Abstract During the course of HIV-1 infection, the status of immune activation has been determined to be a powerful indicator of disease progression. The immune system has adopted self-regulatory mechanisms to counterbalance undesirable immune responses. CD25+CD4+ T regulatory (Treg) cells that express the transcription regulator, forkhead box P3 (FOXP3), play an important role in this immunosuppression. Using a combination of Treg cell discriminatory markers (FOXP3, CD25, CD127), we predicted that an expansion of Treg cell subsets would negatively correlate with immune activation during the early stages of HIV-1 infection. We report that FOXP3+CD127lo expressing CD4+ T cells increases in primary HIV-1 infection over time. Furthermore, the FOXP3+CD127lo CD4+ T cells may, in fact, reduce the levels of T cell activation following primary infection. It is interesting that the positive correlation between FOXP3+CD127lo CD4+ and CD25+CD127lo CD4+ T cells noted in HIV-uninfected persons is not only lost but may also be reversed in early, chronic HIV-1 infection. Unlike FOXP3+CD127lo CD4+, the level of FOXP3+CD25+CD127lo CD4+ T cells did not correlate with T cell activation, suggesting that these cells were not effective in reducing T cell activation. These observations suggest that different Treg populations may have different effects on reducing immune activation in HIV-1 infection and that the FOXP3+CD127lo CD4+ T cell population may be particularly important in limiting immune activation.