adverse drug reactions tend to occur, as a result of the variation in the rate of efavirenz metabolism among individuals. This is partly caused by genetic variation; therefore the study of genes involved in the metabolism of efavirenz, such as CYP2B6, could potentially enhance treatment success. The effect of CYP2B6 SNP 516G>T (part of the CYP2B6*6 allele) is particularly important, as individuals homozygous for the minor allele of this SNP have significantly increased efavirenz levels. Furthermore, nuclear receptors, specifically constitutive androstane receptor, encoded by NR1I3, and pregnane X receptor, encoded by NR1I2, are involved in the regulation of the genes responsible for efavirenz metabolism and could therefore indirectly influence the pharmacokinetics of efavirenz. The current study identified variants in the NR1I3 and NR1I2 genes through in silico analysis, bi-directional sequencing and literature searches. A total of nine NR1I3 and ten NR1I2 target variants were subsequently genotyped in 132 HIV-positive female patients from the Xhosa and Cape Mixed Ancestry populations. The resulting genotype and allele frequencies were statistically analysed to search for correlations between genetic variations and available efavirenz levels in hair samples, treatment outcome as measured by viral load, and the occurrence of adverse drug reactions. The minor allele of a NR1I2 5’-upstream SNP, rs1523128 (6334A>G), was significantly associated with decreased efavirenz levels. From analysis of the effect of composite SNPs, NR1I3 5’-upstream SNP rs55802895 (258G>A) in conjunction with CYP2B6*6, was significantly associated with efavirenz-levels. It was found that the minor allele of rs55802895 inhibited the effect of CYP2B6*6, resulting in normal efavirenz levels for individuals homozygous for the minor allele of both SNPs. Additionally, when the target NR1I3 and NR1I2 variants were analysed in conjunction with six SNPs from CYP1A2, CYP2A6, CYP3A4 and CYP3A5, 11 compound genotypes were shown to be statistically associated with mean EFV plasma levels. The study emphasises the complexity of efavirenz metabolism, and the importance of transcriptional regulation in xenobiotic metabolism. / AFRIKAANSE OPSOMMING: Efavirenz is ‘n antiretrovirale middel wat gebruik word in die behandeling van HIV-positiewe pasiënte as deel van drievoudige hoogs-aktiewe antiretrovirale terapie. Reaksie op behandeling verskil tussen individue en nadelige newe-effekte, wat veroorsaak word deur die verskil in tempo waarteen efavirenz gemetaboliseer word, neig om voor te kom. Hierdie verskille word gedeeltelik veroorsaak deur genetiese variasie; dus kan die studie van gene betrokke by die metabolisme van efavirenz, soos CYP2B6, moontlik die sukses van behandeling verhoog. Die effek van CYP2B6 SNP 516G>T (deel van die CYP2B6*6-alleel) is veral belangrik, want individue wat homosigoties is vir die minderheids-alleel het betekenisvol hoë efavirenz-vlakke. Nukleêre reseptore, spesifiek konstitutiewe androstane reseptor, deur NR1I3 gekodeer, en pregnane X reseptor, deur NR1I2 gekodeer, is betrokke by die regulering van die gene verantwoordelik vir efavirenz-metabolisme en kan dus die farmakokinetika van efavirenz beïnvloed. Die huidige studie het variante in NR1I3 en NR1I2 identifiseer deur in silico-analise, bi-direksionele volgordebepaling en ’n literatuurstudie. Nege NR1I3 en tien NR1I2-variante in totaal is vervolglik gegenotipeer in 132 HIV-positiewe vroulike pasiënte van Xhosa en Kaapse Gemengde Afkoms populasies. Die gevolglike genotipe- en alleelfrekwensies is statisties geanaliseer om vir korrelasies tussen genetiese variasies en beskikbare efavirenz-vlakke in haarmonsters, uitkoms van behandeling gemeet in virale lading en die voorkoms van nadelige newe-effekte te soek. Daar is gevind dat die minderheids-alleel van ’n NR1I2 5’-stroomop SNP, rs1523128 (6334A>G), betekenisvol geassosieer is met ’n daling in efavirenz-vlakke. Vanuit die saamgestelde SNPs, is die NR1I3 5’-stroomop SNP rs55802895 (258G>A), tesame met CYP2B6*6, betekenisvol geassosieer met efavirenz-vlakke. Daar is gevind dat die minderheids-alleel van rs55802895 die effek van CYP2B6*6 demp, en gevolglik normale efavirenz-vlakke in individue homosigoties vir die minderheids-allele van albei SNPs veroorsaak. Addisioneel is die teiken NR1I3 en NR1I2 variante gemeenskaplik met ses SNPs van CYP1A2, CYP2A6, CYP3A4 en CYP3A5 geanaliseer en 11 gekombineerde genotipes is statisties geassosieer met gemiddelde EFV plasma vlakke. Hierdie studie beklemtoon die kompleksiteit van efavirenz-metabolisme en die belangrikheid van transkripsionele regulering in xenobiotiese metabolisme. / National Research Foundation (NRF)

