This study has several strengths and also some important weaknesses to note. Study strengths include the longitudinal assessment of individuals and the absence of confounding by antiretroviral therapy. By using cryopreserved specimens, we were able to batch all of each infant��s specimens in a single experiment; greatly reducing intra-subject experimental error. A limitation of the study was that few infants in the larger cohort had ELISPOT responses of a magnitude and specificity to examine with available tetramers. These phenotypic data may therefore not be representative of HIV-specific CD8 + T cells directed at less dominant epitopes, or T cells from infants with low level responses. Additionally, the number of cellular antigens we were able to examine in the phenotypic studies were restricted by limited cell numbers in the cryopreserved specimens. PF-06291874 Finally, the small sample size of this study limits our ability to perform meaningful statistical comparisons of the data; though some phenotypic markers differed between subsets and time intervals, adjustment for multiple comparisons retained no significant values. In summary, our data suggest a model of infant infection in which high frequencies of phenotypically normal CD8 + T cells fail to contain viral replication during acute infection, resulting in persistent T cell activation during chronic infection. Identifying the mechanisms underlying age-related differential function of T cells will be valuable to the design of an HIV-1 vaccine appropriate for use in infants and to our general understanding of HIV-specific immunity. The study was approved by the Ethics and Research Committee of Kenyatta National Hospital and the Institutional Review Board of the University of Washington. Mothers provided written informed consent for study participation on behalf of themselves and their infants. Details of the cohort recruitment and follow-up have been presented in PF-06651481-00 detail elsewhere. The cohort was enrolled and followed-up before antiretroviral therapy became widely available in Kenya; other than maternal antenatal zidovudine prophylaxis, infants did not receive ART. Serial blood specimens were obtained at delivery and months 1 and 3, and quarterly thereafter.