Characteristics and outcomes of children, adolescents and young adults on antiretroviral therapy in Southern Africa, incorporating additional outcome ascertainment through linkage and tracing studies

Nyakato, Patience

Characteristics and outcomes of children, adolescents and young adults on antiretroviral therapy in Southern Africa, incorporating additional outcome ascertainment through linkage and tracing studies

Thesis / Dissertation

2024

Publisher

University of Cape Town

Department

Department of Public Health and Family Medicine

Faculty

Faculty of Health Sciences

Abstract

Despite significant progress in pediatric HIV care and treatment, children, adolescents, and young adults living with HIV (CAYHIV) continue to face challenges in achieving optimal outcomes compared to adults due to challenges like virologic non-suppression (VNS) among those in care and loss to follow-up (LTFU). Adolescents, in particular, face psychosocial and structural barriers that hinder their adherence to antiretroviral therapy (ART), leading to VNS and associated negative consequences, such as increased morbidity, drug resistance, mortality and a higher risk of HIV transmission to sexual partners and, for those who are pregnant, to their infants. LTFU is concerning as CAYHIV who are not in care are also likely not to be on ART resulting in faster disease progression, VNS, and increased morbidity and mortality. LTFU also poses a challenge to accurately measuring programme outcomes as the true outcomes of those LTFU are unknown. Accurate estimation of mortality rates among CAYHIV requires ascertaining outcomes in those LTFU and is important for the effective management of HIV care programmes. The thesis therefore aimed to describe the characteristics and outcomes of CAYHIV in Southern Africa, including additional outcomes ascertained from linkage and tracing studies among those who had been reported as LTFU at the original sites of ART initiation. The thesis consists of five papers (three published, two submitted) reporting the results from observational HIV cohorts of the International epidemiology Database to Evaluate AIDS -Southern Africa (IeDEA-SA) in six Southern African countries of Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe. Chapter 1 (Introduction) lays the foundation for key issues and concepts. This is followed by the literature review (Chapter 2) which gives a comprehensive discussion on virologic outcomes among adolescents, LTFU, ascertaining outcomes among CAYHIV reported as LTFU and correction of programme-level mortality estimates for LTFU among all CAYHIV using outcomes ascertained through tracing or linkage studies. Chapters 3 and 4 examine virologic outcomes and early LTFU among younger adolescents (10-14 years, Chapter 3) and older adolescents (15-19 years, Chapter 4), with a sub-analysis among those initiating treatment during pregnancy. Chapter 3 reports increasing 75th quantile viral load values with a three-fold increase at age 14 vs age 10 years, but no specific age at which this increase is more marked, and no differences observed by sex. Chapter 4 reports a relatively low rate of virologic non suppression (15%), but a high proportion of early LTFU following ART initiation (around 30%) irrespective of pregnancy status. Chapters 5 and 6 provide results on outcomes of CAYHIV previously reported as LTFU and either traced (Chapter 5) or linked to a health information exchange (Chapter 6). We defined tracing as the physical tracking of patients reported as LTFU using text messages, phone calls and home visits while linkage was defined as the process of linking patient unique identifiers to different healthcare data platforms like pharmacy records, laboratory records, hospital admissions to identify if they have had any interaction with the healthcare system within the province outside of their original facility or ART registration. The tracing approach reveals a high proportion of unreported mortality (9%) and a low proportion of self-transfers (21%) among CAYHIV while the linkage approach reveals a low proportion of mortality (3%), and a high proportion of self transfers (47%). Chapter 7 consolidates the results in Chapters 5 and 6 alongside routinely collected data to correct mortality estimates comparing three uncorrected and three corrected methods. There is a two-fold increase in estimated mortality after incorporating deaths among successfully traced CAYHIV due to the high mortality in traced patients. In contrast, incorporating linkage data has minimal impact on mortality estimates as there were few deaths but a high number of self transfers. Tracing and linkage-informed studies both show substantial variability in mortality among retained children and those LTFU across countries and sites, respectively. The thesis concludes that virologic response among CAYHIV, particularly adolescents, has greatly improved in more recent years with improved ART regimens and is expected to continue improving with the introduction of dolutegravir based therapies. However, this can easily be jeopardized by the persistent high proportion of CAYHIV reported as LTFU across the entire continuum of HIV care. Mortality estimates can also be substantially impacted if no additional outcome ascertainment is conducted among those reported as LTFU. Tracing and linkage informed studies are, therefore, important for accurate estimation of mortality and retention estimates.

Keywords

public health

Reference:

Collections

PhD / Doctoral

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