Improving the care of HIV-infected and -affected children during the implementation phase of the large-scale antiretroviral therapy programme in South Africa
| dc.contributor.advisor | Kruger, Mariana | en_ZA |
| dc.contributor.advisor | Forsyth, Brian | en_ZA |
| dc.contributor.author | Feucht, Ute Dagmar | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health. | en_ZA |
| dc.date.accessioned | 2015-12-14T07:41:59Z | en_ZA |
| dc.date.available | 2016-11-23T03:00:04Z | en_ZA |
| dc.date.issued | 2015-12 | en_ZA |
| dc.description | Thesis (PhD)--Stellenbosch University, 2023. | en_ZA |
| dc.description.abstract | ENGLISH ABSTRACT: Human immunodeficiency virus (HIV)-infection poses a major threat to childhood health and survival. The aim of this research was to evaluate the Prevention of Mother-to-Child Transmission (PMTCT) and paediatric HIV programmes as new child health interventions with the long term goal of improvement if necessary. The research was conducted at Kalafong Hospital, Gauteng Province in South Africa. PMTCT has become a successful childhood HIV prevention strategy in South Africa. We conducted a mixed-methods study using clinical data review and structured caregiver interviews to determine the missed implementation opportunities. PMTCT cascade analysis of 201 children demonstrated improvements in known maternal HIV-diagnosis, mother-infant antiretroviral interventions and infant HIV diagnosis. Gaps identified included a lack of preconception HIV-services, tuberculosis screening and psychosocial support, while infant feeding messaging worsened over time. The need to optimise the implementation of the entire PMTCT cascade is highlighted in order to reach paediatric HIV elimination. Accurate HIV diagnosis is the next crucial step in the children’s care pathway. We reviewed diagnostic tests in children referred for antiretroviral therapy (ART) and assessed predictive values of HIV virological tests. Analysis of 1,526 records revealed 51 HIV-uninfected children (3.3%) referred for ART, with 6.3% false-positive HIV virological tests in children below 18 months. We calculated positive predictive values of HIV virological tests and demonstrated the exponential increase in false-positive test results with declining HIV transmission rates. The need for robust diagnostic algorithms and meticulous confirmation of HIV status before ART initiation was proven. Barriers to HIV-care were subsequently studied. In 250 children, presenting for care five years after establishment of the ART-services, advanced/severe disease was common (82%), with referrals mostly from hospital inpatient services (61%). Caregiver interviews revealed good access to routine healthcare, but gaps included maternal psychosocial support, early infant diagnosis and testing at primary healthcare. One-third of children had prior HIV-diagnoses, with caregivers failing to attend ART-services, which requires further investigation. Additionally a pro-active strategy on paediatric HIV case finding at primary healthcare is required. Emerging HIV drug resistance threatens continued ART programme efficacy. We analysed clinical and drug resistance data of children failing protease inhibitor(PI)-based ART. Of children on PI-based ART-regimens, 43% received ritonavir as single-PI (RTV-sPI), mainly due to concomitant tuberculosis treatment. One-third had virological failure (RTV-sPI group), with a high prevalence of major PI- and multiclass mutations on genotyping. In children failing any PI-regimen, PI mutations were associated with timing of tuberculosis treatment and resultant ART-regimen choice. We assessed growth in children on ART due to the increasing importance of long-term health outcomes in HIV-children. The 159 children demonstrated rapid initial weight gain within the first year of ART initiation, with older age, tuberculosis and