BACKGROUND: T follicular helper (Tfh) cells within germinal centers (GC) of lymphoid tissue play an important role in HIV infection. Recently, circulating Tfh cells have been described, which share phenotypic and functional characteristics with GC Tfh cells. This study aimed to investigate the effect of HIV infection on four circulating Tfh subsets, including CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+PD-1+ cells. PATIENTS AND METHODS: Peripheral blood samples were collected from 33 HIV-infected individuals and 21 healthy controls. The frequency and absolute number of CD3, CD4 and CD8 cells were detected by flow cytometry. The frequency of circulating Tfh cell subsets was also determined by flow cytometry. The correlation between the frequency of Tfh subsets and CD4 T cells counts was assessed by Pearson correlation analysis. RESULTS: There was no significant difference in the frequency of peripheral CD4+CXCR5+ Tfh cells between HIV-infected individuals and healthy controls. However, the percentages of circulating CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+PD-1+ Tfh cells were significantly higher in individuals with HIV infection than those of healthy controls. Furthermore, the percentage of CD4+CXCR5+PD-1+ Tfh cells showed negative correlation with CD4 T cell counts in HIV-infected individuals. CONCLUSION: Our results suggested the potential involvement of circulating CD4+CXCR5+PD-1+ Tfh cells during the development of HIV infection.