Background: Lung disease is a common complication of human immunodeficiency virus (HIV) infection in children and adolescents. As antiretroviral programmes have strengthened and HIV diagnosed earlier, survival of perinatally HIV-infected children has improved. Therefore, an increasing number of perinatally HIV-infected children are surviving into adolescence, with development of chronic multisystem disease including chronic lung disease (CLD). However, there is limited information on the determinants, spectrum and progression of lung disease. Lung function testing, an objective, non-invasive, reproducible tool, is useful in characterising CLD and in monitoring disease progression. Aim: To investigate the spectrum, determinants and progression of lung function in perinatally HIV-infected adolescents on antiretroviral therapy (ART) in Cape Town, South Africa. Specific objectives included describing the spectrum and determinants of lung function; investigating cardiopulmonary dysfunction and investigating progression of lung function over two years. Methods: The study population was from a prospective cohort, the Cape Town Adolescent Anti-retroviral cohort (CTAAC), that enrolled 515 perinatally HIV-infected adolescents on ART and 110 age-matched HIV-uninfected adolescents followed six-monthly for two years in Cape Town, South Africa. Eligibility criteria were adolescents, aged 9-14 years, with perinatally acquired HIV, who had been on ART for at least six months. Comprehensive lung function testing was done, and clinical and lung function data collected at baseline, 12 and 24 months. Results: At baseline, HIV-infected adolescents had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, diffusing capacity for carbon monoxide, respiratory system compliance and functional residual capacity; and higher airway resistance and lung clearance index compared to HIV-uninfected adolescents, p< 0.05 for all. At 24 months, FEV1 and FVC remained lower in the HIV-infected compared to the uninfected, p< 0.05 for both. Impaired cardiopulmonary function was detected in 13% of HIV-infected adolescents and 8% of HIV-uninfected adolescents, p=0.136. Past PTB was significantly associated with a low cardiopulmonary function, OR 2.3, 95%CI 1.2-4.4. Conclusion: Perinatally HIV-infected adolescents had lower lung function and higher resistance and ventilation inhomogeneity compared to age-matched HIV-uninfected adolescents at baseline. Lung function tracked, remaining lower at two years. Previous PTB or severe LRTI were predictors of lower lung function. Co-existent cardiopulmonary dysfunction occurred in a minority. These data highlight respiratory disease risk in this vulnerable group and may inform policy to strengthen strategies to prevent and manage HIV-associated lung or cardiopulmonary disease. Four of the chapters (2-5) of this thesis are presented as published manuscripts. Chapter 1 encompasses an overview of the burden of HIV disease and the spectrum of HIV associated chronic lung disease in adolescents and the utility of lung function in the diagnosis of chronic lung disease. Study methodology is also detailed in this chapter. Chapter 2 (published manuscript) comprises a comprehensive review of published data on lung function (over and above the literature included in the individual papers) in HIV infected children and adolescents and summarises studies that have been done in Africa, USA, Europe and Asia. Chapter 3 (published manuscript) describes the spectrum and determinants of comprehensive lung function parameters (flow, volume, compliance, resistance, ventilation inhomogeneity) in perinatally HIV-infected adolescents with a comparator group of age-matched HIV-uninfected adolescents. Chapter 4 (published manuscript) further explores the prevalence and determinants of coexistent cardiopulmonary dysfunction in perinatally HIV-infected adolescents on ART. Chapter 5 (published manuscript) describes the progressive changes in spirometry over two years in perinatally HIV-infected adolescents compared to HIV-uninfected age matched controls. It also addresses the associations of low lung function, factors amenable to public health interventions. Chapter 6 is a summary of the study findings and recommendations.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uct/oai:localhost:11427/31387 |
| Date | 28 February 2020 |
| Creators | Githinji, Leah Nyawira |
| Contributors | Zar, Heather, Gray, Diane |
| Publisher | Faculty of Health Sciences, Department of Paediatrics and Child Health |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, Doctoral, PhD |
| Format | application/pdf |
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