High Versus Ultra-high Purity Factor VIII Concentrate Therapy: Prospective Evaluation of Immunological and Clinical Parameters in HIV Seronegative and Seropositive Hemophiliacs
D Varon
The National Hemophilia Centre, The Chaim Sheba Medical Centre, Tel-Hashomer, Israel
,
S Schulman
The National Hemophilia Centre, The Chaim Sheba Medical Centre, Tel-Hashomer, Israel
,
R Dardik
The National Hemophilia Centre, The Chaim Sheba Medical Centre, Tel-Hashomer, Israel
,
A Barzilai
The National Hemophilia Centre, The Chaim Sheba Medical Centre, Tel-Hashomer, Israel
,
D Bashari
The National Hemophilia Centre, The Chaim Sheba Medical Centre, Tel-Hashomer, Israel
,
U Martinowitz
The National Hemophilia Centre, The Chaim Sheba Medical Centre, Tel-Hashomer, Israel
This study aimed at evaluation of the immunological status and the clinical course of both HIV seronegative and seropositive hemophiliacs treated with either an ultra-pure factor VIII product (UP-F VIII), or a high-purity F VIII (HP-F VIII) concentrate. Eighteen HIV seronegative patients were divided into two groups of therapy and their immune status was followed for 2 years. During the second year of the study 8 patients of the HP-F VIII and 6 from the UP-F VIII therapy groups were switched to the alternative F VIII concentrates. Eighteen asymptomatic HIV seropositive patients were also divided into therapy groups and their immune status and any development of HIV-related symptoms were followed for 4 years. Evaluation of the HIV seronegative patients during the first year did not reveal any differences between the groups in the CD4 or CD8 cell counts, in natural killer cell (NK) activity, or in the mitogenic responses of T lymphocytes to Phytohemagglutinin (PHA), and of B lymphocytes to Pokeweed mitogen (PWM). The switch of 8 patients from the HP-F VIII and 6 from the UP-F VIII groups to the alternative concentrate did not yield any changes in their immune profile during the second year of the study. The HIV seropositive groups differed in the initial CD4 count, with a lower CD4 count (193 ± 126 vs 437 ± 142) and a higher F VIII consumption (63,000 ± 17,000 vs 26,000 ± 10,000) in the UP-F VIII group. During four years of follow-up the annual decline of CD4 counts in the UP-F VIII group was 8 (5%) compared with 74 (17%) in the HP-F VIII group, with only the latter being significant. The decrease in delayed type hypersensitivity, was also significant in the HP-F VIII group alone. Cumulative HIV-related symptoms with an advancement from CDC category II to category IV were observed in 2 and 5 of the UP-F VIII and HP-F VIII treatment groups, respectively. Our data, taken separately or together with previously published studies, demonstrate the impact of purity of the F VIII concentrate on CD4 decline and possibly also on the clinical course in HIV seropositive hemophiliacs. In the seronegative group, we found no support for a beneficial effect on the immune system by switching to an ultra-pure F VIII concentrate.
References
1
Schulman S.
Effects of factor VIII concentrates on the immune system in hemophilic patients. Ann Hematol 1991; 63: 145-151
3
Froebel KS,
Madhok R,
Forbes CD,
Lennie SE,
Lowe GDO,
Sturrock RD.
Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate?. Br Med J 1983; 287: 1091-1093
5
Mahir WS,
Millard RE,
Booth JC,
Flute PT.
Functional studies of cell-mediated immunity in haemophilia and other bleeding disorders. Br J Haematol 1988; 69: 367-70
7
Thorpe R,
Dilger P,
Dawson NJ,
Barrowcliffe TW.
Inhibition of interleukin-2 secretion by factor VIII concentrates: a possible cause of immunosuppression in haemophiliacs. Br J Haematol 1989; 71: 387-91
8
Mannhalter JW,
Ahmad R,
Lebl H,
Gottlicher J,
Wolf HM,
Eibl MM.
Comparable modulation of human monocyte functions by commercial factor VIII concentrates of varying purity. Blood 1988; 71: 1662-1668
9
Eibl MM,
Ahmad R,
Wolf HM,
Linnau Y,
Gotz E,
Mannhalter JW.
A component of factor VIII preparations which can be separated from factor VIII activity down modulates human monocyte functions. Blood 1987; 69: 1153-1160
10
de Biasi R,
Rocino A,
Miraglia E,
Mastrulle L,
Quirino AA.
The impact of a very high purity factor VIII concentrate on the immune system of human immunodeficiency virus-infected hemophiliacs: a randomized, prospective, two-year comparison with an intermediate purity concentrate. Blood 1991; 78: 1919-1922
11
Mannucci PM,
Gringeri A,
de Biasi R,
Baudo F,
Morfini M,
Ciavarella N.
Immune status of asymptomatic HIV-infected hemophiliacs: randomized, prospective, two-year comparison of treatment with a high-purity or an intermediate-purity factor VIII concentrate. Thromb Haemost 1992; 67: 310-313
13
Seremetis SV,
Aledort LM,
Bergman GE,
Bona R,
Bray G,
Brettler D,
Eyster ME,
Kessler C,
Lau T-S,
Lusher J,
Ruckles F.
Three-year randomised study of high-purity or intermediate-purity factor VIII concentrates in symptom-free HIV seropositive ahemophiliacs: effects on immune status. Lancet 1993; 342: 700-703
15
Higgins JA,
Goodall AH.
Immune changes in HIV seronegative haemophiliacs: is this related to infection with hepatitis C virus?. Brit J Haematol 1991; 77: 2
16
Webster A,
Lee CA,
Cook DG,
Grundy JE,
Emery VC,
Kemoff PBA,
Griffiths PD.
Cytomegalovirus infection and progression towards AIDS in haemophiliacs with human immunodeficiency virus infection. Lancet 1989; 2: 63-66
17
Koot M,
Keet IPM,
Vos AHV,
de Goede REY,
Roos MThL,
Coutinho RA,
Meidema F,
Schellekens PThA,
Tersmetre M.
Prognostic value of HIV-1 syncytium-incuding phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 1993; 118: 681-688
18
Keet IP,
Krijnen P,
Koot M,
Lange JM,
Miedema F,
Goudsmit J,
Goutinho RA.
Predictors of rapid progression to AIDS in HIV-1 seroconverters. AIDS 1993; 7: 51-57
19
Varon D,
Handsher R,
Dardik R,
Gitel S,
Ra’anani P,
Heim M,
Martinowitz U.
Response of hemophilic patients to poliovirus vaccination: correlation with HIV serology and with immunological parameters. J Med Virol 1993; 40: 91-95