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PEDIATRICS Vol. 100 No. 5 November 1997, pp. 817-824

Longitudinal Neurological Follow-up of a Group of HIV-Seropositive and HIV-Seronegative Hemophiliacs: Results From the Hemophilia Growth and Development Study

Received Dec 30, 1996; accepted Mar 31, 1997.

Wendy G. Mitchell*, Henry LynnDagger , James F. Bale Jr§, Margaret A. MaederDagger , Sharyne M. DonfieldDagger , Bhuwan Gargparallel , Ann H. Tilton, John K. Willis#, and Timothy P. Bohan**

From the * Childrens Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, California; Dagger  New England Research Institute, Inc, Watertown, Massachusetts; § University of Iowa College of Medicine, Iowa City, Iowa; parallel  Riley Hospital, University of Indiana, Indianapolis, Indiana;  Childrens Hospital of New Orleans, New Orleans, Louisiana; # Tulane University, New Orleans, Louisiana; ** University of Texas Health Science Center, Houston, Texas.

Background.  Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up.

Methods.  Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models.

Results.  The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change.

Conclusions.  These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.

Key words: hemophilia, human immunodeficiency virus, encephalopathy, neurological, longitudinal.




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