School of Clinical Medicine (ETDs)
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Item Virological response in children and adolescents switching to dolutegravir based regimens in Johannesburg, South Africa – A Longitudinal Cohort Study(University of the Witwatersrand, Johannesburg, 2023) Mafora, Tshiamo; Technau, KarlIntroduction: Dolutegravir (DTG) was introduced into South African HIV management guidelines in November 2019, and has since been the mainstay of both adult and paediatric first line antiretroviral treatment (ART) regimens. Following its rapid and widespread introduction we assessed the rate of virological suppression over two years in paediatric patients switching to DTG as part of first line treatment. Methods: We performed a retrospective cohort study at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Children and adolescents already on first line ART who switched to DTG (between November 2019 and November 2021) were included. Baseline characteristics (at DTG switch) included age, weight, gender, viral load (VL), CD4, and pre-switch regimen. Past ART exposure and past viraemic periods (years VL >1000 copies/ml) were assessed and VL suppression rates (< 50 copies/ml) were calculated at 6, 12 and 24 months post-switch. Associations with non-suppression were assessed using uni- and multivariate analysis. Results: Of the 747 participants that were switched to DTG, 724 (97%) qualified for a VL and 697 (96%) of those had at least one VL done after switch. Overall, 83% (450/543) were suppressed at 6 months, 86% (434/504) at 12, 91% (487/534) at 24 months. Overall, at a median of 637 days after switch, 90% (624/697) were suppressed at their last VL. Factors associated with not being suppressed at the last VL included: missing a follow-up visit by more than 90 days post-switch to DTG (OR: 3.2 [CI:1.5-6.8], p=0.003), switching to DTG with a VL of 50-1000 rather than <50 copies/ml (OR 2.0 [CI:1.1-3.9], p=0.042), having the blood test done during July December (OR 2.0 [CI:1.2-3.4], p=0.011), and having had exposure to viraemia ≥1000 copies/ml for more than two years between first ART start and DTG switch (OR: 1.9 [CI: 0.9-3.7], p=0.071). Conclusion: In our population, similar to other studies, VL suppression was effectively maintained in the majority of patients after switching to DTG. The switch did however result in a loss of suppression in some patients and caution is needed in children and adolescents with missed visits and extensive prior viraemiaItem Long-term outcomes of HIV infected, and uninfected children aged 1-59 months following inpatient management of severe acute malnutrition(2024) Bwakura-Dangarembizi, MutsawasheChildren with complicated severe acute malnutrition (SAM) are at a high risk for mortality and morbidity in the time after hospital discharge, and those with HIV are particularly vulnerable. What is not known is whether this higher risk for poor outcomes in children with HIV has improved in the era of treating all who are infected. The thesis' main aim was to characterize the 52-week outcomes of children aged 1 to 59 months who were hospitalized for complicated SAM and to identify the characteristics present at hospital discharge that were most predictive of these outcomes. The thesis utilised the HOPE SAM study, an observational cohort established in Zimbabwe and Zambia that enrolled children hospitalised for complicated SAM and followed them up for one year after discharge from hospital. The study outcomes were death, morbidity, nutritional recovery and body composition assessed using skinfold thickness and bioelectrical impedance analysis. There were 3 main findings from the thesis; nearly 1 in 10 children treated for SAM died and the risk of dying continued throughout the one year following discharge. Children living with HIV had an almost 4-fold higher mortality compared to those without HIV regardless of whether they were receiving antiretroviral therapy or not; wasted children and those with ongoing SAM had a 2-fold higher mortality compared to those who had oedema on admission; and cerebral palsy was associated with a nearly 6-fold higher mortality risk. Similar risk factors, with the exception of HIV infection and addition of stunting were associated with impaired anthropometric recovery and increased hospital readmission. In this cohort, the time to hospital readmission was correlated with low peripheral fat mass and low lean mass. Overall, this thesis emphasizes the vulnerability of children treated for SAM even after they are released from the hospital and identifies high-risk populations that require focused interventions to enhance outcomes