Sterile α motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) can inhibit reverse transcription of human immunodeficiency virus-1 (HIV-1) by hydrolyzing intracellular deoxy-ribonucleoside triphosphate. However, its role in HIV-1 disease progression has not been extensively studied. To study the impacts of SAMHD1 on HIV-1 disease progression, especially on DNA levels, we investigated SAMHD1 levels in the peripheral blood of HIV-1 elite controllers (ECs), antiretroviral therapy (ART) naive viremic progressors (VPs) and patients with HIV-1 receiving ART (HIV-ARTs) compared with healthy controls. In addition, the present study analyzed the relationship between SAMHD1 and interferon-α, immune activation and HIV-1 DNA levels. The results of the present study demonstrated elevated SAMHD1 expression in the peripheral blood mononuclear cells of all patients withHIV-1, but higher SAMHD1 expression in the CD4+ T cells of only ECs compared with healthy controls. Immune activation was increased in the VPs and decreased in the ECs compared with healthy controls. Substantially lower HIV-1 DNA levels were identified in ECs compared with those in VPs and HIV-ARTs. SAMHD1 expression was associated with low levels of immune activation. No significant correlation was observed between SAMHD1 and HIV-1 DNA levels. Overall, the findings of the present study indicated that SAMHD1 was highly expressed in ECs, which may be associated with low immune activation levels, but was not directly related to HIV-1 DNA levels.