In this study, adolescents were less likely to attain virological suppression and had higher rates of virological failure compared to young adults. Despite the poorer virological outcomes, immunological responses were nevertheless greater in adolescents than young adults. There was no significant difference in mortality and LTFU rates between the two groups. In sub-analyses comparing perinatally infected adolescents with young adults, broadly similar results were observed with regards to mortality, immunological and virological response to ART. However, the association between adolescent status and the higher rates of virological failure was weakened.
Our findings of a lower rate of virological suppression and increased rate of virological failure in this public health sector study are cause for concern considering the long-term antiretroviral need these adolescents have. These results are similar to those of a recent multi-site study in the private health sector of Southern Africa by Nachega et al. ; but differ slightly from those from another public health sector study from a peri-urban settlement (Khayelitsha, Cape Town) by van Cutsem et al.  which observed that virological outcomes were worse for youth (20-24 years) when compared to those in the adolescents (10-19 years) and adults (≥ 25 years).
Virological suppression requires effective ART. This implies the correct dose of appropriate ART being consistently and correctly taken. Adolescents whilst undergoing a range of psychosocial developments are also growing physically. Consequently, it may be important to review the appropriateness of ART dosing as children transition from paediatric doses into adult doses . This may be particularly relevant in younger adolescents. Adequate options for paediatric appropriate antiretroviral drugs may also play a role in the outcomes in adolescents. Often choices are limited and formulations are inappropriate. Adequate adherence to medication may on the other hand, be an important factor in older adolescents and youth where all of the psychosocial factors described here [1, 4] may play a role in an individual's ability or willingness to be adherent. In many low and middle income countries, where prevention of mother-to-child transmission (PMTCT) strategies have include monotherapy with NVP, the impact on non-nucleoside based first-line regimens is also for consideration. The impact of maternal PMTCT, and in particular the impact of single dose NVP on this cohort is unlikely since the youngest adolescents described here were born in 2001 before the clinic and provincial- and country-wide roll-out of PMTCT .
Despite the poorer virological outcomes, we observed that the median change in CD4 count from baseline was higher for all adolescents and perinatally infected adolescents than young adults, suggesting that younger and more robust immune systems occur in adolescents. A study conducted in the United States and Peurto Rico conducted by Flynn et al.  also report improved CD4 cell count measurements in adolescents infected via high- risk behaviours after 3 years of follow-up in subjects with sustained undetectable viral loads. In contrast, a Southern African observational cohort study conducted by Nachega et al.  reported that adolescents (10-19 years) were less likely to experience long-term immune recovery than young adults (20-30 years). These contrasting findings may be due to differences in adolescent population between studies in terms of age and mode of infection; our adolescent population consisted of younger adolescents with predominantly perinatally acquired infection who had relatively better responses to ART compared to the older adolescents (median age, 16.4 years; 73% female) in the Nachega cohort (presumably with sexually acquired infection on the basis of age and sex ratio).
Our findings did not show a significant difference in mortality and LTFU rates between the groups. Literature on mortality and LTFU in adolescents is scant. The absence of any statistically significant difference in mortality and LTFU between adolescents and young adults in the present study is similar to reports from a recent study conducted in a public health sector ART cohort from Uganda by Bakanda et al. . Whilst there was no significant difference between mortality and LTFU, there were still some losses (death and LTFU) to the program that need corrective interventions. Site- and patient-related factors, such as lack of compensation (for participants), lower caregiver education level, older age and higher viral load, have all been associated with increased LTFU in HIV infected children and adolescents in a multi-site cohort study conducted across Puerto Rico and the United States by Williams et al. . This study does not ascertain what factors are important in these two age groups and may be quite different. Further research on factors associated with and the reasons for both LTFU and mortality in adolescents are required.
Compared to analyses using the complete group of adolescents, sub-analyses restricted to perinatally infected adolescents showed a weaker association between adolescent status and higher rates of virological failure compared to young adults. Collectively, these data may suggest that the higher rates of virological failure among adolescents were more strongly associated with those with sexually acquired infection. In addition, perinatally infected adolescents had a significantly lower risk of LTFU, which may be attributable to the fact that such individuals were more likely to attend the treatment facility with the support of parents, family and guardians than the older adolescents with sexually acquired infection. This hypothesis is supported by a recent qualitative study conducted among perinatally infected adolescents aged 7-15 years in Cape Town that found they viewed HIV as physically and emotionally painful, but strong family and friend support systems were viewed as positive aspects of their lives . Thus, differences in outcomes between the two sub-group of adolescents may be related to a range of medical, physiological, psychosocial, psychosexual and neuro-cognitive issues [1, 29, 32].
The recent modification of services in this clinic to include a dedicated adolescent service may or may not be influencing adolescent outcomes since the cohort included adolescents from before as well as after the introduction of new adolescent services. Recommendations from other medical fields where adolescents may have chronic illnesses requiring ongoing medication adherence are that adolescent friendly and specific services are more effective [33–37]. With longer follow up, the programmatic impact of this dedicated adolescent service may be assessed. This study is unusual in that it explores treatment outcomes among all adolescents, including those transferred in on treatment and compares this to young adults. This gives insights into the overall programmatic outcomes of the adolescent population in this public sector ART clinic in Cape Town, especially useful given the traffic between clinics and within services with the realisation of greater treatment accessibility in Southern Africa. Although the study was conducted in a relatively large community-based clinic, and the numbers of adolescents in public sector ART programs in Southern Africa are accumulating, the numbers of adolescents involved in this cohort is still small, which is a limitation of this study. In addition, other limitations include the lack of data on adherence, viral resistance mutations, side-effects to therapy, all of which will require investigation in future studies. The data presented here does however indicate that this group in community-based ART programs should be evaluated separately to the adult population, and where possible perinatally infected adolescents and sexually infected adolescents may have different outcomes and warrant separate evaluation; and similarly adolescent specific corrective interventions should be implemented. Therefore, further research into understanding the reasons for LTFU, mortality, immunological and virological outcomes in this group in whom lifelong antiviral suppression is required.