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Objectives: We studied the risk and circumstances of separation (due to either maternal death or drug use) between women infected by human immunodeficiency virus (HIV) type 1 and their children., Methods: This analysis was based on the French Prospective Study of Infants Born to HIV-seropositive Women (1986 through 1993). Data recorded at each follow-up visit included the mother's effective presence with the child and the child's care after separation., Results: A child's cumulative risk of long-term or permanent separation from his or her mother was 37% at 60 months. Maternal drug use was associated with an added risk during the child's first years (adjusted relative risk [RR]=3.4, 95% confidence interval [CI]=2.3, 5.0). The risk among drug users was even higher when the mother used injection drugs during pregnancy (adjusted RR=2.9, 95% CI=1.9, 4.3). Risk of early separation related to drug use tended to diminish since survey initiation. After separation, 57% of the children were placed through child welfare services and 43% were cared for by relatives., Conclusions: In the French Prospective Study, 2% to 3% of HIV-infected children were separated each year from their mothers as a result of the mothers death from acquired immunodeficiency syndrome (AIDS). Separations related to drug use have decreased over the years, and the family is becoming the most frequent carer after separation.