AEGiS-GMHC: Coagulation Substitutes and CD4 Decline in Hemophilia

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Coagulation Substitutes and CD4 Decline in Hemophilia

Gay Men's Health Crisis: Treatment Issues, Volume 7 no. 8 September, 1993
Naomi Pfeiffer and Greg Haas

Impurities in clotting factor substitutes used by persons with hemophilia to replace their missing factor VIII may hasten CD4 decline in those with HIV, according to a preliminary report released at the Ninth International Conference on AIDS in Berlin. The multicenter study, presented by Dr. Stephanie Seremetis of Mt. Sinai Medical Center in New York City, showed that purer concentrates were associated with slower declines in CD4 counts in HIV-positive persons with hemophilia.[1] According to Dr. Seremetis, the findings were a "surprise" to the researchers themselves. In her presentation, she stated that the study results "should persuade the experts to rethink current treatment of these patients with standard intermediate-purity products."

At least 80 percent of the persons with hemophilia in the United States who repeatedly infused factor VIII concentrates between 1978 and 1985 became infected with HIV. During that period, the internal bleeding which occurs in persons with hemophilia was treated with pooled blood products that contained impurities, including HIV. In 1985, heat-treated intermediate-purity factor concentrates became generally available. These products were free of HIV but contained other viruses and proteins. In 1989, a new generation of high-purity concentrates was approved by the FDA. These products are purified using monoclonal antibodies and contain substantially fewer contaminants. In December 1992, the FDA aproved a second type of high-purity product which is manufactured through recombinant technology. The higher-purity products are significantly more expensive than the earlier concentrates.

Previous studies have indicated that impurities present in intermediate-purity concentrates can suppress lymphocyte function in both HIV-positive and HIV-negative persons with hemophilia and can activate HIV in latently infected cells. Earlier evidence convinced British health authorities to switch to the monoclonal antibody-derived factor VIII concentrates for their HIV-positive population, according to Seremetis. Other countries are weighing the move despite the higher costs. However, some U.S. hematologists are not convinced that the switch is worth the expense and do not prescribe higher-purity concentrates for their clients.

In the randomized, controlled trial of factor VIII products, 60 HIV- positive patients with severe hemophilia were given either an intermediate-purity or high-purity concentrate. After three years, 35 patients remained in the study. Twenty of these were in the high- purity arm and fifteen were in the intermediate-purity arm. Those in the high-purity arm maintained stable CD4 counts (mean 416 at baseline, 393 after three years), while the fifteen on the intermediate-purity arm experienced a significant drop (mean 378 at baseline, 190 after three years). According to the researchers, the difference in CD4 levels was so dramatic that the trial was stopped after three years. However, at the time the trial was stopped, there was no difference in AIDS-defining events (one in each arm). Dr. Seremetis noted that the study was the longest and largest of its kind and that the CD4 difference was independent of antiretroviral therapy. She suggested that repeated infusions of intermediate-purity concentrates may impair cell-mediated immunity.

No one has suggested that high-purity factor VIII concentrates have either immune-restoring or antiviral capabilities. Rather, the study lends preliminary support to the view that reducing the quantity of foreign proteins that the immune system encounters may slow its deterioration.

1 Seremetis S, et al. Abstract PO-B42-2495. Ninth International AIDS Conference. Berlin. June 6-11, 1993.

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