Universal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings

dc.contributor.advisorDavies, Mary-Ann
dc.contributor.advisorTechnau, Karl-Gunter
dc.contributor.authorIyun, Victoria Oluwatoyin
dc.date.accessioned2022-08-30T10:25:17Z
dc.date.available2022-08-30T10:25:17Z
dc.date.issued2022
dc.date.updated2022-08-29T11:22:51Z
dc.description.abstractBackground Sub-Saharan Africa is home to >90% of all children living with HIV worldwide. Since 2008, there has been a shift in paediatric HIV treatment towards universal antiretroviral therapy (ART) allowing for immediate initiation of ART, regardless of clinical or immunologic status initially for infants, and subsequently for progressively older, and ultimately all children. Given the scale-up of early infant diagnosis (EID) and early initiation of ART for infants and young children who are especially vulnerable to rapid progression of HIV and mortality, access to paediatric antiretroviral therapy (ART) services has substantially improved across sub-Saharan Africa (SSA). However, with the changing guidelines and practices, the demographic and clinical characteristics of infants and young children infected in recent years may vary from those infected before the widespread uptake of prevention of mother-to-child transmission of HIV (PMTCT) services and universal ART. This study therefore sought to understand the impact of changing guidelines on key metrics of the paediatric HIV care continuum, including timeliness of ART initiation, mortality, program retention and viral load suppression in order to examine effectiveness of ART in infants and young children enrolled in routine ART programs. Methods Using data from the International epidemiologic Databases to Evaluate AIDS Collaboration (IeDEA), this thesis described the temporal trends in the ART initiation characteristics in a total of 1692 infants initiating ART < 1 year of age and 32,220 young children initiating ART < 5 years of age between 2006-2017 in South Africa and SSA respectively. The trends in outcomes including mortality, loss to follow-up (LTFU), viral suppression. Associated determinants were also examined. Findings The result chapters of this thesis are presented in the form of journal papers in different stages of publication. The first paper reports that disease severity characteristics among all children starting ART aged <5 years in sub-Saharan Africa improved over time. Mortality declined substantially, however, LTFU remained unchanged with one in five children continuing to be lost before two years on ART. There was substantial heterogeneity in outcomes across country income groups. The second paper presents data on infants with HIV starting ART ≤3 months of age in South Africa. Findings suggests a that growing proportion of infants started ART at younger ages and with less advanced HIV disease. Mortality was 10.6% (7.8%-14.4%) in 2006- 2009 and decreases progressively to 4.6% (3.1%-6.7%) in 2013-2017 (p< 0.001), with LTFU remaining unchanged across calendar periods (p=0.274). The third paper presents findings on the trends in viral suppression (viral load [VL] < 400 copies/ml) and immunologic response up to 12 months on ART in infants who started treatment at < 3 months of age. By 6 and 12 months on ART, 56% and 65% infants achieved virologic suppression and the median (IQR) CD4 percentages increased slightly to 30% (22-37) and 31% (25-39) respectively, from a median of 27% (18-38) at ART initiation. There was a trend towards poorer viral suppression levels among infants initiating early ART in recent calendar years, despite improvement in CD4% and lower VL at ART initiation. The final paper suggests that good long-term viral suppression (<70%) among infants in routine care is achievable. However, infants staring ART between 0- 3 months vs those starting at 4-12 months of age had the lowest rate of viral suppression at all timepoints during a follow-up period of five years on ART. Conclusions Findings from this thesis suggest an increase in earlier ART initiation for infants and young children, with associated improvement in health status at ART initiation and declines in mortality following universal ART recommendations. However, substantial inequities existed across country income groups and a quarter of children on antiretroviral therapy across SSA continue to experience LTFU. In addition findings highlight suboptimal short and long-term viral suppression in infants acquiring HIV in the era of birth diagnosis and early infant ART. Targeted interventions are therefore urgently required to improve the outcomes of infants and young children living with HIV, especially among infants initiating ART before three months of age and children in low and lower-middle-income countries.
