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Regulatory T (Treg) cells play a key role in dampening excessive immune activation. However, antiretroviral therapy (ART) -naive HIV-1 infection maintains the immune system in a sustained state of activation that could alter both Treg cell surface markers and functions. As Treg cell surface markers are directly linked to their functions the overall objective of this study was to determine how ART-naive HIV infection affects the phenotypic properties of Treg cells. Our data showed that in ART-naive HIV-1 infection, Treg cells are dominated by effector (CD45RA +  CD27 -  CCR7 - CD62L - ) and effector memory (CD45RA -  CD27 -  CCR7 -  CD62L - ) cells. In contrast Treg cells from HIV-negative individuals were mainly naive (CD45RA +  CD27 +  CCR7 +  CD62L + ) and central memory (CD45RA - CD27 +  CCR7 +  CD62L + ) cells. Whereas effector and effector memory Treg cells showed enhanced expression of CD39 (P < 0·05), CD73 (P < 0·001), HLA-DR and CD38 (P < 0·001); naive and central memory Treg cells showed a significant reduction in the expression of these markers. Overall Treg cell frequencies within total CD4 + T cells correlated positively with plasmatic HIV-1 viral load. As increased viral load is associated with augmented CD4 + T-cell destruction; this could suggest a resistance of peripheral Treg cells to HIV-1 destruction. Hence the modulation of Treg cell phenotype and frequencies could be considered in designing immunotherapeutic strategies targeting immune system restoration during HIV-1 infection., (© 2017 John Wiley & Sons Ltd.)