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This research focuses on the cultural practices in relation to the spread of HIV among the Sena people of the Nsanje district in Malawi. The concern of the study is the high prevalence rate of HIV in the Nsanje district which is 35% higher than in any other district in Malawi. People of Nsanje district have maintained their cultural practices within the context of HIV and AIDS. There are multiple sexual partners involved in the sexual rituals which increase high risk of the spread of HIV and sexual intercourse is used in most rituals as a tool for purification. The key cultural practices that have been maintained are widow cleansing, widow inheritance, bonus wife, fisi (hyena) custom, polygamy and bzyade. It is a great challenge for church and the community to modify or discourage these cultural practices because some of the people in Nsanje district claim that these cultural practices have been practiced since the existence of their forefathers in Nsanje district. The community together with the church should take strong stand in responding to the cultural practices in an attempt to combat the spread of HIV.