Treatment outcomes in perinatally-infected HIV positive adolescents and young adults after 10+ years on antiretroviral therapy

There are currently more than 30 0 000 children under the age of 15 living with HIV in South Africa (SA). Due to a combination of recent success in preventing new vertical infections and success of paediatric antiretroviral treatment (ART) programmes in improving life-expectancy in perinatally HIV-infected (PHIV) children, the burden of paediatric HIV in SA has changed to older children. An increasing population of PHIV children on ART is reaching adolescence, yet information on long-term treatment outcomes in this group is lacking. There is very limited published data on treatment outcomes in PHIV children after ≥10 years on ART in high income countries (HIC), and none in low- and middle-income countries (LMIC). We conducted a retrospective cohort study of PHIV adolescents on ART for ≥ 10 years at a single ART facility. The main objective of the study was to describe long-term clinical, growth, immunologic and virologic outcomes in the cohort. Part A, the protocol, as submitted for departmental and ethical approval, details the purpose and methodology of the study. Part B, the literature review, discusses what is known about long-term treatment outcomes in PHIV children on ART to date. It compares findings between HIC and LMIC. Long-term growth, immunologic and virologic outcomes, as well as factors associated with viral failure are described. The paucity of long-term data is demonstrated, indicating the need for further research on the topic. Part C, the journal-ready manuscript, details the methodology, results and interpretation of the longitudinal analysis of long-term treatment outcomes among 127 PHIV-infected adolescents and young adults on ART for ≥10 years. After median follow-up of 12 years since ART initiation, 80% of the cohort were virally suppressed and 79% had optimal immunologic status (CD4 >500 cells/μl). These results are favourable overall, but >40% of adolescents were on 2nd-line ART with poorer immunologic outcomes than those on 1st-line ART, and approximately one in three children experienced viral failure during adolescence. This highlights the vulnerability of this group, which requires careful further management. Appendices include all supporting documentation necessary for the above parts of the mini-dissertation