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EXPOSURE TO FACTOR
VIII
It has also been argued that cumulative exposure to foreign proteins in Factor VIII concentrates leads to CD4+ T cell depletion and AIDS in hemophiliacs (Duesberg, 1992). This view is contradicted by several large studies. Among HIV-seronegative patients with hemophilia A enrolled in the Transfusion Safety Study, no significant differences in CD4+ T cell counts were noted between 79 patients with no or minimal factor treatment and 53 patients with the largest amount of lifetime treatments (cumulative totals in the latter group ranged from 100,000 to 2,000,000 U in two years) (Hassett et al., 1993). Although the CD4+ T cell counts seen in the low- and high- groups (756/mm3 and 718/mm3, respectively) were 20 to 25 percent lower than controls, such levels are still within the normal range. In a report from the Multicenter Hemophilia Cohort Study, the mean CD4+ T cell counts among 161 HIV-seronegative hemophiliacs was 784/mm3; among 715 HIV-seropositive hemophiliacs, the mean CD4+ T cell count was 253/mm3 (Lederman et al., 1995). In another study, no instances of AIDS-defining illnesses were seen among 402 HIV-seronegative hemophiliacs treated with factor therapy or in 83 hemophiliacs who received no treatment subsequent to 1979 (Aledort et al., 1993; Mosely et al., 1993). In a retrospective study of patients with severe hemophilia A, the rate of CD4+ T cell loss was 31.4 every six months for 41 HIV-seropositive individuals without AIDS and 49.7 every six months for 14 HIV-seropositive individuals with AIDS. In contrast, among 28 HIV-seronegative individuals, CD4+ T cell counts increased at a rate of 13.1 cells/six months (Becherer et al., 1990). In a study of children and adolescents with hemophilia, the median CD4+ T cell count of 126 HIV-seronegative individuals was 895/mm3 at study entry; no individuals had CD4+ T cell counts below 200/mm3. In contrast, 26 percent of seropositive children had CD4+ T cell counts of less than 200/mm3; the mean CD4+ T cell count for seropositive children was 423/mm3 (Jason et al., 1994). Although some reports have suggested that high-purity Factor VIII concentrates are associated with a slower rate of CD4+ T cell decline in HIV-infected hemophiliacs than products of low and intermediate purity (Hilgartner et al., 1993; Goldsmith et al., 1991; de Biasi et al., 1991), other studies have shown no such benefit (Mannucci et al., 1992; Gjerset et al., 1994). In a study of 525 HIV-infected hemophiliacs, Transfusion Safety Study investigators found that neither the purity nor the amount of Factor VIII therapy had a deleterious effect on CD4+ T cell counts (Gjerset et al., 1994). Similarly, the Multicenter Hemophilia Cohort Study found no association between the cumulative dose of plasma concentrate and incidence of AIDS among 242 HIV-infected hemophiliacs and thus "no support for cofactor hypotheses involving either antigen stimulation or inoculum size" (Goedert et al., 1989). In addition to the evidence from the cohort studies cited above, it should be noted that 10 to 20 percent of wives and sex partners of male HIV-positive hemophiliacs in the United States are also HIV-infected (Pitchenik et al., 1984; Kreiss et al., 1985; Peterman et al., 1988; Smiley et al., 1988; Dietrich and Boone, 1990; Lusher et al., 1991). Through December 1994, the CDC had received reports of 266 cases of AIDS in those who had sex with a person with hemophilia (CDC, 1995a). These data cannot be explained by a non-infectious theory of AIDS etiology. |