The small number of subjects precludes us from applying these findings to the general HIV-1 infected pediatric population. These patients were not all PD-0325901 MEK inhibitor receiving the same treatment regimen, but this is an inherent concern in studies where the subjects are drawn from heterogeneous clinic populations. We attempted to minimize this concern, by choosing subjects for the study who: 1) had not received HAART in the first two years of life; 2) had some levels of ongoing viral replication; and 3) were ARV-experienced . Both groups had generally similar treatment adherence rates to antiretroviral drugs, and variable adherence to ART is common in HIV-1 infected adolescents. We used the HXB-2 peptide set from the NIH as antigens, and this may both underestimate and potentially miss autologous epitopic responses. As we were limited with cell numbers, we focused on the HIV-1 Gag antigen, and responses to other HIV-1 proteins are important to consider . Our study was well balanced overall for age with a range from 10 to 18 years between the 2 groups studied. Age of the subject could be contributing to the pattern of immunodominance. However, the age range is relatively narrow with most subjects developmentally considered adolescents. Therefore, age was considered to be less unlikely to yield meaningful relationships to immunodominance patterns and therefore no formal testing for the WZ8040 effect of age was conducted. This study is one of the first to study the patterns of immunodominance and associations with disease progression in a cohort of perinatally infected adolescents. Moreover, this work focused on African American and Hispanic children, two populations that are greatly underrepresented in studies on the HIV-1-specific immune response. We find that in adolescents, as in adults , the immunodominance patterns appear to influence rates of disease progression. This influence seems to be mainly focused on the exquisite targeting of certain Gag epitopes, and not on the differentiation or cytokine secretion profiles of antigenspecific CD8+ T cells. These findings may be of importance to the field of pediatric HIV-1 immunology as well as the larger field of HIV-1 vaccine design. The research involving human participants reported in this study was approved by the UCSF and AECOM institutional review boards, with the approval number H11613�C19149. Informed consent was obtained for all subjects. All clinical investigation were conducted according to the principles expressed in the Declaration of Helsinki.