ACQUIRED IMMUNODEFICIENCY SYNDROME, HUMAN IMMUNODEFICIENCY VIRUS AND HEMOPHILIA
Authors: Levine P H 
Published: August 2018

Less than 15 years ago the National Heart, Lung and Blood Institute surveyed physicians in the United States in order to characterize the demographics of hemophilia. The average age of persons with hemophilia in the United States was found to be 11.5 years old. By 10 years later, the life expectancy was predicted to be normal, and indeed the average age of persons with hemophilia in the U.S. is now in the early twenties. Early, intensive and predictably efficacious control of hemorrhage has made this result possible, and the therapeutic product which has allowed such control is commercial clotting factor concentrate.

We now know that starting in 1978, and with great frquency during 1982 and 1983, the majority of U.S. hemophiliacs were infected with human immunodeficiency virus (HIV). It is estimated that as of January, 1987, approximately two thirds of the 20,000' persons with hemophilia in the United States have been infected with HIV. Among those with severe factor VIII deficiency, more than 9056 are seropositive. As of 1/5/87, there were 288 cases of AIDS among U.S. hemophiliacs, for an AIDS rate of approximately 2.256 of those with HIV infection. This number included 185 with severe, 32 with moderate and 28 with mild hemophilia A; 12 with severe, 6 with moderate and 1 with mild hemophilia B; 9 with vWD, and 4 others. A disproportionate number were older patients: 55 were ages 1-19; 62 ages 20-29; 85 ages 30-39, and 86 age 40 or older. Although the AIDS attack rate is no longer climbing logarhythmically, new cases are certainly still occurring.

A variety of other HIV-related syndromes have emerged. Of great concern is immune thrombocytopenia, which is now relatively common; among a group of 209 carefully followed HIV-positive patients at our center, 31 (1556) are or have been thrombocytopenic. Progressive failure to normally gain height and weight in children with hemophilia has recently been shown by our group to correlate with HIV antibody positivity, and also with decreased T4/T8 ratio, decreased T4 cell count, decreased skin test reactivity, and subsequent development of ARC or AIDS in some such children. Finally, a picture of progressive fall in T4 count associated with recurrent non-specific infections and increased likelihood of positive viral culture, may predict an increased risk of developing AIDS.

We know that the immune dysfunction in hemophilia is complex, and not wholly explained by HIV infection. One important factor may be the many foreign proteins contained in commercial clotting factor concentrates, and their ability to stimulate T cells. It is known that latent HIV infection in cultured T4 lymphocytes can be induced to enter the proliferative, viral secretory phase by the addition of soluble foreign antigens to the cell culture. Recent data of Brettler and colleagues, to be presented at this meeting, suggest that the use of highly purified VI!I:C (specific activity >3000 u/mg) in place of the present extremely impure products, may improve the immune dysfunction in hemophilia. This observation offers a new hypothetical approach to the prevention of progressive T4 cell depletion in HIV infected hemophiliacs, and requires immediate and extensive further study.

The psychosocial burden of HIV infection is immense. The need for extensive, formal education and support programs is largely unmet in most parts of the world. Such programs are best run out of hemophilia treatment centers in most cases, and must include an active program on prevention of sexual transmission, provision of HIV testing before and during pregnancies, provision for maintenance of confidentiality, etc. Education concerning HIV is like all other forms of education. It requires formal organization, a curriculum, active rather than passive learning in which there is interaction between the teacher and the pupil, time for planned repetition, reinforcement with written materials, and assessment of goals achieved. For all of these reasons it is inappropriate to assume that the physician at the hemophilia center will be able to provide an adequate education program. Adquate paramedical personnel will need to undertake this effort, under the directjon of the physician.