From 1995 to 1999, Lewis was Deputy Director of UNICEF. From 2001 until 2006, he worked as United Nations UN Special Envoy for HIV/AIDS in Africa. In this role, he drew attention to the HIV/AIDS crisis and convinced leaders and the public that they have a responsibility to respond. He has been widely praised for his effectiveness in this role. In 2005 he adapted his Massey Lectures in a book titled "Race Against Time", where he describes the disjuncture between what the international community promises and their actions in responding to the pandemic in Africa.