dc.identifier.apacitationIyun, V. O. (2022). <i>Universal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings</i>. (). ,Faculty of Health Sciences ,Department of Public Health and Family Medicine. Retrieved from http://hdl.handle.net/11427/36782en_ZA
dc.identifier.chicagocitationIyun, Victoria Oluwatoyin. <i>"Universal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings."</i> ., ,Faculty of Health Sciences ,Department of Public Health and Family Medicine, 2022. http://hdl.handle.net/11427/36782en_ZA
dc.identifier.citationIyun, V.O. 2022. Universal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings. . ,Faculty of Health Sciences ,Department of Public Health and Family Medicine. http://hdl.handle.net/11427/36782en_ZA
dc.identifier.ris TY - Doctoral Thesis AU - Iyun, Victoria Oluwatoyin AB - Background Sub-Saharan Africa is home to >90% of all children living with HIV worldwide. Since 2008, there has been a shift in paediatric HIV treatment towards universal antiretroviral therapy (ART) allowing for immediate initiation of ART, regardless of clinical or immunologic status initially for infants, and subsequently for progressively older, and ultimately all children. Given the scale-up of early infant diagnosis (EID) and early initiation of ART for infants and young children who are especially vulnerable to rapid progression of HIV and mortality, access to paediatric antiretroviral therapy (ART) services has substantially improved across sub-Saharan Africa (SSA). However, with the changing guidelines and practices, the demographic and clinical characteristics of infants and young children infected in recent years may vary from those infected before the widespread uptake of prevention of mother-to-child transmission of HIV (PMTCT) services and universal ART. This study therefore sought to understand the impact of changing guidelines on key metrics of the paediatric HIV care continuum, including timeliness of ART initiation, mortality, program retention and viral load suppression in order to examine effectiveness of ART in infants and young children enrolled in routine ART programs. Methods Using data from the International epidemiologic Databases to Evaluate AIDS Collaboration (IeDEA), this thesis described the temporal trends in the ART initiation characteristics in a total of 1692 infants initiating ART < 1 year of age and 32,220 young children initiating ART < 5 years of age between 2006-2017 in South Africa and SSA respectively. The trends in outcomes including mortality, loss to follow-up (LTFU), viral suppression. Associated determinants were also examined. Findings The result chapters of this thesis are presented in the form of journal papers in different stages of publication. The first paper reports that disease severity characteristics among all children starting ART aged <5 years in sub-Saharan Africa improved over time. Mortality declined substantially, however, LTFU remained unchanged with one in five children continuing to be lost before two years on ART. There was substantial heterogeneity in outcomes across country income groups. The second paper presents data on infants with HIV starting ART ≤3 months of age in South Africa. Findings suggests a that growing proportion of infants started ART at younger ages and with less advanced HIV disease. Mortality was 10.6% (7.8%-14.4%) in 2006- 2009 and decreases progressively to 4.6% (3.1%-6.7%) in 2013-2017 (p< 0.001), with LTFU remaining unchanged across calendar periods (p=0.274). The third paper presents findings on the trends in viral suppression (viral load [VL] < 400 copies/ml) and immunologic response up to 12 months on ART in infants who started treatment at < 3 months of age. By 6 and 12 months on ART, 56% and 65% infants achieved virologic suppression and the median (IQR) CD4 percentages increased slightly to 30% (22-37) and 31% (25-39) respectively, from a median of 27% (18-38) at ART initiation. There was a trend towards poorer viral suppression levels among infants initiating early ART in recent calendar years, despite improvement in CD4% and lower VL at ART initiation. The final paper suggests that good long-term viral suppression (<70%) among infants in routine care is achievable. However, infants staring ART between 0- 3 months vs those starting at 4-12 months of age had the lowest rate of viral suppression at all timepoints during a follow-up period of five years on ART. Conclusions Findings from this thesis suggest an increase in earlier ART initiation for infants and young children, with associated improvement in health status at ART initiation and declines in mortality following universal ART recommendations. However, substantial inequities existed across country income groups and a quarter of children on antiretroviral therapy across SSA continue to experience LTFU. In addition findings highlight suboptimal short and long-term viral suppression in infants acquiring HIV in the era of birth diagnosis and early infant ART. Targeted interventions are therefore urgently required to improve the outcomes of infants and young children living with HIV, especially among infants initiating ART before three months of age and children in low and lower-middle-income countries. DA - 2022_ DB - OpenUCT DP - University of Cape Town KW - Public Health and Family Medicine LK - https://open.uct.ac.za PY - 2022 T1 - Universal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings TI - Universal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings UR - http://hdl.handle.net/11427/36782 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/36782
dc.identifier.vancouvercitationIyun VO. Universal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings. []. ,Faculty of Health Sciences ,Department of Public Health and Family Medicine, 2022 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/36782en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Public Health and Family Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.subjectPublic Health and Family Medicine
dc.titleUniversal antiretroviral therapy (ART) for infants and young children living with HIV: assessing the effect of guideline changes on ART initiation characteristics and treatment outcomes in resource-limited settings
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationlevelPhD
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
thesis_hsf_2022_iyun victoria oluwatoyin.pdf
Size:
9.76 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
0 B
Format:
Item-specific license agreed upon to submission
Description:
Collections