Thesis (MNutr)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Introduction A paucity of data exists regarding growth patterns and nutrition-related problems in infants (<12 months) on antiretroviral treatment (ART) and the infant feeding knowledge, beliefs, attitude and practices of their caregivers. Aim To describe the growth and nutrition-related problems of infants (<12 months) attending the Antiretroviral (ARV) clinic at Red Cross Children’s Hospital, as well as the knowledge, attitudes, beliefs and practices of their caregivers concerning infant feeding. Methods A cross-sectional, descriptive study was conducted with census sampling. Thirty infants and 31 caregivers were included in the sample. Anthropometric measurements were performed and interviewer-administered questionnaires were utilised to obtain the knowledge, attitude, beliefs and practices of the caregivers. The mean Z-score of each measurement as well as the weight-for-age, length-for-age, weight-forlength and bodymass index-for-age for each infant were determined, analysed, interpreted and described according to the World Health Organisation (WHO) growth standards for children. Results Thirty-nine percent (n=11) of the mothers (n=28) did not receive infant feeding counselling prior to delivery, while only 9 (32%) received the minimum number of at least 4 sessions, as prescribed by the Department of Health. It was not assessed whether the counselling occurred before delivery. The mean age of the infants was 6.9 (SD 3.3) months. Eighty-three percent (n=25) had an opportunistic infection prior to data collection. Twenty-three percent (n=7) were underweight-forage and 40% (n=12) of the infants were stunted. Vomiting and diarrhoea were the most common nutrition-related problems experienced. A statistical significant positive correlation (p=0.003) was found between an infant’s duration on ART and W/A z-score. Only two caregivers were breastfeeding at the time of data collection, but 34% (n=10) of the other caregivers had at some stage breastfed their infant. Formula feeding practices were poor. Sixty-two percent (n=18) were not preparing the feeds correctly and only six (21%) were correctly cleaning and sterilising the bottles. Thirty-nine percent (n=11) of the infants were not receiving an adequate amount of milk per day. Sixty-five percent (n=11) of the infants (>six months) did not receive a diet the previous day which met the minimum WHO dietary diversity indicator and only 18% (n=3) received a minimum acceptable diet. Caregivers had an average knowledge concerning infant feeding. Thirteen percent (n=4) knew the correct definition of exclusive breast- or formula feeding. Sixty-eight percent (n=21) did not know what mixed feeding meant, or the dangers associated with it. Most caregivers (n=25, 81%) knew that oral rehydration solution had to be given when infants developed diarrhoea, but only 48% (n=15) knew how to prepare it and only 6% (n=2) knew how to administer it. Seventy-five percent (n=9) of caregivers did not know what should be done when experiencing breast problems. Sixty-four percent (n=19) of the caregivers believed that if a HIV-positive woman breastfeeds she would definitely transmit HIV to her infant. Conclusion The infant sample showed a variety of erratic growth patterns with a high prevalence of underweight and stunting. Infant feeding knowledge of caregivers was average, but not deemed sufficient to translate into appropriate, safe and optimal infant feeding