A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia

Article Abstract:

AIDS (acquired immunodeficiency syndrome) has been shown to be caused by the human immunodeficiency virus (HIV). However, the onset of the disease does not necessarily occur shortly after the person becomes infected. Infection by the virus itself is judged by the presence of specific antibodies that are produced by the body against the infection, and by the number of a particular class of lymphocytes (a type of white blood cell; the measurement is known as the CD4+ cell count). The rate of individuals developing AIDS after detection of HIV antibodies in their blood (seroconversion) has been studied in a group of individuals for whom the precise time of infection is known, namely hemophiliacs. Unlike individuals who have a high-risk lifestyle (e.g., homosexuals or drug users), patients with hemophilia usually become infected with HIV by medical treatment with contaminated human blood products; treatment records often allow determination of the time of infection. Out of a group of 1,219 individuals with hemophilia or similar conditions, 319 individuals for whom the date of HIV seroconversion was known were studied in detail. Statistical analysis of this group led to the finding that the risk of AIDS is directly related to age in individuals that seroconvert. The risk of an individual developing full-blown AIDS after infection is 2.67 per 100 person-years for the total population, 0.83 for persons between 1 and 11, and 5.66 for individuals 35 to 70. The common predictors, the number of CD4+ lymphocytes and a decrease in the quantity of antibodies produced against the virus (anti-p24 or anti- gp120), were valid indicators of increasing risk of AIDS in adults. Adolescents, on the other hand, had a lower rate of antibody loss, and a lower rate of AIDS after loss of anti-p24. There is thus evidence that the disease is more devastating among older individuals, and that children and adolescents are more resistant to developing AIDS. The article also speculates on the meaning of these findings, and suggests that the problems of AIDS are related to the re-initiation of previous infections that have been accumulated during a longer life.

Measurement, Demographic aspects, HIV (Viruses), HIV, Disease transmission, HIV antigens

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Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia

Article Abstract:

Hemophilia A is a relatively common genetic disorder that affects the blood clotting process, resulting in an tendency to hemorrhage. As an X-linked disorder, it occurs predominantly in men, affecting about 1 in 10,000 males. In its most severe form, it is a life-threatening illness. Patients with hemophilia A do not possess adequate activity of clotting factor VIII. The introduction of factor VIII treatment has resulted in a better quality of life and longer life expectancy for hemophilia patients. However, since the factor VIII has been obtained from blood, hemophilia patients have always been at higher risk for viral hepatitis and immunization against alloantigens. More recently, AIDS has been added as one of the diseases hemophiliacs may contract from contaminated factor VIII. This has provided an incentive to develop recombinant factor VIII, produced by bacteria using the human factor VIII gene. Since recombinant factor VIII does not come from human blood, the opportunity for the transmission of viral diseases is effectively eliminated. Two research groups have reported success with the cloning of factor VIII, one of the largest molecules cloned to date. Now, investigation of the effectiveness of recombinant factor VIII in treating 107 hemophiliacs has revealed that the new substance is safe and effective. The new recombinant factor VIII was no less effective or long-lasting in the blood than the traditional preparations. Furthermore, the new preparation proved to be no more antigenic than blood-derived factor VIII. As is the case with insulin and other protein factors, one of the major impediments to continued use of a factor VIII preparation is the development of antibodies. A small fraction of patients with hemophilia develop antibodies against factor VIII, which not only bind to the molecule, but inhibit its function. Such inhibitor antibodies developed in eight of the patients; the antibodies were strong in only one. This is comparable to the incidence of inhibitor antibodies seen using blood-derived factor VIII. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects

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Use of recombinant antihemophilic factor in the treatment of two patients with classic hemophilia

Article Abstract:

Classic hemophilia is an inherited disease characterized by a deficiency of factor VIII which is essential for normal blood clotting. Men having this disease can take a preparation of factor VIII concentrated from human blood to control bleeding. Although this treatment has resulted in fewer complications of the disease, patients receiving these human blood concentrates have been found to have a higher exposure to the human immunodeficiency virus (HIV), the virus responsible for AIDS. It is estimated that 80 percent of the patients with hemophilia have been exposed to HIV; 659 cases of AIDS were reported in hemophiliac patients during 1988. New techniques inactivating the virus in factor VIII concentrates and improved prescreening of blood donors have reduced the amount of HIV transmission but, symptoms similar to HIV infections are still reported in some patients. Laboratory preparations using recombinant DNA techniques have created a synthetic factor VIII very similar to human factor VIII. Two patients using this new preparation obtained good results in the treatment of hemophilia and continued research is currently underway.

Methods, Innovations, Prevention, Recombinant DNA, Hepatitis, column

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