Background Regulatory T cells (Tregs) may play an important role in immunopathology during HIV-1 infection.Transcription factor forkhead box P3 (FoxP3) orchestrates the development of Tregs and is a useful marker to identify this population.Using a FoxP3 phenotype to define Tregs,we investigated the level and phenotype of peripheral blood natural CD4+Tregs and assessed the relationship between the frequencies and absolute numbers of CD4+Tregs and disease progression among untreated HIV-infected men who have sex with men (HIV+MSM) in China.Methods Fifty-two untreated HIV+MSM with CD4+T-cell counts of ≤350 cells/μl or ＞350 cells/μl were compared in a cresssectional study.Twelve age-matched HIV-uninfected MSM and nine patients receiving antiratroviral therapy for at least 1 year were also included.Expression of CD25,CD127,CD45RA,CCR7 and CTLA-4 was assessed on CD4+Tregs using polychromatic flow cytometry.Results The percentage of CD4+Tregs was increased significantly,whereas CD4+Tregs expressed less CTLA-4 in HIV+MSM compared with controls.CD4+Tregs displayed predominantly an effector memory phenotype (CD45RA-CCR7-),phenotypically distinct from conventional CD4+T cells.Moreover,the expansive frequencies of CD4+Tregs coincided with lower CD4+T-cell counts and higher viral loads whereas the absolute numbers of CD4+Tregs were associated with higher CD4+T-cell counts and lower viral loads.The expansion of Tregs was also associated with CD8+T-cell activation.Conclusion Increased proportions and decreased numbers of CD4+Tregs are associated with HIV progression,and their functions may impair with the progression of HIV infection.