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Background: Long term survival of children living with HIV due to improved early access to antiretroviral therapy (ART) is contributing to a growing population of adolescents living with perinatally acquired HIV (PHIV+) at risk of developing chronic multisystem comorbidity. There is limited knowledge on the overall burden, progression and causes of morbidity in PHIV+ adolescents, especially in resource limited settings. Much of what is known about morbidity in PHIV+ adolescents relates to single organ system pathology and there is a lack of a holistic approach to PHIV+ adolescents and their overall health. The aim of this PhD project was therefore to investigate the spectrum and determinants of chronic morbidity, the progression of disease and intercurrent illness in PHIV+ adolescents on ART over a 4- year period. Methods: This was a prospective study of participants enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC), a longitudinal cohort study, that recruited 515 PHIV+ adolescents and 110 HIV negative (HIV-) adolescents matched by age from 7 health care sites in Cape Town, South Africa. Eligibility criteria included PHIV+ adolescents who were aged 9-14 years, who had been on ART for at least 6 months and were aware of their HIV status. All adolescents and caregivers gave informed consent/assent. Participants were followed 6-monthly with questionnaires, clinical examination with detailed pulmonary (lung function), neurocognitive (magnetic resonance imaging and a battery of neurocognitive tests), cardiovascular (echocardiogram and ECG) and laboratory investigations. Analyses for each specific objective of the PhD were developed. Three analyses used data from the enrolment visit and were primarily descriptive and two were longitudinal and examined the incidence of hospitalizations, QuantiFERON conversion (an interferon gamma release assay used to measure Mycobacterium tuberculosis infection) and Tuberculosis (TB) disease. Results: Five hundred fifteen PHIV+ and 109 HIV- participants had a median follow-up of 4.1 years (IQR: 3.7–4.6). At enrollment, PHIV+ adolescents had a median duration of ART of 7.6 years (IQR: 4.6–9.2), median CD4 count of 713 cells/mm3 (IQR: 561.0–957.5) and 387 (75%) had a viral load of |