lack of electricity negatively affecting weight gain, while height improvement was delayed and negatively affected by tuberculosis co-infection. The importance of monitoring growth outcomes is discussed, as well as the need to determine the best nutritional interventions when poor growth is detected. Long-term outcomes in HIV-exposed-but-uninfected (HEU) children are equally important, since so many infants are born to HIV-infected mothers in South Africa. We studied growth in a prospective, longitudinal cohort showing consistently worse growth outcomes in HEU-children compared to HIV-unexposed children. Exposure to tenofovir-containing combination ART was particularly associated with lower weight and length gain over time for the HEU children. Maternal ART-duration significantly affected length, especially with first trimester-exposure versus later in pregnancy. This important finding highlights the need to carefully assess the outcomes of children born to mothers who are on ART during conception and pregnancy in order to balance the risks and benefits of these interventions in preventing paediatric HIV infection, but ensuring optimal child health. The PMTCT and paediatric HIV programmes have been successful in improving outcomes for HIV-infected and HIV-affected children. However, continued clinical governance is critical to ensure access to care and excellence in service provision within the clinical practice setting. Operational research is crucial to determine which aspects of the HIV care pathway need improvements or interventions. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING: Menslike immuungebrekvirus (MIV)-infeksie hou ʼn groot bedreiging vir die gesondheid en oorlewing van kinders in. Die doel van hierdie navorsing was om die voorkomingsprogram vir moeder-na-kind-MIV-oordrag en kinder-MIV-programme as nuwe kindergesondheidsintervensies te evalueer met die oog op verbetering. Die navorsing is gedoen by Kalafong-hospitaal in die Gauteng-provinsie, Suid-Afrika. Die voorkomingsprogram vir moeder-na-kind-MIV-oordrag is ʼn suksesvolle kindergesondheidsprogram in Suid-Afrika. Ons studie, met gemengde metodologie, het kliniese data sowel as gestruktureerde ouer/voog-onderhoude gebruik om leemtes in die implementering van die voorkomingsprogram vir moeder-na-kind-oordrag te ondersoek. Ontleding van die kaskade van die voorkomingsprogram vir moeder-na-kind-MIV-oordrag onder 201 kinders het verbeteringe in die moeder-MIV-diagnose, moeder-baba antiretrovirale intervensies en kinder-MIV-diagnose gedemonstreer. Tekortkominge sluit ʼn gebrek aan prekonsepsie-MIV-dienste, tuberkulosesifting en psigososiale ondersteuning in, terwyl babavoedingsboodskappe met tyd versleg het. Die volle kaskade van die voorkomingsprogram vir moeder-na-kind-MIV-oordrag behoort geoptimeer te word om kinder-MIV te voorkom. Akkurate MIV-diagnose is die volgende beslissende stap in die mediese versorgingspad. Ons het die diagnostiese toetse van alle kinders wat vir antiretrovirale terapie (ART) verwys is, nagegaan en die voorspellingswaarde van virologiese MIV-toetse bepaal. Ontleding van 1,526 rekords het 51 MIV-negatiewe kinders (3.3%) opgelewer wat vir ART verwys is, met 6.3% vals-positiewe virologiese MIV-toetse onder kinders onder 18 maande. Ons het die positiewe voorspellingswaarde van virologiese MIV-toetse bereken en die eksponensiële toename in vals-positiewe toetsuitslae met dalende MIV-oordrag gedemonstreer. Die behoefte aan robuuste diagnostiese algoritmes en noukeurige bevestiging van MIV-status voor die aanvang van ART is bewys. Hindernisse in MIV-gesondheidsorg is verder bestudeer. Gevorderde siekte was algemeen (82%) onder 250 kinders wat vyf jaar na die ontstaan van die ART kliniek verwys is, met meeste verwysings vanaf hospitaaldienste (61%). Ouer/voog-onderhoude het aangetoon dat daar goeie toegang tot basiese