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We analyzed the effect of interferon α (IFN-α) and ribavirin (RBV) therapy on cell-associated human T-lymphotropic virus type 2 (HTLV-2) DNA in HIV-1-coinfected patients receiving antiretroviral therapy. Sixty-one patients under suppressive antiretroviral therapy were included: 37 with hepatitis C virus (HCV) infection, 15 with sustained virologic response (N= 10), relapse (N= 2), or with nonresponse (N= 3) after IFN-α/RBV treatment, and 9 with spontaneous HCV RNA clearance. Patients who were treated with IFN-α/RBV or had spontaneous HCV clearance had lower level of cell-associated HTLV-2 DNA (P= 0.022 and P= 0.040, respectively). Both IFN-alpha treatment and the ability to spontaneously clear HCV infection seem to reduce cell-associated HTLV-2 DNA in HIV-1-coinfected patients.