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A negative association between human immunodeficiency virus (HIV) infection and multiple sclerosis (MS) is expected, as MS pathogenesis is triggered by auto-reactive T-cells, which are depressed in case of HIV infection. Furthermore, there is increasing evidence that HIV-infected MS patients may benefit from antiretroviral therapy. We report the case of a woman suffering from relapsing-remitting MS (RR-MS) who contracted HIV-1 infection while she was treated with low-dose interferon (IFN) beta-1a since five years. With combination antiretroviral therapy (cART) in addition to IFN beta-1a, the patient had normal CD4+ cell counts, undetectable viral load, and no more clinical and radiological evidence of MS activity. The reason why HIV infection has a protective role for developing MS, and how antiretroviral therapy is effective in modifying MS course are intriguing questions which need further investigations.