practices. The breastfeeding prevalence was low. Formula preparation, feeding and hygiene practices were poor and dietary intake of infants was not optimal. The quality and quantity of HIV infant feeding counselling sessions received at antenatal clinic visits were poor and need to be addressed. / AFRIKAANSE OPSOMMING: Inleiding Daar is 'n tekort aan data oor groeipatrone en voedingsverwante probleme by babas (<12 maande) op antiretrovirale behandeling asook die babavoedingkennis, -oortuigings, -houdings en -praktyke van hul versorgers. Doelwit Om ondersoek in te stel na die groei- en voedingsverwante probleme by babas (<12 maande) in die antiretrovirale kliniek by Rooikruis-kinderhospitaal, sowel as die babavoedingkennis, - oortuigings, -houdings en -praktyke van hul versorgers. Metodes 'n Beskrywende dwarssnitstudie is met sensussteekproefneming onderneem. Dertig babas en 31 versorgers is by die steekproef ingesluit. Antropometriese metings was gedoen en onderhoude was met behulp van vraelyste gevoer ten einde inligting oor die versorgers se kennis, houdings, oortuigings en praktyke te bekom. Elke baba se gemiddelde z-telling per meting sowel as die gewig-vir-ouderdom, lengte-vir-ouderdom en liggaamsmassa-indeks-vir-ouderdom was volgens die Wêreldgesondheidsorganisasie (WGO) se groeistandaarde vir kindersbepaal, ontleed, vertolk en beskryf. Resultate Altesaam 39% (n=11) van die moeders (n=28) het nie voor die bevalling voorligting oor babavoeding ontvang nie, terwyl slegs 9 (32%) die Departement van Gesondheid se voorgeskrewe minimum 4 sessies, deurloop het. Dit was nie bepaal of hierdie sessies voor die bevalling ontvang was nie. Die gemiddelde ouderdom van die babas was 6,9 (standaardafwyking 3,3) maande. 'n Totaal van 83% (n=25) het voor data-insameling 'n opportunistiese infeksie gehad, 23% (n=7) was ondergewig-vir-ouderdom, en 40% (n=12) van die babas se lengtegroei was ingekort. Die algemeenste voedingsverwante probleme was braking en diarree. Daar blyk 'n statisties beduidende positiewe korrelasie (p=0.003) te wees tussen die duur van die baba se antiretrovirale behandeling en sy/haar gewig-vir-ouderdom-z-telling. Slegs twee versorgers het hul babas ten tyde van die studie geborsvoed, hoewel 34% (n=10) van die versorgers in 'n stadium geborsvoed het. Voedingspraktyke met die gee van melkformule was swak. Altesaam 62% (n=18) het die melkformule verkeerd aangemaak en slegs ses (21%) het die bottels behoorlik skoongemaak en gesteriliseer. Nege-en-dertig persent (n=11) van die babas het te min melk per dag ontvang. Vyf-en-sestig persent (n=11) van die babas (>6 maande) se melkinname die vorige dag het nie aan die minimum WGO aanbevole dieetdiversiteitsaanwyser voldoen nie, en slegs 18% (n=3) het 'n minimum aanvaarbare dieet gevolg. Versorgers se kennis ten opsigte van babavoeding was gemiddeld, met net 13% (n=4) wat die korrekte omskrywing van eksklusiewe bors- of formulevoeding geken het. 'n Totaal van 68% (n=21) het nie geweet wat gemengde voeding beteken of watter gevare dit inhou nie. Die meeste versorgers (n=25, 81%) het geweet dat orale rehidrasie oplossing toegedien moet word wanneer babas aan diarree ly, maar slegs 48% (n=15) het geweet hoe om dit aan te maak en 'n skrale 6% (n=2) hoe om dit toe te dien. Vyf-en-sewentig persent (n=9) van die versorgers het nie geweet wat om te doen as hulle probleme met hul borste ervaar nie. Altesaam 64% (n=19) van die versorgers het geglo dat 'n MIV-positiewe vrou definitief haar baba MIV sal gee indien sy hom/haar sou borsvoed. Samevatting Die steekproef babas het 'n verskeidenheid onreëlmatige groeipatrone getoon en baie was ondergewig of het ook dwerggroei getoon. Versorgers se kennis van babavoeding was gemiddeld, maar nie voldoende om tot toepaslike, veilige en optimale babavoedingspraktyke aanleiding te gee nie. Die voorkoms van borsvoeding was laag. Melkformulevoorbereiding, - voeding en -higiëne was swak, en babas se voedinginname was nie ideaal nie. Die gehalte van en hoeveelheid voorligting oor MIV-babavoeding met besoeke aan voorgeboorteklinieke was swak en moet aangespreek word.