The critical role of interleukin-28B (IL28B)/interferon-λ3 (IFN-λ3) polymorphisms on the susceptibility to hepatitis C virus infection and the response to peginterferon-ribavirin therapy has encouraged exploration of similar effects on other viruses. Given that IFN-λ mediates anti-HIV-1 activity, the protective role of IL28B polymorphisms was examined in 29 seronegative individuals at risk for HIV-infection and in 68 HIV-positive carriers with and without rapid progression of immunodeficiency. No protective role of IL28B polymorphism was found examining both HIV-disease progression and HIV-protection.