Abstract Background The acute phase of HIV infection is characterized by massive depletion of CD4 T cells, high viral plasma levels and pronounced systemic immune activation. Regulatory T cells (Tregs) have the potential to control systemic immune activation but also to suppress antigen specific T and B cell response. The co-expression of FoxP3 and Helios transcription factors, has been described for identification of highly suppressive Tregs. The aim of this study was to characterize the phenotype of classic Tregs during early HIV infection, and to assess the correlations between the frequencies and phenotype of Tregs with the plasma viral load, CD4 counts, immune activation and the frequency of antibodies reactive to HIV-1 proteins, measured by an immunochromatographic test. Results The relative frequency of classic Tregs cells in peripheral blood correlated positively with HIV viral load and immune activation of CD8 T cells, and inversely with absolute CD4 counts and development of anti-HIV antibodies in subjects with early HIV infection. However, the expression of Helios in classic Tregs was inversely correlated with viral replication and immune activation, and positively with recovery of CD4 T cell counts and appearance of antibodies reactive to HIV-1 proteins. Conclusion These results raise the hypothesis that classic Tregs are inefficient at controlling systemic immune activation in subjects with early HIV infection and may be associated with delayed production of antibodies against HIV proteins, delaying the control of viral replication. Conversely, Helios expressing Tregs might contribute to control of viral replication by mechanisms involving the limitation of systemic immune activation.