The depletion in circulating dendritic cells (DCs) and inverse correlation with viral load have been described in human immunodeficiency virus (HIV)-infected patients. The aim of this study was to investigate whether the DC blood count in antiretroviral-treated patients might be predictive of viral load control independent of CD4+ T cell count. Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were enumerated using a newly developed flow cytometric assay based on TruCOUNT. A significant reduction of circulating pDCs and mDCs was detected both in untreated and -treated subjects. The probability of experiencing viral load increase according to pDC, and CD4 count at baseline was evaluated in 39 treated patients. Individuals with lower baseline pDCs were more likely to have an increase of HIV-RNA during the 30 month follow-up in comparison with patients with high pDCs (p < 0.001). In particular, the pDC measurement may be useful in the context of a high CD4 count, to distinguish the patients who have virological failure despite high CD4 counts. These findings suggest that in treated patients the enumeration of circulating DCs, especially pDC count, can augment the predictive value of CD4 measurement in predicting virologic failure.