gesondheidsorg was, maar tekortkominge wat betref die psigososiale ondersteuning van moeders, vroeë diagnose onder babas en toetsing op primêre gesondheidsvlak was. Een derde van kinders is vooraf met MIV gediagnoseer, maar versorgers het versuim om van ART-dienste gebruik te maak – ʼn saak wat verdere ondersoek vereis. ʼn Strategie vir pro-aktiewe identifikasie van kinder-MIV op primêre gesondheidsorgvlak is nodig. MIV-geneesmiddelweerstandigheid is ʼn bedreiging vir die ART-program se voorgesette doeltreffendheid. Ons het kliniese en weerstandigheidsdata van kinders ontleed wat protease inhibeerder (PI)-gebaseerde ART gefaal het. Van alle kinders op PI-gebaseerde ART het 43% ritonavir as enkel-PI ontvang, hoofsaaklik weens gepaardgaande tuberkulosebehandeling. Een derde het die terapie virologies gefaal (ritonavir-groep), met ʼn hoë voorkoms van major PI- en multiklasmutasies op genotipering. Onder kinders wat enige PI-behandeling gefaal het, was die tydsberekening van tuberkulosebehandeling en die gevolglike ART-keuse van belang. Ons het groei onder kinders op ART nagegaan gesien die toenemende belangrikheid om langtermyn-gesondheidsuitkomste van MIV-geïnfekteerde kinders te ondersoek. Vinnige aanvanklike gewigstoename binne die eerste jaar van ART is onder 159 kinders aangetoon, met toenemende ouderdom, tuberkulose en gebrek aan elektrisiteit wat gewigstoename negatief beïnvloed het. Verbetering in lengte was stadiger, en is negatief deur tuberkulose-infeksie beïnvloed. Die belang van die monitering van groei-uitkomste word bespreek, sowel as die nodigheid om die beste voedingsingrepe te bepaal wanneer kwyning geïdentifiseer word. Langtermynuitkomste van onbesmette kinders wat wel aan MIV blootgestel was is ewe belangrik, aangesien baie MIV-geïnfekteerde moeders in Suid-Afrika geboorte skenk. Ons studie van ʼn prospektiewe, longitudinale kohort het swakker groei-uitkomste onder MIV-blootgestelde kinders aangetoon. Blootstelling aan die ART-kombinasie wat tenofovir bevat is veral geassosieer met laer gewig en lengte oor tyd. Die duur van moeder-ART het lengtegroei beduidend beïnvloed, veral met blootstelling in die eerste trimester vergeleke met later in die swangerskap. Hierdie belangrike bevinding dui daarop dat daar in die toekoms noukeurig gelet behoort te word op die uitkomste van kinders van MIV-geïnfekteerde moeders op ART voor en tydens swangerskap, om te verseker dat die risiko’s en voordele van die ingrepe in die voorkoming van MIV-infeksie onder kinders gebalanseer word met die uitkoms van optimale kindergesondheid. Die voorkomingsprogram vir moeder-na-kind-MIV-oordrag en kinder-MIV-programme is suksesvol om die uitkomste onder MIV-besmette en MIV-geaffekteerde kinders te verbeter. Voortgesette kliniese bestuur is krities belangrik om toegang tot sorg en uitnemendheid in dienslewering te verseker. Operasionele navorsing is noodsaaklik om die aspekte in die mediese versorging van MIV wat verbeteringe of intervensies benodig, te bepaal. | af_ZA |
| dc.description.version | Doctoral | en_ZA |
| dc.embargo.terms | 2016-11-23 | en_ZA |
| dc.format.extent | ix, 135 pages : illustrations | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/97730 | en_ZA |
| dc.language.iso | en | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject.lcsh | HIV (Viruses) -- Prevention -- South Africa | en_ZA |
| dc.subject.lcsh | HIV-positive women -- South Africa | en_ZA |
| dc.subject.lcsh | Child health services | en_ZA |
| dc.subject.lcsh | Antiretroviral agents -- South Africa | en_ZA |
| dc.subject.lcsh | Antenatal care -- South Africa | en_ZA |
| dc.subject.lcsh | Pregnant women -- South Africa | en_ZA |
| dc.title | Improving the care of HIV-infected and -affected children during the implementation phase of the large-scale antiretroviral therapy programme in South Africa | en_ZA |
| dc.type | Thesis | en_ZA |