Doctoral Degrees (Paediatrics and Child Health)

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Browsing Doctoral Degrees (Paediatrics and Child Health) by Subject "Antiretroviral drugs"

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    The neurodevelopmental outcomes of perinatally HIV-infected children on different antiretroviral treatment (ART) strategies
    (Stellenbosch : Stellenbosch University, 2019-12) Laughton, Barbara; Cotton, Mark F.; Kruger, Mariana; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    ENGLISH 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.