The neurodevelopmental outcomes of perinatally HIV-infected children on different antiretroviral treatment (ART) strategies

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dc.contributor.advisorCotton, Mark F.en_ZA
dc.contributor.advisorKruger, Marianaen_ZA
dc.contributor.authorLaughton, Barbaraen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.en_ZA
dc.date.accessioned2020-02-25T12:08:39Z
dc.date.accessioned2020-04-28T15:13:36Z
dc.date.available2020-02-25T12:08:39Z
dc.date.available2020-04-28T15:13:36Z
dc.date.issued2019-12
dc.descriptionThesis (PhD)--Stellenbosch University, 2019.en_ZA
dc.description.abstractENGLISH ABSTRACT: At the commencement of this study, it was apparent that antiretroviral therapy (ART) improved neurodevelopmental outcomes of children infected with HIV. Little was known about the long-term outcomes in infants who commenced early ART, or whether there would be consequences of temporary ART interruption. We conducted a prospective, longitudinal, observational study to determine the neurodevelopmental outcomes of children perinatally infected with HIV on different ART strategies from the Children with HIV Early antiRetroviral treatment (CHER) trial. We compared the outcomes of children whose ART was deferred to children who started early ART but with planned interruption of treatment. We also assessed the neurodevelopmental outcomes at 11months of age in a cohort of children perinatally infected with HIV, who started ART within the first few weeks of life. The Griffiths mental development scales (GMDS) were used to assess neurodevelopment at 11, 20, 30, 42 and 60 months, and the Beery-Buktenica developmental tests of visual motor integration were performed at 60 months. HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children from similar neighbourhoods were enrolled for comparison. Mixed model repeated measures were used to compare groups over time. We found that children whose ART was deferred, had worse locomotor and general development in the first year of life compared to those who started treatment early and whilst asymptomatic with planned interruption. However, by five years of age the GMDS scores were similar. Children who started very early ART at a median age of 6 days, had similar GMDS scores at 11 months of age to the early treatment arm on CHER, who had started ART at median of 8 weeks. During the study we noted that children developed HIV encephalopathy, despite being on ART, including some with viral suppression. These children were followed for a median or 6.2 years and most recovered. This suggested a temporary insult, possibly due to inflammation associated with immune reconstitution that then resolved over time. An important finding was the visual perceptual deficit noted in HIV-infected children, compared to uninfected controls at 5 years of age. This study demonstrated that initiation of ART at a young age in an asymptomatic HIV- infected cohort had encouraging neurodevelopmental outcome at 5 years, apart from visual perception which was noted regardless of ART treatment strategy. Planned treatment interruption did not affect neurodevelopmental outcome by 5 years of age, but this was with careful clinical surveillance. Longer-term outcomes in older children would continue to provide further knowledge on ART treatment strategies.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Met die aanvang van hierdie studie, was dit duidelik dat antiretrovirale terapie (ART) die neurologiese ontwikkelings uitkomste van kinders met HIV besmetting verbeter het. Daar was 'n gebrek aan inligting oor die langtermyn uitkomste van kinders wat vroeë ART behandeling gekry het, en of daar gevolge sou wees vir tydelike onderbreking van ART. Ons het 'n voornemende, langtermyn, observasionele studie na die neurologiese ontwikkelings uitkomste van kinders wat perinataal met MIV besmet was, en op verskillende ART behandelings strategieë, gedoen om die uitslae te vergelyk met die van kinders met MIV en wat op vroeë antiretrovirale behandeling is. Ons het die uitkomste van kinders wie se ART behandeling uitgestel is vergelyk met die van kinders wat ART behandeling vroeg begin het en beplande onderbreking van behandeling ondergaan het, in die Children with HIV early antiretroviral treatment (CHER) studie. Ons het ook die neurologiese ontwikkeling uitkomste op 11 maande van ouderdom in 'n groep van kinders wat perinataal met MIV besmet was, en wat ART binne die eerste paar weke van die lewe begin het, geassesseer. Die Griffiths Mental Development Scales (GMDS) is gebruik om die neurologiese ontwikkeling van kinders op 11, 20, 30, 42 en 60 maande te bepaal, en die Beery- Buktenica ontwikkelings toetse van visuele motoriese integrasie is uitgevoer op 60 maande. MIV-blootgestelde onbesmette (HEU) en MIV-onbesmette (HU) kinders van soortgelyke buurte is ingeskryf vir 'n vergelyking. 'n Gemengde model herhaal maatreëls is gebruik om groepe oor ‘n tydperk te vergelyk. Ons het gevind dat kinders wie se ART uitgestel is, slegter lokomotoriese en algemene ontwikkeling getoon het in die eerste jaar, in vergelyking met diegene wat behandeling vroeg begin het wanneer hulle asimptomaties was en wat beplande onderbreking van behandeling ondergaan het. Tog op vyf jaar van ouderdom was die GMDS tellings soortgelyk. Kinders wat vroeë ART behandeling by 'n gemiddelde ouderdom van 6 dae begin, het soortgelyke GMDS tellings op 11 maande van ouderdom gehad as die van die vroeë behandeling arm op CHER, wat ART by mediaan van 8 weke begin het. Tydens die studie is opgemerk dat kinders MIV enkefalopatie ontwikkel, ten spyte daarvan dat hulle op ART behandeling was, insluitend 'n paar wat virale onderdrukking gehad het. Hierdie kinders is opgevolg vir 'n mediaan van 6,2 jaar en die meeste van hulle het herstel. Hierdie was 'n aanduiding van tydelike skade, waarskynlik weens inflammasie, gepaartgaande met immuun-herstel, wat daarna met verloop van tyd opgeklaar het 'n Belangrike bevinding was die opmerking van 'n visuele perseptuele gebrek in kinders wat met MIV besmet is, in vergelyking met die onbesmette kontroles op 5 jaar van ouderdom. Hierdie studie het getoon dat die aanvang van ART behandeling op 'n jong ouderdom, in 'n asimptomatiese MIV-besmette groep, bemoedigende neurologiese uitkomste op 5 jaar getoon het. Die bevinding is tenspyte van visuele persepsie wat ongeag die ART behandelings strategie opgemerk was. Beplande behandeling onderbreking het geen invloed op die neurologiese uitkomste teen die ouderdom van 5 jaar aangedui nie, maar hierdie met noukeurige kliniese toesig. Die langer termyn uitkomste in ouer kinders sal voortaan verdere kennis verskaf oor ART behandelings strategieë.af_ZA
dc.description.versionDoctoralen_ZA
dc.embargo.terms2021-02-28
dc.format.extent116 pagesen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/108431
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subjectNeurodevelopmental treatment for infantsen_ZA
dc.subjectMaternal health servicesen_ZA
dc.subjectHIV-positive childrenen_ZA
dc.subjectAntiretroviral drugsen_ZA
dc.titleThe neurodevelopmental outcomes of perinatally HIV-infected children on different antiretroviral treatment (ART) strategiesen_ZA
dc.typeThesisen_ZA
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